Gotowa bibliografia na temat „Blood coagulation tests”

Abstract Background: Laboratory tests can be an important source of blood loss in hospitals, especially for newborns and patients in intensive care. The aim of this study was to quantify blood loss for laboratory diagnostic tests in a large number of patients in a teaching hospital. Methods: We estimated blood loss by multiplying the number and volumes of sampling tubes collected from 2654 adult inpatients. We compared the number of tests per patient for all inpatients and intensive care unit patients during the first period and again in the same time period 1 year later when cumulative blood-loss volumes were being reported to physicians and educational information had been given to decrease blood loss from laboratory tests. Results: For 95% of the patients, blood loss during hospitalization was <196 mL. The largest proportion of the blood samples was used for clinical chemical tests (median, 45%), followed by hematologic (median, 26%) and coagulation (median, 17%) tests. In the surgical and cardiovascular surgical intensive care units, however, blood gas analyses accounted for 19–34% (medians) of the use. For 5% of the patients, all undergoing intensive care, blood loss was >200 mL and for 0.7% was >600 mL during their hospital stay. Such high blood losses were observed in patients with long-term ventilation, coagulation disorders, and repeated surgery. The largest median blood loss was in patients undergoing cardiovascular surgery (median, 201 mL). The mean number of tests was 44 per inpatient before cumulative blood loss was being reported and 46 when it was being reported. Conclusions: Blood loss from laboratory diagnostic testing is not likely to pose a problem for most hospitalized patients. Blood loss is greater in intensive care patients and after cardiovascular surgical procedures. Reporting of the cumulative individual blood loss did not decrease blood loss for laboratory testing.

Background: Rejection of hemolysed samples for coagulation test is the standard practice.However, when clinicians deal with extremely sick patients where repeat sampling is difficult toobtain, rejection of the sample is a lost opportunity for the lab physician to assist inpatient care.Proceeding with the test and providing a clinically helpful interpretation of the results will ensure theactive participation of the laboratory physician. Different principles of coagulation testing handle thehemolysed samples differently. It is essential to know the best principle to proceed with thehemolysed sample if need be. This study set out to estimate the predictive values of post-hemolyticsample coagulation test results with various coagulation test principles. Methods: This is aprospective experimental study where the non-hemolysed samples were processed for coagulationtests. Part of the sample was deliberately hemolysed, and the coagulation tests were repeated.Results: Two hundred and forty-eight samples were studied. A median of 11% hemolysis wasachieved experimentally. The mean difference in prothrombin time between pre and post hemolyticsamples with normal PT was 0.9 and with abnormal PT, it was 1.1 seconds. The same for APTT was4.9 and 1.1 seconds, respectively. The majority of the samples showed prolonged coagulation posthemolysis. Positive (PPV) and negative (NPV) predictive values for prothrombin time are 97.3 and73.4%, respectively. Similarly, PPV and NPV for APTT are 97.4 and 47.1%, respectively.Conclusions: Samples with normal values after hemolysis are more likely to be normal.

Background: Coagulation has notoriously been a topic that medical trainees find challenging to learn. A lack of understanding around coagulation has led to widespread inappropriate ordering of commonly used coagulation tests, including the prothrombin time (PT) and the activated partial thromboplastin time (aPTT). Despite these tests being validated for specific clinical indications, they are frequently ordered as screening tests in unselected patients, and often ordered together, suggesting a gap in physician understanding of coagulation and appropriate testing. To explore this further, we conducted a root-cause-analysis survey of 10 medical trainees. 70% of the surveyed trainees did not feel comfortable with their knowledge regarding coagulation and the appropriate use of coagulation tests. Trainees attributed their suboptimal knowledge to the manner in which coagulation is taught in training programs. Furthermore, they identified a scarcity of practical resources on coagulation and expressed interest in a web-accessible resource. Methods: We created an educational module on coagulation testing for trainees, available online at www.coagtesting.com. This module was created with the intent of simplifying the teaching of coagulation, with a focus on emphasizing clinically-relevant concepts. The module was evaluated at the University of Toronto with 50 participating medical trainees (11 medical students, 39 internal medicine residents [14 PGY1, 15 PGY2, 10 PGY3 residents]). Participation in our study included completing a validated knowledge pre-quiz on coagulation, completion of the educational module, and then the post-quiz following the module. To assess longer term knowledge retention, participants were asked to repeat the knowledge quiz three months following their initial participation. Our educational intervention was evaluated according to the Kirkpatrick Model, a framework for learning evaluation, with educational outcomes organized into four ranked levels (level 1, reaction; level 2, learning; level 3, behaviour; level 4, results). The primary objective of this study was to determine if the module improves trainee knowledge of coagulation, as indicated by their quiz results (level 2, learning). The secondary objective was to evaluate if the module has an influence on trainee ordering practices as assessed by a follow-up survey (level 3, behaviour). Results: The median pre-module quiz score was 67% (range 24% - 86%) with an increase of 24% to a median post-module quiz score of 91% (range 64% - 100%). Notably, in the pre-module quiz, 94% of trainees overestimated the sensitivity and specificity of the PT and aPTT in detecting a bleeding disorder, and 44% of trainees underestimated the cost of a PT test. 80% of trainees described increased confidence regarding their knowledge of coagulation and the use of coagulation tests following completion of the module. In addition, we have demonstrated sustained knowledge acquisition with a 3-month post-quiz median score of 89% (n=15, range 67%-100%). 100% of trainees who completed the 3-month follow-up survey (n=15) felt that the educational module had a positive influence on their practice and 87% of trainees were more likely to consider the sensitivity, specificity, and cost of a lab test prior to ordering it. In the seven months since the module was launched, it has been completed by over 2,000 unique visitors worldwide, with use in Canada, the United States, the United Kingdom, Australia, France, and Saudi Arabia according to data from our website host. Furthermore, several visitors to the website have re-visited the module multiple times. Conclusion: We have successfully demonstrated a significant increase in trainee knowledge and confidence regarding coagulation and appropriate use of coagulation tests with our educational intervention. Using the expertise of medical educators and incorporating feedback from trainees, we have employed a novel approach to the teaching of coagulation to maximize its approachability and clinical relevance. Our module also incorporates education on the cost of coagulation testing and appropriate use of these tests thus in line with the tenets of Choosing Wisely. The degree to which trainees have been utilizing and re-referring to our educational module worldwide emphasizes the need for this resource and its importance in bridging a large gap in medical training. Disclosures Sholzberg: Novartis: Honoraria; Amgen: Honoraria, Research Funding.

A descriptive study was conducted to test the null hypothesis: There will be no statistically significant difference between serum activated partial thromboplastin time (aPTT) obtained by two methods; venipuncture and large bore femoral arterial catheter. The convenience sample consisted of seventeen adults who had undergone percutaneous transluminal coronary angioplasty (PTCA) for the treatment of coronary artery disease. After the PTCA procedure, patients returned to an intensive care unit with a femoral intra-arterial catheter in place. Seventeen pairs of serum samples were obtained; one by venipuncture and one through the femoral intra-arterial catheter. Prior to obtaining the sample from the femoral intra-arterial catheter, 6.0 milliliters (3 times the deadspace of the catheter) of blood was withdrawn and discarded. aPTT samples were analyzed. T-tests were used to compare the results. Findings revealed that there was no statistically significant difference in the aPTT value when drawn from venipuncture versus the femoral intra-arterial catheter.

Thesis (Ph.D. in Clinical Science) -- University of Colorado Denver, 2008.
Typescript. Includes bibliographical references (leaves 136-146). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

