Dissertations / Theses: 'Antiphospholipid syndrome'

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Dennen, Gabrielle. "Assessment of perinatal nurses' knowledge of antiphospholipid syndrome and nursing management of pregnant women with antiphospholipid syndrome." Honors in the Major Thesis, University of Central Florida, 2013. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/841.

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Ames, Paul Richard Julian. "Atherogenesis and atherosclerosis in primary antiphospholipid syndrome." Doctoral thesis, Faculdade de Ciências Médicas. UNL, 2013. http://hdl.handle.net/10362/10293.

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ABSTRACT: In the late seventies the term “Haematological Stress Syndrome” defined some haematological abnormalities appearing in the course of acute and chronic disorders, such as raised plasma levels of fibrinogen (FNG) and factor VIII, reduced fibrinolytic activity and hyperviscosity. In the early nineties the “Membrane stress syndrome hypothesis” proposed the unification of the concepts of haematological stress syndrome with those of oxidation, inflammation and immune activation to explain the pathogenesis of the antiphospholipid syndrome (APS) Antiphospholipid antibodies, coagulation, fibrinolysis and thrombosis. This chapter investigated the occurrence of the “Haematological Stress Syndrome” and thrombosis in 144 participants positive for aPL detected by clotting and immune tests. Among the clotting assays for the detection of lupus anticoagulant, dilute Russell's viper venom time better correlated with a history of venous thrombosis than activated partial thromboplastin time (p<0.0002 vs p<0.009) and was the only test correlated with a history of arterial thrombosis (p<0.01). By regression analysis, serum levels of IgG anticardiolipin antibodies (aCL) associated with the number of venous occlusions (p<0.001). With regards to FNG and von Willebrand factor (vWF), the former rose by 36% (95% CI; 21%, 53%) and the latter by 50% (95% CI; 29%, 75%) at the first venous occlusion and remained unchanged after subsequent occlusions. At variance FNG rose by 45% (95% CI; 31%, 60%) per arterial occlusion and vWF by 27% (95% CI; 10%, 47%) per arterial occlusion throughout. The coagulation/fibrinolytic balance was cross-sectionally evaluated on 18 thrombotic PAPS patients, 18 subjects with persistence of idiopathic aPL and in healthy controls. Markers of thrombin generation prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and of fibrin turnover D-Dimer (D-D) were higher in thrombotic (p=0.006)and non-thrombotic subjects (p=0.0001) than in controls as were those of D-D (p<0.0001 and p=0.003 respectively). TAT levels did not differ. Gender analysed data revealed blunted tPA release (hence a negative venous occlusion test) in thrombotic females but neither in thrombotic males (p=0.01) nor in asymptomatic subjects of either sex. Also, in both patient groups females had higher mean PAI than males (p<0.0002) and control females (p<0.02). The activity of factor XIII (FXIIIa) was evaluated was evaluated in 29 patients with PAPS, 14 persistent carriers of aPL without thrombosis, 24 thrombotic patients with inherited thrombophilia, 28 healthy controls and 32 patients with mitral and aortic valve prosthesis as controls for FXIII only. FXIIIa was highest in PAPS (p=0.001), particularly in patients with multiple (n=12) than single occlusion (p=0.02) and in correlation with PAI (p=0.003) and FNG (p=0.005). Moreover FXIIIa was strongly associated with IgG aCL and IgG anti-2GPI (p=0.005 for both) in the PAPS group and to a lesser degree in the aPL group (FXIIIa with IgG aCL, p=0.02, with IgG anti-2GPI, p=0.04). Altogether these results indicate: 1) a differential relationship of aPL, vWF and FNG with venous and arterial thrombosis; 2) heightened thrombin generation, accelerated fibrin turnover and fibrinolysis abnormalities also in asymptomatic carriers of aPLs; 3) enhanced FXIIIa that may contribute to atherothrombosis via increased fibrin/fibrinogen cross-linking. Lipid profile, lipid peroxidation and anti-lipoprotein antibodies in thrombotic primary antiphospholipid syndrome. Given the atherogenic lipid profile of SLE, the same possibility was explored in PAPS by comparing high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (CHO), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), triglycerides (TG), anti-lipoprotein antibodies, beta-2-glycoprotein I complexed to oxidized low-density lipoprotein (oxLDL-2GPI) and C-reactive protein (CRP) in 34 thrombotic PAPS patients compared to 36 thrombotic patients with inherited thrombophilia (IT), to 18 subjects persistently positive for antiphospholipid antibodies (aPL) with no underlying autoimmune or non-autoimmune disorders and to 28 healthy controls. Average concentrations of HDL (p<0.0001), LDL (p<0.0001), CHO (p=0.0002), ApoAI (p=0.002) were lower in PAPS whereas average TRY was higher (p=0.01) than other groups. Moreover PAPS showed higher IgG anti-HDL (p=0.01) and IgG anti-ApoAI (p<0.0001) as well as greater average oxLDL-2GPI (p=0.001) and CRP (p=0.003). Within PAPS, IgG anti-HDL correlated negatively to HDL (p=0.004) and was an independent predictor of oxLDL-2GPI (p=0.009). HDL and ApoAI correlated negatively with CRP (p=0.001 and p=0.007, respectively). IgG anti-HDL may hamper the antioxidant and anti-inflammatory effect of HDL favouring low-grade inflammation and enhanced oxidation in thrombotic PAPS. Indeed plasma 8-epi-prostaglandin F2α (a very specific marker of lipid peroxidation) was significantly higher in 10 patients with PAPS than 10 age and sex matched healthy subjects (p=0.0002) and strongly related to the titre of plasma IgG aCL (r=0.89, p=0.0004). Hence oxidative stress, a major player in atherogenesis, also characterises PAPS. Nitric oxide and nitrative stress in thrombotic primary antiphosholipid syndrome. Oxidative stress goes hand in hand with nitrative stress and to address the latter plasma nitrotyrosine (NT, marker of nitrative stress), nitrite (NO2-) and nitrate (NO3-) were measured in 46 thrombotic PAPS patients, 21 asymptomatic but persistent carriers of antiphospholipid antibodies (PCaPL), 38 patients with inherited thrombophilia (IT), 33 patients with systemic lupus erythematosus (SLE) and 29 healthy controls (CTR). Average crude NT was higher in PAPS and SLE (p=0.01) whereas average plasma NO2- was lower in PAPS and average NO3- highest in SLE (p<0.0001). In PAPS, IgG aCL titer and number of vascular occlusions negatively predicted NO2-, (p=0.03 and p=0.001, respectively) whereas arterial occlusions and smoking positively predicted NO3- (p=0.05 and p=0.005). Moreover CRP (an inflammatory marker) positively predicted NT (p=0.004). Nitric oxide metabolites relates to type and number of vascular occlusions and to aPL titers, whereas nitrative stress relates to low grade marker) positively predicted NT (p=0.004). Nitric oxide metabolites relates to type and number of vascular occlusions and to aPL titers, whereas nitrative stress relates to low grade inflammation and both phenomena may have implications for thrombosis and atherosclerosis in PAPS Inflammation and immune activation in thrombotic primary antiphospholipid syndrome. To investigate inflammation and immune activation in thrombotic PAPS high-sensitivity CRP (hs-CRP), serum amyloid A (SAA), oxLDL-2GPI, CRP bound to oxLDL-2GPI (CRP-oxLDL-2GPI) (as inflammatory markers) neopterin (NPT) and soluble CD14 (sCD14) (as immune activation markers) were measured by ELISA in 41 PAPS patients, in 44 patients with inherited thrombophilia (IT) and 39 controls (CTR). Compared to other groups, PAPS presented with higher plasma concentrations of inflammatory, hs-CRP (p=0.0004), SAA (p<0.01), CRP-oxLDL-2GPI (p=0.0004) and immune activation markers, NPT (p<0.0001) and sCD14 (p=0.007). By regression analysis SAA independently predicted thrombosis number (p=0.003) and NPT independently predicted thrombosis type (arterial, p=0.03) and number (p=0.04). These data confirm that low-grade inflammation and immune activation occur and relate to vascular features of PAPS. Antiphosholipid antibodies, haemostatic variables and atherosclerosis in thrombotic primary antiphospholipid syndrome To evaluate whether IgG aCL titre, haemostatic variables and the lipid profile bore any relationship to the intima media thickness (IMT) of carotid arteries high-resolution sonography was applied to the common carotid (CC), carotid bifurcation (CB) and internal carotid (IC) of 42 aPL subjects, 29 with primary thrombotic antiphospholipid syndrome and 13 with persistence of aPL in the absence of any underlying disorder. The following were measured: plasma FNG, vWF, PAI, homocysteine (HC), CHO, TG, HDL, LDL, platelet numbers and aCL of IgG and IgM isotype. By multiple regression analysis, IgG aCL titre independently predicted IMT at all carotid segments examined (p always <0.005). Plasma FNG and HC independently predicted IMT at the CB (p=0.001 and p<0.0001, respectively) and IC (p=0.03 and p<0.0001, respectively). These data strongly support an atherogenic role for IgG aCL in patients with aPL in addition to traditional risk factors. The atherosclerosis hypothesis was investigated in an age and sex-matched case-double-control study including 49 thrombotic PAPS patients (18 M, 31 F, mean age 37 ± 11), 49 thrombotic patients for IT and 49 healthy subjects. Average IMT was always greater in PAPS than control patients (CC: p=0.004, CB: p=0.013, IC: p=0.001). By dividing participants into age tertiles the IMT was greater in the second (CC: p=0.003, CB: p=0.023, IC: p=0.003) and third tertiles (CC: p=0.03, CB: p=0.004, IC: p=0.007). Conclusion: Coagulation activation, fibrinolysis depression, hightened fibrin turnover, oxidative and nitrative stress in parallel with low grade inflammation and immune activation characterise thrombotic PAPS: all these are early atherogenic processes and contribute to the demonstrated premature atherosclerosis that should be considered a clinical feature of PAPS.

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Gómez, Puerta José Alfredo. "Antiphospholipid Syndrome: Expanding the Spectrum of Autoimmune Thrombosis." Doctoral thesis, Universitat de Barcelona, 2007. http://hdl.handle.net/10803/2227.

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The antiphospholipid syndrome (APS) is an acquired prothrombotic syndrome characterized by venous or arterial thromboses and pregnancy morbidity. It can present as primary APS without any discernable underlying disease, or in association with systemic autoimmune disease [usually systemic lupus erythematosus (SLE)], infections (mainly chronic viral infections) and malignant process, among others. It may also occur rapidly over days or weeks, when it is known as "catastrophic" APS (CAPS).
The first study described one of the largest known cohorts of patients with primary APS from 4 different referral centers. The final study sample included 128 patients with primary APS with a median age of 42 years and mean follow-up of 9 years. After a median disease duration of 8.2 years, 110 (86%) patients remained with primary APS; 11 (8%) patients developed SLE; 6 (5%), LLD; and 1 (1%), myasthenia gravis. At the end of the study, 113 (88%) patients were alive and 15 (12%) patients had died. Our study confirms that progression from primary APS to SLE or LLD is unusual, even after a long follow-up.
In the second study, we evaluated 120 cases of antiphospholipid antibodies associated with malignancies with a mean age of 56 years, The main hematological malignancies found were B-cell lymphoma, spleen lymphoma and chronic myeloid leukemia. The main solid tumors were renal cell carcinoma, primary tumor of unknown origin, lung adenocarcinoma and breast carcinoma. Around one third of patients achieved aPL remission after treatment.
In the third study, we analyzed 15 cases of CAPS that appeared during pregnancy or the puerperium with a mean age at the time of the CAPS event of 27 years. In 7 of the 14 (50%) cases, CAPS appeared during pregnancy, in 6 (43%) cases it presented during puerperium and in 1 (7%) after curettage for a fetal death. The main clinical and serological characteristics were similar to those of patients with CAPS triggered by other factors, however we found some particular features including placental infarctions, pelvic vein thrombosis and myometrial thrombotic microangiopathy and HELLP syndrome.
Final conclusion: Primary APS is a widely recognized distinct entity which rarely progresses to SLE, even after long-term follow-up. APS may also be associated with other chronic disorders, such as solid tumors or hematological malignancies. In cases with the life-threatening variant of APS known as CAPS, pregnancy and the puerperium are periods of high susceptibility for the development of this often fatal form of presentation.
"SINDROME ANTIFOSFOLIPIDICO: EXPANDIENDO EL ESPECTRO CLÍNICA DE LA TROMBOSIS AUTOINMUNE"

El síndrome antifosfolipídico (SAF) es un síndrome protrombótico adquirido caracterizado por trombosis venosas y arteriales y pérdidas fetales recurrentes. Puede estar presente como SAF "primario" cuando no esta asociado a ninguna enfermedad autoinmune [fundamentalmente el lupus eritematoso sistémico (LES)] o en asociación a otros procesos tales como infecciones y procesos neoplásicos, entre otros. También puede manifestarse de una forma acelerada en días o semanas, caracterizado por trombosis de pequeños órganos y fallo multiorgánico, lo que se conoce como SAF "catastrófico".

En el primer estudio se analizó una de las series más amplia y con más largo seguimiento de pacientes con SAF primario. Se incluyeron 128 pacientes con un seguimiento medio de 9 años. Después de una duración media de la enfermedad de 8 años, 110 (86%) pacientes continúan con el diagnóstico de SAF primario, 11 (8%) pacientes desarrollaron un LES, 6 (5%) una forma incompleta de lupus ("lupus-like disease") y 1 (1%) paciente desarrolló una miastenia gravis. La presencia del test de Coombs positivo confiere un riesgo estadísticamente significativo para el desarrollo de LES. . Nuestro estudio confirma que es inusual que un SAF primario evolucione hacia un LES o una forma incompleta de lupus, incluso tras un período largo de seguimiento.
En el segundo estudio se incluyeron un total de 120 casos con anticuerpos antifosfolipídicos (AAF) asociados a procesos neoplásicos. Las principales neoplasias hematológicas relacionadas a los AAF fueron el linfoma de células B, el linfoma esplénico y la leucemia mieloide crónica. Los principales tumores sólidos fueron el carcinoma de células renales, los tumores de primario desconocido, el adenocarcinoma de pulmón y el cáncer de mama. Alrededor de una tercera parte de los paciente negativizaron los AAF después del tratamiento de la neoplasia.
En el tercer estudio se analizaron 15 pacientes con SAF catastrófico que ocurrieron durante el embarazo o el puerperio. Las características clínicas generales del SAF catastrófico durante el embarazo o el puerperio fueron similares a las del SAF catastrófico desencadenado por otros factores a excepción de una tasa mayor de abortos previos. Sin embargo se encontraron una serie de características particulares, como el síndrome de HELLP, la trombosis placentaria, la microangiopatía trombótica de miometrio o la trombosis de la vena pélvica.

CONCLUSIÓN FINAL: El SAF primario es una entidad propia ampliamente reconocida que en raras ocasiones evoluciona a un LES, incluso tras un período largo de seguimiento. El SAF puede asociarse a una serie de procesos crónicos como lo son las neoplasias hematológicas y los tumores sólidos. En aquellos casos con la variante "catastrófica" del SAF, el embarazo y el puerperio, constituyen un período de alta susceptibilidad para el desarrollo de esta variante altamente letal del SAF.

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Poulton, K. S. "Understanding mechanisms of cellular injury in the antiphospholipid syndrome." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1396605/.

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Patients with the Antiphospholipid Syndrome (APS) have circulating antiphospholipid antibodies (aPL) which cause vascular thrombosis (VT) and/or pregnancy morbidity (PM). Previously we have shown that IgG isolated from patients with APS and VT alone (APS-VT) caused activation of p38 MAPK and NFκB signalling pathways and up-regulation of tissue factor (TF) activity in monocytes. These effects were not seen with IgG from patients with APS and PM alone (APS-PM) or healthy controls. TF up-regulation caused by the APS-VT samples was reduced by p38 MAPK, NFκB, and TLR4 inhibitors, thus implicating a TLR4-MyD88 dependent signalling mechanism. Therefore, my PhD aimed to examine whether IgG isolated from patients with different manifestations of the APS have differential effects upon activation of a pregnancy related cell type; trophoblast cells and a thrombotic related cell type; endothelial cells (EC). IgG was purified from the serum of APS-VT patients, APS-PM patients and two control groups. Using a human first trimester trophoblast cell line, HTR-8 cells, I identified that APS-PM but not APS-VT increased TLR4 and TRIF mRNA expression. HTR-8 cell migration was significantly inhibited in cells treated with APS-PM but not APS-VT and this inhibited migration was restored after pre-treatment with a TLR4 inhibitor. I also identified that both APS-VT and APS-PM increased protease-activated receptor (PAR)-1 and PAR-2 mRNA expression in HTR-8 cells, which was not seen in control IgG treated cells. Work carried out in HUVEC identified that only APS-VT phosphorylated p38 MAPK and not APS-PM or healthy controls. When investigating p38 MAPK phosphorylation in HTR-8 cells however, neither APS-PM nor APS-VT phosphorylated p38 MAPK in this pregnancy related cell type. The results obtained in this thesis identify that IgG purified from patients with different clinical manifestations of the APS have differential effects on a pregnancy related cell type than they do on a thrombotic related cell type.

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Donohoe, Siobhan. "An investigation of antiphospholipid antibody associated obstetric complications." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312964.

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Giannakopoulos, Bill Clinical School St George Hospital Faculty of Medicine UNSW. "Investigations on beta 2-glycoprotein I and antiphospholipid antibodies." Publisher:University of New South Wales. Clinical School - St George Hospital, 2008. http://handle.unsw.edu.au/1959.4/41440.

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An outline of the work contained in this thesis is presented. The first chapter is a critical review of the literature pertaining to the pathophysiological mechanisms operational with regards to the antiphospholipid syndrome (APS). The syndrome is characterised by venous and arterial thrombosis, and recurrent fetal loss, in association with the persistent presence of antibodies targeting the main autoantigen beta 2-glycoprotein I (β2GPI). The second chapter reviews the literature delineating the diverse physiological functions of β2GPI, and then relates them to its role in our current understanding of the pathophysiology of APS. The third chapter presents a critical review of the evidence base for the diagnosis and management of APS. The fourth chapter describes the interaction between β2GPI and the glycoprotein Ib alpha (GPIbα) subunit of the platelet receptor GPIb-IX-V. GPIbα is an important platelet adhesion receptor, which mediates multiple additional functions on the platelet surface, including binding coagulation factor XI (FXI). The implication of the interaction between β2GPI and GPIbα on platelet activation and the release of thromboxane in the presence of anti-β2GPI antibodies is explored, as well as the intracellular pathways via which this activation occurs. The relevance of these findings to understanding APS pathogenesis, in particular thrombosis, is discussed. The fifth chapter delineates the interaction between the fifth domain of β2GPI and FXI and its activated form factor XIa (FXIa). The ability of FXIa to cleave β2GPI between lysine (Lys) 317 and threonine (Thr) 318, and modulate its function is reported. The sixth chapter describes the ability of β2GPI to inhibit FXIa autoproteolytic hydrolysis at the specific FXIa residues arginine (Arg) 507, Arg532 and Lys539. This interaction with β2GPI stabilizes FXIa activity over time, and leads to enhanced FXIa mediated fibrin formation. This is a novel physiological function of β2GPI with important implications. Recent epidemiological studies by others have emphasized the critical role of FXIa in pathological thrombus propagation. The seventh chapter defines the relevance of the FXIa residues Arg507, Arg532 and Lys539 to FXIa mediated inactivation by the main FXIa inhibitor Protease Nexin 2 (PN2), and by Antithrombin III (ATIII). Insights into future directions for research are presented and discussed within each individual chapter.

