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1

Cheng, Hai, Dian Zhou, Jiang Cao, Wei Chen, Kunming Qi, Kailin Xu, and Jianlin Qiao. "A Study about the Relationship between Thrombotic Events and Peripheral Neutrophil-to-Lymphocyte Ratio in Patients with Newly Diagnosed Essential Thrombocythemia." Blood 132, Supplement 1 (November 29, 2018): 5465. http://dx.doi.org/10.1182/blood-2018-99-112785.

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Abstract To explore the role of neutrophil-to-lymphocyte ratio (NLR) in patients with newly diagnosed essential thrombocythemia (ET) and the relationship with thrombotic events.150 ET patients with ET from January 2013 to December 2017 were retrospectively enrolled in this study to investigate the risk factors of thrombosis and analyse the role of NLR in thrombotic events. The following parameters were evaluated: age, sex, blood routine examination, JAK2V617F mutation, cardiovascular risk factors, history of previous thrombosis, thrombosis during follow-up, examination and biopsy of bone marrow.Age(P=0.001) and JAK2 V617F mutation(P=0.003) were independent risk factors for thrombotic events at diagnosis after Logistic multivariate analysis. WBC count (P=0.047), NLR (P<0.001), age (P=0.037) and thrombosis at diagnosis (P=0.036) were independent risk factors for future thrombotic events and NLR was better for prediction of future thrombotic events than other risk factors in ROC curve. The thrombosis-free survival of thrombotic events in patients with higher NLR(median survival 22.3 months, 95% CI:17.8-26.8) was significantly shorter than that of patients with lower NLR(median survival 55.5 months, 95% CI:53.4-57.5) in Kaplan-Meier analysis (P<0.001). After 60 months of follow-up, patients with lower NLR had a thrombosis-free survival of 97.4%, while patients with higher NLR had a thrombosis-free survival of 46.7%. NLR at diagnosis was a better predictive parameter for future thrombotic events than other clinical parameters in ET patients, but was not associated with thrombosis at diagnosis. Disclosures No relevant conflicts of interest to declare.
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2

Mancuso, Salvatrice, Vincenzo Accurso, Marco Santoro, Simona Raso, Angelo Davide Contrino, Alessandro Perez, Florinda Di Piazza, Ada Maria Florena, Antonio Russo, and Sergio Siragusa. "The Essential Thrombocythemia, Thrombotic Risk Stratification, and Cardiovascular Risk Factors." Advances in Hematology 2020 (March 27, 2020): 1–5. http://dx.doi.org/10.1155/2020/9124821.

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Essential thrombocythemia is a rare hematological malignancy with good overall survival, but moderate to high risk of developing arterial or venous thrombosis lifelong. Different thrombotic risk scores for patients with essential thrombocythemia have been proposed, but only one of them (the IPSET-t scoring system) takes into account the classical cardiovascular risk factors as one of the scoring items. Currently, in clinical practice, the presence of cardiovascular risk factors in patients with diagnosis of ET rarely determines the decision to initiate cytoreductive therapies. In our study, we compared different risk models to estimate the thrombotic risk of 233 ET patients and the role of specific driver mutations and evaluated the impact that conventional cardiovascular risk factors (hypertension, cigarette smoking, diabetes, obesity, and dyslipidaemia) have on thrombotic risk in patients with ET. Perspective studies conducted on a polycentric large cohort of patients should be conducted to estimate the impact of cardiovascular risk factors in determining thrombosis in ET patients, evaluating the opportunity of initiating a cytoreductive therapy in patients with cardiovascular risk factors, even if classified into low to moderate risk groups according to other scoring systems.
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Yamamoto, J., T. Taka, K. Yamada, Y. Ijiri, M. Murakami, Y. Hirata, A. Naemura, et al. "Tomatoes have natural anti-thrombotic effects." British Journal of Nutrition 90, no. 6 (December 2003): 1031–38. http://dx.doi.org/10.1079/bjn2003988.

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The prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet may be an important risk factor for thrombotic events. The daily intake of an anti-thrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to test tomato extracts for anti-thrombotic effects and to identify those varieties that have such an effect. A shear-induced platelet-function test (haemostatometry) was used to test anti-thrombotic potentialin vitro. Extracts from those tomato varieties that showed a significant anti-thrombotic activityin vitrowere further assessedin vivo, using a laser-induced thrombosis test in mice. One tomato variety (KG99-4) showed significant anti-thrombotic activity bothin vitroandin vivo. KG99-4 inhibited not only platelet-rich thrombus formation but also had a thrombolytic effect. It is concluded that haemostatometry can detect and classify the anti-thrombotic potential of fruits and vegetables and offers a simple way of screening for such effects.
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Navarro, Luana Magalhães, Damila Cristina Trufelli, Debora Rodrigues Bonito, Auro Del Giglio, and Patricia Weinschenker Bollmann. "Application of prognostic score IPSET-thrombosis in patients with essential thrombocythemia of a Brazilian public service." Revista da Associação Médica Brasileira 62, no. 7 (October 2016): 647–51. http://dx.doi.org/10.1590/1806-9282.62.07.647.