Orientador: Erich Vinicius de Paula
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-19T11:03:42Z (GMT). No. of bitstreams: 1 Quaino_SusanKellyPicoli_M.pdf: 2874691 bytes, checksum: aa96cc1f9d7979751213f3bda6ad0681 (MD5) Previous issue date: 2011
Resumo: Pacientes com neutropenia febril apresentam risco aumentado de infecções severas e complicações da sepse. A ativação descontrolada da coagulação é uma das características mais marcantes da sepse. O quadro clínico e laboratorial mais característico desta ativação é chamado de coagulação intra-vascular disseminada. Do ponto de vista da fisiopatologia, a coagulação intravascular disseminada é caracterizada por ativação da coagulação pela expressão anômala intravascular de fator tissular, pelo consumo de inibidores naturais da coagulação e pela liberação excessiva de PAI-1, levando a hipofibrinólise. O quadro resultante destes processos é a hipercoagulabilidade. Acredita-se que parte das complicações da sepse, entre elas a chamada falência de múltiplos órgãos, seja decorrente de trombose de microvasos e isquemia tecidual. Assim, o estudo da coagulação intravascular disseminada tem grande relevância clínica. A avaliação laboratorial da hemostasia em pacientes com sepse e coagulação intravascular disseminada é limitada pelo fato de os testes disponíveis não ilustrarem de forma global e completa o resultado de todos estes processos na hemostasia. Além disso, é reconhecido que esta avaliação só é relevante se feita em mais de um momento ao longo da evolução do quadro na medida em que mais importante do que medidas isoladas é a tendência de mudança de variáveis como tempo de protrombina, dímeros D e fibrinogênio. Por este motivo, os chamados testes globais da hemostasia, capazes de avaliar de forma mais completa a interação de todos os processos citados acima, vêm ganhando importância nos últimos anos. Em pacientes com sepse, o teste de geração de trombina já foi avaliado em medidas isoladas, mostrando resultados que indicam lentificação do processo de ativação da coagulação. Estes resultados são distintos daqueles classicamente aceitos de hipercoagulabilidade durante as fases iniciais da sepse. No entanto, o número de estudos realizados nestes pacientes é escasso, sendo que em nenhum deles foi avaliada a variação temporal deste parâmetro. Em nosso estudo avaliamos parâmetros do teste da geração de trombina em pacientes com sepse e neutropenia febril. A avaliação foi feita no tempo basal, no momento da febre e após 48 horas. Além disso, avaliamos os parâmetros clássicos da hemostasia.. Nossos resultados contrariam a hipótese de presença de hipercoagulabilidade nas fases iniciais da sepse. Nenhum parâmetro do teste de geração de trombina mostrou-se capaz de segregar pacientes com maior risco de evolução para choque séptico
Abstract: Patients with febrile neutropenia are at increased risk of severe infections and complications of sepsis. The uncontrolled activation of coagulation is one of the most striking features of sepsis. The clinical and laboratory most characteristic of this activation is called disseminated intravascular coagulation. The pathophysiology of disseminated intravascular coagulation is characterized by activation of coagulation by anomalous intravascular expression of tissue factor, the consumption of natural inhibitors of coagulation and excessive release of PAI-1, leading to hipofibrinolysis. The net resulting picture of these processes is the hypercoagulability. It is believed that some of the complications of sepsis, including the so-called multiple organ failure, is due to thrombosis of microvasculature and tissue ischemia. Thus, the study of disseminated intravascular coagulation has great clinical relevance. Laboratory evaluation of hemostasis in patients with sepsis and disseminated intravascular coagulation is limited because the available tests do not depict in a comprehensive and completely way the results of all these processes in hemostasis. Moreover, it is recognized that this assessment is only relevant if done in more than one time-point along during disease progression to capture the trends of variables such as prothrombin time, D dimers and fibrinogen. For this reason, the so-called global tests of hemostasis, able to assess more fully the interaction of all the above processes are gaining importance in recent years. In patients with sepsis, thrombin generation test has been evaluated on single measures, showing results that show slowing the process of coagulation activation. These results are distinct from those classically accepted which assume that hypercoagulability would be present in early phases of sepsis. However, the number of patients in these studies is scarce, and none of them evaluated the temporal variation of this parameter. In our study we evaluated the test parameters of thrombin generation in patients with sepsis and febrile neutropenia. The evaluation was performed at baseline, at the time of fever and 48 hours thereafter. In addition, we evaluated classical parameters of hemostasis. Our results contradict the hypothesis of the presence of hypercoagulabilit in the early stages of sepsis and deserve further evaluation in larger studies. No parameter of thrombin generation was able to segregate patients with higher risk to progress to septic shock
Mestrado
Ciencias Basicas
Mestre em Clinica Medica