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Tolomeo, Tanya. "The role of beta2-glycoprotein I-reactive T cells in antiphospholipid syndrome." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19246.

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Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of autoantibodies to phospholipid (PL)-binding proteins, such as beta2-glycoprotein I (beta2GPI), and clinical manifestations including thrombosis and/or recurrent pregnancy loss. Beta2GPI-reactive T cells have been shown to be activated in patients with APS, but the mechanism responsible for this activation remains unclear. Recent studies have proposed that exposure of a cryptic epitope on beta2GPI, as a consequence of binding to PL, leads to the activation of beta2GPI-autoreactive T cells in APS patients. To test this hypothesis, we evaluated the development of beta2GPI-reactive T cells in a murine model of aPL production. C57BL/6 mice were immunized repeatedly with human beta2GPI in the presence of lipopolysaccharide (LPS) to induce aPL production. High levels of circulating aPL were observed as early as the second immunization, but splenic T cell reactivity to beta2GPI was not detectable in vitro until after the fourth immunization. Splenic T cells from mice producing high levels of aPL proliferated in response to native human beta2GPI, alone or bound to anionic PL, but PL-bound beta2GPI appeared to be a more potent antigen. Beta2GPI-reactive T cells produced IL-2 and IFN-gamma, but not IL-4 or IL-10, suggesting a TH1 bias of this T cell response. These results demonstrate that T cell reactivity to beta2GPI can develop in nonautoimmune individuals repeatedly exposed to this antigen in a proinflammatory context (e.g., LPS). Our data further suggest that the beta2GPI-reactive T cells induced in this model have a TH1 bias and may be more reactive to a PL-dependent epitope on beta2GPI than to native beta2GPI.
Le syndrome antiphospholipide (SAPL) est une maladie autoimmune caractérisée par la présence d'auto-anticorps antiphospholipides (aPL) dirigés contre des protéines liant les phospholipides anioniques dont la beta2-glycoproteine I (beta2GPI), ainsi que par des manifestations cliniques incluant la thrombose et la perte foetale récurrente. Il a été démontré que des lymphocytes T spécifiques à la beta2GPI étaient activés chez les patients atteints du SAPL. Cependant, le mécanisme responsable de cette activation lymphocytaire reste nébuleux. Des études récentes ont proposé que l'exposition d'épitopes cryptiques de la beta2GPI, suite à la liaison de cette glycoprotéine à des phospholipides anioniques, engendre l'activation de lymphocytes T autoréactifs spécifiques à la beta2GPI chez les patients atteints du SAPL. Afin de vérifier cette hypothèse, nous avons évalué le développement de lymphocytes T spécifiques à la beta2GPI dans un modèle murin de production d'aPL. Des souris C57BL/6 ont été immunisées à répétition avec de la beta2GPI humaine en présence de lipopolysaccharide (LPS) dans le but d'induire la production d'aPL. Des titres élevés d'aPL circulants ont été observés dès la deuxième immunization, tandis que les lymphocytes T spécifiques à la beta2GPI n'ont été détectés que suite à la quatrième immunisation. Ainsi, les lymphocytes T provenant de la rate des souris produisant des niveaux élevés d'aPL ont proliféré en réponse à la forme native de beta2GPI et encore plus fortement en réponse au complexe beta2GPI-PL. Ces lymphocytes T réactifs à la beta2GPI ont démontré une production d'interleukine 2 et d'interféron gamma. Cependant, aucune interleukine 4 ou 10 n'

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Miranda, Sébastien. "Modulation de la dysfonction endothéliale et de l'altération du glycocalyx endothélial au cours du Syndrome des Antiphospholipides primaire artériel.Approche translationnelle et aspects pharmacologiques Infliximab improves endothelial dysfunction in a mouse model of antiphospholipid syndrome: role of reduced oxidative stress. New insights into antiphospholipid related endothelial dysfunction by assessment of vascular glycocalyx layer. Results from a preliminary case control study." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR006.

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Ce travail a permis chez des patients atteints d'un SAPL artériel primaire mais également dansdes modèles de cultures cellulaires et dans un modèle murin de SAPL de confirmer l'existence d'unedysfonction endothéliale et de montrer pour la première fois l’altération du GCX endothélial.L'implication de l’altération du GCX dans la survenue d'une dysfonction endothéliale, d'un étatpro-thrombotique permanent à distance de toute poussée de la maladie a pu être établie de façondirecte tant au niveau clinique qu'expérimental tout comme son association au développement d'uneathérosclérose précoce infra clinique.L'approche pharmacologique a montré l'effet favorable d'un traitement par un anticorpsmonoclonal anti-TNFα sur la dysfonction endothéliale vasomotrice et d'en caractériser lesmécanismes d'action dans le SAPL. Ainsi, son administration se traduit principalement par laréduction du stress oxydant en modulant la voie de la NADPH oxydase, en diminuant l'expression dela NOS inductible et en luttant contre le découplage de la NOS endothéliale.De même, l'utilisation de l'hydroxychloroquine dans le modèle expérimental de SAPL a pourla première fois, montré un effet protecteur de ce traitement sur la fonction endothéliale, en restaurantune vasorelaxation normale et un niveau de génération de thrombine basal après injection d'anticorpsantiphospholipides humains purifiés.Enfin, le rôle clé de l’héparanase dans l’altération du GCX a pu être démontré et sa modulationtant par l’hydroxychloroquine que par des agents spécifiques laisse entrevoir un effet protecteurendothélial bénéfique qu’il faudra évaluer dans des essais cliniques futurs
This transversal work conducted among antiphospholipid patients, mice and cells confirmedthe existence of an endothelial dysfunction and bring first evidence that glycocalyx shedding couldbe an important part of the pathophysiology of the disease. Glycocalyx shedding is associatedwith prothrombotic state, endothelial dysfunction and led to subclinical atherosclerosis.In this study, we have demonstrated that TNF alpha was responsible of increased oxidative stress anddecreased relaxation response of mesenteric arteries in mice. Anti TNF alpha was able to improve theendothelial function as well as the oxidative stress but failed to improve the eNOS mRNA transcription.Then we have investigated the ability of hydroxychloroquine to prevent the prothrombotic state in miceand cells. The results demonstrated that HCQ completely reversed the prothrombotic state as well as theendothelial function.Finally, we have demonstrated that antiphospholipid antibodies were associated with glycocalyxshedding. This shedding was triggered by an increased heparanase activity in mice and cells. Usingspecific siRNA against heparanase improved the tissue factor expression and the thrombin generationin endothelial cells exposed to antiphospholipid antibodies.Taken together our finding bring evidences that heparanase could be an important target in thepathophysiology of the antiphospholipid antibodies

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Harris, Simon Leigh. "The antigenic binding site of antibodies to factor XII associated with antiphospholipid syndrome." Thesis, University of Kent, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399595.

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Pereira, Delgado Alves Jose Antonio. "Oxidative stress and vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome." Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412911.

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Bertolaccini, Maria Laura. "Antiprothrombin antibodies : detection, immunological characteristics and clinical significance in patients with antiphospholipid syndrome." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408765.

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Popovytch, L. O., and B. V. Doskaliuk. "Identification of anti-moesin antibodies in the serums ofpatients with antiphospholipids syndrome." Thesis, Sumy State University, 2015. http://essuir.sumdu.edu.ua/handle/123456789/41260.

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The antiphospholipid syndrome (APS) is an acquired autoimmune disease characterized by recurrent vascular thrombosis and obstetric complications. However, the precise mechanisms by which the autoantibodies mediate disease remain to be elucidated. Moesin is an intracellular protein that links the cell membrane and cytoskeleton, mediating the formation of microtubules and cell adhesion sites as well as ruffling of the cell membrane, which is crucial for platelet activation.

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Tinning, Lucy J. B. "Cognitive functioning and health related quality of life in patients with primary antiphospholipid syndrome." Thesis, Canterbury Christ Church University, 2011. http://create.canterbury.ac.uk/10259/.

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Section A: This paper reviews the literature surrounding cognitive functioning in patients with Antiphospholipid syndrome (APS) in the context of quality of life as an indicator of adaptation to chronic illness. The review focuses on cognitive functioning in APS patients and related clinical populations, describing and critiquing the empirical research literature exploring the evidence for cognitive deficits in these populations. Psychological theories of adaptation to chronic illness are discussed in relation to the concept of quality of life and research examining the relationship between cognitive dysfunction in APS and related clinical populations and health- related quality of life (HRQoL) is summarised. The limitations of previous research examining these factors are highlighted, demonstrating the need for empirical studies that address cognitive functioning and quality of life in patients with primary APS (PAPS). Section B: Objective: To explore the relationship between cognitive functioning and health related quality of life (HRQoL) in patients with PAPS. Method: Cross sectional comparisons of PAPS patients (PAPS thrombosis; n = 15; PAPS pregnancy; n = 15) and healthy controls (n = 15) on a battery of neuropsychological assessments and a measure of HRQoL. Results: PAPS thrombosis patients were twice as likely to be designated as cognitively impaired compared to PAPS pregnancy patients. PAPS thrombosis patients demonstrated lower performance on measures of memory and executive functioning compared to controls. PAPS pregnancy patients also performed more poorly on these measures compared to controls although not significantly. Both groups demonstrated poor HRQoL across physical and mental subscales. Both groups were significantly more impaired in all physical domains and one mental domain of HRQoL compared to controls. Neuropsychological outcomes in general intellectual abilities, memory and executive functioning were significantly associated with mental HRQoL subscales in PAPS thrombosis and executive functioning and memory were significantly associated with physical HRQoL subscales in PAPS pregnancy. Conclusions: Cognitive impairment is associated with and is more prevalent in PAPS thrombosis patients when compared with PAPS pregnancy patients. Both PAPS groups demonstrate poor HRQoL which is associated with executive functioning and memory. Section C: The critical review is structured to address four specific questions providing a reflective account of how the involvement in this project has contributed to the researcher’s skills and abilities and highlighted areas where further learning is necessary. The review also discusses further clinical applications and research for cognitive functioning and HRQoL in patients with PAPS.

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Hamid, Colleen G. "Identification of anti-beta₂ glycoprotein I auto-antibody regulated gene targets in the primary antiphospholipid syndrome using gene microarray analysis." Thesis, University of Wolverhampton, 2007. http://hdl.handle.net/2436/14407.

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Anti-Beta2-Glycoprotein I antibodies (anti-b2GPI) are strongly associated with thrombosis in patients with primary antiphospholipid syndrome (PAPS). Anti-b2GPI activate endothelial cells (EC) resulting in a pro-thrombotic and pro-inflammatory phenotype. In order to characterise EC gene regulation in response to anti-b2GPI, early global gene expression was assessed in human umbilical vein endothelial cells (HUVEC) in response to affinity purified anti-b2GPI. Sera were collected from patients with PAPS and IgG was purified using HiTrap Protein G Sepharose columns. Polyclonal anti-b2GPI were prepared by passing patient IgG through NHS activated sepharose coupled to human b2GPI. Anti-b2GPI preparations were characterized by confirming their b2GPI co-factor dependence, binding to b2GPI and ability to induce leukocyte adhesion molecule expression and IL-8 production in vitro. Two microarray experiments tested differential global gene expression in 6 individual HUVEC donors in response to 5 different PAPS polyclonal anti-b2GPI (50 mg/ml) compared to 5 normal control IgG (50 mg/ml) after 4 hours incubation . Total HUVEC RNA was extracted and cRNA was prepared and hybridised to Affymetrix HG-133A (Exp.1) and HG-133A_2 (Exp.2) gene chips. Data were analyzed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. Significant change in gene expression was defined as greater than two fold increase or decrease in expression (p<0.05). Novel genes not previously associated with PAPS were induced including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL-18 receptor 1 and growth factors, CSF2, CSF3, IL-6, IL1b and FGF18. Downregulated genes were transcription factors/signaling molecules including ID2. Microarray results were confirmed for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C) using quantitative real-time RT-PCR analysis. This study revealed a complex anti-b2GPI-regulated gene expression profile in HUVEC in vitro. The novel chemokines and pro-inflammatory cytokines identified in this study may contribute to the vasculopathy associated with PAPS.

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Sim, Derek Shu Kay. "The interactions among ß2-glycoprotein I, natural anticoagulants, and complement, significance for the antiphospholipid syndrome." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0017/NQ48714.pdf.

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Cronin, Jennifer. "Behandling med eculizumab vid katastrofalt antifosfolipidsyndrom." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-72856.

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Bakgrund: Eculizumab (Solirisâ) är en monoklonal antikropp som är riktad mot C5 i komplementsystemet. Bindning av eculizumab till C5 förhindrar proteinets klyvning och därmed också aktivering. Eculizumab är godkänt för behandling av atypiskt hemolytiskt uremiskt syndrom och paroxysmal nokturn hemoglobinuri. Sedan behandlingen blivit godkänd för dessa tillstånd har även ”off-label use” vid andra tillstånd varit betydande. En tidigare studie har visat att uppemot 50 % av behandling med eculizumab är off-label use, det vill säga behandling utanför de idag godkända indikationerna. Ett av dessa tillstånd är katastrofalt antifosfolipidsyndrom (KAPS), ett mycket allvarligt tillstånd som karaktäriseras av multipla tromboser som utvecklas under kort tid i flera organ vid vilket eculizumab visat sig ha en potentiellt positiv effekt. KAPS kan uppstå om man har bakomliggande antifosfolipid syndrom (APS) och kan utlösas vid en så kallad ”second hit”, en inflammatorisk stressreaktion orsakad av exempelvis en infektion eller kirurgiskt ingrepp. Eculizumab är ett särläkemedel och är en av de dyraste läkemedelsbehandlingarna i världen. Syfte: Syftet med denna studie var att analysera fall där KAPS behandlats med eculizumab för att utvärdera om eculizumab bör vara standarbehandling vid detta tillstånd. Likheter och olikheter mellan fallen studerades för att utvärdera när det kan vara lämpligt att behandla med eculizumab. Syftet var också att utvärdera detta utifrån ett ekonomiskt perspektiv. Metod: Detta är en litteraturstudie där sökningar i PubMed gjorts efter rapporter som beskriver fall där patienter med KAPS eller som ansetts haft en risk att utveckla KAPS behandlats med eculizumab. Åtta rapporter med totalt tio fall inkluderades och analyserades. Resultat: De rapporter som analyserades visade övergripande en tydlig effekt av behandling med eculizumab. Eculizumab tolkades också i vissa fall som ett kostnadseffektivt alternativ genom bland annat förkortad intensivvård och dialysbehov. Slutsats: Eculizumab har i de fall som analyserats visat sig ha en avgörande betydelse för att reversera ett livshotande tillstånd och skulle kunna vara standardbehandling vid KAPS och förebyggande av KAPS. För att eculizumab, eller en annan komplementhämmare, ska kunna bli standardbehandling krävs ytterligare forskning på KAPS och dess relation till komplementsystemet.
Catastrophic antiphospholipidsyndrome (CAPS) is a rare but highly fatal condition characterized by thrombosis in multiple organs, often associated with a rapid progression of disease and serious complications for the patient. A rapid diagnosis and treatment is therefore a key to manage this condition. The conventional treatment, which consists of anticoagulation, steroids, plasma exchange and intravenous immunoglobulins, reduces mortality but CAPS is still associated with high mortality. To find the mechanism of how and why this condition evolves is therefore important. There has been progress to find out the pathogenesis and one clue appears to be the complement system. Therefore, a new type of treatment has been used in patients who have been diagnosed with antiphosphlipidsyndrome (APS) and have had a risk of developing CAPS, or have been diagnosed with definitive or probable CAPS. This treatment is aimed at inhibiting parts of the complement system and consists of a monoclonal antibody called eculizumab. Lately eculizumab has been used off label in patients diagnosed with CAPS and in patients that has been at risk of developing CAPS. The results of this treatment have been positive and have therefore been considered as a possible alternative for treating CAPS. The aim of this study was to evaluate if eculizumab can be an alternative to treat patients with CAPS and patients diagnosed with APS who have a risk of developing CAPS. In order to evaluate treatment with eculizumab in patients with CAPS, searches on cases were done in the database PubMed for reports of patients with CAPS or at risk of developing CAPS who have been treated with eculizumab. Eight reports with a total of ten cases were found and used in order to answer the hypothesis of this study. In the ten cases that were analyzed there was a clear connection between the treatment and the recovery. In both patients with CAPS and patients at risk of developing CAPS the treatment with eculizumab was considered of significant importance. Because of the rarity of this condition, every case makes significant impact into the understanding of this potentially fatal condition. For future new cases, the present report will stand as an important source for making decisions about treatment with eculizumab. With time and more cases with positive results eculizumab has the potential to become conventional treatment for CAPS.

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Ghassemifar, Sara. "Streptococcal mAb10F5 interacts with synaptic vesicles due to antiphospholipod activity." Virtual Press, 2008. http://liblink.bsu.edu/uhtbin/catkey/1398710.

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Hypermetabolism, observed in Sydenham's chorea (SC); a complication of acute rheumatoid fever (ARF) involving binding of streptococcal M protein antibodies in the brain, may result from an increase in glutamate release. The interaction of mAb 1 OF5, a specific M protein antibody subtype, with brain proteins (e.g. Rabphilin-3A), synaptic vesicles (SVs) and synaptosomal fraction (SF) was examined. Rat brain slices immunostained with mAb l OF5 revealed an interaction with choroid plexus and elements appearing to be neuropils. Dot blotting demonstrated an interaction of mAb I OF5 with both SVs and SFs. Western blotting revealed a smear from mAb 10F5 against the SF fraction. However, both modified SVs and pure liposomes examined by fluorescent and confocal microscopy bound mAbl0F5 suggesting a direct interaction with phospholipids. ELISA demonstrated binding of mAb1OF5 with negatively charged phospholipids involved in antiphospholipid syndrome (APS). Hypermetabolism and binding at the choroid plexus is observed in SC and APS supporting the connection between these disorders.
Department of Physiology and Health Science

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Mangerona, Lucilene Rossilho [UNESP]. "Trombofilias e abortos recorrentes." Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/88102.