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Summary Introduction: In patients with essential thrombocythemia (ET), the vascular complications contribute to morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET-thrombosis) has recently been proposed. We present the application of this score and compare its results with the usual classification system. Method: We retrospectively evaluated the characteristics and risk factors for thrombosis of 46 patients with a diagnosis of ET seen in the last 6 years at Faculdade de Medicina do ABC (FMABC). Results: Thrombosis in the arterial territory was more prevalent than in venous sites. We observed that cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) were also risk factors for thrombosis (p<0.001). Age over 60 years and presence of JAK2 V617F mutation were not associated with the occurrence of thrombotic events. No patient classified by IPSET-thrombosis as low risk had a thrombotic event. Furthermore, using the IPSET-thrombosis scale, we identified two patients who had thrombotic events during follow-up and were otherwise classified in the low-risk group of the traditional classification. Leukocytosis at diagnosis was significantly associated with arterial thrombosis (p=0.02), while splenomegaly was associated with venous thrombotic events (p=0.01). Conclusion: Cardiovascular risk factors and leukocytosis were directly associated with arterial thrombosis. IPSET-thrombosis appears to be better than the traditional classification at identifying lower risk patients who do not need specific therapy.
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Chang, Simon, Christian Fynbo Christiansen, Anders Bojesen, Svend Juul, Anna-Marie B. Münster, and Claus H. Gravholt. "Klinefelter syndrome and testosterone treatment: a national cohort study on thrombosis risk." Endocrine Connections 9, no. 1 (January 2020): 34–43. http://dx.doi.org/10.1530/ec-19-0433.

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Objectives Klinefelter syndrome (KS), 47,XXY, can be viewed as a disease model for investigating the risk of thrombosis in male hypogonadism and the subsequent risk related to testosterone treatment. We describe rates of thrombotic risk factors, thrombosis and thrombosis mortality in KS and the association with testosterone treatment. Methods National registry-based matched cohort study with follow-up from 1995 to 2016 set in Denmark. For the study, 1155 men with KS were each matched by year and month of birth to 100 men from the background population. First thrombotic events and thrombosis mortality was evaluated by event rates and hazard ratios (HRs) and by applying testosterone treatment as a time-dependent covariate. Results The KS cohort had higher incidence of venous thromboembolism relative to the comparison cohort (HR, 3.95; 95% CI, 2.83–5.52). Total thrombotic deaths were increased in KS (HR, 1.76; 95% CI, 1.18–2.62), and all-cause mortality was increased in KS following arterial thrombosis (HR 1.73; 95% CI 1.22–2.47). Only 48.7% of men with KS redeemed prescriptions for testosterone. Untreated men with KS were on average born 12 years before those treated, and the majority of untreated men with KS with available biochemistry were hypogonadal. Testosterone treatment in KS was associated with a non-significant decrease in venous thromboembolism and thrombotic deaths. Conclusion Thrombosis and thrombotic deaths are increased in KS. Only half of the men with KS ever received testosterone treatment, despite overt hypogonadism in the non-treated. Testosterone treatment in Klinefelter syndrome was insignificantly associated with lower incidence rates of venous thrombosis and thrombotic deaths.
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Henni, Samir, Pierre Ramondou, Guillaume Duval, Jean Picquet, Georges Leftheriotis, and Pierre Abraham. "The risk of lower-limb superficial vein thrombosis relative to lower-limb venous thrombotic events is not increased in winter months." Phlebology: The Journal of Venous Disease 35, no. 7 (January 10, 2020): 533–37. http://dx.doi.org/10.1177/0268355519896729.

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Objectives Ambient temperature (that impacts differently venous flow in superficial and deep veins) could have a different effect on the risk of superficial and deep venous thrombosis. We searched for a trimestral variation of the risk of superficial venous thrombosis among all lower-limb thrombotic events (lower-limb thrombotic events = superficial venous thrombosis + deep venous thrombosis). Methods We retrospectively analyzed the results of venous ultrasound investigations performed among 11,739 patients (aged 67 ± 19 years old, 56.1% males) referred for suspected lower-limb thrombotic events over a 12-year period. Chi-square test was used to compare the superficial venous thrombosis/lower-limb thrombotic events ratio observed by trimesters to a homogeneous distribution. Results The proportion of lower-limb thrombotic events were 30.7%, 28.8%, 31.1%, and 31.4% (Chi2: 0.133; p = 0.987) of total investigations, while that of superficial venous thrombosis among all lower-limb venous thrombotic events were 27.2%, 30.0%, 31.4%, and 31.0%, for the first, second, third, and fourth trimesters respectively (Chi2: 0.357; p: 0.949). Conclusion No trimestral variation of the superficial venous thrombosis/lower-limb venous thrombotic events ratio was observed.
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Lim, Sunghee, Ji Yoon Lee, Seok Jin Kim, and Won Seog Kim. "The International Prognostic Index Is a Better Predictor of Thrombotic Complications Than the Khorana Score for Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: Results of a Single Center Prospective Cohort Study." Blood 120, no. 21 (November 16, 2012): 5095. http://dx.doi.org/10.1182/blood.v120.21.5095.5095.