Thesis (MScMedSc)--Stellenbosch University, 2012.
Bibliography
ENGLISH ABSTRACT: Background: In the era of antiretroviral therapy (ART), the risk of acquired immune deficiency syndrome (AIDS) related deaths has decreased and people living with Human Immunodeficiency Virus (HIV) now have prolonged life spans. However, an increasing trend of non-AIDS associated deaths has been reported despite adequate control of viral loads. HIV infection is established as a chronic inflammatory condition which is associated with an increased risk for thrombosis. Thus HIV infected patients are at a higher risk of developing cardiovascular disease (CVD) and other inflammatory-associated complications. Inflammation is linked with thrombosis and promotes the formation of thrombin, which plays an important role in platelet activation. Furthermore, activated platelets have been shown to play a key role during infection and the inflammatory process, particularly by mediating interactions between cells of innate immunity. Soluble markers of platelet activation have been shown to be increased in HIV-infection. However, these have not been well documented by flow cytometry. P-selectin CD62P is stored in the alpha granules of platelets and is expressed on the surface only upon platelet activation. This facilitates interaction with other blood cells and the endothelium. Activated platelets may play a role in HIV-induced atherosclerosis through the expression and release of mediators that induce endothelial activation and support the adhesion of leukocytes to the inflamed vessel wall. Fibrinogen is a precursor of the blood coagulatory protein fibrin and the degradation of fibrin to D-dimer is a measure of the formation and the subsequent dissolution of blood clots. In HIV infected patients, chronic inflammation induces the up-regulated expression of tissue factor (TF) on monocytes which triggers the activation of the clotting cascade and increases the level of D-dimers. Methods: This pilot study consisted of ART naïve patients and all platelet flow analyses were carried out on whole blood. In this study, a total of 57 adult South Africans were recruited from a clinic in the Western Cape. These included 32 HIV positive patients and 25 HIV negative individuals. The levels of platelet activation and platelet function were investigated using a novel platelet cytometry assay. The method was optimized to ensure minimal platelet activation: no centrifugation or red blood cell (RBC) lysis steps were performed. The platelet-specific markers CD41a and CD42b were used to ensure gating on platelets only. CD62P expression was used to evaluate platelet activation and these levels were correlated with Fibrinogen, hsCRP, Ddimer, CD4 counts and viral load. Furthermore, platelet function was evaluated by investigating the response of platelets to endogenous agonists which included adenosine diphosphate(ADP) and arachidonic acid (AA) at varying concentrations. Results:This study demonstrated higher baseline levels of CD62P expression in treatment naïve HIV positive patients as compared to uninfected controls (mean %CD62P 71.74 ± 2.18 vs control 54.52 ± 2.42; p=<0.0001). In addition it was shown that %CD62P expression correlated directly with platelet counts (r=0.374, p=0.042). Platelet counts showed an inverse correlation with viral loads (give values) Fibrinogen levels correlated with the absolute WCC (r=0.659, p=0.0021); absolute neutrophil count (r=0.619, p=0.0105); absolute monocyte count (0.562, p=0.0235) and hsCRP (r=0.688 p=0.0011). In addition, fibrinogen showed a strong negative correlation with CD4 counts (r=-0.594, p=0.0014) and therefore, may be a valuable marker of both disease progression and risk of thrombosis in treatment naïve HIV positive patients. HsCRP levels correlated with the absolute neutrophil counts (r=0.392, p=0.0005). The HIV Group showed an overall hyper-response to ADP at a concentration 0.025 μM as compared to uninfected controls (62.34 ± 9.7 vs control 36.90 ± 5.7, p=0.0433). Conclusions: In this study we describe a novel Flow Cytometry technique that may be used to evaluate the levels of platelet activation and platelet function in HIV infected patients. In addition we report a cost-effective panel in the form of fibrinogen, WCC and platelets that may be valuable in predicting the progression of HIV infection to AIDS or other inflammatory- associated complications in treatment naïve HIV infected patients. Platelet counts showed an inverse correlation with viral loads and a direct correlation with the level of activated platelets. These findings taken together suggest the potential prognostic value of platelet activation and platelet counts in the context of asymptomatic HIV infected patients. Our findings suggest WCC and Fibrinogen may be used to evaluate the inflammatory profile of individual HIV infected patients. This may have a direct impact on HIV patient management prior to initiation of antiretroviral therapy and valuable in monitoring responses to treatment. Further, we present a novel flow cytometry based platelet functional assay and suggest the use of ADP at a concentration of 0.025 μM to evaluate platelet function optimally in HIV infected patients. The utilization of the novel Flow Cytometry technique as described in this study would add significant value in the assessment of thrombotic risk and disease progression in HIV infected patients and may additionally prove to be of value in other chronic inflammatory conditions.
AFRIKAANSE OPSOMMING: Voorkennis: In die era van antiretrovirale terapie (ART), het die risiko van vigs-verwante sterftes verminder en mense wat nou met volle naam (MIV) leef, het ‘n verlengde lewensduur. Nogtans, word 'n toenemende neiging van nie-vigs geassosieer sterftes berig wat hoofsaaklik toegeskryf word aan trombotiese toestande. MIV-infeksie word as 'n chroniese inflammatoriese toestand beskou met ʼn verhoogde trombose risiko geassosieer word. Dus, MIV-besmette pasiënte het 'n hoër risiko om kardiovaskulêre siekte (CVD) te ontwikkel ongeag of hulle ARV naïef is of op behandeling is nie. Inflammasie word geassosieer met trombose en bevorder die vorming van trombien, wat 'n belangrike rol in plaatjie aktivering speel. Verder, word daar bewys dat geaktiveerde bloedplaatjies 'n belangrike rol speel tydens infeksie en die inflammatoriese proses.Hulle bemiddel interaksies tussen die selle van ingebore immuniteit. Daar word bewys dat oplosbare merkers van plaatjie aktivering verhoog is in MIV-infeksie, maar die bewyse is nie so goed gedokumenteer deur vloeisitometrie nie. P-selectin (CD62P) word gestoor in die alfa korrels van plaatjies en word uitgedruk op die oppervlak slegs wanneer plaatjies geaktivering word; daardeur fasilitering dit die interaksie met ander bloedselle en die endoteel. Geaktiveerde plaatjies kan ook 'n rol in MIV-geïnduseerde aterosklerose speel deur middel van die uitdrukking en vrylating van bemiddelaars wat endoteel aktivering induseer asook die adhesie van leukosiete aan die ontsteekte vat wand ondersteun.. Fibrinogeen, 'n voorloper van die bloed koagulatories proteïen fibrin en die degradasie van fibrin na D-dimeer is' n maatstaf van die vorming en die daaropvolgende ontbinding van bloedklonte. Kroniese inflammasie in MIVbesmette pasiënte, induseer die op-gereguleerde uitdrukking van weefsel faktor (TF) op monosiete wat die aktivering van die stolling kaskade inisieer en die D-dimere vlakke verhoog. Metodes: Hierdie loodsstudie bestaan uit ART naïewe pasiënte en al die plaatjie vloei ontleding was op vol bloed uitgevoer. In hierdie studie, 'n totaal van 57 volwasse Suid-Afrikaners was van' n kliniek in die Wes-Kaap gewerf. Dit sluit 32 MIV-positiewe pasiënte en 25 MIV negatiewe individue in. Die vlakke van plaatjie aktivering en plaatjie funksie was ge ondersoek deur middel van 'n nuwe plaatjie sitometrie toets. Die metode was geoptimaliseer om minimale plaatjie aktivering te verseker: dus geen sentrifugering of volle naam (RBS) liseer stappe was gebruik nie. Die plaatjie-spesifieke merkers, CD41a en CD42b was gebruik om te verseker dat slegs bloedplaatjes gekies word. Die uitdrukking van CD62P was gebruik vir die evaluering van plaatjie aktivering en hierdie vlakke was gekorreleer met fibrinogeen, hsCRP, D-dimeer, CD4- tellings en virale lading. Verder, was plaatjie funksie geëvalueer deur die reaksie van plaatjies aan endogene agoniste wat ADP en AA by wisselende konsentrasies insluit te ondersoek. Results: Hierdie studie het getoon hoër basislyn vlakke van CD62P uitdrukking in behandeling naïewe MIV-positiewe pasiënte in vergelyking met onbesmette beheermaatreëls (beteken% CD62P 71,74 ± 2,18 vs beheer 54,52 ± 2,42, p <0.0001). Daar is ook getoon dat% CD62P uitdrukking direk gekorreleer met plaatjie tellings (r = 0,374, p = 0,042). Plaatjie tellings het 'n omgekeerde korrelasie met virale ladings (gee waardes) fibrinogeen vlakke korreleer met die absolute WCC (r = 0,659, p = 0,0021), absolute neutrofiel telling (r = 0,619, p = 0,0105); absolute monosiet telling (0,562, p = 0,0235) en hsCRP (r = 0,688 p = 0,0011). Daarbenewens, fibrinogeen het 'n sterk negatiewe korrelasie met 'n CD4-tellings (r = -0,594, p = 0,0014) en daarom kan 'n waardevolle merker van beide die siekte en die risiko van trombose in behandeling naïewe MIV-positiewe pasiënte. HsCRP vlakke gekorreleer met die absolute neutrofiel tellings (r = 0,392, p = 0,0005). Die MIV-groep het 'n algehele hiper-reaksie op die ADP by 'n konsentrasie 0,025 μM in vergelyking met onbesmette beheermaatreëls (62,34 ± 9,7 vs beheer 36,90 ± 5.7, p = 0,0433). Gevolgtrekkings: In hierdie studie beskryf ons 'n roman vloeisitometrie tegniek wat gebruik kan word om die vlakke van Plaatjie aktivering en plaatjie funksie in die MIV-besmette pasiënte te evalueer. Verder het ons 'n verslag van 'n koste-effektiewe paneel in die vorm van fibrinogeen, WCC en plaatjies wat waardevol kan wees in die voorspelling van die vordering van MIVinfeksie tot VIGS of ander inflammatoriese-verwante komplikasies in die behandeling naïewe MIV-besmette pasiënte. Plaatjie tellings het 'n omgekeerde korrelasie met die virale laste en 'n direkte verband met die vlak van geaktiveerde bloedplaatjies. Hierdie bevindinge saam, dui op die moontlike prognostiese waarde van Plaatjie aktivering en die plaatjie tel in die konteks van die asimptomatiese MIV-geïnfekteerde pasiënte. Ons bevindinge dui daarop WCC en fibrinogeen kan gebruik word om die inflammatoriese profiel van individuele MIV-geïnfekteerde pasiënte te evalueer. Dit kan 'n direkte impak op MIV pasiënt vooraf aan die inisiasie van antiretrovirale terapie en waardevolle in die monitering van die reaksie op behandeling. Verder bied ons 'n roman vloeisitometrie gebaseer plaatjie funksionele toets en dui op die gebruik van die ADP teen 'n konsentrasie van 0,025 μM plaatjie funksie optimaal te evalueer in MIVgeïnfekteerde pasiënte. Die benutting van die roman vloeisitometrie tegniek soos beskryf in hierdie studie sal 'n beduidende waarde toevoeg in die beoordeling van die die trombotiese risiko en die siekte in MIV-geïnfekteerde pasiënte en kan addisioneel bewys van waarde te wees in 'n ander chroniese inflammatoriese toestande.
National Reserach Foundation

INTRODUÇÃO: sangramento por coagulopatia é problema comum durante o transplante hepático (TH). O uso adequado da monitorização da coagulação pode reduzir a transfusão de hemocomponentes, como o Plasma Fresco Congelado (PFC). Exames Convencionais da Coagulação (ECC), tais como Tempo de Protrombina (TP) e Tempo de Tromboplastina Parcial Ativada (TTPa), são os testes mais amplamente utilizados para monitorizar a coagulação durante o TH, mas algumas limitações têm sido apontadas acerca do seu uso em pacientes cirróticos. OBJETIVO: investigar o uso de ECC como variáveis preditoras da indicação de transfusão de PFC durante o TH em pacientes cirróticos. MÉTODO: analisou-se coorte histórica de 297 transplantes hepáticos com enxertos provenientes de doadores cadáveres. Foram incluídos receptores cirróticos de uma única instituição durante nove anos (2002-2010). A infusão profilática de ácido épsilon-aminocaproico (20 mg/kg/h) e outros pré-requisitos hemostáticos foram mantidos na cirurgia. O TP [expresso na forma de Percentual de Atividade da Protrombina (TP%) e de Relação Normalizada Internacional (INR)] e o TTPa foram medidos no pré-operatório e no fim de cada fase do TH. Os participantes só receberam transfusão de PFC quando se diagnosticou coagulopatia, independentemente dos resultados dos ECC. Os pacientes foram distribuídos em dois grupos, de acordo com a ocorrência de transfusão intraoperatória de PFC. Examinou-se o comportamento dos resultados dos ECC durante a cirurgia. Analisaram-se os fatores de risco para a transfusão de PFC por análises uni e multivariada. Os resultados pós-operatórios de ambos os grupos foram comparados. A acurácia dos ECC para predizer o uso de PFC em cada fase da cirurgia foi investigada por curvas ROC. Além disso, pontos de corte dos ECC não associados à coagulopatia foram calculados para cada fase da cirurgia. RESULTADOS: a análise multivariada demonstrou que hematócrito pré-operatório (odds ratio [OR] = 0,90, P < 0,001), fibrinogênio pré-operatório (OR = 0,99, P < 0,001) e ausência de carcinoma hepatocelular (OR = 3,57, P = 0,004) foram as únicas variáveis preditoras independentes para a transfusão de PFC durante o TH. As mortalidades precoce e tardia, a permanência em UTI e a incidência de reoperações por sangramento microvascular foram semelhantes entre os grupos. Os ECC demonstraram baixa acurácia global para a predição de transfusão de PFC durante o TH (as áreas sob as curvas ROC não chegaram a 70%, independentemente do teste da coagulação e do momento da aferição). Pontos de corte de ECC com alta especificidade para a não transfusão de PFC foram determinados em cada fase do TH para TP% (39,4, 27,8 e 20,3), INR (2,14, 2,62 e 3,52) e TTPa (50,5, 80,2 e 119,5 segundos). CONCLUSÕES: os únicos preditores independentes para a transfusão de PFC durante o TH foram hematócrito pré-operatório, fibrinogênio pré-operatório e ausência de carcinoma hepatocelular. Os ECC demonstraram baixa correlação com a transfusão intraoperatória de PFC, independentemente do momento da coleta ou dos pontos de corte adotados
BACKGROUND & AIMS: Bleeding due to coagulopathy is a common problem during liver transplantation (LT). Coagulation monitoring may reduce transfusion of blood components, including Fresh Frozen Plasma (FFP). Conventional coagulation assays (CCA), like Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT), are the most widely employed tests to monitor coagulation during LT, but some limitations have been assigned to their use in cirrhotic patients. This study investigated the predictive value of these blood coagulation tests in predicting FFP transfusions during LT in cirrhotic patients. METHODS: This historical cohort study analyzed 297 isolated, deceased donor LTs performed in cirrhotic patients from a single institution during a nine-year period (2002 - 2010). Prophylactic infusion of epsilon-aminocaproic acid [EACA] (20 mg/kg/h) and other hemostatic requirements were maintained intraoperatively. PT [expressed as Activity Percentage (PT%) and International normalized ratio (INR)] and aPTT [expressed in seconds] were measured preoperatively and by the end of each phase of LT. Hemostatic blood components were transfused only in case of coagulopathy. Patients were divided in two groups according to intraoperative FFP transfusion: FFP group and Non-FFP group. Behavior of CCA results during LT were examined in both groups. Univariate and multivariate analyses of risk factors associated with FFP transfusion were performed. Post-operative outcomes were compared between groups. Accuracy of CCA to predict FFP transfusions was investigated using receiver operating characteristic (ROC) curves. Also, alert values of CCA unassociated with coagulopathy in each phase of surgery were calculated. RESULTS: Multivariate analysis showed that preoperative hematocrit (odds ratio [OR] = 0.90, P < 0.001), preoperative fibrinogen (OR = 0.99, P < 0.001) and absence of hepatocellular carcinoma (OR = 3.57, P = 0.004) were the only significant predictors for FFP transfusion. Short- and long-term survival, ICU stay and incidence of early reoperations for bleeding were similar between the groups. CCA demonstrated poor overall accuracy for predicting FFP transfusions (area under the ROC curves did not reach 0.70, irrespective of assay and of phase of sampling). High-specificity values of CCA unassociated with coagulopathy in each of 3 phases of LT were identified for INR (2.14, 2.62 and 3.52), PT% (39.4, 27.8 and 20.3%) and aPTT (50.5, 80.2 and 119.5 seconds). CONCLUSIONS: the only significant predictors for FFP transfusion were preoperative hematocrit, preoperative fibrinogen and absence of hepatocellular carcinoma. CCA, regardless of adopted cutoffs and of time of sampling during LT, have poor correlation with intraoperative FFP transfusion