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Made available in DSpace on 2014-06-11T19:23:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-28Bitstream added on 2014-06-13T19:49:52Z : No. of bitstreams: 1 mangerona_lr_me_botfm.pdf: 551674 bytes, checksum: fa33b5ef943c594fe040a66778a352bd (MD5)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Ministério da Saúde
Secretaria do Estado da Saúde de São Paulo
A perda gestacional recorrente idiopática é multifatorial, pois envolve fatores de risco clínicos e biológicos. A trombofilia pode ser definida como uma predisposição para trombose. Anormalidades na hemostasia que estão associadas com trombofilias clínicas incluem defeitos hereditários, tais como os anticoagulantes naturais Antitrombina III, Proteína S e Proteína C ou fatores de coagulação, as mutações do fator V Leiden, gene da protrombina G20210A, metilenotetrahidrofolato redutase MTHFR C677T, e defeitos adquiridos, tal como Síndrome Antifosfolípide e a Hiperhomocisteinemia. O presente trabalho foi realizado com 70 mulheres, sendo que 35 mulheres apresentavam 3 ou mais abortos recorrentes inexplicáveis, e 35 mulheres voluntárias clinicamente normais, para todas as mulheres foram feitas as investigações para os anticoagulantes naturais da coagulação e investigação para as mutações do fator V Leiden, gene da protrombina G20210A e metilenotetrahidrofolato redutase MTHFR C677T e as deficiências adquiridas. Em nosso estudo, encontramos resultados estatísticamente significantes para a síndrome do anticorpo antifosfolípide (trombofilia adquirida). Em nosso estudo observamos um grande número de defeitos trombofílicos adquiridos sendo que alguns estão em associação com a mutação do fator V Leiden e MTHFR C677T, porém mais pesquisas são necessárias para confirmar ou contestar as causas das trombofilias,e avaliar a eficiência e segurança da tromboprofilaxia em mulheres grávidas.
The idiopathic appealing gestational loss is multifactorial because it involves clinical and biological risk factors. Thrombophilia can be defined as a predisposition for thrombosis. Abnormalities in homeostasis that are associated with clinical thrombophilia include hereditary defects, such as natural anticoagulants as Antithrombin III, S Protein and C Protein or coagulation factors, mutations of V Leiden factor, gene of G20210A prothrombin, MTHFR C677T methilene redutase tetrahydropholat, and acquired defects just as Antiphospholipid Syndrome and Hyperhomocisteinemy. The present work was accomplished with 70 women, and 35 women showed 3 or more inexplicable appealing abortions, and 35 women voluntary clinically normal. For all women were made investigations for natural anticoagulants of coagulation and investigations for mutations of V Leiden factor, gene of G20210A prothrombin, MTHFR C677T methilene redutase tetrahydropholat, and acquired defects. In study we found statistically significant results for antiphospholipid antibody syndrome (acquired thrombophilia). In our study it was observed a great number of thrombophilics acquired defects, and some of then are associated to mutation of V Leiden factor and MTHFR C677T, however more researches are necessary to confirm or to answer the causes of the thrombophilia and to evaluate the efficiency and safety of the thromboprophylaxis in pregnant women.

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19

Salvan, Elisa. "L'efficacia del trattamento in rapporto al rischio nella sindrome da antifosfolipidi in corso di gravidanza. Studio retrospettivo multicentrico europeo." Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3422649.

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Background. The optimal treatment for obstetric Antiphospholipid Syndrome (APS) has yet to be established. Therapy based on Low Dose Aspirin (LDA) alone or in combination with heparin is considered conventional treatment for the disorder, although approximately 20% of pregnancies thus treated have nevertheless negative outcomes. Additional risk factors for pregnancy loss were recently identified during a multicentre study conducted by us on APS pregnant women treated with conventional treatment. Objectives. To compare pregnancy outcomes in APS patients following different treatment strategies and to define risk profiles depending on additional risk factors in order to utilize risk stratification methods to identify subsets of patients who would most likely benefit from one strategy or another. Materials and Methods. An European, multicentre, retrospective, follow-up study was conducted. Basal and pregnancy data were collected from pregnant APS patients, diagnosed on the basis of the Sidney Criteria. The recruitment criteria for our study were at least one of the following additional risk factors for pregnancy loss: Systemic lupus erythematosus, triple positivity for antiphospolipid antibodies (aPL), previous thrombosis. Patients being treated with the following therapies were considered: LDA, prophylactic dose heparin ± LDA, therapeutic dose heparin ± LDA, second-line treatment protocols (plasmapheresis/immunoabsorption and/or intravenous immunoglobulins). Anticardiolipin and anti-beta2glycoprotein I antibodies of IgG and IgM isotypes were determined by an ELISA method utilizing different home-made or commercial procedures. Lupus Anticoagulants were assessed by a series of coagulation tests using platelet-poor plasma samples and following internationally accepted guidelines. Univariate and logistic regression analyses were carried out. Results. Two hundred two pregnancies in 158 APS patients were assessed. The women’s mean age when the pregnancy began was 32.5 years ± 4.6 SD (range 20-44) and the mean disease duration was 5.2 years ± 4.5 SD (range: 0-22). Pregnancy outcome was positive in 149 cases (73.8%), which produced 150 (there was a twin delivery) viable infants (78 males = 52% and 72 females = 48%), born at 36.2 ± 3 SD mean gestational weeks. The infants’ mean Apgar score at 5 minutes was 9.1 ± 1.3 SD and their percentile weight was 55.8 ± 24.9 SD. There were 53 (26.2%) pregnancy losses. When pregnancy outcome was assessed without taking additional risk factors into consideration, there were no significant differences in the live birth rate in the women treated with different therapies. Pregnancy outcome was then assessed in relation to the risk profiles defined on the basis of the three additional risk factors considered. The only risk profile which led to significant differences in outcomes depending on the treatment utilized was the “triple positivity aPL and previous thrombosis” subset: the live birth rate in that subset was 92.9% in the patients treated with second line therapy compared to 58.3% in those treated with conventional therapy (Fisher test, p-value < 0.05; OR=9.3, CI 95%: 1.3–65.6). Those results were confirmed when a logistic regression analysis adjusted for confounding variables was conducted (OR=9.6; 95% CI: 1.1-84.3). Discussion. This study identified a subset of APS women with “triple aPL positivity + previous thrombosis”, in whom the second line treatment seemed to be more effective than the conventional treatments. It can be concluded that treatment of obstetric APS should be differentiated on the basis of the additional risk factors outlined here. In particular, the best treatment for patients with “triple aPL positivity + previous thrombosis” seems to be second line treatment in addition to the conventional therapy.
Background. Il trattamento ottimale della Sindrome da Antifosfolipidi (APS) ostetrica è attualmente sconosciuto. La terapia con aspirina a basso dosaggio (LDA) da sola o associata all’eparina rappresenta il trattamento convenzionale per l’APS ostetrica. Nonostante questo trattamento, circa il 20% delle gravidanze hanno esito sfavorevole. Recentemente abbiamo individuato alcuni fattori di rischio aggiuntivi di perdita gravidica in corso di gravidanza trattata con terapie convenzionali. Scopo della Tesi. Confrontare gli outcomes di gravidanza ottenuti a seguito dei diversi trattamenti e definire dei precisi profili di rischio al fine di analizzare l’efficacia della terapia sulla base della stratificazione del rischio. Materiali e Metodi. E’ stato condotto uno studio europeo di tipo retrospettivo e multicentrico. Sono stati raccolti i dati basali e quelli in corso di gravidanza di donne affette da APS, diagnosticata sulla base dei Criteri di Sydney, che presentavano almeno uno dei seguenti tre fattori di rischio aggiuntivi: associazione con il Lupus Eritematoso Sistemico (LES), triplice positività per Antifosfolipidi (aPL) e pregressa trombosi. Sono state prese in considerazione le pazienti trattate con le seguenti terapie: LDA, eparina a dose profilattica ± LDA, eparina a dose terapeutica ± LDA, protocolli di II livello (plasmaferesi/immunoassorbimento e/o immunoglobuline endovena) e nessuna terapia. Le determinazioni degli anticardiolipina e anti-Beta2 Glicoproteina I sono state eseguite presso i singoli Centri con il metodo ELISA seguendo procedure diverse sia “home-made” che commerciali, mentre il Lupus Anticoagulant è stato testato con una serie di metodi emocoagulativi in accordo con la corrente letteratura. I metodi statistici utilizzati sono stati l’analisi univariata e la regressione logistica. Risultati. Il numero di gravidanze considerate nello studio è stato complessivamente 202, relative a 158 pazienti. L’età media delle donne al momento della gravidanza era 32,5 anni ± 4,6 DS (range: 20-44) con una durata media di malattia di 5,2 anni ± 4,5 (range: 0-22). L’esito favorevole è stato osservato in 149 gravidanze (73,8%), che si sono concluse con la nascita di 150 neonati (un parto gemellare), di cui 78 (52%) maschi e 72 femmine (48%), nati mediamente alla 36,2^ SG ± 3 DS, con un Apgar medio a 5 minuti di 9,1 ± 1,3 DS e un peso in percentili di 55,8 ± 24,9 DS. Ci sono state 53 perdite (26,2%). In assenza della considerazione del rischio non si sono osservate differenze significative nelle prevalenze dei nati vivi tra le donne che assumevano le diverse tipologie di trattamento prese in considerazione. L’outcome primario è stato analizzato in relazione ai 7 profili di rischio definiti sulla base delle combinazioni di: pregressa trombosi, LES e triplice positività aPL. Accorpando i trattamenti convenzionali, l’unico profilo su cui è stata rilevata una differenza statisticamente significativa è stato quello caratterizzato dai fattori “triplice positività aPL + pregressa trombosi”, dove si è osservata una prevalenza di bambini nati vivi pari al 92,9% nei trattamenti di II livello versus il 58,3% nei trattamenti convenzionali (Fisher test, p-value < 0,05 e OR 9,3; 95% CI:1,3 - 65,6). Questi risultati sono stati confermati dall’analisi di regressione logistica che ha fornito una stima dell’odds ratio aggiustata per le variabili confondenti (OR 9,6; 95% CI: 1,1-84,3). Discussione. Da questo studio è emerso un sottogruppo di donne caratterizzato dalla presenza di “triplice positività aPL + pregressa trombosi”, dove la terapia di II livello è risultata più efficace per numero di nati vivi rispetto al trattamento convenzionale. In particolare si è messa in evidenza l’importanza dell’uso del trattamento di II livello nell’APS ostetrica. Possiamo concludere che la terapia dell’APS ostetrica andrebbe differenziata sulla base del rischio. In particolare, nelle donne con “triplice positività aPL + pregressa trombosi” il trattamento di elezione potrebbe essere quello di II livello associato alla terapia convenzionale.

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Mangerona, Lucilene Rossilho. "Trombofilias e abortos recorrentes /." Botucatu : [s.n.], 2007. http://hdl.handle.net/11449/88102.

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Orientador: Izolete Aparecida Thomazini Santos
Banca: Paulo Eduardo de Abreu Machado
Banca: Márcia Aparecida Sperança
Resumo: A perda gestacional recorrente idiopática é multifatorial, pois envolve fatores de risco clínicos e biológicos. A trombofilia pode ser definida como uma predisposição para trombose. Anormalidades na hemostasia que estão associadas com trombofilias clínicas incluem defeitos hereditários, tais como os anticoagulantes naturais Antitrombina III, Proteína S e Proteína C ou fatores de coagulação, as mutações do fator V Leiden, gene da protrombina G20210A, metilenotetrahidrofolato redutase MTHFR C677T, e defeitos adquiridos, tal como Síndrome Antifosfolípide e a Hiperhomocisteinemia. O presente trabalho foi realizado com 70 mulheres, sendo que 35 mulheres apresentavam 3 ou mais abortos recorrentes inexplicáveis, e 35 mulheres voluntárias clinicamente normais, para todas as mulheres foram feitas as investigações para os anticoagulantes naturais da coagulação e investigação para as mutações do fator V Leiden, gene da protrombina G20210A e metilenotetrahidrofolato redutase MTHFR C677T e as deficiências adquiridas. Em nosso estudo, encontramos resultados estatísticamente significantes para a síndrome do anticorpo antifosfolípide (trombofilia adquirida). Em nosso estudo observamos um grande número de defeitos trombofílicos adquiridos sendo que alguns estão em associação com a mutação do fator V Leiden e MTHFR C677T, porém mais pesquisas são necessárias para confirmar ou contestar as causas das trombofilias,e avaliar a eficiência e segurança da tromboprofilaxia em mulheres grávidas.
Abstract: The idiopathic appealing gestational loss is multifactorial because it involves clinical and biological risk factors. Thrombophilia can be defined as a predisposition for thrombosis. Abnormalities in homeostasis that are associated with clinical thrombophilia include hereditary defects, such as natural anticoagulants as Antithrombin III, S Protein and C Protein or coagulation factors, mutations of V Leiden factor, gene of G20210A prothrombin, MTHFR C677T methilene redutase tetrahydropholat, and acquired defects just as Antiphospholipid Syndrome and Hyperhomocisteinemy. The present work was accomplished with 70 women, and 35 women showed 3 or more inexplicable appealing abortions, and 35 women voluntary clinically normal. For all women were made investigations for natural anticoagulants of coagulation and investigations for mutations of V Leiden factor, gene of G20210A prothrombin, MTHFR C677T methilene redutase tetrahydropholat, and acquired defects. In study we found statistically significant results for antiphospholipid antibody syndrome (acquired thrombophilia). In our study it was observed a great number of thrombophilics acquired defects, and some of then are associated to mutation of V Leiden factor and MTHFR C677T, however more researches are necessary to confirm or to answer the causes of the thrombophilia and to evaluate the efficiency and safety of the thromboprophylaxis in pregnant women.
Mestre

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Rehder, Patricia Moretti 1973. "Prevalencia de anticorpos antifosfolipides em gestantes diabeticas e os resultados gestacionais e perinatais." [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310790.

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Orientador: Belmiro Gonçalves Pereira
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A prevalência de anticorpos antifosfolípides em gestantes diabéticas é alta, ocasionando alterações gestacionais e perinatais. O objetivo do estudo foi diagnosticar e tratar as gestantes diabéticas com anticorpos presentes e descrever os resultados gestacionais e perinatais. Foram analisadas 56 gestantes diabéticas que deram entrada no Pré-Natal Especializado do CAISM/Unicamp, entre julho de 2003 a março de 2004. Todas as que aceitavam participar do estudo foram submetidas à coleta de sangue para dosagem de anticorpos antifosfolípides (anticoagulante lúpico e anticorpo anticardiolipina). Se um ou outro anticorpo estivesse presente, a gestante seria tratada com AAS e Heparina. Foram caracterizados os perfis da gestante, da evolução da gestação e do recém-nascido. Foram diagnosticados anticorpos antifosfolípides em 7% das 56 gestantes e os resultados gestacionais e perinatais foram descritos. Nas gestantes diabéticas com anticorpos antifosfolípides a duração do diabetes foi de cinco em uma das gestante e dez anos nas outras três gestantes. A idade variou entre 27 e 38 anos e uma das gestantes era primigesta, outra secundigesta e as outras duas multíparas. As gestantes com anticorpos antifosfolípides, que foram tratadas, tiveram resultados gestacional e perinatal satisfatórios
Abstract: The prevalence of antiphospholipid antibodies in pregnant women with pre-gestational diabetes is high, causing gestational and perinatal alterations. The purpose of this study was to diagnose and treat diabetic pregnant women with presence of antibodies and describe the gestational and perinatal results. An analysis was made of 56 diabetic pregnant women who enrolled in the pre-natal specialization at CAISM/UNICAMP, between July, 2003 and March, 2004. All the diabetic pregnant women who agreed to participate in the study had blood collected for antiphospholipid antibody dosage (lupus anticoagulant and anticardiolipin antibody). If any other antibodies were present, the pregnant woman would be treated with Aspirin and Heparin. The following data with reference to the pregnant woman were recorded: age, gestational age, time of diabetes mellitus duration, treatment prior to and during gestation, previous illnesses, hypertension in pregnancy, amniotic liquid index, parturition, way of giving birth, Apgar index, fetal malformation, fetal hypoglycemia and birth weight. Antiphospholipid antibodies were diagnosed in 7% of the 56 pregnant women and their gestational and perinatal results were described. In the diabetic pregnant women with antiphospholipid antibodies, the duration of the diabetes was from five to ten years, that is to say, pregnant women with long-standing diabetes. The pregnant women with antiphospholipid antibodies ranged from 27 to 38 years of age, and some of the descriptions indicated that they had gone through a bad obstetric experience. The pregnant women with antiphospholipid antibodies, who were treated, had satisfactory gestational and perinatal results
Mestrado
Tocoginecologia
Mestre em Tocoginecologia

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Rodrigues, Carlos Ewerton Maia. "Adipocitocinas na síndrome antifosfolípide primária: potenciais marcadores de inflamação, resistência insulínica e síndrome metabólica." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-17062011-163644/.

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INTRODUÇÃO: Síndrome antifosfolípide está associada com aterosclerose acelerada. Embora adipocitocinas exerçam um papel fundamental na interface entre obesidade, inflamação, resistência insulínica e aterosclerose, a exata natureza e relativa contribuição das adipocitocinas, como potenciais marcadores, requer investigação na síndrome antifosfolípide primária (SAFP). OBJETIVO: Este estudo foi desenvolvido para avaliar a possível associação das adipocitocinas com síndrome metabólica (SM), inflamação e outros fatores de risco cardiovascular na SAFP. MÉTODOS: 56 pacientes com SAFP e 72 controles saudáveis pareados por sexo e idade foram incluídos. Adiponectina, leptina, visfatina, resistina, inibidor do ativador de plasminogênio-1 (PAI-1), lipoproteina (a), glicemia, insulina, VHS, PCR, ácido úrico e perfil lipídico foram dosados. SM foi definida de acordo com os critérios da Federação Internacional de Diabetes (IDF) e resistência insulínica foi estabelecida pelo índice de homeostasis model assessment (HOMA). RESULTADOS: Leptina [21,5 (12,9- 45,7) vs 12,1 (6,9-26,8) ng/mL, P=0.001] foi maior em SAFP do que em controles. Adiponectina (P=0,10), resistina (P=0,23), visfatina (P=0,68) and PAI-1 (P=0,77) não diferiu entre os grupos. Em SAFP, leptina e PAI-1 foram positivamente correlacionada com IMC (r=0,61 and 0,29), HOMA-IR (r=O,71 and 0,28) and CRP (r=0,32 and 0,36). Adiponectina foi negativamente correlacionada com IMC (r=-0,28), triglicérides (r=-0,43), HOMA-IR (r=-0,36) e positivamente correlacionada com HDL (r=0,37), aCL IgG (r=0,41), anti- 2GPI IgG (r=0,31) e anti- 2GPI IgM (r=0,38). A análise de pacientes com e sem SM revelou uma associação positiva com leptina (P=0,002) e PAI-1 (P=0,03) e uma associação negativa com adiponectina (P=0,042). No modelo de regressão linear múltipla, observamos que as variáveis que independentemente influenciam a adiponectina foram triglicérides (P<0,001), VLDL-c (P=0,002) e anti-2GPI IgG (P=0,042), leptina foram IMC (P<0,001), glicemia (P=0,046), HOMA-IR (P<0,001) e VHS (P=0,006) e PAI-1 foram PCR (P=0,013) e SM (P=0,048). CONCLUSÕES: O presente estudo demonstra que as adipocitocinas podem estar envolvidas com inflamação, resistência insulínica e SM em pacientes com SAFP
INTRODUCTION: Antiphospholipid syndrome is associated with accelerated atherosclerosis. Although adipocytokines play a key role in the interface between obesity, inflammation, insulin resistance and atherosclerosis, the exact nature and relative contribution of adipocytokines as potential markers warrant further investigation in primary antiphospholipid syndrome (PAPS). OBJECTIVE: This study was undertaken to evaluate a possible association of adipocytokines with metabolic syndrome (MetS), inflammation and other cardiovascular risk factors in PAPS. METHODS: Fifty-six PAPS patients and 72 age- and gender-matched healthy controls were included. Sera samples were tested for adiponectin, leptin, visfatin, resistin, plasminogen activator inhibitor-1 (PAI-1), lipoprotein (a), glucose, insulin, ESR, CRP, uric acid and lipid profiles. MetS was defined according to the guidelines of the International Diabetes Federation (IDF) and insulin resistance was established using the homeostasis model assessment (HOMA) index. RESULTS: Concentrations of leptin [21.5 (12.1-45.7) vs 12.1 (6.9-26.8) ng/mL, P=0.001] were higher in PAPS than in controls. Concentrations of adiponectin (P=0.10), resistin (P=0.23), visfatin (P=0.68) and PAI-1 (P=0.77) did not differ between patients and controls. In PAPS, leptin and PAI-1 levels were positively correlated with BMI (r=0.61 and 0.29), HOMA-IR (r=0.71 and 0.28) and CRP (r=0.32 and 0.36). Adiponectin was negatively correlated with BMI (r=-0.28), triglycerides (r=-0.43) and HOMA-IR index (r=-0.36) and positively correlated with HDL (r=0.37), aCL IgG (r=0.41), anti- 2GPI IgG (r=0.31) and anti- 2GPI IgM (r=0.38). Further analysis of patients with and without MetS revealed a positive association of the syndrome with leptin (P=0.002) and PAI-1 (P=0.03) and a negative association with adiponectin (P=0.042). In the multiple linear regression model, we observed that the variables that independently influence the adiponectin were triglycerides (P<0.001), VLDL-C (P=0.002) and anti-2GPI IgG (P=0.042), leptin were BMI (P<0.001), glucose (P=0.046), HOMA-IR (P <0.001) and ESR (P=0.006) and PAI-1 were CRP (P=0.013) and MetS (P=0.048). CONCLUSION: The findings of the present study provide evidence that adipocytokines may be involved in inflammation, insulin resistance and metabolic syndrome of PAPS patients

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Weel, Ingrid Cristina. "Avaliação do inflamassoma NLRP3 e autofagia em placentas de gestantes portadoras de pré-eclâmpsia." Botucatu, 2016. http://hdl.handle.net/11449/143845.