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Abstract Abstract 5095 Background Thrombotic complication is a major life threatening condition in lymphoma patients because chemotherapy as well as lymphoma cell itself can result in thrombosis. Although high rates of thrombotic complication have been reported in patients with lymphoma, the majority of data were from retrospective studies with heterogeneous group of patients. Furthermore, the frequency of thrombotic complications varied depending o the nature of studies and subtypes of lymphoma included. Thus, it is still not determined about the risk factors for thrombotic complications in lymphoma patients. As a predictive model for cancer-associated thrombosis, Khorana risk score has been proposed including cancer type, body mass index (BMI), prechemotherapy white blood cell, hemoglobin, and platelet count. However, there is few data prospectively validating the role of this risk model in Asian lymphoma patients. Therefore, we explored risk factors influencing the occurrence of venous and arterial thrombotic complications in diffuse large B-cell lymphoma (DLBCL) patients who were uniformly treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Methods We analyzed the incidence of venous and arterial thrombotic complications from DLBCL patients enrolled in our prospective cohort study (NCT00822731). Patients were pathologically confirmed and treated with R-CHOP. Thrombotic complications defined as venous thrombosis including pulmonary thromboembolism (PTE) and deep vein thrombosis (DVT), and arterial thrombosis including stroke and infarction occurred after diagnosis. The thrombotic complications were diagnosed with radiologic imaging studies including CT scan and ultrasound imaging. Results 352 patients were enrolled between 2008 and 2011, and they were prospectively monitored regarding the occurrence of thrombotic complications with the median follow-up duration of 22. 6 months. The median age was 56 years old (range 16–86) and male to female ratio was 1. 3:1. Thrombotic complications occurred in 48 patients (crude incidence: 13. 6%) including venous thrombosis (n = 37, 10. 5%) and arterial thrombosis (n = 11, 3. 1%). Venous thrombosis including DVT and PE occurred within 6 months after diagnosis (32/37, 86. 5%), so the actuarial incidence of venous thrombosis at one year was 10. 1%. However, arterial thrombosis mainly occurred around 12 months after diagnosis. Among 37 cases of venous thrombosis, anticoagulation therapy was used for 22 patients with symptomatic DVT or PE. Incidental cases of DVT or PE which were found during imaging follow-up for evaluation of tumor response did not require therapy. There were two deaths-related with venous thrombosis including refractory hypoxemia due to PE and bleeding due to anticoagulation while no death was found in arterial thrombosis. Age older 60 years and poor performance status (≥ ECOG grade 2) were significantly associated with thrombotic complications. However, other host factors including co-morbidity, body mass index (BMI), and gender were not related (P > 0. 05). Disease-related factors representing high tumor burden such as elevated serum LDH, two or more than two extranodal involvements, and Ann Arbor stage III/IV were significantly associated with increased risk of thrombotic complications (P < 0. 05). However, a particular extranodal site including stomach, pancreas, intestine, and mediastinum did not influence the thrombotic complications. Khorana score-based risk model failed to predict the occurrence of thrombotic complications in our study population. Furthermore, each parameter such as the level of hemoglobin, white blood cell and platlet count before chemotherapy, and BMI did not show a significant association with venous and arterial thrombotic complications. In fact, the number of patient more than 35 kg/m2 BMI was extremely small in our population. As a result, the International Prognostic Index was predictive for the occurrence of thrombotic complications in diffuse large B-cell lymphoma patients treated with R-CHOP. Conclusions The incidence of venous and arterial thrombotic complications in our study population was significantly associated with the IPI rather than Khorana score model. These results may help better defining lymphoma patients at high risk of thrombotic complications in Asian lymphoma patients. Disclosures: No relevant conflicts of interest to declare.
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Miller, Mariel, Kamil K. Khanipov, Christopher Zahner, and George K. Golovko. "Increased Risk of Thrombosis in Patients with Polycystic Ovarian Syndrome." Blood 142, Supplement 1 (November 28, 2023): 5544. http://dx.doi.org/10.1182/blood-2023-190997.