Introdução: Pacientes com cirrose possuem altos níveis de fator VIII e preservação da trombomodulina (TM) (ativador da proteína C) apesar da redução global nas concentrações dos procoagulantes e anticoagulantes naturais. Isto não é levado em conta no teste de TP/INR, o qual não requer a adição de trombomodulina. Deste modo, o TP/INR não é capaz de demonstrar a magnitude da geração de trombina, em condições similares à que ocorre in vivo. De fato, o teste de TP/INR mede o lado procoagulante e se correlaciona com somente 5% do total de trombina gerada. Nossa hipótese é que a geração de trombina está bem preservada na cirrose, ainda que avançada, apesar dos resultados anormais do TP/INR, os quais indicariam coagulopatia. Objetivo: correlacionar os resultados do teste TP/INR com a geração de trombina nos pacientes com cirrose após procedimento invasivo (ligadura elástica de varizes esofagianas - LEVE). Pacientes e métodos: 97 pacientes foram consecutivamente incluídos no estudo (58 homens; 54±10 anos) e divididos em dois grupos INR < 1,5 e INR >= 1,5. Todos os pacientes passaram por uma criteriosa análise clínica e laboratorial, que incluiu revisão dos prontuários, determinação do TP/INR e da geração de trombina (ETP) com e sem adição de trombomodulina e cálculo do rETP (razão dos resultados com e sem adição de trombomodulina). Resultados: Não houve diferença significante na média dos valores de ETP sem trombomodulina no grupo INR < 1,5 (n=72), que foi 1.250±315,7 nmol/min quando comparada ao grupo INR >= 1,5 (n=25), cujos valores foram 1.186±238 nmol/min, p=0,3572. Após adição de trombomodulina, os valores mudaram para 893,0±368,6 e 965,9±232,3 nmol/min, respectivamente (p=0,6265). Ambos os grupos apresentaram preservação da geração de trombina, com valores mais elevados no grupo INR >= 1,5 do que no grupo de pacientes com INR < 1,5 (rETP 0,81±0,1 versus 0,69±0,2; p=0,0042). Evidência de hipercoagulabilidade (valores altos de rETP) foi demonstrada em 80% dos pacientes. Mesmo pacientes com INR >= 1,5 apresentam geração de trombina preservada, o que justificaria a baixa prevalência de sangramento após ligadura elástica de varizes esofagianas (5,2%; 3 pacientes no grupo INR < 1,5 e 2 pacientes no grupo INR >= 1,5). Conclusões: a geração de trombina se encontrou preservada nos pacientes com cirrose e os valores anormais de INR não refletiram a ocorrência de sangramento. A maioria dos pacientes mostrou evidência de hipercoagulabilidade, apesar do INR alargado. Sangramento após LEVE ocorreu em pequena parcela dos pacientes e não foi relacionado ao status da coagulação
Introduction: Patients with cirrhosis have higher levels of factor VIII and preservation of endothelial thrombomodulin (protein C activator) in spite of the global reduction in procoagulant and natural anticoagulant concentrations. This is not taken into account in the laboratory test of INR/PT, which does not require the addition of thrombomodulin and, thus, is not able to emulate the generation of thrombin that happens in vivo. In fact, INR/PT is a measure of procoagulant status and correlates with only 5% of the total amount of generate thrombin. We hypothesized that thrombin generation is well preserved in cirrhosis, even in advanced stages, despite the abnormal result of INR/PT, which would indicate coagulopathy. Aims: to correlated INR/PT with thrombin generation in patients with cirrhosis in the elective setting of an invasive procedure (endoscopic variceal ligation- EVL). Patients and Methods: 97 consecutive patients were prospectively included in this study (58 men; 54±10 years old) and divided into two groups INR < 1.5 and INR >= 1.5. All patients underwent a stringent clinical and laboratory assessment which included review of the clinical chart, INR/PT determinations and assessment of endogenous thrombin potencial (ETP) without and with the addition of thrombomodulin and calculation of the ETP ratio (rETP= without/with thrombomodulin). Results: There was no significant difference in the mean value of ETP without thrombomodulin that was 1,250±315.7nmol/min for patients with INR < 1.5 (n=72) and 1,186±238 in those with INR >= 1.5 (n=25); p= 0.3572. After the addition of thrombomodulin, values changed to 893.0±368.6 and 965.9±232.3, respectively (p= 0.6265). Both groups had preserved thrombin generation, which was higher in patients with INR >=1.5 than in patients with INR < 1.5 (rETP 0.81±0.1 versus 0.69±0.2; p=0.0042). Evidence of hypercoagulability (high rETP) was demonstrated in 80% of patients. Even patients with INR >= 1.5 had preserved thrombin generation, which is likely to account for the low prevalence of post-EVL bleeding (5.2%; n=3 with INR < 1.5 and n=2 with INR >= 1.5). Conclusions: thrombin generation was well preserved in patients with cirrhosis and was not reflected by abnormal results of INR. Most of the patients had evidence of hypercoagulability, despite enlarged INR. Post-procedure bleeding occurred in a small subset of the patients and was not related to the coagulation status