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Orientador: Maria Terezinha Serrão Peraçoli
Resumo: A pré-eclâmpsia (PE) é uma síndrome clinicamente identificada por hipertensão arterial e proteinúria e está associada à produção excessiva de citocinas proinflamatórias, deficiência na produção de citocinas reguladoras e aumento nos níveis séricos de anticorpos antifosfolípides (aPLs) em pacientes com PE grave. Os aPLs são uma família de autoanticorpos que reagem com proteínas ligantes de fosfolipídios, sendo seu principal alvo a beta-2 glicoproteina I (β2GPI). Estes anticorpos são responsáveis por inibir a diferenciação do sinciciotrofoblasto e restringir a migração trofoblástica, resultando em remodelação anormal das arteríolas espiraladas, alteração característica da PE. O inflamassoma é um complexo proteico que promove a secreção das citocinas proinflamatórias interleucina-1 beta (IL-1β) e interleucina 18 (IL-18) e, também a secreção da proteína “high-mobility group box 1” (HMGB1) após ativação por patógenos e/ou produtos endógenos associados ao dano celular. A autofagia é uma via de degradação celular ou de eliminação de organelas e proteínas através de processos lisossomais que são importantes para a manutenção da homeostase celular, promovendo a sobrevivência das células em resposta ao estresse. O presente trabalho teve como objetivos: 1. Investigar as proteinas relacionadas ao inflamassoma e à autofagia em placenta de gestantes portadoras de pré-eclâmpsia e de normotensas; 2. Avaliar a relação existente entre inflamassoma e autofagia em células de trofoblasto extravil... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Preeclampsia (PE) is a syndrome clinically identified by hypertension and proteinuria and is associated with excessive production of proinflammatory cytokines, deficiency in the production of regulatory cytokines, and increased serum levels of antiphospholipid antibodies (aPLs) in patients with severe forms of PE. aPLs are a family of autoantibodies that react with phospholipid binding proteins, which the main target is beta 2 glycoprotein-I (β2GPI). These antibodies are responsible for inhibiting the differentiation of syncytiotrophoblast and restrict trophoblast migration, resulting in abnormal remodeling of the spiral arterioles, characteristic alteration in PE. The inflammasome is a protein complex that promotes the secretion of the proinflammatory cytokines interleukin-1 beta (IL-1β) and interleukin 18 (IL-18), and also the secretion of high-mobility group box 1 (HMGB1) protein after activation by pathogens and/or endogenous products associated with cellular damage. Autophagy is a pathway of cell degradation or elimination of organelles and proteins by lysosomal processes that are important for the maintenance of cellular homeostasis by promoting the survival of cells in response to stress. The objectives of the present study are: 1. To investigate the proteins related to inflammasome and autophagy in placenta from pregnant women with PE and from normotensive control; 2. To evaluate the relationship between inflammasome and autophagy in human extravillous trophoblast cel... (Complete abstract click electronic access below)
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Hisano, Danielle Martins de Medeiros. "Imunização contra influenza pandêmica em síndrome antifosfolípide primária: gatilho para trombose e produção de autoanticorpos?" Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-20042016-163848/.

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Os pacientes com doenças reumáticas crônicas exibem um risco aumentado de contrair infecções. Consequentemente, sua vacinação é indispensável. Há relatos da produção de anticorpos antifosfolípides e tromboses após infecções e vacinação nesta população, exceto em síndrome antifosfolípide (SAF) primária. O objetivo principal deste estudo foi avaliar a curto e longo prazos um painel de anticorpos antifosfolípides após a vacinação contra influenza A/H1N1 (sem adjuvante) em SAF primária e controles saudáveis. Quarenta e cinco pacientes com SAF primária e 33 controles saudáveis foram imunizados e prospectivamente avaliados antes da vacinação e 3 semanas e 6 meses após a vacinação. Os anticorpos antifosfolípides foram determinados por ensaio imunoenzimático (ELISA) e incluíram os anticorpos IgG e IgM a seguir: anticardiolipina (aCL), anti-beta2glicoproteína I (anti-beta2GPI), anti-anexina V, anti-fosfatidilserina e anti-protrombina. O anticorpo anti-Sm foi igualmente determinado por ELISA e o anti-DNA dupla hélice, por imunofluorescência indireta. Avaliamos clinicamente à ocorrência de tromboses arterial e venosa. A frequência pré-vacinação de pelo menos um anticorpo antifosfolípide foi significativamente maior nos pacientes com SAF primária comparados aos controles (58% vs 24%, p = 0,0052). A frequência global de anticorpos antifosfolípides pré-vacinação e 03 semanas e 06 meses após a vacinação permaneceu inalterada tanto em pacientes (p = 0,89) como em controles (p = 0,83). A frequência de cada anticorpo específico nos dois grupos permaneceu estável nas três avaliações (p > 0,05). A frequência de cada anticorpo mantevese invariável nos pacientes tratados com cloroquina (p > 0,05). Em 3 semanas, 2 pacientes com SAF primária deselvolveram um anticorpo antifosfolípide novo porém transitório (aCL IgG e IgM), enquanto que em 6 meses novos anticorpos foram observados em 6 pacientes e nenhum apresentou altos títulos. Anti-Sm e anti-DNA dupla hélice foram negativos e nenhuma nova trombose arterial ou venosa foi observada durante o estudo. Este foi o primeiro estudo a demonstrar que a vacina contra influenza pandêmica em pacientes com SAF primária não induz tromboses e uma produção significante de anticorpos antifosfolípides a curto e longo prazos. (ClinicalTrials.gov, #NCT01151644).
Chronic rheumatic disease patients exhibit an increased risk for infections. Therefore, vaccination is imperative. Antiphospholipid antibodies (aPL) and thrombosis triggering after infections and vaccination in this population were reported, except for primary antiphospholipd syndrome (PAPS). Study\'s main objective was short and long-term evaluation of a panel of antiphospholipid autoantibodies following pandemic influenza A/H1N1 non-adjuvant vaccine in primary antiphospholipid syndrome patients and healthy controls. Forty-five PAPS and 33 healthy controls were immunized with A/H1N1 pandemic influenza vaccine. They were prospectively assessed at pre-vaccination, 3 weeks and 6 months after vaccination. aPL autoantibodies were determined by an enzyme-linked immunosorbent assay (ELISA) and included IgG/IgM: anticardiolipin (aCL), anti-beta2GPI; anti-annexin V, anti-phosphatidyl serine and antiprothrombin antibodies. Anti-Sm was determined by ELISA and anti-dsDNA by indirect immunfluorescence. Arterial and venous thrombosis were also clinically assessed. Pre-vaccination frequency of at least one aPL antibody was significantly higher in PAPS patients versus controls (58% vs. 24%, p=0.0052). The overall frequencies of aPL antibody at pre-vaccination, 3 weeks and 6 months after immunization remained unchanged in patients (p=0.89) and controls (p=0.83). The frequency of each antibody specificity for patients and controls remained stable in the three evaluated period (p > 0.05). The frequency of each antibody kept invariable in PAPS patients under chloroquine treatment (p > 0.05). At 3 weeks, 2 PAPS patients developed a new but transient aPL antibody (aCL IgG and IgM), whereas at 6 months new aPL antibodies were observed in 6 PAPS patients and none had high titer. Anti-Sm and anti-dsDNA autoantibodies were uniformly negative and no new arterial or venous thrombosis were observed throughout the study. This was the first study to demonstrate that pandemic influenza vaccine in PAPS patients does not trigger short and long-term thrombosis or a significant production of aPL related antibodies. (ClinicalTrials.gov, #NCT01151644)

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Lambrianides, A. "An investigation of the molecular basis of interactions between human monoclonal antibodies and antigens that are clinically relevant in systemic lupus erythematosus and the Antiphospholipid Syndrome." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1444917/.

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Autontibodies to a wide variety of antigens are associated with systemic lupus erythematosus (SLE) and the Antiphospholipid Syndrome (APS). Previous studies have demonstrated the importance of somatic mutations and arginine residues in the complementarity determining regions (CDRs) of pathogenic anti-dsDNA and antiphospholipid antibodies. This thesis describes the study of two human monoclonal IgG antibodies, B3 (anti-DNA) and IS4 (antiphospholipid) that were derived from a patient with active SLE and primary APS respectively. I have demonstrated in-vitro expression and mutagenesis of B3 and IS4 and used this expression system to investigate the importance of the arginine residues in B3VH and IS4VH. The mutant heavy chains, as well as the wild-type VH were expressed with different light chains and the resulting antibodies assessed for binding to nucleosomes, alpha-actinin, cardiolipin (CL), phosphatidylserine (PS), beta-2-glycoprotein I (foGPI), and the N-terminal domain of p2GPI (Domain I) using direct binding assays. The results obtained have shown that the presence of arginine at position 53 in B3VH was essential but not sufficient for binding to dsDNA and nucleosomes. Conversely, the presence of this arginine reduced binding to alpha-actinin, pzGPI and Domain I of P2GPI. The fact that the arginine to serine substitution at position 53 in B3VH significantly alters binding of B3 to different clinically relevant antigens, but in opposite directions implies that this arginine residue plays a critical role in the affinity maturation of the antibody B3. Furthermore, of four arginine residues in IS4VH CDR3 substituted to serine, two at positions 100 and 100g reduced binding to all antigens, while two at positions 96 and 97 reduced binding to fcGPI but increased or decreased binding to CL and PS. Only one H/L chain combination bound neutral phospholipid and none bound dsDNA hence, these effects are particularly relevant to antigens important in APS. Therefore, my findings suggest that these four arginine residues have developed as a result of somatic mutations driven by an antigen containing both phospholipid and frGPI. These results extend our knowledge of the structure-function relationship of human anti-DNA and anti phospholipid antibodies and aid in our understanding of how these antibodies lead to pathogenicity and what we need to target in the future for possible therapies.

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Santos, Mário Sérgio Ferreira. "Neuropatia periférica em pacientes com síndrome antifosfolípide primária." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-22022010-161123/.

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O envolvimento do sistema nervoso periférico em diversas doenças auto-imunes é bem estabelecido. No entanto, não existem estudos, com desenho metodológico apropriado, que tenham investigado a relação entre síndrome antifosfolípide primária (SAFP) e neuropatia periférica. Nosso objetivo nesse trabalho foi investigar a ocorrência de neuropatia periférica em pacientes com SAFP. Vinte e seis pacientes com SAFP (critérios de Sapporo) e vinte controles, saudáveis, pareados por sexo e idade, foram recrutados em dois centros de referência. Foram excluídas as causas secundárias de neuropatia periférica e um exame neurológico completo, seguido de estudo de neurocondução, foi realizado em todos os indivíduos. Parestesias foram observadas em oito pacientes (31%). Leve fraqueza distal e anormalidades nos reflexos tendíneos profundos, foram observados em três (11,5%) pacientes. Evidência eletrofisiológica de neuropatia periférica foi observada em nove (35%) pacientes: quatro (15,5%) pacientes apresentaram neuropatia sensitiva ou sensitivo-motora axonal distais (em dois deles, com a superposição de síndrome do túnel do carpo), um (4%) paciente apresentou neuropatia sensitivo-motora, axonal e desmielinizante, acometendo os membros superiores e inferiores, enquanto que em quatro (15,5%) pacientes, observou-se a presença isolada de síndrome do túnel do carpo. As alterações clínicas e sorológicas dos pacientes com SAFP não guardaram qualquer correlação, com as alterações eletrofisiológicas. Em conclusão, neuropatia periférica, em geral assintomática, é comum na SAFP. Estudo de condução nervosa deve ser considerado na avaliação desses pacientes.
The involvement of the peripheral nervous system in diverse autoimmune diseases is well established. However, no appropriately designed studies have been performed in primary antiphospholipid syndrome (PAPS)-related peripheral neuropathy. We aimed to investigate the occurrence of peripheral neuropathy in patients diagnosed with PAPS. Twenty-six consecutive PAPS (Sapporo\'s criteria) patients and twenty age- and gender-matched healthy controls were enrolled at two referral centers. Exclusion criteria were secondary causes of peripheral neuropathy. A complete clinical neurological exam followed by nerve conduction studies (NCSs) were performed. Paresthesias were reported in 8 patients (31%). Objective mild distal weakness and abnormal symmetric deep tendon reflexes were observed in three (11.5%) patients. With regard to the electrophysiological evidence of peripheral neuropathy, nine (35.0%) patients had alterations: four (15.5%) had pure sensory or sensorimotor distal axonal neuropathy (in two of them a carpal tunnel syndrome was also present) and one (4%) had sensorimotor demyelinating and axonal neuropathy involving upper and lower extremities, while four patients (15.5%) showed isolated carpal tunnel syndrome. Clinical and serological results were similar in all PAPS patients, regardless of the presence of electrophysiological alterations. In conclusion, peripheral neuropathy is a common asymptomatic abnormality in PAPS patients. The routine performance of NCS may be considered when evaluating such patients.

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Мірошниченко, О. О., Є. С. Світлична, Ірина Миколаївна Нікітіна, Ирина Николаевна Никитина, and Iryna Mykolaivna Nikitina. "Людський імуноглобулін в комплексному лікуванні антифосфоліпідного синдрому." Thesis, Сумський державний університет, 2014. http://essuir.sumdu.edu.ua/handle/123456789/36465.

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Мета дослідження: оцінити перебіг вагітності й її результат у вагітних із синдромом втрати плода (СВП), обумовленим антифосфоліпідним сидромом (АФС), у динаміці лікування з застосуванням людського імуноглобуліну – імунологічно активної білкової фракції імуноглобуліну G. При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/36465

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Paschoa, Adilson Ferraz. "Impacto da pesquisa laboratorial de trombofilia na prevençao secundaria e orientação dos doentes com troboembolismo venoso." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310501.

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Orientador: Ana Terezinha Guillaumon
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-07T00:25:35Z (GMT). No. of bitstreams: 1 Paschoa_AdilsonFerraz_D.pdf: 1209751 bytes, checksum: 841d1a79e90d1ef1c6bb14b58b807236 (MD5) Previous issue date: 2006
Resumo: O tromboembolismo venoso (TEV) afeta de 1 a 3 indivíduos por mil habitantes/ano. O conhecimento atual das trombofilias permite a associação com cerca de 40% dos casos de TEV. Há controvérsias quanto ao valor da pesquisa laboratorial de trombofilia para o benefício dos doentes com tromboembolismo venoso. Procuraram-se as variáveis preditivas para a pesquisa positiva de trombofilia e avaliar o impacto desses resultados nas decisões clínicas. Foram avaliados 84 doentes consecutivos com TEV confirmado por métodos de imagem no período entre janeiro de 2001 e novembro de 2003. Após o período previsto de anticoagulação definido por critérios clínicos, os doentes foram submetidos à pesquisa das principais causas de trombofilia. Os resultados laboratoriais permitiram a dois examinadores independentes reavaliar caso-a-caso a indicação de ¿mudança de conduta¿, caracterizada pela interferência no tempo de profilaxia secundária ou ¿atenção especial¿ para medidas de maior vigilância diante de situações de risco ou para a extensão da pesquisa aos familiares assintomáticos. A trombofilia foi encontrada em 35 dos 84 casos (41,66%), sendo que em 27 (32,12%) havia uma causa genética. O fator V Leiden foi a alteração mais freqüente (15,47%), seguida do conjunto de deficiência dos anticoagulantes naturais (11,9%). Não houve diferença significativa da freqüência de trombofilia relacionada à faixa etária nem diferença de idade de aparecimento do primeiro evento trombótico entre doentes trombofílicos e não trombofílicos. Houve significância estatística para ocorrência de trombofilia nos doentes com tromboflebite superficial, recorrência e na associação com fatores de risco não cirúrgicos. A ¿mudança de conduta¿ foi atribuída a 6 dos 84 doentes (7,14%), estatisticamente significativa para aqueles com recorrência em relação aos que tiveram apenas um episódio de TEV. A ¿atenção especial¿ foi atribuída a 34 dos 84 casos (40,47%).A tromboflebite superficial de aparecimento espontâneo, a ocorrência de TEV relacionada a causas não cirúrgicas e a recorrência foram os principais achados preditivos de trombofilia. A ¿mudança de conduta¿ aplicou-se a uma pequena porcentagem de doentes, e refletiu predominantemente a confirmação da necessidade de prolongamento da profilaxia secundária. A ¿atenção especial¿ diante de situações de risco e a extensão da profilaxia primária a familiares de primeiro grau assintomáticos expostos a situações de risco parecem-nos a melhor indicação para a pesquisa laboratorial da trombofilia. Palavras-chave: trombofilia, fator V Leiden, mutação G20210A, proteína S, proteína C, antitrombina, hiperhomocisteinemia, anticorpos antifosfolípides, tromboembolismo venoso
Abstract: The venous thromboembolism (VTE) affects 1 to 3 individuals per a thousand habitants/year. Nowadays its possible to associated VTE with a cause of thrombophilia in about 40% of patients. There are some inconclusive points about the real benefit of the laboratorial investigation on thrombophilia for patients with VTE. We tried to identify the variables that point to the positive test results and the impact of these results on clinical decisions.The screening for the more common causes of thrombophilia was applied to 84 consecutive patients with VTE confirmed by image examination between January 2001 and November 2003. After test results, two independent observers evaluated, in a case by case basis, the indication of a ¿change on prophylaxis¿, in order to modify the period of anticoagulant intake (secondary prophylaxis), or ¿special attention¿ when considering to have a higher medical surveillance before risk situations or for the extension of the research to the first degree asymptomatic relatives.Thrombophilia was found in 41.66% (35/84), and in 32.12% (27/84) it involved agenetic cause. The factor V Leiden was the more prevalent alteration, identified in 15.47% of the cases, followed by the natural anticoagulants disfunction (11.9%). There was no significative difference of thrombophilia frequency between ages, nor a difference of age in the onset of the first thrombotic event between thrombophilic and non-thrombophilic patients. There was a higher prevalence of thrombophilia in patients with superficial thrombophlebitis of spontaneous onset, in cases of recurrence and when associated with non-surgical predisponent factors. The ¿change on prophylaxis¿ resulted in 7.14% (6/84), and there was statistically significance for patients with recurrent episodes when compared to patients with just one. The ¿special attention¿ was applied in 40.47% (34/84). Spontaneous superficial thrombophlebitis, occurrence of VTE related to nonsurgical causes and recurrence, were the main findings which suggested thrombophilia. The ¿change of prophylaxis¿ was applied to a small percentage of patients. The ¿special attention¿ for risk situations and the extension of the primary prophylaxis to the asymptomatic family members seem to be the best indication for the laboratorial research on thrombophilia. Key words: thrombophilia, factor V Leiden, G20210A mutation, protein C, protein S, antithrombin, hyperhomocysteinaemia, antiphospholipids antibodies, venous thromboembolism
Doutorado
Cirurgia
Doutor em Cirurgia

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Andrade, Danieli Castro Oliveira de. "Avaliação não-invasiva das propriedades da parede arterial em pacientes com síndrome antifosfolípide primária." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5145/tde-10032008-152144/.