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Polycystic Ovarian Syndrome (PCOS) is the most common endocrine-metabolic disorder in reproductive age women, with an estimated prevalence of 6-12% of assigned female at birth women in the US. We identified a pattern in our coagulation diagnostic management team, wherein women with PCOS had increased rates of and repeated histories of thrombotic events, such as strokes, heart attacks, pulmonary embolisms, and deep vein thromboses. However, clinical coagulation assays on these PCOS patients with repeated thrombotic events were all within the normal reference range. Our goal was to investigate the validity of this pattern and its occurrence in both local and national populations. This was accomplished by 1) Determining the incidence rate of thrombosis in PCOS and 2) Analyzing clinical presentations of thrombosis in PCOS. Methods/Study populations : Analyses on the rate of thrombotic events in PCOS patients locally at UTMB and in the US were performed on the TriNetX health research network. Using the incidence and prevalence and compared outcomes analytic functions on TriNetX, we determined the rate of thrombosis from 2013-2018 and explored patient characteristics. We further analyzed thrombosis in PCOS with the Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) method. Through the compare outcomes analysis on the TriNetX platform, we looked at PCOS and control patients who experienced thrombotic events between 2013-2018 and analyzed clinical presentations that occurred in the 90 days prior to the index event. Patient queries included the diagnostic code for PCOS, ICD10 E28.2, women age 15-75, who had a clinical encounter since 2013. Exclusion criteria included inherited thrombotic disorders, smoking history, and human immunodeficiency virus. Events of interest included myocardial infarctions, cerebral infarctions, pulmonary embolisms, arterial embolisms and thrombosis, and portal vein thromboses. Statistical analysis: For evaluating statistical significance of the rate of thrombosis, we performed a compare outcome analysis on the UTMB network, with propensity score matching for current age. A Kaplan-Meier Analysis and a student's t-test were performed on the number of instances/events, and statistical significance was defined as a p-value &lt;0.0001. Results:Between 2013-2018, the incidence rate of thrombosis in PCOS patients was 4.35% with 5.36% prevalence, this was statistically significantly higher than the control cohort at 2.66% incidence and 3.5% prevalence. The incidence rate of thrombosis in PCOS increased dramatically in post-menopausal women. Of the 60 outcomes investigated, 24 were determined to be statistically significant between control and PCOS, 22 symptoms and 2 procedures. Discussion: This is the first study to analyze the rate of thrombotic events in PCOS. We identified significant presentations and gaps that could assist in the early detection of thrombotic events in PCOS. However, the mechanisms of thrombosis in PCOS are unknown and are poorly detected with current clinical assays. Future studies will examine clinical assays in the detection of thrombosis in PCOS and investigate thrombotic mechanisms in PCOS.
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Kreidy, Raghid. "Pathophysiology of Post-Thrombotic Syndrome: The Effect of Recurrent Venous Thrombosis and Inherited Thrombophilia." ISRN Vascular Medicine 2011 (November 9, 2011): 1–4. http://dx.doi.org/10.5402/2011/513503.

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Post-thrombotic syndrome is an important chronic complication of deep vein thrombosis. This syndrome can be debilitating to patients and has a major economic impact on health care services. The pathophysiology of post-thrombotic syndrome is currently incompletely understood. Because therapeutic options for post-thrombotic syndrome are extremely limited and results are often disappointing, recognizing of the pathophysiology and risk factors of this syndrome is essential to prevent the disabling consequences of this disease. The present paper focuses on risk determinants of post-thrombotic syndrome after deep vein thrombosis. The contribution of recurrent venous thrombosis and inherited thrombophilia to the pathogenesis of this syndrome is reviewed and discussed in details.
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Park, D. J., S. E. Choi, H. Xu, J. H. Kang, and S. S. Lee. "AB0442 RISK FACTORS ASSOCIATED WITH THROMBOTIC EVENTS IN KOREAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1519.3–1520. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1674.

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Background:Objectives:Up to 30~40% of all patients with systemic lupus erythematosus (SLE) experience thrombosis, presenting as stroke and myocardial infarction, and these thrombotic events cause substantial morbidity and mortality in SLE. We explored the risk factors associated with the occurrence of thrombotic events in SLE patients.Methods:This study enrolled 259 SLE patients (mean age, 34.0 ± 13.7; 239 females) with available clinical data at the time of SLE onset from the lupus cohort at Chonnam National University Hospital. Sociodemographic, clinical, and laboratory data, and history of concomitant diseases were obtained. Thrombotic events were defined as the presence of arterial or venous thrombosis. The multivariable Cox’s model was performed to investigate the possible risk factors for thrombotic events.Results:During a mean follow-up of 103.3 months (SD, 53.4), 27 patients (10.4%) developed thrombotic events: stroke in 15 patients, venous thrombosis in five patients, myocardial infarction in four patients, and angina in three patients. In the multivariable Cox’s regression analysis, hypertension (hazard ratio [HR], 16.946; P=0.031), antiphospholipid syndrome (APS) (HR, 18.348; P=0.001), cumulative prednisolone >5 mg/day (HR, 14.374; P<0.001), use of ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB) (HR, 0.110; P=0.004), and Systemic Lupus International Collaborating Clinics Group (SLICC) damage index (HR, 1.972; P=0.004) were significant predictors of the development of thrombotic events in patients with SLE.Conclusion:Patients with SLE showed significant thrombotic events during the course of their disease. Risk factors associated with thrombotic complications were higher cumulative dose of prednisolone, diagnosis of APS, and higher SLICC damage index. On the other hand, the use of ACEi or ARBs was associated with a reduced risk of thrombotic complications in patients with SLE. Our results support the need for increased monitoring of thrombotic complications in SLE patients.Disclosure of Interests: :None declared
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Siddiqui, Nadeem A., Ziad Sophie, Farhan Zafar, Delvene Soares, and Iram Naz. "Predictors for the development of post-thrombotic syndrome in patients with primary lower limb deep venous thrombosis: A case–control study." Vascular 25, no. 1 (July 10, 2016): 10–18. http://dx.doi.org/10.1177/1708538116636250.