INTRODUÇÃO: a albumina sérica reduzida em pacientes em diálise peritoneal (DP) é associada à aterosclerose, causa de morte mais comum entre esses pacientes. Semelhantemente à síndrome nefrótica, supõe-se que a perda de proteínas conjuntamente a de fatores de regulação da hemostasia leva ao estímulo da síntese hepática de fatores pró-coagulantes, como o fibrinogênio, deslocando o equilíbrio hemostático em direção ao estado pró-trombótico. Pacientes em DP apresentam valores séricos elevados de marcadores da ativação endotelial e fatores pró-coagulantes, quando comparados a pacientes em hemodiálise (HD). A tromboelastografia (TEG) é um método que avalia propriedades do sangue global e dinâmica da coagulação, fornecendo, por meio de um traçado, valores absolutos do tempo de formação de fibrina (K), a agregação plaquetária (amplitude máxima - AM), a firmeza do coágulo (G), entre outros dados. Por final, classifica a coagulação em normal, hipocoagulante ou hipercoagulante segundo o índice de coagulação (IC) apresentado, sendo assim útil no diagnóstico precoce de coagulopatias. Por ser pouco utilizado em pacientes com DRC, utilizou-se o TEG na avaliação da hemostasia dos pacientes em diálise peritoneal automatizada (DPA) e investigou-se a relação com a perda de proteínas, bem como outras condições clínicas inerentes ao tratamento dialítico. MÉTODOS: este estudo foi do tipo transversal que incluiu pacientes estáveis em DPA. Foram obtidos dados demográficos, clínicos e bioquímicos de rotina do prontuário médico eletrônico. Adicionalmente, foram avaliados a coagulometria, a hemostasia primária [antitrombina (AT), proteína S, fator VIII (FVIII), fator IX (FIX), fator V (FV), fibrinogênio e dímero-D] e o TEG. Os pacientes foram submetidos ao teste de equilíbrio peritoneal (PET), a avaliação da perda de proteínas para a solução de diálise (PSD) e a absorção de glicose. O estado nutricional dos pacientes foi avaliado por meio de métodos objetivos e subjetivos. RESULTADOS: vinte pacientes (38±16 anos de idade, 55% mulheres, 22,4±14,8 meses em DPA, 40% de glomerulopatia, 70% transportadores médio lento/lento e em bom estado nutricional) foram incluídos no estudo. O FVIII e FIX elevados em 85% e 50% da amostra, respectivamente. O fibrinogênio (553,8±100,5 mg/dL) e o dímero-D (720 (520-1940) ug/L) foram elevados em mais da metade dos pacientes. O TEG revelou 55% dos pacientes hipercoagulantes, 45%, normais, e nenhum era hipocoagulante. Os pacientes hipercoagulantes foram caracterizados por um tempo K menor (1,3±0,4 vs. 1,8±0,3 minutos, p=0,007); AM (72,1±2,4 vs. 64,7±3,6 mm, p=0,000) e G (13,1±1,6 vs. 9,3±1,5 K, p= p=0,000) elevados, também alterados em 78% e 33%, respectivamente, nos pacientes com coagulação normal. Pacientes hipercoagulantes também apresentaram maiores valores de plaquetas (251±28 vs. 214±51 mil/mm³, p=0,038), que se correlacionou positivamente com AM/G (r=0,594, p=0,006), enquanto a proteína C foi menor (108±12 vs. 117±20 %, p=0,034) e a AT se correlacionou positivamente com o tempo K (r=0,635, p=0,011). Não houve diferença de albumina sérica, PSD, cinética de creatinina e estado nutricional entre os grupos normal e hipercoagulante. Os pacientes hipercoagulantes, entretanto, apresentaram menores valores de hemoglobina (10,3±1,4 g/dL vs. 12,0±1,1 g/dL; p=0,007), que se correlacionou negativamente com AM/G (r=-0,673, p=0,001), bem como o hematócrito (31±4 % vs. 36±3 %; p=0,010), que também se correlacionou negativamente com AM/G (r=-0,640; p=0,002). CONCLUSÃO: demonstramos que pacientes em DPA estáveis apresentaram uma tendência pró-trombótica caracterizada pela hiperfunção plaquetária e maior força de coágulo. Mesmo não havendo linearidade na relação com a hemostasia a perda de proteínas pode ter contribuído para a hipercoagulabilidade nesses pacientes. Entretanto, os eritrócitos reduzidos representaram um fator de confusão para o resultado do
INTRODUCTION: reduced serum albumin in patients on peritoneal dialysis (PD) is associated to atherosclerosis that is the leading cause of death. Similarly to nephrotic syndrome they lose protein; it is assumed that together with regulating factors of haemostasis this loss leads to liver synthesizes of procoagulants factors, such as fibrinogen, shifting the hemostatic equilibrium to a prothrombotic state. Patients on PD present elevated serum markers of endothelial activation and coagulant factors when compared with hemodialysis (HD) patients. Thromboelastography (TEG) is a method that evaluate blood properties through coagulation\'s global and dynamic perspectives, providing through a trace absolute values of fibrin\'s time formation (K), platelet aggregation (maximum amplitude - MA), clot strength (G), among other data. Finally it classifies the coagulation in normal, hypocoagulant or hypercoagulant according to the coagulation index (CI), so that it is useful in the early diagnosis of coagulopathies. TEG is not often used in patients with CKD, because of this we chose to use TEG for hemostatic evaluation in patients on APD and investigated its relation with protein loss as well as other clinical conditions intrinsic to the dialytic therapy. METHODS: this was a cross-sectional study that included stable patients on automated peritoneal dialysis (APD). Demographic, clinical and routine biochemical data were obtained from electronic medical chart. Additionally the coagulometry, primary hemostasis [antithrombin (AT), protein S, factor VIII (FVIII), factor IX (FIX), factor V (FV), fibrinogen and D-dimer] and TEG were evaluated. Patients were submitted to peritoneal equilibrium test (PET), protein loss to dialysis solution (PDS) and glucose absorption evaluations. Patients nutritional status was evaluated by objective and subjective methods. RESULTS: twenty patients (38±16 years old, 55% women, 22.4±14.8 months on APD, 40% of glomerulopathy, 70% slow average/slow transporters and well nourished) were included in this study. FVIII and FIX were elevated in 85% and 50% of the sample, respectively. Fibrinogen (553.8±100.5 mg/dL) and D-dimer (720 (520-1940) ug/L) were elevated in over half of the patients. TEG showed 55% of the patients hypercoagulant, 45% were normal and nobody was hypocoagulant. Hypercoagulant patients were characterized by a lower K-time (1.3±0.4 vs. 1.8±0.3 minutes; p=0.007); elevated MA (72.1±2.4 vs. 64.7±3.6 mm; p=0.000) and G (13.1±1.6 vs. 9.3±1.5 K; p= p=0.000); altered too in 78% and 33%, respectively, in normal coagulation patients. Hypercoagulant patients presented too higher values of platelet count (251±28 vs. 214±51 mil/mm³, p=0,038), but within the normal range, that correlated positively with MA/G (r=0.594; p=0.006) while protein C was lower (108±12 vs. 117±20 %; p=0,034) and AT correlated positively with K-time (r=0.635; p=0.011). There was no difference to serum albumin, PDS, creatinin kinetic and nutritional status between hypercoagulant and normal groups. However hypercoagulant patients presented lower values of hemoglobin (10.3±1.4 g/dL vs. 12.0±1.1 g/dL; p=0.007); that correlated negatively with MA/G (r=-0.673; p=0.001), as well as hematocrit (31±4 % vs. 36±3 %; p=0,010), which also correlated negatively with MA/G (r=-0.640; p=0.002). CONCLUSION: we demonstrated that stable patients on APD presented a prothrombotic tendency characterized by platelet hyperfuntion and clot strength. Even though there was no linearity in relation to hemostasis; protein loss may have contributed to the hypercoagulability in these patients. However reduced erythrocytes were a confounding factor in the TEG analysis

O ato cirúrgico sempre deve ser precedido de uma avaliação das condições de saúde local e sistêmica do paciente, sendo os exames complementares, o subsídio utilizado para avaliar e confirmar as suspeitas clínicas e hipóteses diagnósticas, adequando o paciente à terapêutica proposta. A literatura é ampla no que diz respeito a testes de hemostasia por meio de diferentes métodos, contudo, não há estudos na literatura revisada que comparem o tempo de sangramento pelo método de Ivy com o tempo de sangramento aferido na mucosa bucal. A proposta deste estudo é de avaliar a técnica de aferição do tempo de sangramento da mucosa bucal e comparar com o tempo de sangramento pelo método de Ivy convencional, em pacientes com história de diátese hemorrágica relacionada a procedimentos cirúrgicos anteriores. Tais pacientes apresentaramse no ambulatório de Cirurgia da Faculdade de Odontologia da Universidade de São Paulo com necessidade de procedimentos relacionados à cirurgia oral menor. Foi realizado o tempo de sangramento pelo método de Ivy previamente ao teste do tempo de sangramento da mucosa bucal em 30 pacientes. O tempo de sangramento da mucosa bucal não apresentou diferença estatística quando comparado ao tempo de sangramento de Ivy (p=0,755). Os resultados avaliados pelo método de KOLMOGOROV-SMIRNOV seguiram uma distribuição normal em ambas amostras (p>0,15) sendo que o tempo médio de sangramento na pele e na mucosa bucal foi de 295 segundos e 291 segundos respectivamente, demonstrando semelhança entre os tempos aferidos.
Surgical procedures must be preceded by an accurate evaluation of the local and systemic health status and complementary exams can confirm or not clinical suspect and diagnosis hypothesis in order to adequate the patient to the proposed surgical treatment. The world literature is generous with respect of hemostasia tests employing several methodologies although there are not studies that compare the bleeding time test by Ivy?s method with bleeding time accessed at the oral mucosa. We propose at this study the evaluation of a bleeding time method in the oral mucosa comparing the results with the conventional Ivy?s test in patients with bleeding disorders history in past oral minor surgical procedures. The patients were those selected in the Oral Surgery Clinic of the Dental School of University of São Paulo that underwent to oral minor surgery. The Ivy?s bleeding time test were previously obtained before bleeding time of the mucosa in 30 patients and it was concluded that the bleeding time of the mucosa did not present statistically difference significant comparing the Ivy?s test (p=0,755). The results evaluated by KOLMOGOROV-SMIRNOV?s method followed a normal distribution in both samples (p>0,15) and that the mean bleeding time at the skin and at the oral mucosa was 295 seconds and 291 seconds respectively showing similarity between the groups.