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Objetivo: A aterosclerose prematura e acelerada tem sido recentemente reconhecida como um fator adicional de dano vascular nos pacientes com Síndrome Antifosfolípide Primária (SAFP). Esses pacientes podem ser beneficiados com o emprego de métodos para detecção precoce de aterosclerose como a Velocidade de Onda de Pulso (VOP) e o Echo-tracking (ET). Esses métodos têm sido reconhecidos pela capacidade de avaliar de forma não-invasiva a progressão da aterosclerose na parede vascular. Portanto, nosso principal objetivo foi avaliar a aterosclerose prematura nesses pacientes com SAFP. Pacientes e Métodos: 27 pacientes do sexo feminino com SAFP definida pelos critérios de Sapporo e 27 pacientes controles pareadas por sexo, idade e índice de massa corpórea foram selecionadas de forma consecutiva. Todas as pacientes sofreram trombose e foram subdivididas de acordo com o sítio vascular: arterial (n=12) e venoso (n=11). Os critérios de exclusão foram: idade > 55 anos, raça negra, hipertensão descontrolada, uso de corticosteróides e estatinas, diabetes, dislipidemia prévia, gravidez, menopausa, outras trombofilias, colagenoses, doenças vasculares de outras etiologias, obesidade definido por Índice de massa corpórea (IMC) >30 m/kg2 e tabagismo. Todas as pacientes foram submetidas à VOP no leito fêmoro-carotídeo (Complior) e echo-tracking pelo Wall Track System no leito carotídeo para avaliação das propriedades funcionais dos vasos. Resultados: Ambos os grupos SAFP e controles não mostraram diferença em relação à idade (41.5 ± 9.3 vs. 41.2 ± 10.2 anos; p=0.92) e IMC (22.7 ± 3.4 vs. 22.6 ± 3.7 kg/m2; p=0.91). Todas as pacientes apresentaram VOP semelhante às controles (p=0.34), o espessamento íntima-média (EIM) foi semelhante nos dois grupos (p=0.29) assim como os demais parâmetros do echo-tracking como o diâmetro carotídeo (p=0.26), a distensibilidade (p=0.92), os coeficientes de complacência (p=0.36) e o módulo elástico (p=0.78). A pressão sistólica (PS) das pacientes estava aumentada em relação às controles (p=0.02). De acordo com o sítio de trombose, as pacientes com eventos arteriais demonstraram um aumento na VOP em relação àquelas com eventos venosos (p=0.01) mesmo com mesmo EIM (p=0.52). Ambos resultados não foram influenciados pela idade ou duração de doença. Os níveis de colesterol total (p=0.002), LDL (p=0.02) e apolipoproteína B (p=0.03) foram mais altos nas pacientes com SAFP com eventos arteriais exclusivos. Na análise multivariada, observamos correlação da VOP com a idade (r=0.584; p=0.001) e com o diâmetro do vaso (DV) (r=0.407; p=0.04). Foi observada uma correlação positiva da VOP com o colesterol total (r=0.507, p=0.01), LDL (r=0.402, p=0.05), e triglicérides (r=0.583, p=0.003). O EIM apresentou correlação direta com o DV (r=0.393; p=0.04) e com a distensibilidade (r=0.373, p=0.05). Conclusão: A aterosclerose na SAFP apresenta curso peculiar e de forma precoce. A VOP foi um método mais adequado para detectar a disfunção vascular secundária à rigidez arterial, visto que, não foram detectadas alterações vasculares funcionais pelo ET.
Objective: Premature and accelerated atherosclerosis has been recently recognized as an additional vascular damage in Primary Antiphospholipid Syndrome (PAPS). These patients could benefit from non-invasive diagnostic methods to detect atherosclerosis as the Pulse Wave Velocity (PWV) and the Echo-Tracking (ET) device. By precise measurement of arterial stiffness, these methods output an indirect way to evaluate the vascular wall lesion progression. Our main objective was to evaluate premature atherosclerosis in PAPS.PATIENTS AND METHODS: 27 female patients with PAPS (Sapporo criteria) and 27 age-, body mass index- and sex-matched controls were consecutively selected. All PAPS patients had previous thrombosis and were subdivided according to the type of vascular exclusive event: arterial (n=12) and venous (n=11). Exclusion criteria were: age >55 years, black race, uncontrolled hypertension, smoking, diabetes, previous dyslipidemia, other thrombophilias, vascular and collagen diseases, corticosteroids and statins use, pregnancy, menopause, and obesity defined as body mass index (BMI)>30 m/kg2. All subjects underwent the PWV in femoral-carotidal bed (Complior) and echo-tracking by a Wall Track System in carotidal bed to analyze vascular wall functional properties. RESULTS: Both groups PAPS and controls did not show any difference regarding age (41.5 ± 9.3 vs. 41.2 ± 10.2 years; p=0.92) and BMI (22.7 ± 3.4 vs. 22.6 ± 3.7 kg/m2; p=0.91). All PAPS patients had PWV values similar to controls (p=0.34). Intima-media thickness (IMT) was also similar between groups (p=0.29) as well as all the other echo tracking parameters such as carotideal diameter (p=0.26), distensibility (p=0.92), compliance coefficients (p=0.36), and elastic modulus (p=0.78) were similar among groups. A higher systolic blood pressure was observed was observed in PAPS patients than controls (p=0.02). According to the site of thrombosis, PAPS patients with exclusive arterial events showed a higher PWV compared to those with venous (p=0.01) but had similar IMT (p=0.52). Both results were not influenced by age or disease duration. Total cholesterol (p=0.002), LDL (p=0.02), and apolipoprotein B (p=0.03) levels were higher in PAPS with exclusive arterial events compared to those with exclusive venous events. Multivariate analysis in PAPS showed that PWV was related to age (r=0.584; p=0.001) and blood vessel diameter (VD) (r=0.407; p=0.04). Moreover, PWV did also positively correlated with total cholesterol (r=0.507, p=0.01), LDL (r=0.402, p=0.05), and triglycerides (r=0.583, p=0.003). IMT also had a positive correlation with VD (r=0.393; p=0.04) and distensibility (r=0.373; p= 0.05). CONCLUSION: Atherosclerosis in PAPS has a peculiar course with an early onset, remarkably in those patients with arterial events. PWV was a sensible method to detect impaired functional vessel related to stiffness since no significant changes were observed in functional vascular properties by Echo- Tracking (ET) device.

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Devico, Charles Ariel. "Syndrome des antiphospholipides." Montpellier 1, 1994. http://www.theses.fr/1994MON11175.

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Sarno, Manoel Alfredo Curvelo. "Associação entre antecedentes morbidos, dopplervelocimetria de arterias uterinas, anticorpos antifosfolipideos e resultados perinatais adversos em um grupo de gestantes." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311741.

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Orientador: Ricardo Barini
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Introdução: A presença de anticorpos antifosfolipídeos freqüentemente está associada a complicações obstétricas como aborto de repetição, óbito fetal, descolamento prematuro da placenta e pré-eclâmpsia grave e precoce. Objetivo: avaliar associação dos antecedentes mórbidos, da Dopplervelocimetria de artérias uterinas, dos anticorpos antifosfolipídeos (AAF) e resultados obstétricos/perinatais em um grupo de gestantes. Sujeitos e Métodos: foi conduzido um estudo de coorte e corte transversal, onde foram analisadas gestantes atendidas nos Ambulatórios de Pré-Natal da Unicamp que aceitaram participar do estudo. Foi aplicado um questionário sobre os antecedentes mórbidos, realização de dosagem dos AAF, realizada Dopplervelocimetria de artérias uterinas e analisada correlação com resultados obstétricos/perinatais. Resultado: foram avaliadas 385 gestantes com média de idade de 26,6 (±6,3) anos. A anticardiolipina (aCL) e o anti-ß2 glicoproteína I (anti-ß2-gpI) foram avaliados em 382 gestantes, dos quais 4,4% apresentaram o anti-ß2gpI IgM positivo, 4,7% IgG, 6,2% aCL IgG e 6,7% IgM. O anticoagulante lúpico (AL) foi avaliado em 137 gestantes com positividade em 2,3%. 33,4% das gestantes tinham, pelo menos, um antecedente obstétrico desfavorável (aborto recorrente, óbito fetal, pré-eclâmpsia, parto prematuro, filho anterior nascido com peso menor que 2.500g ou descolamento prematuro de placenta) e 2,6% tinham eventos trombóticos (infarto, acidente vascular cerebral, tromboembolismo pulmonar ou trombose venosa profunda). 16,5% tinham pelo menos um antecedente e um AAF positivo, contra 13,3% sem antecedente (p=0,44). 10% apresentavam antecedente trombótico e AAF positivo contra 14,4% sem história de evento trombótico e AAF negativo (p=0,88). As complicações obstétricas/perinatais foram avaliadas em 305 gestantes sendo que no grupo com antecedentes 31,7% evoluíram para alguma complicação obstétrica na gestação em curso contra 28,4% do grupo sem antecedente (p=0,59). Analisando o desfecho pré-eclâmpsia com pelo menos um antecedente, 7,7% x 4,5% (p=0,29), índice Apgar no 5º minuto menor ou igual a 7, 4,9% x 5,6% (p=0,57), peso abaixo de 2.500g, 15,5% x 12% (p=0,47). Quando separados os grupos com e sem antecedentes e comparados ao Doppler de artérias uterinas as mulheres que relataram peso inferior a 2.500g tiveram 4,0 [IC95: 1,16-13,7] vezes mais chance de apresentar índice de pulsatilidade acima do percentil 95 (IP>P95) e 4,68 [IC95: 1,37-15,9] quando apresentavam antecedente de elevação da pressão arterial antes das 34 semanas em gestação anterior. Não foram encontradas correlações dos outros antecedentes com o Doppler. Quando o IP>P95 houve um risco relativo (RR) de 2,77 [IC95: 1,87-4,11] para pelo menos uma complicação obstétrica/perinatal, 5,19 [IC95: 1,41-19,1] para Apgar do 5º minuto menor que 7 e 6,94 [IC95: 4,31-11,1] de peso abaixo de 2.500g. Quando associado IP>P95 e pelo menos um antecedente o RR para peso abaixo de 2.500g foi de 6,06 [IC95: 3,19-11,5] e 6,61 [IC95: 3,46-12,6] para parto antes das 37 semanas. Quando comparados os dois grupos não foi encontrada significância estatística no desfecho de pré-eclâmpsia com RR de 4.70 [IC95: 0,80-27,4]. Na avaliação do IP>P95 e AAF, 11,1% tinham o IP>P95 e pelo menos um AAF, contra 14,4% no grupo sem essas características, com Razão de Prevalência (RP)=0,77 [IC95: 0,11-4,96]. A RP para o grupo com IP>P95 e pelo menos um antecedente para a presença de pelo menos um AAF, foi de 1,75 [IC95: 0,31-9,75]. Conclusão: os antecedentes obstétricos desfavoráveis, assim como o Doppler de artérias uterinas não se correlacionaram com os AAF. O aumento da resistência ao Doppler nas artérias uterinas, isoladamente ou em associação aos antecedentes mórbidos, apresentou maior chance de complicações obstétricas/perinatais. Não foram encontradas diferenças estatísticas quando avaliado o Doppler associado com antecedentes e AAF
Abstract: The presence of antiphospholipid antibodies is often associated with obstetrical complications such as recurrent miscarriage, fetal death, placental abruption and severe early preeclampsia. Objective: To evaluate the association between a history of morbidity, uterine artery Doppler flow, serum antiphospholipid antibodies (APA) and perinatal/obstetric outcomes in a group of pregnant women. Subjects and methods: A cross-sectional cohort study evaluated pregnant women receiving care at Unicamp's prenatal clinic, who agreed to participate in the study. A questionnaire was applied to obtain data on the patient's history of morbidity, serum antiphospholipid antibodies were measured and a Doppler scan of the uterine arteries was performed. Results were correlated with obstetrical/perinatal outcome. Results: A total of 385 pregnant women with a mean age of 26.6 ± 6.3 years were evaluated. Anticardiolipin (aCL) and anti-ß2 glycoprotein I (anti-ß2-gpI) were evaluated in a group of 382 pregnant women, 4.4% of whom tested positive for anti-ß2-gpI IgM, 4.7% for IgG, 6.2% for ACL IgG and 6.7% for IgM. Lupus anticoagulant (LA) was evaluated in 137 pregnant women, 2.3% of whom tested positive. Overall, 33.4% of patients had a medical history that included recurrent miscarriage, fetal death, preeclampsia, prematurity, previous pregnancy resulting in an infant with birthweight of <2.500g or placental abruption. In addition, 2.6% had experienced a thrombotic event such as myocardial infarction, stroke, pulmonary thromboembolism or deep vein thrombosis. Overall, 16.5% of patients had at least one of the above-mentioned conditions and tested positive for APA compared to 13.3% of those with no medical history of any of these conditions (p=0.44). Ten percent of the women had experienced a thrombotic event and tested positive for APA while 14.4% had never had a thrombotic event and tested negative for APA (p=0.88). Obstetric and perinatal outcomes were analyzed in 305 women, and results showed that 31.7% of the women with a medical history of morbidities suffered at least one obstetrical complication in the current pregnancy compared to 28.4% in the group of women who had no medical history of morbidity (p=0.59). When each outcome was correlated with a history of at least one medical condition, preeclampsia was found in 7.7% of cases versus 4.5% in the group with no medical history (p=0.29), 5th minute Apgar score = 7 in 4.9% compared to 5.6% (p=0.57) and birthweight <2.500g in 15.5% compared to 12% (p=0.47). When the groups of women with and without a medical history of complication were analyzed separately and correlated with uterine artery Doppler, the women who reported having had an infant with a birthweight <2.500 grams were four times more likely (95%CI: 1.16-13.7) to have a pulsatility index (PI) above the 95th percentile and 4.68 times more likely (95%CI: 1.37-15.9) if they had a history of increased blood pressure prior to 34 weeks in their previous pregnancy. No significant correlations were found between other medical conditions and PI above the 95th percentile. When the PI was above the 95th percentile, there was a relative risk (RR) of 2.77 (95%CI: 1.87-4.11) of developing at least one obstetrical/perinatal complication, a RR of 5.19 (95%CI: 1.41-19.1) of 5th minute Apgar score being = 7 and a RR of 6.94 (95%CI: 4.31-11.1) of birthweight <2.500 grams. When PI above the 95th percentile was associated with at least one prior complication, the RR for birthweight <2.500 grams was 6.06 (95%CI: 3.19 - 11.5) and 6.61 (95%CI: 3.46 - 12.6) for delivery prior to 37 weeks. When the two groups were compared, no statistically significant correlation was found with respect to eclampsia (RR 4.70; 95%CI: 0.80 - 27.4). In the evaluation of PI above the 95th percentile and APA, 11.1% of patients had PI above the 95th percentile and at least one APA compared to 14.4% in the group without these characteristics (prevalence ratio [PR] 0.77; 95%CI: 0.11-4.96). The PR for the group with PI above the 95th percentile and at least one previous medical condition was 1.75 (95%CI: 0.31-9.75). Conclusion: Neither history of morbidity nor uterine artery Doppler was found to be associated with antiphospholipid antibodies. A significant correlation was found between increased uterine artery Doppler resistance, both when analyzed alone or in association with medical history, and obstetric/perinatal complications. No statistically significant differences were found between uterine artery Doppler associated with medical history and antiphospholipid antibodies
Doutorado
Tocoginecologia
Doutor em Tocoginecologia

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Pozzi, Nicola. "Structure and Function of Coagulation Factors in Health and Disease. Thrombin, beta2-Glycoprotein I and von Willebrand factor." Doctoral thesis, Università degli studi di Padova, 2010. http://hdl.handle.net/11577/3426567.