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Introduction Post-thrombotic syndrome is a common and debilitating sequelae of lower limb deep venous thrombosis. Very little awareness is present about the risk factors and about the diagnosis, prevention, and treatment of this condition. Objective The objective of this study is to identify the predictors of post-thrombotic syndrome after lower limb deep venous thrombosis. Materials and methods A case–control study was conducted on all adult patients who were admitted with lower limb deep venous thrombosis at our institution from January 2005 to June 2012. These patients were scheduled for a research clinic visit, which included informed consent, data collection, and physical examination. Patients found to have post-thrombotic syndrome served as cases and those without post-thrombotic syndrome served as controls. Villalta scoring system was used to diagnose the post-thrombotic syndrome and then to assess the severity of the condition in both the groups. Cox regression risk factor analysis was performed to identify the predictors of post-thrombotic syndrome. Results Out of the 125 patients examined, 49 were found to have post-thrombotic syndrome. Risk factors found to be significant were body mass index of more than 35 kg/m2 ( n = 13, p = 0.003), history of immobilization ( n = 19, p = 0.003), one or more hypercoagable disorders ( n = 32, p = 0.02), iliofemoral deep venous thrombosis ( n = 18, p = 0.001), complete obstruction on ultrasound ( n = 26, p = 0.016), unstable range of international normalized ratio ( n = 23, p = 0.041) and non-compliance for the use of compressions stockings ( n = 14, p = 0.001). On multivariate analysis, one or more hypercoagable disorder, iliofemoral deep venous thrombosis, and non-compliance to the use of compression stockings were found to be independent risk factors for the development of post-thrombotic syndrome. Conclusion One or more hypercoagable disorders, iliofemoral deep venous thrombosis and non-compliance to the use of compression stockings were independent predictors of post-thrombotic syndrome after deep venous thrombosis. These findings will help prognosticate and prevent development of PTS in similar patient populations.
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Vassalli, Laura Coutinho, Emilia Carolina Malafaia, Maria L. Chauffaille, and Daniella Kerbauy. "Leukocytosis Can Predict Thrombotic Events in Myelofibrosis." Blood 126, no. 23 (December 3, 2015): 5191. http://dx.doi.org/10.1182/blood.v126.23.5191.5191.

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Abstract Thrombotic events are the main complication of Philadelphia-negative chronic myeloproliferative neoplasms (MPN). In polycythemia vera (PV) and essential thrombocythemia (ET), risk factors for thrombosis are well established, such as age greater than 60 years and previous thrombosis. However, the role of JAK2 V617F mutation and leukocytosis at diagnosis as risk factor for thrombosis is still controversial. Our aim was to identify factors related to the risk for thrombotic events in the studied population.This study is a retrospective non-interventional cohort. All of the analyses were performed using the database of 142 patients with MPN regularly followed at the Hematology Division (at UNIFESP-SP) from 1992 to 2014. Diagnosis was established according to WHO criteria. We analyzed the JAK2 V617F mutation, hemoglobin (g/dL), hematocrit (%), white blood cells (x109/L) and platelets (x109/L) at the diagnosis and DIPSS-Plus risk score (International Working Group for Myelofibrosis Research and Treatment, 2009). These variables were associated with thrombotic event at any time.Of the 142 patients, 54 had diagnosis of PMF, 28 of PV, 33 of ET and 27 of post-essential thrombocythaemic myelofibrosis (post ET MF) or post-polycythaemic myelofibrosis (post-PV MF). This last group was included in myelofibrosis group for statistical purposes. Thrombotic events were more frequent in PV patients (39.2%), followed by ET (33.3%), and PMF (20.9%). From those which JAK2 mutation was obtained, it was positive in 92.4% of PV patients, 62% of PMF and 50% of ET. In none of the three groups, the presence of JAK2 V617F mutation was related to increased risk of thrombosis. In myelofibrosis, leukocytosis was higher among thrombotic patients (median of 13.7 in thrombotic group versus 9.7x 109/L; p 0.0379). None of the other parameters, hemoglobin, hematocrit, platelets and DIPSS-Plus were statistically significant. In ET, the hemoglobin level at diagnosis was significantly higher in the presence of thrombosis (mean of 14.57 in thrombotic group against 13.03 g/dL in the non-thrombotic one, p 0.0428). The other parameters, hematocrit, white blood cells and platelets were not relevant. The median WBC in the thrombotic group was 9.4 and in the non-thrombotic one 9.3 x109/L. Finally, in polycythemia vera, none of the variables were related to thrombosis. Among the studied population, leukocytosis was increased in patients with thrombotic event in MF. Thus, monitoring leukocyte count in MF is essential to predict thrombosis risk and should be further studied in order to define therapeutic goals in these patients. Disclosures No relevant conflicts of interest to declare.
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Siscovick, David, Frits Rosendaal, and Alexander Reiner. "Hemostatic Risk Factors and Arterial Thrombotic Disease." Thrombosis and Haemostasis 85, no. 04 (2001): 584–95. http://dx.doi.org/10.1055/s-0037-1615638.

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SummaryThe pathogenesis of arterial thrombotic disease involves multiple genetic and environmental factors related to atherosclerosis and thrombosis. Acute thrombosis at the site of a ruptured, lipid-rich atherosclerotic plaque is the usual precipitating event in the transition from stable or subclinical atherosclerotic disease to acute myocardial infarction (MI), stroke, or peripheral arterial occlusion (1). Pathologic studies of coronary arteries in acute MI suggest that the acute thrombosis likely involves activation of both platelets and the coagulation system.
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Dho-Nagy, Eszter-Anna, Attila Brassai, Patrick Lechsner, Corina Ureche, and Erika-Gyöngyi Bán. "COVID-19 and Antipsychotic Therapy: Unraveling the Thrombosis Risk." International Journal of Molecular Sciences 25, no. 2 (January 9, 2024): 818. http://dx.doi.org/10.3390/ijms25020818.