INTRODUÇÃO: Dengue é uma doença viral prevalente e potencialmente fatal associada à alteração da permeabilidade capilar e coagulopatia. Entretanto, não há estudos concernentes aos achados tromboelastométricos nesta doença. Realizamos o presente estudo para analisar pacientes com dengue e plaquetopenia por meio de um exame rápido, efetivo e a beira leito comparando com os exames convencionais de coagulação. MÉTODOS: Trata-se de um estudo observacional e transversal conduzido entre os dias 6 de abril a 5 de maio de 2015, em São Paulo, Brasil, durante epidemia de dengue. Foi realizado tromboelastometria ROTEM® em 53 pacientes com dengue e trombocitopenia em associação com exames convencionais de coagulação: tempo de protrombina (TP), international normalized ratio (INR), tempo de tromboplastina parcial ativado (TTPa), tempo de trombina (TT), contagem de plaquetas, fibrinogênio e d-dímero. Um grupo controle de pacientes foi estabelecido para comparação do status tromboelastométrico. RESULTADOS: Um total de 38 pacientes de 53 (71,7%) apresentaram anormalidades no INTEM e 29/53 (57,4%) no EXTEM. Em contrapartida, alterações no FIBTEM foram encontradas apenas em 3/53 (5,7%). Houve significância estatística em pacientes correlacionando alterações tromboelastométricas no EXTEM e INTEM e contagem de plaquetas (p=0,052) e (p=0,005), respectivamente; assim como os valores de fibrinogênio (p=0,006) e (p=0,021), respectivamente. O grupo controle (GC) apresentou status tromboelastométrico normal em 10/10 (100%) na análise do INTEM, EXTEM, FIBTEM. Avaliação do EXTEM demonstrou significância estatística entre o GC e o grupo Dengue: CT (p=0,044); CFT (p<0,001); MCF (p < 0,001) e Alpha (p < 0,001). Foram observados níveis normais de fibrinogênio (mediana: 290) e altos níveis de d-dímero (mediana: 1330) com IQR (800-1840). Todos os pacientes (53/53) apresentavam trombocitopenia abaixo de 100 x 109/L (mediana 77 x 109/L) IQR (63-88). Exames convencionais de coagulação revelaram-se completamente normais: TP (mediana: 100%) IQR (90-100); INR (mediana: 1,0) IQR (1,0-1,1); TTPa (mediana: 28,9 segundos) IQR (26,0-32,5) e TT (mediana: 18,2 segundos) IQR (17,0-19,5). Apenas (7/49) 14,3% pacientes apresentaram sangramento e (3/52) 5,8% necessitou de hospitalização. Não houve associação entre alterações tromboelastométricas com sangramento ou hospitalização. CONCLUSÕES: Dengue representa um processo inflamatório intenso, mantendo níveis normais de fibrinogênio. Portanto, FIBTEM mantém-se normal promovendo boa formação do coágulo sem risco imediato de sangramento. Não houve correlação entre os achados tromboelastométricos com os exames convencionais de coagulação, sugerindo que testes viscoelásticos são exames mais sensíveis para análise de coagulopatia precoce nessa população
INTRODUCTION: Dengue is a prevalent and potentially fatal viral disease associated with plasma leakage and coagulopathy, though no information is available on thromboelastometric profile. We performed this study to analyze dengue fever patients with thrombocytopenia clot changes through point-ofcare thromboelastometry tests and standard coagulation tests. METHODS: This was an observational, transversal and cross sectional study conducted between April 6th and May 5th 2015 in São Paulo, Brazil, during a dengue outbreak. Thromboelastometry ROTEM® was performed in 53 patients with dengue and thrombocytopenia, in association with conventional coagulation tests: prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT); platelet count, fibrinogen level, and d-dimer. A control group of 10 patients was established to compare thromboelastometry profiles. RESULTS: A total of 38 patients in 53 (71,7%) had abnormalities in INTEM, 29 in 53 (57,4%) in EXTEM. Conversely, FIBTEM was abnormal in 3/53 (5,7%). Statistical analysis revealed significant relation in those patients with impairment EXTEM and INTEM with lowered platelet (p=0,052) and (p=0,005) respectively and lowered fibrinogen levels (p=0,006) and (p=0,021) respectively. Control group (CG) had normal status in 10/10 (100%) of INTEM, EXTEM, FIBTEM analysis. EXTEM analysis demonstrated statistical differences between CG and dengue group: CT (p=0,044); CFT (p < 0,001); MCF (p < 0,001) and Alpha (p < 0,001). Normal levels of fibrinogen (median: 290) and high levels of ddimer (median: 1330) IQR (800-1840) were found. All patients (53/53) had platelet under 100 x 109/L (median 77 x 109/L) IQR (63-88). Standard coagulation tests were completely normal: PT (median: 100%) IQR (90-100); INR (median: 1,0) IQR (1,0-1,1); aPTT (median: 28,9 seconds) IQR (26.0- 32,5) and TT (median: 18,2 seconds) IQR (17,0-19.5). Only (7/49) 14,3% patients had bleeding manifestations and (3/52) 5,8% needed hospitalization. There was no association between altered thromboelastometry with bleeding manifestations or hospitalization. CONCLUSIONS: Dengue represents an intense inflammatory process, maintaining normal levels of fibrinogen. FIBTEM remains normal providing good clot strength without immediate bleeding risk. There were no correlation between thromboelastometry findings and standard coagulation exams, suggesting that viscoelastic tests are more sensible method to analyze early coagulation impairments in this population

Acquired disorders of coagulation may be the consequence of many underlying conditions, and although they may share abnormality of a coagulation test, for example, a prolonged prothrombin time, their clinical effects are diverse and often opposing. General clinical approach: diagnosis—most acquired disorders of coagulation can be identified by screening haemostasis tests, including (1) prothrombin time; (2) activated partial thromboplastin time; (3) thrombin clotting time; (4) fibrinogen degradation products, including (5) the cross-linked fibrin assay (D-dimer); and (6) complete blood count with examination of a blood film. Few bleeding disorders give normal results in all these tests, but disorders predisposed to thrombosis as a result of deficiency of natural anticoagulants (e.g. antithrombin, protein C, and protein S) or certain mutations (e.g. factor V Leiden) must be specifically sought. Treatment—patients with coagulopathies who are bleeding or who require surgery are usually treated with blood products such as platelets and frozen plasma. Other treatments used in particular circumstances include (1) vitamin K—required for the post-translational modification of factors II, VII, IX, and X as well as the anticoagulant factors, protein C, and protein S; (2) cryoprecipitate—used principally for the treatment of hypofibrinogenaemia; (3) concentrates of specific factors—used in isolated deficiencies (e.g. of factors VIII, IX, XI, VIIa, or fibrinogen); (4) antifibrinolytic agents (e.g. ε‎-aminocaproic acid and tranexamic acid); (5) desmopressin (1-deamino-8-d-arginine vasopressin)—increases factor VIII and von Willebrand factor.

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention option for critically ill patients with cardiac and/or respiratory failure. Worldwide many medical centers started to use ECMO as a rescue treatment option when conventional therapies failed. This chapter describes conventional strategies of anticoagulation for ECMO. Indeed, during ECMO support the continuous flow and the contact between the patient’s blood and nonbiological surfaces such as cannulae or the oxygenator triggers the activation of the coagulation cascade, with formation of clots and consumption of coagulation factors and platelets, leading to peculiar alteration in the hemostasis. Therefore, the activation of coagulation pathways increases the risk of both thrombosis and hemorrhage. Unfractionated heparin remains the anticoagulant of choice for several reasons in patients supported by ECMO, among them the consolidated experience in its use, its low cost, and the presence of protamine, which can be used as an antagonist, even though its use is very rare in ECMO patients. There are different methods of monitoring the anticoagulation level while on heparin infusion for patients supported by ECMO, and among them the two most common are the activated coagulation time (ACT) and the activated partial thromboplastin time (aPTT), while the routine uses of viscoelastic tests and levels of anti-Xa activity are less common.