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Cardiovascular disease (CVD) is the leading cause of death globally. According to the World Health Organization (WHO), it was responsible for 30% of all deaths in 2005 with respect, for instance, to cancer related diseases that cover only the 10-15%. Unfortunately this scenario is dramatically evolving year after year, not only in the high-income countries where risk factors such as smoking, diet and pollution are elevated but also in some developing nations where the wellness and industrialisation are changing the lifestyle and the mores of the people. Cardiovascular disease usually stems from vascular dysfunction or heart failure which can be the result of atherosclerosis, thrombosis, high blood pressure, angina pectoris and congenital cardiovascular defects. Generally the cardiovascular disease is a long term treated disease that during time compromises not only the single district where the injury takes place but the overall organism leading to death. Among all cardiovascular diseases, thrombosis — localized pathological clotting of the blood — can occur in the arterial or the venous circulation and has a major medical impact. Acute arterial thrombosis is the proximal cause of most cases of myocardial infarction (heart attack) and of about 80% of strokes, collectively the most common cause of death in the developed world. Venous thromboembolism is the third leading cause of cardiovascular-associated death. A great complication regarding the study of the CVD is the multiplicity and the heterogeneous system that has to be consider. For instance the pathophysiology of arterial thrombosis totally differs from that of venous thrombosis, as reflected by the different ways in which they are treated. In broad terms, arterial thrombosis is treated with drugs that target platelets, and venous thrombosis is treated with drugs that target proteins of the coagulation cascade. The available antithrombotic drugs are effective at reducing arterial thrombosis and venous thrombosis in patients with cardiovascular disease. However, the main side effect of these drugs is bleeding, which limits their use. To develop a new generation of safe and effective antithrombotic drugs with larger therapeutic windows (that is, a larger difference between the dose that prevents thrombosis and the dose that induces bleeding), a better understanding of the pathogenic processes that lead to thrombotic occlusion of blood vessels is needed. During my Ph.D. course my efforts have been devoted to investigate specific aspects of the structure and function of blood coagulation factors and their inhibitors (i.e., thrombin, hirudin, haemadin, protease nexin-1, beta2-glycoprotein-I, ADAMTS-13 protease and von Willebrand factor) using chemical (solid-phase peptide synthesis, mass spectrometry), biochemical (enzyme kinetics) and biophysical (fluorescence, circular dichroism, surface plasmon resonance, calorimetry) techniques. Herein reported in my Ph.D. Thesis, the different treated subjects are divided into independent chapters each containing a single case study. Briefly in chapter 2 it has been proposed the study on the structure and function of thrombin, a serine protease that exerts a pivotal role in blood coagulation. In particular it was investigated the allosteric nature of thrombin and information obtained about the enzyme was further applied to propose a rational model to finally design new possible antiaggregant and anticoagulant agents. In chapter 3 it has been reported the study on the β2-Glycoprotein I (β2GpI), a plasma glycoprotein that has been recently recognized as the primary target for some autoantibodies (aPL) found in the autophospholipid syndrome (APS). In this study we contributed to identify a conformational epitope, corresponding to the first domain of the full-length protein, that was efficiently recognized by the plasma autoantibodies of the patients. Starting form these considerations we further propose a new therapeutic and diagnostic approach for the antiphospholipid syndrome. Finally in chapter 4, it has been reported a study concerning the effect of the oxidation mediated by peroxynitrite on von Willebrand factor. Von Willebrand factor is a plasma glycoprotein extremely complex whose dimensions play a pivotal role in maintaining haemostasis. Since peroxynitrite oxidizes a single residue of methionine in the A2 domain of VWF, protease ADAMTS-13 results unable to process the full-length VWF leading to a multimer accumulation and consequently to a prothrombotic event. Notably this mechanism has been demonstrated in vitro and, more interestingly, in patients possessing an elevated oxidative stress conditions, such as diabetes mellitus type 2.
Oggigiorno le malattie cardiovascolari rappresentano la principale causa di morte nel mondo. Secondo i dati riportati dall’Organizzazione Mondiale della Sanità (OMS), il 30% di tutti i decessi è dovuto alle malattie cardiovascolari, mentre solamente il 10-15% è dovuto alle malattie oncologiche. Tale percentuale assume maggiore rilevanza se si considera che il numero di decessi è in aumento anno dopo anno, non solo nei paesi industrializzati ad elevato reddito ma anche nei paesi in via di sviluppo dove il benessere sta lentamente alterando le abitudini alimentari e sociali dei popoli. Il termine malattie cardiovascolari rappresenta un’ampia serie di patologie che, in modo generico, si possono ricondurre ad una disfunzione vascolare o cardiaca, quale ad esempio aterosclerosi, trombosi, ipertensione arteriosa, angina pectoris e malattie cardiache congenite. Molto spesso le malattie cardiovascolari hanno un decorso molto lungo e nel tempo invalidano gravemente la funzione non solo del distretto anatomico coinvolto, ma di tutto l’organismo. Nell’ambito delle malattie cardiovascolari, la trombosi — ovvero un fenomeno patologico spontaneo che porta alla coagulazione del sangue —rappresenta in assoluto la prima causa di morte. La trombosi arteriosa improvvisa è di fatto la principale causa di disfunzione e di infarto del miocardio, mentre il tromboembolismo venoso è la terza causa di morte. Un’importante complicazione che riguarda lo studio delle malattie cardiovascolari consiste nella diversa morfologia ed eziogenesi dei fenomeni di trombosi arteriosa e/o venosa. Tale diversità si riflette anche sul tipo di terapia utilizzata nella pratica clinica in cui i trombi arteriosi vengono preferenzialmente trattati con antiaggreganti piastrinici mentre quelli venosi, di norma, vengono trattati con farmaci anticoagulanti. Tuttavia, molto spesso, il decorso clinico dei pazienti genera un quadro terapeutico molto più complesso in cui le strategie utilizzate devono seguire percorsi integrati e trasversali. I farmaci ad ora utilizzati, pur essendo molto efficaci nel ridurre gli episodi di trombosi nei pazienti con malattie cardiovascolari, sono limitati nel loro impiego terapeutico poiché portano frequentemente ad episodi emorragici fatali. Per ridurre l’incidenza di tale effetto collaterale e migliore pertanto la loro finestra terapeutica è necessario studiare nei dettagli l’eziogenesi di tali patologie e quindi ottenere nuovi e più efficaci strumenti terapeutici e/o di prevenzione. Durante il mio dottorato di ricerca la mia attenzione è stata focalizzata sullo studio della struttura e della funzione di alcuni fattori della coagulazione e di loro inibitori (i.e., trombina, irudina, emadina, nexina 1, beta2-glicoproteina I, ADAMTS-13 e fattore di von Willebrand), utilizzando metodi chimici (sintesi di peptidi in fase solida, spettrometria di massa), biochimici (cinetica enzimatica e ELISA) e biofisici (fluorescenza, dicroismo circolare e SPR). In particolare in questa Tesi di Dottorato gli argomenti di studio sono stati trattati singolarmente, distinguendo i lavori in capitoli indipendenti. Brevemente nel capitolo 2 è stato indagato il rapporto struttura-funzione della trombina, una proteasi serinica cruciale nella cascata emocoagulativa, considerando dapprima la sua natura allosterica e quindi sfruttando le informazioni ottenute come base per lo sviluppo di nuovi possibili farmaci anticoagulanti ed antiaggreganti piastrinici. Nel capitolo 3, l’attenzione è stata trasferita alla β2-glicoptoteina I (β2GpI), una glicoproteina plasmatica che è stata recentemente identificata come il principale target di autoanticorpi coinvolti nella sindrome antifosfolipidica (APS). Lo studio della β2GpI ha contribuito ad individuare un dominio della proteina quale epitopo conformazionale riconosciuto dagli autoanticorpi, evidenziando così la possibilità di nuovi approcci terapeutici e diagnostici nella sindrome antifosfolipidica. Infine, nel capitolo 4, è stato riportato uno studio sull’effetto dell’ossidazione mediata da perossinitrito a carico del fattore di von Willebrand (VWF). Il fattore di von Willebrand è una glicoproteina plasmatica estremamente complessa le cui dimensioni contribuiscono a regolare l’equilibrio emostatico. Nello studio di seguito riportato è stato proposto e dimostrato come l’ossidazione di un residuo di metionina situato nel dominio A2 della glicoproteina impedisca il taglio proteolitico da parte di ADAMTS-13, promuovendo uno stato protrombotico nei pazienti sottoposti ad un elevato stress ossidativo.

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GOSSET, OLIVIER. "Anticorps antiphospholipides anioniques, syndrome antiphospholipide et neuroleptiques : a propos d'une etude realisee chez 124 patients suivis en milieu psychiatrique." Amiens, 1993. http://www.theses.fr/1993AMIEM036.

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Soligo, Adriana de Goes e. Silva 1974. "Prevalencia dos fatores trombofilicos em mulheres com infertilidade." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311746.

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Orientadores: Ricardo Barini, Egle Cristina Couto de Carvalho
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Objetivo: determinar a prevalência dos fatores trombofílicos em mulheres inférteis. Método: estudo de corte transversal, no qual foram admitidas mulheres inférteis (atendidas em clínica privada) e submetidas à investigação de trombofilia, conforme protocolo da referida clínica, no período de março de 2003 a março de 2005. Foram incluídas mulheres em idade fértil com história de infertilidade, definida como um ano de coito sem método contraceptivo e sem concepção. Foram excluídas mulheres com hepatopatia e dados incompletos em prontuário, obtendo-se a amostra de 144 mulheres. Os fatores trombofílicos avaliados foram: o anticorpo anticardiolipina (ACL) e o anticoagulante lúpico (ACGL); a deficiência de proteína C (DPC), a deficiência de proteína S (DPS), a deficiência de antitrombina III (DAT), a presença do fator V de Leiden, uma mutação no gene da protrombina e a mutação da metileno tetrahidrofolato redutase (MTHFR). Resultados: os valores de prevalência obtidos para ACL e ACGL foram de 2%. A prevalência dos fatores trombofílicos hereditários foram: DPC 4%, DPS 6%, DAT 5%, fator V de Leiden 3%, mutação da protrombina 3%, mutação MTHFR 57%. Conclusões: das 144 pacientes selecionadas, 105 mulheres, ou seja, 72,9% apresentavam pelo menos um fator trombofílico presente. Isto reforça a importância e justifica a necessidade da investigação neste grupo
Abstract: Purpose: to establish the prevalence of thrombophilic factors in infertile women. Methods: a cross-sectional study was performed, in which infertile women were included, seen in a private clinic with investigation for thrombophilia, according to the protocol of the clinic, between March 2003 and March 2005, after the approval of the Research Ethics Committee of UNICAMP. One hundred and forty four infertile women without any liver disease were evaluated. Infertility is defined as one year of unprotected sexual intercourse without contraception and with no conception. The acquired and/or inherited thrombophilic factors are: anticardiolipin antibody (aCL) and lupus anticoagulant (LA); protein C deficiency (PCD), protein S deficiency (PSD), antithrombin III deficiency (ATD), presence of the factor V Leiden, mutation in the prothrombin gene, and mutation of Methylene tetrahydrofolate reductase (MTHFR). Results: the prevalence values obtained for aCL and LA were 2%. The prevalence of hereditary thrombophilic factors were: PCD 4%, PSD 6%, ATD 5%, factor V Leiden 3%, prothrombin mutation 3%, MTHFR mutation 57%. Out of the selected 144 patients, 105 women (72, 9%) presented at least one thrombophilic factor. This reinforces the importance and justifies the need of investigation in this grou
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Tocoginecologia
Mestre em Tocoginecologia

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Lopes, Michelle Remião Ugolini. "Assinatura de interferon tipo I na síndrome antifosfolípide primária." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5140/tde-05122018-125757/.

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Introdução: a síndrome antifosfolípide (SAF) primária é uma vasculopatia autoimune mediada por autoanticorpos com trombose como sua principal manifestação clínica. A presença de anticorpos antifosfolípides (aPL), embora relevante para confirmar o diagnóstico, não parece ser suficiente para explicar completamente a fisiopatologia da doença e um segundo gatilho é usualmente necessário. Além das hipóteses de infecções virais e insulto inflamatório como possíveis desencadeantes, parece que os receptores toll like (TLR) e o Interferon (IFN) tipo I são possíveis protagonistas nesse processo, contribuindo para o início da trombose. Recentemente, dois pequenos estudos demonstraram que uma porcentagem relevante de pacientes com SAF primária tem uma regulação positiva de genes IFN em células mononucleares do sangue periférico (CMSP). Entretanto, 20% e 28% dos pacientes nessas duas coortes tiveram anticorpos anti-dsDNA positivos, um autoanticorpo altamente específico do lúpus eritematoso sistêmico (LES). Objetivo: avaliar se os pacientes com SAF bem caracterizados apresentam assinatura para interferon nas células mononucleares periféricas. Secundariamente foram avaliadas possíveis associações clínico laboratoriais com a assinatura de IFN. Métodos: foram selecionados 53 pacientes do sexo feminino com diagnóstico de SAF primária de acordo com os critérios de Sidney, com idade igual ou maior a 18 anos, selecionados no Ambulatório de SAF da Disciplina de Reumatologia do HCFMUSP, pareados por sexo e idade com 50 controles saudáveis. Um terceiro grupo com 29 paciente com antecedente de trombofilias não imunomediadas também foi incluido. Após a coleta de sangue as CMSPs foram purificadas por metodologia de Ficoll. A expressão gênica das CMSPs foi realizada através do TaqMan® RNA Assay em placas TLDA. Foram pesquisados 41 genes induzidos por IFN (GIIs). Uma análise de componente principal (ACP) foi realizada para determinar quais genes deveriam compor a assinatura de IFN. O teste de z-score foi utilizado para normalizar e calcular a assinatura de IFN para cada paciente. O cutoff da assinatura de IFN foi definido por uma curva ROC, e foi escolhido o ponto que maximizava a sensibilidade e especificidade. Características demográficas, clínicas e laboratoriais foram analisadas buscando por associações com a assinatura de IFN. Resultados: 11 genes estavam superexpressos nos pacientes com SAF em comparação aos controles. Após a análise de ACP foram escolhidos 6 genes que representavam mais de 95% do comportamento da amostra para compor a assinatura de IFN: DNAJA1, IFI27, IFI6, IFIT5, MX1 e TYK2. O cutoff encontrado pela curva ROC foi de 3,9 folds (AUC = 0,706, S = 0,49, E = 0,86, VPP = 0,79, VPN = 0,61). A assinatura de IFN estava presente em 49% dos pacientes com SAF primário vs. 14% dos controles saudáveis e 17% dos controles positivos (p < 0,001). Foi encontrada associação entre a assinatura de IFN e uma ocorrência mais precoce do primeiro evento clínico (p = 0,023), e com ocorrência de eventos obstétricos (em especial pré-eclâmpsia, p = 0,032). Não foi econtrada nenhuma associação entre a assinatura de IFN e número de eventos trombóticos, exames laboratoriais, comorbidades, antecedentes familiares de doenças autoimunes, e escores de risco de retrombose. De todos os tratamentos em uso a única associação encontrada foi entre uma menor assinatura de IFN e o uso de estatinas (p = 0,026). Conclusão: esse estudo indica que pacientes com SAF primária bem caracterizados apresentam uma assinatura de IFN tipo I, não observada em outras trombofilias não imunidade-mediadas ou em controles saudáveis. Também demonstrou-se que essa superexpressão de genes regulados por IFN tipo I está associada a um início mais precoce dos eventos e pré-eclâmpsia. Mais estudos são necessários para determinar se este subgrupo de pacientes se beneficiará de intervenções terapêuticas direcionadas à via de sinalização IFN tipo I
Introduction: primary antiphospholipid syndrome (PAPS) is an autoimmune vasculopathy mediated by autoantibodies with thrombosis as its main clinical manifestation. The presence of antiphospholipid antibodies, while relevant to confirm the diagnosis, does not seem to be sufficient to fully explain the pathophysiology and a second trigger is usually needed. Besides the hypotheses of viral infections and inflammatory insult as possible triggers, type I Interferon (IFN) has been pointed as a possible protagonist. Recently, two studies have demonstrated that a relevant percentage of PAPS patients have an up-regulation of IFN genes in peripheral blood mononuclear cells (PBMC). However, 20% and 28% of patients in these 2 cohorts, had antidsDNA positive antibodies, a highly specific Systemic Lupus Erythematosus (SLE) autoantibody. Objective: The aim of this study is to determine the prevalence of type I IFN signature in PBMC of patients with PAPS without specific SLE autoantibodies and search for it with clinical and laboratorial associations. Methods: 53 PAPS patients (according to Sydney´s criteria) were consecutively selected and age-matched with 50 healthy controls. A third group, with non-immune-mediated thrombophilia patients, was also included. The expression of 41 IFN induced genes was analysed using real time quantitative PCR (TaqMan Low Density Array). A principal component analysis (PCA) was used to determine which genes should compose the IFN signature and z-score was calculated. The IFN signature score cut-off was defined with a ROC curve, as the point that maximized both the specificity and sensitivity. Clinical and laboratorial features were analysed searching for associations with IFN signature. Results: 11 IFN genes were highly expressed in primary APS patients. After PCA, 6 genes remained in the IFN signature: DNAJA1, IFIT5, IFI27, MX1, IFI6, TYK2. The ROC cutoff was 3,9 folds (AUC = 0.706, S = 0.49, E = 0.86, VPP = 0.79, VPN = 0.61). The type I IFN signature was present in 49% of patients with primary APS compared to 14.0% of healthy controls and 17% of non-immune-mediated thrombophilia patients (p < 0.0001). The mean IFN score was significantly higher in PAPS patients (4.0 fold higher, p < 0.0001) than in controls. A higher IFN signature was associated with a younger age at the first APS event (p = 0.023) and with the presence of obstetric events, especially with preeclampsia (p = 0.032). There was no association between IFN signature and number of thrombotic events, laboratory exams, comorbidities, family history of autoimmune diseases, and thrombosis risk scores. Treatment with statins was associated with lower levels of IFN scores (p = 0.026). Conclusion: our result indicates that PAPS patients, without lupus specific antibodies, have an enhanced type I IFN gene signature, not observed in non-immune mediated thrombophilia. We also provide novel data demonstrating that this overexpression of type I IFN-regulated genes is associated with an earlier onset of APS events and preeclampsia. Further studies are necessary to determine if this subgroup of patients will benefit of interventions targeting the type I IFN signalling pathway

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Vita, Natalia Mastantuono Nascimento de. "O fator de von Willebrand, ligação com fator VIII e estudo da atividade da ADAMTS-13 em pacientes com síndrome antifosfolípide primária." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5167/tde-25022015-095418/.