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In the context of the COVID-19 pandemic, this study investigates the potential correlation between the increased use of antipsychotic medications and the rising incidence of venous thromboembolism (VTE). As psychiatric disorders surged, the consequential escalation in antipsychotic drug use raised concerns about thrombotic risks. We conducted a comprehensive literature review using PubMed, focusing on articles that intersected COVID-19, antipsychotic medication, and thrombosis. This approach allowed for a nuanced examination of the historical and recent data on antipsychotic drugs and their association with thrombotic events. Our findings reveal a notable link between the use of antipsychotic medications, particularly second-generation antipsychotics, and an increased risk of VTE, including pulmonary embolism and deep vein thrombosis. This association was evident, despite variations in study designs and populations. The study underscores the need for cautious medication management in psychiatric care, especially during pandemic conditions like COVID-19, to mitigate thrombotic risks. It advocates a personalized approach to prescribing antipsychotics, considering individual patient factors and comorbidities, to balance the benefits against potential thrombotic complications.
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Puetz, John, Ginger Darling, Petr Brabec, Jan Blatny, and Prasad Mathew. "The Risk of Thrombotic Events in Neonates Treated with Recombinant Factor VIIa." Blood 110, no. 11 (November 16, 2007): 3193. http://dx.doi.org/10.1182/blood.v110.11.3193.3193.

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Abstract Background: In recent years, recombinant factor VIIa (rFVIIa) has been used in non-hemophilia bleeding situations (factor VII deficiency, trauma, liver disease, uremia, surgical bleeding, platelet disorders, and intracranial hemorrhage) for achievement of hemostasis. Although, the risk of thrombosis in hemophilia patients with inhibitors receiving rFVIIa is quite low, its use in other clinical situations has been complicated by some reports of thrombotic events. Recently, rFVIIa has been used to treat coagulopathic and/or bleeding neonates with good success. However, the prevalence of thrombotic events in these neonates is completely unknown. This study was initiated to determine the risk of thrombotic events associated with rFVIIa use in neonates. Methods: We reviewed all published literature in neonates receiving rFVIIa. In addition, we reviewed all data submitted to the SeveN Bleep Registry, a database developed by the scientific standardization subcommittee on pediatric and neonatal hemostasis of the International Society on Thrombosis and Haemostasis (ISTH) to record all uses of rFVIIa in pediatric non-hemophilic patients. As the baseline prevalence of thrombosis for bleeding and/or coagulopathic neonates is also unknown, we also reviewed the records of 100 consecutive neonates from a single institution who received fresh frozen plasma (FFP) alone to treat their coagulopathy and/or bleeding. Results: A total of 98 non-hemophilic neonates received rFVIIa. The majority of these neonates received rFVIIa only after failing to achieve hemostasis with standard care (FFP, cryoprecipitate, platelet transfusions). Of those receiving rFVIIa, 7 had a thrombotic event reported. In the control group that received FFP alone, 7 neonates also suffered a thrombotic event. Although the risk of thrombosis in these two groups is similar, neonates receiving rFVIIa tended to have indwelling line related thrombosis, while those receiving FFP tended to have strokes or myocardial insults. Overall the prevalence of thrombotic events in bleeding and/or coagulopathic neonates appears to be 7%, whether or not they received rFVIIa. Conclusions: In this study, the overall prevalence of thrombotic events was similar in the rFVIIa and FFP group. As data for this study was collected in a retrospective manor, and thereby subject to publication and submission bias, a more accurate determination of the prevalence of thrombosis in neonates will require a prospective study.
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Khidirova, L. D., N. P. Ilyinykh, and P. G. Madonov. "Thrombosis on background of COVID-19 in middle-aged people." Medical alphabet, no. 19 (October 16, 2022): 38–43. http://dx.doi.org/10.33667/2078-5631-2022-19-38-43.

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This review presents the features of coagulopathy and thrombotic risk in COVID-19 in middle-aged people. A consistent increase in the D-dimer and the presence of thrombosis and PE in seriously ill middle-aged patients with COVID-19 was shown with a decrease in other blood clotting parameters, such as fibrinogen, platelets or antithrombin, which are associated with DIC syndrome. Therefore, there is a need to identify an increased risk of thrombotic events at an early stage and prevent thrombotic events and organ damage as much as possible. The use of thrombolytic therapy is also being considered. Currently, great efforts are being made by the international medical and scientific communities, the new coronovirus infection COVID-19 is a problem and the prognosis for hospitalized patients with COVID-19, especially in the critical form, continues to be unfavorable not only for elderly and old patients, but also for middle-aged patients. age. Despite the fact that this disease is considered multifactorial, thrombotic complications play an important role in the further prognosis in this category of patients.
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Roach, Rachel E. J., Willem M. Lijfering, Astrid van Hylckama Vlieg, Frans M. Helmerhorst, Frits R. Rosendaal, and Suzanne C. Cannegieter. "The risk of venous thrombosis in individuals with a history of superficial vein thrombosis and acquired venous thrombotic risk factors." Blood 122, no. 26 (December 19, 2013): 4264–69. http://dx.doi.org/10.1182/blood-2013-07-518159.