This chapter reviews the causes and outlines an approach to the management of coagulopathy following cardiac surgery. Bleeding after cardiac surgery is common and expected up to a rate of 2 mL/kg/h for the first 6 hours. A more significant hemorrhage needs to be investigated and treated. Causes are often multifactorial. It is imperative that surgical causes be excluded early concomitant to providing resuscitation, investigating other medical causes for bleeding, and treating coagulopathy empirically until laboratory testing becomes available. The most frequent causes for coagulopathy post–cardiac surgery are excess heparinization, prolonged cardiopulmonary bypass time, hypothermia, acidosis, and preexisting bleeding diathesis. The management of coagulopathy implies maintenance of the normal physiological conditions for coagulation, reversal of excess heparinization, treatment of hyperfibrinolysis, maintaining normal levels of coagulation factors, and transfusion of platelets if thrombocytopenia or platelet dysfunction occurs. The chapter reviews what is involved in standard laboratory testing (complete blood count, prothrombin time, activated partial thromboplastin time, fibrinogen level, etc.) for coagulopathy. Also discussed is point-of-care testing and how the results from these tests should be interpreted. The chapter details the various blood products that are required in this scenario and suggests doses and transfusion thresholds.

CASE PRESENTATION A 16-year-old previously healthy girl, Aria, presents to the emergency department (ED) with headache and confusion. While in triage, Aria has 2 episodes of emesis and several staring episodes. While being transported to a room, she has 20 seconds of convulsive movements that self-resolve, after which she is confused, sleepy, and does not recognize her parents. The ED physician obtains initial laboratory studies including a complete blood cell count (CBC) with differential, comprehensive metabolic panel, C-reactive protein (CRP) level, procalcitonin level, coagulation studies, urinalysis, urine drug screen, and pregnancy test. All of these studies are unremarkable. A blood culture is pending. A computed tomography (CT) scan of the head is performed, and the preliminary read is negative for any acute intracranial pathology. The ED physician gives Aria a dose each of acetaminophen and ondansetron, and due to concern for seizures, the physician also gives her a loading dose of levetiracetam. She also starts Aria on a continuous electroencephalogram (EEG). In the intervening 2 hours, Aria has not returned to her baseline neurologic status. The ED physician calls you to request admission for further evaluation and monitoring.

There is considerable market interest for miniature blood diagnostic kits for cholesterol, ovulation, glucose, bacteria, leukemia cells, coagulation tests, drugs etc. However, the presence of blood cells in the blood samples introduces an array of micro-fluidic issues that have become main obstacles to commercialization of these products. We discuss some of these anomalous micro-fluidic features of blood here. Some devices and designs developed at the Notre Dame Center for Micro-fluidics and Medical Diagnostics will be presented as solutions to these micro-fluidic challenges.

Background: With advent of surgical advancements like HIPEC several unstudied pathophysiological aspects need to be evaluated. We studied the trends in coagulation profile in patients undergoing CRS with HIPEC in the peri-operative period, utilizing Thromboelastography (TEG) in comparison with standard coagulation tests. The utility of TEG as a guide for transfusion of blood products was also evaluated. Materials and Methods: It was a Prospective observational Cohort study which included 30 consecutive patients undergoing CRS with HIPEC at RGCI in 2015. Methodology: Preoperatively standard coagulation tests were done as a baseline. Intra-operative arterial blood samples were collected for ABG, PT, APTT, and TEG at following time points: before starting of HIPEC, after completion of HIPEC and on 1 and 2 postoperative days. Statistical analysis was done using Chi-square test and unpaired t-test for categorical and continuous variables. Pearson’s correlation coefficient was calculated for analysing the correlation between the variables. P < 0.05 was considered statistically significant. Results: A strong correlation was observed between PT & R values of TEG. Similar correlation was also observed between the α angle, MA of TEG and platelet count throughout the peri-operative period. Immediately post HIPEC, we observe value of APPT decreases while the other parameters of coagulation profile showed a rising trend. R value showed rising trend after CRS, a dip after HIPEC followed by a rising trend on first post operative day which normalizes only after second post operative day. It gives a mixed picture of both hypo and hyper coagulable state. α angle, MA rise immediately after HIPEC and continue to rise till the second postoperative day. There was no requirement of transfusion of blood and blood products as guided by the TEG findings and no clinical evidence of any bleeding or thromboembolic episode occurred. Conclusion: To conclude, our study demonstrated TEG to be a useful and comprehensive tool to assess coagulopathy and accordingly guide blood product transfusion in patients undergoing CRS with HIPEC.

Blood samples were collected from 17 volunteers between 8-14, 26-28 and 32-34 weeks of pregnancy. Control samples were collected from 12 non-pregnant female volunteers not using oral contraceptives. All samples were assayed for fibrinopeptide A (FPA), B beta 15-42 and for cross linked D-dimer fragments. A sample was collected for measurement of the in vitro rate of generation of fibrinopeptide A from whole blood (FPA-R).These results are consistent with an increased activation of coagulation (increased FPA and shortened FPA-R) during normal pregnancy, which is compensated for by a concomitant rise in fibrinolytic activity (increased D-dimer and B beta 15-42). In 2 patients who miscarried and 2 patients who developed hypertension during pregnancy changes indicative of a non compensated hypercoagulable state could be seen. The study shows that the progress of pregnancy is associated with increased activation of coagulation and a concomitant rise in fibrin(ogen) degradation products. This data shows that a combination of these tests may be capable of detecting changes in the haemostatic balance that occur before the onset of clinical signs of gynaecological problems.

It has been suggested that mortality due to upper gastrointestinal haemorrhage may be reduced by restricting blood transfusion [1], We have assessed whether this is due to an anticoagulant effect in a prospective randomised trial.One hundred patients with severe, acute gastrointestinal haemorrhage were randomised to receive either at least 2 units of blood during the first 24 hours of admission, or no blood unless their haemaglobin was lessthan 8g/dl or they were shocked. Minor bleeds and varices were excluded As hypercoagulation cannot be measured using conventional coagulation tests, fresh whole blood coagulation was measured by the Biobridge Impedance Clotting Time (ICT). Coagulation was assessed at 24 hour intervals and compared to age matched controls with the results expressed as mean ± sem.The ICT on admission for the transfusion group (n=50) was 3.2±0.2 mins compared to 10±0.2 mins in controls. This hyper-coagulable state was partially reversed to 6.4±0.3 mins at 24 hours (p<0.001). The 50 allocated to receive no blood had a similar ICT on admission of 4.4±0.4 mins but the hypercoagulable state was maintained with ICT at 24 hours of 4.320.4 mins. Only 2 patients not transfused rebled compared to 15 in the early transfusion group (p<0.001). Five patients died, and they were all in the early transfusion group.These findings show there is a hypercoagulable response to haemorrhage which is partially reversed by blood transfusion leading to rebleeding

Borderline hypertension causes mortality and morbidity rates similar to those associated with estabilished hypertension. However, there is no univocal guideline for its therapeutic management. Hypercoagulability in hypertension has been demonstrated. The aim of our study was to evaluate some coagulation factors in agroup of patients affected by borderlinehypertension. The following tests were carried out: PT and PTT, Factor VIII coagulant activity, FVIII antigen and FVIII ristocetin cofactor, Factor XII and Factor XI activities. These tests were selected for their relationship to the contact coagulative activation near the vascular wall. In our patients statistically significant higher FVIII and FXII coagulant activities than normal control subjects were found. Moreover, an evident even though not statistically significant PTT shortening was seen. Other tests taken into consideration were all within normal limits. Our results suggest that an increased FVIII and FXII synthesis and/or release is present, and an activated coagulation system exists in borderline hypertension. Furthermore, it is not clear why an excess of FVIII:C over FVIIIR:Ag and FVIIIR:RCof was found in our patients. In conclusion, an activation of haemostatic mechanism was found in borderline hypertension. The young age of patients and the absence of evident hypertensive angiopathy are in agreement with an overactivity of blood vessel tone. Haemostatic activation could be an useful marker in favour of the precious management of patients with borderline hypertension.

A cohort study was performed to determine the postnatal development of the coagulation system in the “healthy” premature infant. Mothers were approached for consent and a total of 132 premature infants were entered into the study. The group consisted of 64 infants with gestational ages of 34-36 weeks (prem 1) and 68 infants whose gestational age was 33 weeks or less (prem 2). Demographic information and a 2 ml blood sample were obtained on days 1, 5, 30, 90, and 180. Plasma was fractionated and stored at −70°C for batch assaying of the following tests: screening tests, PT, APTT; factor assays (biologic (B)); fibrinogen, II, V, VII, VIII:C, IX, X, XI, XII, prekallikrein, high molecular weight kininogen, XIII (immunologic (I)); inhibitors (I), antithrombin III, aα2-antiplasmin, α2-macroglobulin, α-anti-trypsin, Cl esterase inhibitor, protein C, protein S, and the fibrinolytic system (B); plasminogen. We have previously reported an identical study for 118 full term infants. The large number of premature and full term infants studied at varying time points allowed us to determine the following: 1) coagulation tests vary with the gestational age and postnatal age of the infant; 2) each factor has a unique postnatal pattern of maturation; 3) near adult values are achieved by 6 months of age; 4) premature infants have a more rapid postnatal development of the coagulation system compared to the full term infant; and 5) the range of reference values for two age groups of premature infants has been established for each of the assays. These reference values will provide a basis for future investigation of specific hemorrhagic and thrombotic problems in the newborn infant.