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A Síndrome Antifosfolípide (SAF) é uma doença autoimune na qual há presença de anticorpos antifosfolípides [anticoagulante lúpico (AL), anticardiolipina (ACL), anti-beta2glicoproteína I (a-beta2GPI)]. É caracterizada por eventos trombóticos e/ou perdas gestacionais de repetição. Existe um ambiente pró-coagulante na SAF, pois os antifosfolípides (AFL) são capazes de induzir disfunção endotelial aumentando a expressão de moléculas de adesão como o fator de von Willebrand (FVW). Entre os inúmeros elementos envolvidos neste processo, o FVW e a relação com: sua principal enzima proteolítica, a ADAMTS-13, e com o FVIII são relativamente menos conhecidos. Os objetivos deste estudo foram: 1-verificar alterações no endotélio de pacientes com SAF primária (SAFP), através do marcador de lesão endotelial, o FVW, da ADAMTS-13 e do FVIII, avaliando a concentração antigênica, a atividade e a correlação entre estas proteínas; 2- Verificar se alguma destas variáveis é capaz de diferenciar os tipos de eventos trombóticos ocorridos nestes pacientes e se a presença dos AFL influenciam estas proteínas. O estudo, do tipo transversal, envolveu 39 pacientes com SAF primária, com idade mediana de 43 anos, em tratamento no ambulatório de Reumatologia do Hospital das Clínicas, e 39 controles sadios doadores da Fundação Pró-Sangue Hemocentro de São Paulo, pareados por sexo e idade com os pacientes. Os títulos de ACL e a-beta2GPI, as determinações antigênicas e de atividade das proteínas FVW, ADAMTS-13, FVIII e PF4 foram realizados por ELISA, e a atividade do FVIII foi determinada pelo método cromogênico. A análise das subunidades do FVW foi realizada por Western immunoblotting. AL foi detectado utilizando ensaios de coagulação de acordo com as recomendações da Sociedade Internacional de Trombose e Hemostasia. Os resultados foram apresentados em: 1- pacientes SAFP e controles, e 2- pacientes SAFP agrupados em relação ao tipo de evento e ao tipo de AFL presente. Os pacientes apresentaram aumento da concentração antigênica do FVW (74±6 x 69±11 UI/dL; p=0,016), ADAMTS-13 (1,3±0,34 x 0,82±0,12 Ug/mL; p < 0,0001), FVIII (106±19 x 91±15 UI/dL; p=0,0003),da ligação FVW:FVIII (144±17 x 134±20%; p=0,082) e da atividade do FVIII (117±38 x 98±30%; p=0,0021) comparado aos controles. O PF4 apresentou-se diminuído nos pacientes em relação aos controles (96±12 x 101±8 UI/mL; p=0,014). Os pacientes com trombose arterial apresentaram correlação positiva e significante entre a atividade e o antígeno do FVW (r=0,468; p=0,028) e da ADAMTS-13 (r =0,635; p=0,001); os pacientes com trombose venosa apresentaram esta correlação positiva e significante na ADAMTS-13 (r=0,635; p=0,001). Quando os pacientes foram analisados pelo tipo de antifosfolípide, não se observou diferenças nas variáveis estudadas. Os pacientes com SAFP parecem apresentar disfunção endotelial. No entanto, aparentemente existe um mecanismo de equilíbrio para evitar a formação de um novo trombo. O papel do FVW e a sua relação com a ADAMTS-13, em diferentes doenças, ainda é relativamente pouco conhecido, mas está sendo apontado como importante na patogênese de estados pró-trombóticos como os presentes em pacientes com SAF
Antiphospholipid syndrome (APS) is an autoimmune disease, characterized by vascular thrombosis and /or pregnancy morbidity, in association with antiphospholipid antibodies (aPL) (lupus anticoagulant (LA), anticardiolipin (ACL), anti-beta2glicoprotein I (a-beta2GPI). Antiphospholipid (APL) seems to induce endothelial dysfunction by increasing the expression of adhesion molecules such as von Willebrand factor (VWF). This results in a prothrombotic state in APS. Among the several elements involved in this process, some are relatively less known, such as VWF and its relationship with ADAMTS-13, its main proteolytic enzyme. The aim of this study was to evaluate endothelial dysfunctions in patients with primary APS (PAPS), by examining correlation among the soluble endothelial marker, VWF, the enzyme ADAMTS-13, and FVIII protein. The relationship of these proteins and the presence of arterial and/or venous thrombosis, and presence of APL was also evaluated. This cross-sectional study involved 39 PAPS patients, with a median age of 43 years, who have been treated in the Outpatient Clinics, Department of Rheumatology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, and 39 healthy subjects blood donors from the Fundação Pró-Sangue Hemocentro de São Paulo, matched for sex and age with patients. Levels of APL (ACL and a-beta2GPI), concentration and activities of VWF, ADAMTS-13, FVIII and PF4 proteins were measured with ELISA. LA was detected with coagulation assays according to updated guidelines from the International Society on Thrombosis and Haemostasis, and FVIII activity was measured by chromogenic method. Analysis of VWF subunits was performed by Western immunoblotting. The results were evaluated according to:1- PAPS patients and controls, and2- PAPS patients grouped in relation to type of event and the type of APL. Patients showed higher VWF antigen concentration (74±6 x 69±11 IU/dL, p=0.016), ADAMTS-13 (1.3±0.34 x 0.82±0.12 Ug/mL, p < 0.0001), FVIII (106±19 x 91 ± 15 IU/dL, p=0.0003), VWF binding to FVIII (144±17 x 134 ± 20%, p=0.082) and activity of FVIII (117±38 x 98±30%, p=0.0021) than controls. The PF4 was decreased in patients compared to controls (96±12 vs. 101±8 IU/mL, p=0.014). VWF antigen and activity correlated well (Pearson´s r =0.468; p=0.028) as well as ADAMTS-13(Pearson´s r=0.635; p=0.001) in patients with arterial thrombosis. However, in patients with venous thrombosis only ADAMTS-13 had a good correlation (Pearson´s r =0.492; p=0.045). When patients were analyzed by the type of aPL, no differences in the studied variables were observed. Patients with PAPS seem to present endothelial dysfunction. However, apparently there is an attempt to balance mechanism to prevent a new thrombus formation. The role of VWF and its relation with ADAMTS-13 in different diseases is still relatively unknown. However it has been considered as important in the pathogenesis of prothrombotic states such as those present in patients with APS

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Junior, Carlos Nobre Rabelo. "Avaliação da função gonadal em pacientes do sexo masculino com síndrome antifosfolípide." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5165/tde-24022012-131540/.

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INTRODUÇÃO. A síndrome antifiosfolípide (SAF) é uma condição trombofílica autoimune associada a títulos elevados e persistentes de anticorpos antifosfolípides. Caracteriza-se por tromboses em diversos órgãos, incluindo os testículos. OBJETIVO. Realizar uma avaliação global da função gonadal em pacientes masculinos com SAF primária (SAFP) e SAF associada ao lúpus eritematoso sistêmico (SAF-LES). MÉTODOS. Estudo transversal realizado em 22 pacientes (12 com SAFP e 10 com SAF-LES) e 20 controles saudáveis pareados por sexo e idade. Os pacientes foram avaliados em relação a dados demográficos, exame urológico, ultrassonografia testicular, perfil hormonal, análise do sêmen, anticorpos antiespermatozóides e características clínicas e laboratoriais. RESULTADOS. A mediana da idade atual foi semelhante nos pacientes com SAFP e controles (p=0,27), assim como naqueles com SAF-LES e controles (p=0,31). Disfunção erétil foi significantemente maior nos pacientes com SAFP comparado aos controles (25% vs. 0%, p=0,044), e nos SAF-LES comparado aos controles (30% vs. 0%, p=0,029). Com relação à antropometria do pênis, a análise dos subgrupos de pacientes com (n=7) e sem (n=5) tromboses arteriais prévias demonstrou que a mediana da circunferência do pênis foi significantemente menor em SAFP com trombose arterial versus sem trombose arterial [8,1 (6-10) vs. 10,2 (10-11) cm, p=0,007], bem como também observado em pacientes com SAF-LES com (n=2) e sem (n=8) eventos arteriais prévios [7,5 (7-8) vs. 9,18 (8-10,5) cm, p=0,039]. A mediana da circunferência do pênis foi significantemente menor nos pacientes com SAFP com disfunção erétil versus sem essa alteração [7,5 (6-9,5) vs. 9,5 (7,5-11) cm, p=0,039], assim como no grupo de SAF-LES [8,17 (8-8,5) vs. 9,14 (7-10,5) cm, p=0,0397]. Com relação à avaliação da função testicular, todos os parâmetros foram semelhantes nos pacientes com SAFP e controles (p>0,05). Por sua vez, as medianas de concentração e de mobilidade dos espermatozóides foram significantemente menores nos pacientes com SAF-LES comparado aos controles [41,1 (0-145) vs. 120,06 (34,5-329) x 106/mL, p=0,003; 47,25 (0-87,5) vs. 65,42 (43-82)%, p=0,047; respectivamente], assim como a frequência de oligo/azoopermia (40% vs. 0%, p=0,007). A análise dos pacientes com SAF-LES mostrou que as medianas da concentração e da contagem total de espermatozóides foram significantemente menores nos que usaram ciclofosfamida endovenosa versus os que não usaram tal medicação [6,87 (0-23,5) vs. 63,9 (7,5-145) x 106/mL, p=0,04; 16,12 (0-55,5) vs. 226,25 (8,5-471) x 106, p=0,035; respectivamente]. CONCLUSÕES. Diminuição do tamanho peniano nos pacientes com SAFP e SAF-LES com disfunção erétil associada foi evidenciada, além de disfunção testicular secundária ao uso de agentes alquilantes nos pacientes com SAF-LES
INTRODUCTION. Antiphospholipid syndrome (APS) is an autoimmune thrombophilic condition associated with persistent high titers of antiphospholipid antibodies. It is characterized by thrombosis in various organs including the testes. OBJECTIVE. To perform a global testicular assessment in male primary antiphospholipid syndrome (PAPS) and secondary systemic lupus erythematosus-APS (SLE-APS) patients, and healthy controls. METHODS. A cross-sectional study was conducted in 22 APS (12 PAPS and 10 SLE-APS) male patients, and 20 healthy controls. They were assessed by demographic data, systematic urological examination, testicular ultrasound, hormone profile, sperm analysis, antisperm antibodies, clinical features and treatment. RESULTS. The median of current age was similar in PAPS patients and controls (p=0.27), likewise in SLE-APS and controls (p=0.31). Erectile dysfunction was significantly higher in PAPS patients compared than controls (25% vs. 0%, p=0.044), and in SLE-APS and controls (30% vs. 0%, p=0.029). Regarding the penile anthropometry, the analysis of subgroups of PAPS patients with (n=7) and without (n=5) previous arterial thrombosis demonstrated that the median circumference penis was significantly lower in PAPS with arterial thrombosis versus without [8.1 (6-10) vs. 10.2 (10-11) cm, p=0.007], as also observed in SLE-APS patients with (n=2) and without (n=8) previous arterial events [7.5 (7-8) vs. 9.18 (8-10.5) cm, p=0.039]. In addition, the median penis circumference was significantly lower in PAPS patients with erectile dysfunction versus without this alteration [7.5 (6-9.5) vs. 9.5 (7.5-11) cm, p=0.039], likewise in SLE-APS patients [8.17 (8-8.5) vs. 9.14 (7-10.5) cm, p=0.0397]. Regarding gonadal evaluation, these parameters were uniformly normal in PAPS versus controls (p>0.05). In contrast, the median of sperm concentration and sperm motility were significantly lower in SLE-APS patients compared to controls [41.1 (0-145) vs. 120.06 (34.5-329) x 106/mL, p=0.003; 47.25 (0-87.5) vs. 65.42 (43-82)%, p=0.047; respectively], likewise the frequency of oligo/azoopermia (40% vs. 0%, p=0.007).The analysis of SLE-APS patients showed that the median of sperm concentration and total sperm count were significantly lower in SLE-APS patients treated with intravenous cyclophosphamide versus untreated [6.87 (0-23.5) vs. 63.9 (7.5-145) x 106/mL, p=0.04; 16.12 (0-55.5) vs. 226.25 (8.5-471) x 106, p=0.035; respectively]. CONCLUSIONS. We have identified reduced penile size in PAPS and SLE-APS patients with deleterious erectile function, and testicular dysfunction due to alkylating agents in SLE-APS patients

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Kitzmiller, Kathryn Jean. "Variation of Complement Factor H and Mannan Binding Lectin in Human Systemic and Vascular Immune-Mediated Diseases." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1261493418.

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Neau, Didier. "Le syndrome primaire des anticorps antiphospholipides." Bordeaux 2, 1993. http://www.theses.fr/1993BOR23050.

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AMARANTO, MIRANDA PAULA. "Syndrome des antiphospholipides : revue de la litterature." Lyon 1, 1994. http://www.theses.fr/1994LYO1M248.

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Ferrari, Ana Luisa Vanalle 1981. "Perda auditiva neurosensorial no lúpus eritematoso sistêmico." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310438.

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Orientadores: Lilian Tereza Lavras Costallat, Simone Appenzeller
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-23T07:49:05Z (GMT). No. of bitstreams: 1 Ferrari_AnaLuisaVanalle_M.pdf: 849343 bytes, checksum: f0c264713a909a78bdd04a6d3e6f65da (MD5) Previous issue date: 2013
Resumo: Introdução: Perda auditiva neurosensorial é conhecida como uma manifestação incomum do Lúpus Eritematoso Sistêmico(LES), podendo ocorrer como primeira manifestação de doença, já tendo sido associada com Síndrome do Anticorpo Antifosfolípide (SAF) e doença cardiovascular. Objetivo: Determinar a frequência de perda auditiva em um grupo de pacientes com lúpus eritematoso sistêmico e avaliar a associação entre a perda auditiva e idade, tempo de doença, atividade de doença e dano, anticorpos antifosfolípides e fatores de risco para doença cardiovascular. Método: Foi realizado um estudo transversal que incluiu pacientes com LES do sexo feminino acompanhadas no ambulatório de Reumatologia da Unicamp de forma consecutiva. Em todas as pacientes foram realizadas avaliação clínica, laboratorial e audiometria. Análise Estatística: Foi realizada análise de componentes principais (PCA), correlação de Speaman e regressão logística. Resultados: Foram estudadas 89 pacientes, todas do sexo feminino e com média de idade de 38,98 (±7,77) anos. A média de duração de doença foi 10,29 (± 9,19). Perda auditiva neurosensorial avaliada por audiometria e avaliação clínica foi encontrada em 14 pacientes, o que corresponde a 16%. Não se observou associação entre a perda auditiva e idade, tempo de doença, atividade de doença (SLEDAI), dano de doença (SLICC) e anticorpos antifosfolípides. Quanto aos fatores de risco para doença cardiovascular observou-se associação entre perda auditiva e níveis elevados de LDL (p=0,008), corroborando a associação entre perda auditiva e dislipidemia. Não foram observadas associações com outros fatores de risco cardiovasculares estudados como triglicérides, HDL, hipertensão arterial, glicemia de jejum e índice de massa corporal (IMC). Conclusões: Apesar de considerada incomum, perda auditiva foi observada em 16% dos nossos pacientes. Não se observou associação entre a perda auditiva e idade, tempo de doença, atividade de doença, dano e anticorpos antifosfolípides. Foi encontrada associação com níveis elevados de LDL, apontando que a presença de dislipidemia pode ser responsável por estas alterações no LES
Abstract: Introduction: Sensorioneural hearing loss (SHL) is a uncommon condition in systemic lupus erythematosus (SLE) but it can occur as the first manifestation of disease. Some authors have associated this manifestation with Antiphospholipid Syndrome (APS), and cardiovascular disease. Objective: To determine the frequency of neurosensorial hearing loss in a group of SLE patients and the association between SHL and age, years of disease, activity and damage of SLE, antiphospholipid antibodies profile and cardiovascular comorbidities. Methods: We conducted a cross-sectional study including patients with SLE followed at the Rheumatic Clinic in UNICAMP in a consecutive way. We performed in all patients audiometry, clinical and laboratorial evaluation. Statistical Analysis: Our data were submitted to logistic regression. We also used principal component analysis (PCA) and Spearman correlation. Results: The study included 89 patients. They were all women with mean age 38,98 (± 7,77) years and mean disease's duration of 10,29 (± 9,19) years. We found neurosensorial hearing loss evaluated using audiometry test and clinical evaluation in 14 patients, representing 16%. It was not observed any association between hering loss and age, time of disease, disease activity (SLEDAI), and damage (SLICC), APS and antiphospholipid antibodies. Considering cardiovascular risk factors, significant association between hearing loss and LDL level (p=0,008) was found, corroborating the association of hearing loss and dyslipidemia as a predictor of vascular disease. Other risk factors were not associated, as HDL, triglycerides, hypertension and body mass index (BMI). Conclusion: Although uncommon, we found hearing loss in 16% of cases studied. Also, we found a positive association with LDL level, pointing that cardiovascular disease (not only immune) can be responsible for these alterations. It was not observed any association between hearing loss and age, time of disease, disease's activity, damage, APS and antiphospholipid antibodies. Our study indicates an important risk factor for neurosensorial hearing loss in SLE patients
Mestrado
Clinica Medica
Mestra em Clínica Médica

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Poindron, Vincent. "Hétérogénéité des mécanismes physiopathologiques du syndrome des anti-phospholipides." Strasbourg, 2011. http://www.theses.fr/2011STRA6122.

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Le syndrome des antiphospholipides est défini par l’association d’un événement clinique (avortements répétés et/ou morts fœtales in utero et/ou thromboses vasculaires) associé à un événement biologique, la présence d’un anticorps antiphospholipide (anticardiolipides et/ou antiβ2GPI et/ou anticoagulant circulant). En réalité, cette définition souligne déjà l’hétérogénéité clinique et biologique de ce syndrome et interroge le ou les mécanismes pathogéniques impliqués. Compte tenu des manifestations thrombotiques observées au cours de la maladie, on a avancé qu’il y existe un mécanisme thrombophilique univoque. Dans les manifestations obstétricales, la destruction du bouclier d’annexine V créerait les conditions pro-thrombotiques dans le placenta. Plus récemment, l’étude d’un modèle murin est venu souligner l’importance du complément et en particulier des anaphylatoxines C3 et C5, faisant ainsi du syndrome des antiphospholipides, obstétrical et peut être vasculaire, une maladie inflammatoire, ce qui suggère un mécanisme radicalement différent. Le présent travail participe à l’élucidation de certains des mécanismes mis en jeu dans le syndrome des antiphospholipides obstétrical grâce à l’usage d’un modèle murin faisant appel au transfert passif d’anticorps monoclonaux. Il a pu voir le jour grâce à un important travail préalable conduit au laboratoire. En utilisant une technique de tri sélectif sur vésicules phospholipidiques par cytométrie en flux, les Lymphocytes B anti phospholipides ont été isolés. Les régions variables de ces lymphocytes ont été clonées dans des Baculovirus et les anticorps monoclonaux ont ainsi pu être produits dans des cellules d’insectes, et leur spécificité fine étudiée. Cent microgrammes d’anticorps monoclonaux ont été injectés par voie intraveineuse à des souris gestantes balb/c à J0 et J1 suivant l’accouplement des souris. Ces dernières ont été sacrifiées à J10 et les structures embryonnaires et placentaires étudiées (nombre de résorptions fœtales, histologie conventionnelle et immunofluorescence). L’effet de ces anticorps a également été étudié chez des souris invalidées pour les récepteurs activateurs Fcgamma RI et RIII au fragment Fc des immunoglobulines G. L’effet de différents anticoagulants (héparines de bas poids moléculaire, hirudine et fondaparinux) a également été évalué. Sur le plan histologique, des souris traitées selon le protocole décrit ont également été étudiées vers J5 et l’on a pratiqué des études d’immunofluorescence indirecte sur des coupes d’utérus gravides. L’effet de l’antiphospholipide pathologique sur la coagulation a été étudié en utilisant une épreuve fonctionnelle de génération de thrombine. En collaboration avec l’équipe d’Alain Brisson (Bordeaux), nous avons évalué l’effet de l’anticorps pathogène sur le réseau d’annexine V par microscopie à force atomique. L’injection de différents anticorps monoclonaux produits à partir d’une seule patiente à des souris gestantes entraîne des effets variables : seul l’anticorps CIC15 parmi ceux qui ont été injectés déclenche environ 30% de résorptions fœtales. Cet anticorps présente des mutations siégeant dans la troisième région déterminant la complémentarité, et qui sont responsables de la pathogénicité. En effet, la configuration germinale de l’anticorps obtenue par mutagenèse dirigée a été éprouvée et n’exerce pas d’effet pathogène dans notre modèle. La chronologie d’injection est primordiale puisque l’injection tardive ne perturbe pas la gestation alors que l’injection précoce est pathogène ; cette observation expérimentale rapproche ce modèle des observations humaines d’avortements répétés plutôt que de morts fœtales in utero faites en clinique humaine. Bien qu’il ne soit pas possible de repérer précisément la cible de l’anticorps directement responsable de la pathogénicité, en raison de sa polyréactivité qui empêche l’analyse fine des expériences d’immunofluorescence, CIC15 se dépose dans le placenta et entraîne localement la formation de thrombose. In vitro, CIC15 est d’ailleurs capable d’accélérer la génération de thrombine mais n’a pas d’effet sur l’organisation du réseau d’annexine V. L’effet pathogène s’exerce indépendamment des récepteurs activateurs Fcgamma RI RIII. Différents anticoagulants sont capables d’abolir les effets pathogènes de CIC15. Cette observation et l’absence d’infiltrat neutrophilique dans les différentes analyses histologiques constituent un faisceau d’arguments lourds en défaveur de l’intervention du complément même si les souris déficientes pour le récepteur du C5a n’ont pu être utilisées. En effet, certaines souches de souris (nous avons éprouvé notre anticorps pathogène sur des souris C57bl/6) dont celle qui est invalidée pour le récepteur du C5a, sont résistantes à CIC15, et ce constat souligne l’importance du fond génétique dans la survenue du syndrome expérimental des antiphospholipides par transfert passif murin. Notre modèle est donc un modèle obstétrical fondé sur la thrombose intra placentaire par accélération de la génération de thrombine en présence de CIC15. Le mécanisme exact du phénomène reste inconnu mais nos résultats indiquent qu’il n’y a pas de réaction inflammatoire dans ce système expérimental. Ces résultats accentuent l’hétérogénéité de la physiopathologie du syndrome des antiphospholipides. Toutefois, et même si les modèles murins restent un outil très performant, il est important de pouvoir démontrer l’existence de ces mécanismes chez l’homme, ce qui relève, actuellement, de la gageure, en particulier parce que les mécanismes sont multiples. Cette hétérogénéité physiopathologique pourrait rendre compte au moins en partie des différents phénotypes du syndrome des antiphospholipides observés (vasculaire versus obstétrical, précoce versus tardif, veineux versus artériel, anticardiolipides versus anticoagulants circulants, etc. ). Identifier les différents mécanismes est d’importance pour deux raisons : (a) permettre de mieux prédire ainsi le risque individuel et (b) mieux cibler les traitements et les rendre mieux tolérés que ne l’est l’anticoagulation utilisées actuellement
The anti-phospholipid syndrome associates a clinical event (repeated abortions and/or foetal deaths in utero and/or vascular thrombosis) and a biological event, the presence of (an) anti-phospholipid antibody(ies) (anti-cardiolipid and/or antiβ-2GPI and/or circulating anticoagulant). This definition underlines the clinical and biological heterogeneity of the syndrome and the potential complexity of the pathogenic mechanisms. Single anti-phospholipid B cells from patient's peripheral blood were sorted by flow cytometry using cardiolipin-labeled vesicles. Messenger RNAs of these single B cells were subjected to reverse transcriptase-polymerase chain reaction to amplify the V region genes of the H and L chains. The amplification products were cloned into recombinant Baculovirus to produce monoclonal human anti-phospholipid antibodies. In the present work, we studied the passive transfer of monoclonal anti-phospholipid antibodies to pregnant mice. Injection of various monoclonal antibodies produced from B cells arising from a randomly selected patient shows that only monoclonal antibody CIC15, among those which were injected, leads to a resorption rate of 30%. This antibody recognizes the cardiolipin and is dependent on annexin A5; it presents three somatic mutations in the first complementary determining region of the light chain [CDR]. Germinal configuration of antibody CIC15 [GL] is poly-reactive, recognizes cardiolipin less strongly and is independent of annexin A5. In our model, GL does not exert any pathogenic effect. These results demonstrate that fine specificity and pathogenic potential of CIC15 is due to the presence of three mutations in CDR, suggesting that it appeared after antigen driven maturation. Chronology of injection is quite important since late injection does not disturb gestation whereas the early injection induces pathological phneomena. Although it is not possible to precisely identify target of CIC15 directly involved in the pathogenicity, because of its poly-reactivity, CIC15 forms deposits in the placenta and involves the formation of local thrombosis. In vitro, CIC15 is able to accelerate the generation of thrombin but does not have any effect on organization of annexin V network. The pathogenic effect is exerted independently of activators Fcgamma RI-RIII receptors. Various anticoagulants are able to abolish the pathogenic effects of CIC15. This observation and the absence of neutrophil infiltrate, as confirmed by various histological analyses, constitute a strong arguments against the activation of complement in this model. Several mice strains (we tested CIC15 on C57/bl6 mice and several deficient mice on C57/bl6 background) are resistant to this antibody, and this result underlines the importance of the genetic background in anti-phospholipid syndrome. Our model is thus an obstetric model relying on placental thrombosis by acceleration of thrombin generation in the presence of CIC15. The exact mechanism remains unknown but our results indicate that there are no inflammatory reaction nor annexin V shield destruction in this experimental system. These results accentuate the heterogeneity of the physiopathology of anti-phospholipid syndrome. Such a physiopathological heterogeneity could at least partially explain the various phenotypes associated to anti-phospholipid syndrome (vascular versus obstetric, early versus late, venous versus arterial, anti-cardiolipid versus lupus anticoagulant, etc). To identify the various mechanisms involved is of importance for two reasons: (a) to make it possible to better predict the individual risk (b) and thus to better target the treatments and render them more tolerated than the currently used classical anti-coagulation administration