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Key Points Superficial vein thrombosis combined with an acquired thrombotic risk factor increases the risk of venous thrombosis 10- to 100-fold. If confirmed, these findings have important implications for the future prevention of venous thrombosis.
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Hobbs, Gabriela Soriano, Minal Patel, Young Rock Chung, Omar Abdel-Wahab, Gerald A. Soff, and Raajit K. Rampal. "Identification Of Markers Of Thrombotic Risk and Response To Cytoreductive Intervention In Philadelphia-Chromosome Negative Myeloproliferative Neoplams." Blood 122, no. 21 (November 15, 2013): 3627. http://dx.doi.org/10.1182/blood.v122.21.3627.3627.

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Abstract Background Thrombosis is a major cause of morbidity and mortality in the Philadelphia-chromosome negative myeloproliferative neoplasms (MPN). However, the pathogenesis of thrombosis in patients with MPN is poorly understood. MPNs are associated with elevated levels of inflammatory cytokines and abnormal platelet activation including elevated platelet factor 4 (PF4), B-thromboglobulin (B-TG) and p-selectin levels. However the relationship between these inflammatory markers and the onset of thrombosis is unclear. Current treatment guidelines recommend the use of cytoreductive agents to decrease thrombosis risk based on history of prior thrombosis and age. The effect of cytoreduction on inflammatory markers has only been partially characterized. Furthermore, current clinical guidelines fail to predict thrombotic events in all patients. Thus, more accurate risk stratification is necessary. Aim To determine if levels of p-selectin and PF4 correlate with thrombotic events and if levels of p-selectin and PF4 are affected by cytoreductive therapy. Methods Biobanked samples from 16 patients with a confirmed diagnosis of chronic phase MPN (per WHO 2008 criteria) were included in this study. Seven patients had primary myelofibrosis, five had polycythemia vera, and four had essential thrombocythemia. Median age of patients was 65.5 (range 44-81). Fourteen patients had a JAK2 V617F mutation. Four patients with samples collected before and after thrombotic episodes, four patients with post-thrombotic samples, four without a history of thrombosis, and four patients with samples obtained before and after cytoreduction were analyzed. Patient characteristics are summarized in Table 1. Plasma samples were analyzed for levels of PF4 and p-selectin using commercially-available ELISA assays under standard conditions. Results Measurement of p-selectin levels in MPN patients with a history of a thrombotic event versus disease matched control MPN patients with no history of thrombosis demonstrated an increase in the level of p-selectin in patients with thrombosis. Elevated levels of PF4 were noted in only one patient who had a history of thrombosis, and who was maintained on Aspirin. This suggests that elevated levels of p-selectin may be an indicator of thrombosis risk in patients with MPN. Levels of PF4 and p-selectin were next assessed in patients who had suffered a thrombotic event, both before and after the event had occurred. No changes in p-selectin or PF4 levels pre and post thrombosis were noted. The effect of cytoreduction was measured using samples from patients pre- and post-cytoreduction. No differences in the level of PF4 were noted with cytoreduction. In contrast, reductions in p-selectin were noted in two patients in whom cytoreduction was achieved with Ruxolitinib, but not in two patients in whom cytoreduced with hydroxyurea or pomalidomide. This suggesting that Ruxolitinib may have role in thrombosis risk reduction. Platelet levels were recorded for all 16 patients. There was no difference in platelet levels in each group of patients. In contrast to the changes observed with p-selectin, there was no difference in platelet levels in patients with out a thrombotic event compared to those with a history of thrombosis. This suggests that platelet activation, as measured by p-selectin, may be a stronger indicator of thrombotic risk than platelet levels. Conclusions Improvements in risk stratification of thrombotic risk for patients with MPN are needed. Platelet activation in MPNs is abnormal and may serve as an additional marker of thrombotic risk. Our results suggest that levels of p-selectin, but not PF4, may be associated with increased thrombotic risk. Furthermore, treatment with the JAK1/2 inhibitor Ruxolitinib resulted in reduction in levels of p-selectin, suggesting that the role of Ruxolitinib in preventing thrombotic event should be further investigated. Additional studies with larger numbers are in progress to validate these results. Disclosures: Rampal: Foundation Medicine: Consultancy.
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Radaelli, Franca, Stefania Bramanti, Mariangela Colombi, Alessandra Iurlo, and Alberto Zanella. "Essential Thrombocythemia: Analysis of Risk Factors for Thrombotic Events in a Series of 306 Patients." Blood 106, no. 11 (November 16, 2005): 4937. http://dx.doi.org/10.1182/blood.v106.11.4937.4937.