A pilot open controlled study of FOY was performed in 20 intensive care patients (pts, age 18-63) with DIC diagnosed with standard laboratory criteria (at least 3 of the following: Normotest 70%, fibrinogen 150 mg%, AT III 80%, FDP 20 ug/ml, platelets 150000). Besides the usual treatments, FOY was given to 10 pts (FOY G.) by continuous i.v. infusion (1mg/kg/h) for up to 7 days, while in 10 control pts (Hep.G.) the treatment included low dose s.c. heparin. Blood clotting tests were performed at admission to the study and daily for 7 days; we consider here results obtained at baseline and at the 4th (7 survivors in FOY G. and 10 in Hep.G.) and the 7th day (6 surv. in FOY G. and 9 in Hep. G.). Statistical evaluation was made by means of the twotailed Wilcoxon test for non parametric paired data. In the FOY G. depressed baseline AT III and plasminogen (Plgn) activities (61.8+/-5.3% and 57+/-5.5% respectively) significantly increased at 4th day (92+/-11.2% and 83+/-3.1% p<0.05), Plgn furtherly significantly increased at 7th d. (p<0.05). In the Hep.G. Normotest, Plgn and Platelets significantly (p<0.05) increased at 4th day, but no changes in AT III were found. Fibrinogen increased in both groups during the observation period (pA0.05). Serum and especially "plasma" FDP (specific monoclonal Ab to fgn and fibrin degradation products), as well as D-Dirner and HMW fgn complexes measured by exclusion chromatography, decreased especially in the FOY G. These results show that FOY modifies the clotting laboratory pattern in DIC pts, likely by an antithrombin effect. The clinical significance of these effects remains, however, to be explored.

The production of pharmaceuticals from human plasma that are useful in the treatment of bleeding disorders had its beginning with the development of the Cohn fractionation procedure in the 1940's. As a result of these advances, concentrates became available for the treatment of the hemophilias. Although of low purity and subject to contamination by hepatitis virus, the availability of these compounds resulted in dramatic improvements in the life expectancy and quality of life of afflicted individuals. The numerous problems associated with production of pharmaceuticals from pooled plasma made these products obvious goals for recombinant DNA technology as soon as the commercial aspects of the field became apparent. The subsequent contamination of blood products with the AIDS virus has resulted in an urgent need for a production source that is independent of human plasma. Several industrial and academic laboratories have cloned the cDNA's for human factors VIII and IX. In addition to these proteins, the utility of factor Vila in the treatment of hemophiliacs with inhibitors has shown promise. Efforts to develop a recombinant preparation of factor Vila are at a comparable stage of development as factors VIII and IX. Continuing efforts have resulted in the successful expression of these recombinant proteins in mammalian cell lines, thereby successfully completing the first steps of commercial development.Although much interest has focused upon the theoretical superiority of recombinant proteins as therapeutics, one must keep in mind that there are numerous developmental aspects of large-scale production and regulatory issues that must be addressed and solved before these drugs will be available. The coagulation proteins are complex glycoproteins that will in all probability require mammalian cell cell culture in order to produce functional proteins. The fact that these preparations will be administered over the lifetime of the patient serves to reinforce that the recombinant products be as similar to the natural proteins as possible, further supporting the concept of mammalian cell expression systems.Regulatory approval of a recombinant product are fundamentally no different than those for any other product in regards to efficacy, potency, purity, and identity. There are, however, additional considerations that must be addressed in the production of recombinant cell culture derived biologies. These relate to the possible presence in the final product of pathogenic and tumorigenic agents, and possible contamination by cell culture and cell substrate compounds. A detailed characterization of the production cell line will therefore be required, including identification and characterization of any associated viral particles. These cells must be capable of being reproducibly grown, while maintaining protein production, on ascale (tens of thousands of liters) suitable to meet the market demand of the specific protein. Apurification process must be established capable of handling the resulting large volumes of feedstock, generating a protein preparation of high purity (greater than 99% pure). Numerous assays must be developed to quantitate the purity and identity of the resulting recombinant pharmaceutical on a lot by lot basis.Studies to date have shown that recombinant forms of factors VIII and IX, produced by laboratory processes, are very similar to the plasma-derived forms as assessed by a variety of in vitro and in vivo tests. Although these results are promising, the ultimate safety and efficacy testing of these drugs will have to await the initiation of human clinical trials. Such studies will have to await the successful completion of the certain regulatory concerns. Clinical trials should begin within the near future, hopefully leading to a source of these products independent of pooled human plasma.

Thromboembolism has been frequently reported in cancer patients, mainly in cases with solid tumors. Besides in several animal models, fibrin deposition around the tumor and platelet aggre gates appear to be involved in invasion and metastasis. This study was aimed at evaluating the extent of in vivo platelet activation and fibrin formation in several kinds of human cancer. We excluded from this study patients whose blood was sampled with difficulty as well as those having clinical evidence of thrombosis or embolism, those with thrombocytopenia, increased fibrinogen degradation products or biological pattern of disseminated intravascular coagulation. Fibrinopeptide A (fpA) and β-thrombo-globulin (β-tg) were determined by RIA. Free platelet count ratio (PCR) was determined on whole blood samples as an index of circulating aggregates. Usual coagulation tests, antithrombin III activity, protein C plasma level, F VIII related antigen (F VIII RAG), F VIII Ristocetin cofactor (F VIII RCF) and F VIII procoagulant activity (F VIII C) were also determined.It was found that in more than fifty percent of patients, fpA was significantly increased above the upper reference limit. Cases with increased B-tg were less frequent. Separate increases in β-tg or fpA levels were often observed. PCR remained within the reference values in almost all patients. F VIII RAG, RCF and C were usually above 150 % of the reference mean.We conclude that platelet release and fibrinoformation frequently occur in cancer patients showing no sign of thrombotic process. Increased level of fpA with normal plasma β-tg level suggests that thrombin generation occurs only in the extravascular compart ment, probably next to the tumoral tissues. Increased levels of plasma β-tg with normal fpA levels may result from platelet activation by other stimuli than thrombin. It must be emphasized that normal PCR does not exclude the presence of fibrinous circulating aggregates which cannot be dispersed by EDTA. High F VIII activities may be due to the release of the von Willebrand factor from tumoral vessels.

Sulfatides are sulfated glycolipids which are negatively charged and thought to influence receptor mediated activities. Sulfatides have the capacity to provide a surface for the initiation of in vitro coagulation tests and these acidic lipids represent the potential biological surface for the initiation of the contact and intrinsic systems in vivo. Several sulfatides have been demonstrated in blood platelets. We have investigated sulfatides and other glycolipids in endothelial cells and platelets in order to define the cellular sources for sulfatides that would be available for influencing hemostasis. Endothelial cells were derived from primary cultures of human umbilical veins and human platelets were obtained from freshly-collected blood. Cellular lipids were extracted by the Folch method. Sulfatides and glycolipids were purified by silicic acid chromatography, separated by thin-layer chromatography, and quantitated by the assay of sphingosine. Glycolipids were also analyzed by HPLC. Globoside was found to be the predominant glycolipid in endothelial cells while lactosyl ceramide was the predominant glyco-lipid in platelets. Sulfatides were detected by two approaches: 1) Sulfatide synthesis by the incorporation of [35S]-Sulfate; 2) The specific binding of [125I]-thrombospondin and [125I]-von Willebrand’s factor (vWF) to sulfatides separated by thin-layer chromatography (TLC). Several sulfatides were identified in endothelial cells and platelets by virtue of the incorporation of [35S]-sulfate into glycolipids separated by TLC. [125I]-TSP and [125I]-vWF bound to the glycolipids that had incorporated [35S]-sulfate. [35S]-sulfate was primarily incorporated into sulfated galactosyl ceramide but both cells also synthesized complex glycolipids. TSP and vWF were shown to bind to sulfated galactosyl ceramide, a band that comigrated with glycosyl ceramide as well as with two more complex sulfatides in both cells. However, differences in sulfatide synthesis and binding of TSP to sulfatides were observed in endothelial cells from that in platelets. The study indicates that endothelial cells and platelets contain several sulfatides and thus are potential sources for sulfatides for the initiation of coagulation.

Data include following variables: Demographics, epidemiological history, comorbidities, diagnosis, complications, and symptoms on admission to the hospital. Also, body’s temperature and SpO2. Blood cells: white cells count (WBC), neutrophils (Neu), lymphocytes (Ly), eosinophils (Eo) and monocytes (Mo), percentages of segmented and banded neutrophils, erythrocytes (RBC), platelet count (PLT), hemoglobin (Hb), and hematocrit (HCT); Inflammatory indicators: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Tissue damage indicators: alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and troponin T (TnT); Electrolytes: potassium and sodium concentration; Renal function indicators: creatinine and glomerular filtration rate (GFR); Coagulation tests: D-dimer, prothrombin time, and prothrombin index on admission to the hospital.