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Zuily, Stéphane. "Proposition de nouveaux critères cliniques et biologiques dans l'évaluation du risque thrombotique des patients atteints de syndrome des antiphospholipides." Thesis, Université de Lorraine, 2014. http://www.theses.fr/2014LORR0064.

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Le syndrome des anticorps antiphospholipides (SAPL) est caractérisé par une atteinte auto-immune systémique à l’origine d’événements cliniques thrombotiques ou obstétricaux en présence d’anticorps antiphospholipides (aPL) persistants sur 2 prélèvements. Ce travail de thèse s’est intéressé à des manifestations cliniques et des tests biologiques dont le but est d’évaluer le risque thrombotique dans ce syndrome. En premier lieu, le risque de valvulopathie associé aux aPL chez les patients lupiques a été étudié. L’existence d’une telle association faisait l’objet d’une controverse non résolue. En ayant recours à une revue systématique de la littérature et à une méta-analyse d’études observationnelles, les fréquences des valvulopathies chez les patients lupiques en fonction de la présence ou non d’aPL ont été comparées. Le résultat principal est, qu’en présence d’aPL chez les patients lupiques, ce risque est multiplié par 3. En second lieu, la valeur pronostique sur le risque de thrombose des thromboses veineuses superficielles (TVS) a été étudiée chez les patients atteints d’un SAPL. Une étude de cohorte prospective monocentrique a montré que la présence d’un antécédent de TVS était prédictive du risque de thrombose ultérieure. D’autre part, l’apport de nouveaux marqueurs biologiques, les anticorps spécifiquement dirigés contre le domaine I de la [bêta]2-Glycoprotéine I ainsi que les paramètres de thrombinographie prenant en compte la sensibilité à la protéine C activée ont été étudiés. Les résultats montrent que ces 2 tests sont prédictifs du risque thrombotique incident. Enfin, les données de qualité de vie d’une cohorte multicentrique de patients atteints de lupus et/ou porteurs d’aPL, ont été analysées. Les résultats montrent que la présence d’un antécédent de thrombose artérielle était associée à une altération de toutes les dimensions de la qualité de vie évaluée par un auto-questionnaire généraliste (MOS-SF36) en comparaison à des patients atteints de maladie auto-immune sans ce type de thrombose. Ces résultats pourront avoir un impact significatif dans la réflexion sur l’évolution des critères de classification de ce syndrome
Antiphospholipid syndrome (APS) is characterized by an auto-immune disorder with thrombotic and obstetrical morbidity in the presence of persistant antiphospholipid antibodies (aPL). This work studied clinical manifestations and laboratory assays for the determination of thrombotic risk in APS patients. Firstly, the risk of heart valve disease associated with aPL in systemic lupus erythematosus (SLE) patients was studied. Since 20 years, data regarding this association yielded conflicting results. A systematic review and a meta-analysis were performed to compare frequencies of heart valve disease in SLE patients with and without aPL. Main result concluded that the presence of aPL in SLE patients is associated with a 3-fold increased risk for heart valve disease in comparison with SLE patients without these antibodies. Secondly, prognostic significance of superficial vein thrombosis (SVT) was studied in APS patients. A prospective cohort study was performed and showed that SVT was predictive of thrombotic events overtime in this population. Moreover, the contribution of new laboratory assays were studied (antibodies directed against the domain I of [beta]2-Glycoprotein I and thrombin generation assay assessing sensitivity to activated protein C). Results demonstrated that these two assays were predictive of thrombotic events in APS patients. Finally, health-related quality of life was assessed in a multicentric cohort study of patients with aPL and/or SLE. Results showed that the presence of a history of arterial thrombosis was significantly associated with an impairment of all dimensions scores assessed by the MOS-SF36 questionnaire in comparison with patients with an auto-immune disease but without arterial thrombosis. This work provides new insights in the field of APS and may have an impact in the evolution leading to new classification criteria for definite APS

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Garcia, Carolina Borges. "Avaliação da capacidade aeróbica e do controle autonômico cardíaco em pacientes com síndrome antifosfolípide primária." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-08042014-091752/.

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A Síndrome Antifosfolípide (SAF) primária está associada com o risco aumentado de doenças cardiovasculares e mortalidade. A capacidade aeróbia e o controle autonômico cardíaco também estão associados a esses riscos. Objetivos: Avaliar a capacidade aeróbia e o controle autonômico cardíaco em pacientes com SAF primária. Métodos: Treze mulheres com SAF e treze controles saudáveis pareados por idade, sexo e índice de massa corporal foram incluídos no estudo. Ambos os grupos eram sedentários e não estavam em uso de medicações cronotrópicas, antidepressivas e hipolipemiantes. Todos os indivíduos realizaram o teste ergoespirométrico em esteira. A capacidade aeróbia foi avaliada através do pico do consumo de oxigênio (VO2pico), tempo no limiar anaeróbio ventilatório (LAV) e no ponto de compensação respiratória (PCR) e tempo no pico de esforço, enquanto o controle autonômico do coração foi avaliado através da reserva cronotrópica (RC) e frequência cardíaca na recuperação no primeiro e segundo minutos após o exercício (FCR1min e FCR2min, respectivamente). Resultados: Todos os índices de capacidade aeróbia estavam reduzidos nos pacientes com SAF primária em comparação com os controles saudáveis: VO2pico (30,2 ± 4,7 vs. 34,6 ± 4,3 mL.kg-1.min-1 P = 0,021), tempo no LA (3,0 ± 1,5 vs. 5,0 ± 2,0 min; P = 0,016), tempo no PCR (6,5 ± 2,0 vs. 8,0 ± 2,0 min; P = 0,050), tempo no pico de esforço (8,5 ± 2,0 vs. 11,0 ± 2,5 min; P = 0,010). As FCR1min (22 ± 9 vs. 30 ± 7 bpm; P = 0,032) e FCR2min (33 ± 9 vs. 46 ± 8 bpm; P = 0,002) foram menores nos pacientes com SAF em comparação com os controles saudáveis mas a RC não foi significativamente diferente (P = 0,272). Dessa forma, observamos uma diminuição na capacidade aeróbia e no controle autonômico nos pacientes com SAF
Primary antiphospholipid syndrome (PAPS) is associated with increased risk of cardiovascular disease and mortality. Aerobic capacity and cardiac autonomic control are also associated with these risks. Objective: To assess aerobic capacity and cardiac autonomic control in PAPS patients. Methods: Thirteen women with PAPS and 13 healthy controls matched for age, gender, and body mass index were enrolled for the study. Both groups were sedentary and were not under chronotropic, antidepressants and hypolipemiant drugs. All subjects performed a treadmill graded maximal exercise. Aerobic capacity was assessed by peak oxygen uptake (VO2peak), time at anaerobic ventilatory threshold (VAT) and respiratory compensation point (RCP), and time-to-exhaustion, whereas cardiac autonomic control by chronotropic reserve (CR) and heart rate recovery of the first and second minutes after graded exercise (HRR1min and HRR2min, respectively). Results: All aerobic capacity indexes were reduced in PAPS patients than healthy subjects: VO2peak (30.2 ± 4.7 vs. 34.6 ± 4.3ml.kg-1.min-1, P = 0.021), time at LAV (3.0 ± 1.5 vs. 5.0 ± 2.0 min, P = 0.016), time at RCP (6.5 ± 2.0 vs. 8.0 ± 2.0 min, P = 0.050), time-to-exhaustion (8.5 ± 2.0 vs. 11.0 ± 2.5 min, P = 0.010). HRR1min (22 ± 9 vs. 30 ± 7bpm, P = 0.032) and HRR2min (33 ± 9 vs. 46 ± 8bpm, P = 0.002) were delayed in PAPS patients compared to healthy controls but CR was not significantly different (P = 0.272). In conclusion, an impaired aerobic capacity and cardiac autonomic control was identified in PAPS

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Cerqueira, Sheylla Maryelleen Felau. "Eficácia e segurança da suplementação de ômega 3 em pacientes com a síndrome do anticorpo antifosfolípide primário." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-20022018-115936/.

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A síndrome do anticorpo antifosfolípide (SAF) é uma doença autoimune sistêmica caracterizada por episódios trombóticos recorrentes e/ou complicações durante a gravidez e presença de anticorpos antifosfolípides séricos (aPL). Os pacientes com SAF apresentam maior risco de aterosclerose e doenças cardiovasculares (DCVs). Estudos sugerem que as células endoteliais desempenham um papel central na patogênese do SAF uma vez que pacientes com SAF apresentam comprometimento da função endotelial quando comparados a controles saudáveis. A suplementação de ácidos graxos poliinsaturados ômega-3 (n-3 PUFA) parece melhorar a função endotelial em pacientes com diabetes tipo 2 (DM2), dislipidemia, e lúpus eritematoso sistêmico. Dessa forma, ela poderia ser de grande relevância clínica na SAF. Objetivo: Avaliar a eficácia da suplementação de PUFA n-3 na função endotelial (desfecho primário) de pacientes com SAF primária. Desfechos secundários incluíram inflamação sistêmica, perfil lipídico e segurança. Métodos: Foi realizado um estudo clínico randomizado de 16 semanas com 22 mulheres adultas com SAF primário. As pacientes foram alocadas aleatoriamente (1: 1) para receber suplementação com placebo (PL) ou n-3 PUFA (w-3). Antes (pré) e após (Pós) 16 semanas de intervenção, elas foram avaliadas quanto a função endotelial (usando tonometria da artéria periférica), marcadores de função endotelial (concentrações circulantes de adesão intercelular molécula-1 [ICAM-1], molécula de adesão vascular-1 [VCAM-1], e-selectina e fibrinogênio), marcadores inflamatórios (concentrações circulantes de proteína C reativa [PCR], IL-6, IL-10, TNF [fator de necrose tumoral] , IL-1ra e IL-1beta), perfil lipídico, segurança (razão internacional normalizada [INR] e efeitos adversos auto-relatados. Resultados: Após a intervenção, o grupo w-3 apresentou aumento significativos no RHI (Índice de Hiperemia reativa) e LnRHI (transformação logarítmica do Índice de hiperemia reativa)q uando comparados com PL (+13% versus -12%, p = 0,06, ES = 0,9 e +23% versus -22%, p = 0,02, ES = 1,0). Não foram observadas alterações nas concentrações de e-selectina, VCAM-1 e fibrinogênio (p > 0,05). Em contrapartida, grupo ?-3 apresentou diminuição nas concentrações circulantes de IL-10 (-4% vs. + 45%, p = 0,04, ES = -0,9) e concentração reduzida não significativa de TNF (-11% vs. + 0,3%, p = 0,12, ES = -0,7), IL-1beta (-22% vs. + 12%, p = 0,2, ES = - 0,7) e ICAM-1 (+ 3% vs. + 48%, p = 0,12, ES = -0,7) quando comparado ao PL após a intervenção. Apesar das concentrações aumentadas de colesterol total e LDL-colesterol (+ 6% vs. -2%, p = 0,07, ES = 0,7; + 11% vs. -0,3%, p = 0,02, ES = 0,8), não foram observadas diferenças entre w -3 e PL na relação LDL-colesterol/HDL-colesterol (+ 7% vs. + 1%, p = 0,4, ES = 0,3) e triglicerídeos (-20% vs. -18%, p = 0,5, ES = -0,06). Nenhuma alteração no INR foi observada e nenhum efeito adverso foi relatado. Conclusão: Suplementação de PUFA n-3 por 16 semanas levou a melhorias na função endotelial e à ligeira diminuição no millieu inflamatório de pacientes com SAF primária bem controlada. Esses resultados dão suporte à suplementação de PUFA n-3 como terapia adjuvante em SAF
Antiphospholipid Syndrome (APS) is a systemic autoimmune disease characterized by recurrent thrombotic episodes and/or complications during pregnancy, and persistent serum antiphospholipid antibodies (aPL). Patients with APS are at increased risk for atherosclerosis and cardiovascular diseases (CVDs). It has been suggested that endothelial cells play a central role in the pathogenesis of APS as patients with APS show impaired endothelial function when compared with their healthy peers. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in type 2 diabetes (T2D), dyslipidemia, and systemic lupus erythematosus. Thus, it could be of high clinical relevance in APS. Objective: To evaluate the effectiveness of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS. Secondary outcomes were systemic inflammation, lipid profile, safety, and clinical parameters. Methods: A 16-week randomized clinical trial was conducted with 22 adult women with primary APS. Patients were randomly assigned (1:1) to receive either placebo (PL) or n-3 PUFA (?-3) supplementation. Before (Pre) and after (Post) 16 weeks of the intervention patients were assessed for endothelial function (using peripheral artery tonometry), endothelial function markers (circulating levels of intercellular adhesion molecule-1 [ICAM-1], vascular adhesion molecule-1 [VCAM-1], e-selectin and fibrinogen), inflammatory markers (circulating levels of C-reactive protein [CRP], IL-6, IL-10, TNF, IL-1ra, and IL-1beta), lipid profile, safety (international normalized ratio [INR] and self-reported adverse effects. Results: Following the intervention, w-3 presented significant increases in RHI and LnRHI when compared with PL (+13% vs. -12%, p=0.06, ES=0.9; and +23% vs. -22%, p=0.02, ES=1.0). No changes were observed for e-selectin, VCAM-1 and fibrinogen levels (p > 0.05). In contrast, w-3 showed decreased circulating levels of IL-10 (-4% vs. +45%, p=0.04, ES=-0.9) and nonsignificant decreased levels of TNF (-11% vs. +0.3%, p=0.12, ES=-0.7), IL-1beta (-22% vs. +12%, p=0.2, ES=-0.7), and ICAM-1 (+3% vs. +48%, p=0.12, ES=-0.7) when compared with PL after the intervention. Despite increased levels of total cholesterol and LDL-cholesterol (+6% vs. -2%, p=0.07, ES=0.7; +11% vs. -0.3%, p=0.02, ES=0.8), no differences between ?-3 and PL were observed in LDL-cholesterol/HDL-cholesterol ratio (+7% vs. +1%, p=0.4, ES=0.3) and triglycerides (-20% vs. -18%, p=0.5, ES=-0.06). No changes in INR were observed and no adverse effects were reported. Conclusion: Sixteen weeks of n-3 PUFA supplementation led to improvements in endothelial function and a slight decrease in the inflammatory milieu of patients with well-controlled primary APS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS

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BAERT, WILLERON BEATRICE. "Le syndrome des antiphospholipides : a propos d'une observation." Lille 2, 1994. http://www.theses.fr/1994LIL2M007.

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Lieby, Patricia. "Aspects moléculaires et spécificités fines des auto-anticorps antiphospholipides : contribution à la compréhension de leur origine et de leur pathogénicité." Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13116.

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Eszto, Marie-Laure Monnier-Barbarino Patricia. "Etude de la cinétique des anticorps anticardiolipines dans les grossesses à risque." [S.l] : [s.n], 2004. http://www.scd.uhp-nancy.fr/docnum/SCDMED_T_2004_CAMBON_ESZTO_MARIE_LAURE.pdf.

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Moustey, Francois. "Le syndrome catastrophique des antiphospholipides : état actuel des connaissances. Expérience personnelle : à propos d'un cas." Bordeaux 2, 2001. http://www.theses.fr/2001BOR2M042.

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DELALEUX, POTIER ISABELLE, and YVES DELALEUX. "Infarctus du myocarde de cause inexpliquee et syndrome des antiphospholipides." Lille 2, 1994. http://www.theses.fr/1994LIL2M074.

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Dissertations / Theses on the topic 'Antiphospholipid syndrome'

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