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Abstract Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by peripheral thrombocytosis and abnormal proliferation of megakariocytes in the bone marrow. Even thought thrombosis is frequently associated to ET, the risk factors of this clinical complication are still controversial. The aim of this retrospective, single institution study was to investigate clinical and laboratory characteristics associated with the occurrence of thrombotic events, with the purpose of identifying subgroups of patients who could benefit from antiaggregant and/or cytostatic treatment. 306 consecutive ET patients (109 men and 197 females, median age 58 yr) diagnosed between January 1979 and December 2002 were included in the study. At the time of analysis, 196 patients were still alive with a median follow up of 96 months. The following variables were investigated for the association with thrombotic complications: age, platelet count, previous history of thrombotic events, time from diagnosis, treatment with antiaggregant/cytostatic drugs, and cardiovascular risk factors such as arterial hypertension, obesity, hypercolesterolemia, diabetes, cigarette smoking. At the time of last follow up, 46 patients (15%) experienced at least one thrombotic event. The occurrence of thrombotic events was observed in 26/64 (40.6%) patients with previous history of thrombosis and in 20/242 (8.3%) patients with no previous history of thrombosis (p&lt;0.0001 Fisher’s exact test, odd ratio 7.6). A significant difference between the two groups of patients was also confirmed when Kaplan Meier estimates of thrombosis-free survival were compared by log-rank test (p&lt;0.0001). By logistic regression, platelet number at diagnosis did not associate with occurrence of thrombosis in the whole patient population. When patients without previous history of thrombosis were stratified according to the number of cardiovascular risk factors (none vs one vs more than one), a significant correlation with occurrence of thrombotic events was observed (Mantel-Haenszel Chi-square 5.47, p&lt;0.05). This study confirms that history of thrombosis is strongly related with risk of further thrombotic events in patients with ET, whereas platelet number at diagnosis does not seem to represent a prognostic factor. In patients with no previous history of thrombosis, the presence of other cardiovascular risk factors has to be taken into account when establishing the therapeutic approach.
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20

Lim, Wendy. "Prevention of thrombosis in antiphospholipid syndrome." Hematology 2016, no. 1 (December 2, 2016): 707–13. http://dx.doi.org/10.1182/asheducation-2016.1.707.

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Abstract Antiphospholipid syndrome (APS) is an acquired autoimmune condition characterized by thrombotic events, pregnancy morbidity, and laboratory evidence of antiphospholipid antibodies (aPL). Management of these patients includes the prevention of a first thrombotic episode in at-risk patients (primary prevention) and preventing recurrent thrombotic complications in patients with a history of thrombosis (secondary prevention). Assessment of thrombotic risk in these patients, balanced against estimated bleeding risks associated with antithrombotic therapy could assist clinicians in determining whether antithrombotic therapy is warranted. Thrombotic risk can be assessed by evaluating a patient’s aPL profile and additional thrombotic risk factors. Although antithrombotic options for secondary prevention of venous thromboembolism (VTE) have been evaluated in clinical trials, studies in primary prevention of asymptomatic aPL-positive patients are needed. Primary prevention with aspirin may be considered in asymptomatic patients who have a high-risk aPL profile, particularly if additional risk factors are present. Secondary prevention with long-term anticoagulation is recommended based on estimated risks of VTE recurrence, although routine evaluation of thrombotic risk can assist in determining whether ongoing anticoagulation is warranted. Studies that stratify thrombotic risk in aPL-positive patients, and patients with APS evaluating antithrombotic and non-antithrombotic therapies will be useful in optimizing the management of these patients.
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21

Bertina, Rogier. "Genetic Approach to Thrombophilia." Thrombosis and Haemostasis 86, no. 07 (2001): 92–103. http://dx.doi.org/10.1055/s-0037-1616205.

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SummaryVenous thrombosis is a multifactorial disease. Multiple interactions between genetic and environmental factors contribute to the development of the disease. Presently, we know of six or seven genetic risk factors for venous thrombosis. However, together these defects can explain the clustering of thrombotic events in only a small subset of families with thrombophilia. As to the identification of new genetic risk factors for thrombosis, we seem to have arrived at the end of a practicable road with the classical approach of thrombophilia, which usually starts with the study of the association of hemostatic phenotypes and thrombotic risk. At the same time we have undertaken various genetic approaches aiming at identifying polymorphisms/ mutations causing thrombotic risk. This review summarizes what we have learnt so far, what to do and what not to do. The odds for finding remaining common genetic risk factors for venous thrombosis during the next ten years may be predicted to be fairly high.
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Wang, Xuekun, Yansong Tu, Mei Cao, Xiaoyan Jiang, Yazhi Yang, Xiaoyan Zhang, Hurong Lai, Huaijun Tu, and Jian Li. "The Predictive Value of Neutrophil-Lymphocyte Ratio in Patients with Polycythemia Vera at the Time of Initial Diagnosis for Thrombotic Events." BioMed Research International 2022 (August 8, 2022): 1–8. http://dx.doi.org/10.1155/2022/9343951.

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Objective. To investigate and discuss the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in patients with polycythemia vera (PV) at the time of initial diagnosis, as well as its clinical significance in predicting the occurrence of thrombotic events and the progression of future thrombotic events during follow-ups, with the goal of providing a reference for the early identification of high-risk PV patients and the early intervention necessary to improve the prognosis of PV patients. Method. A total of 170 patients diagnosed with PV for the first time were enrolled in this study. The risk factors affecting the occurrence and development of thrombotic events in these patients were statistically analyzed. Results. NLR ( P = 0.030 ), WBC count ( P = 0.045 ), and history of previous thrombosis ( P < 0.001 ) were independent risk factors for thrombotic events at the time of initial diagnosis. Age ≥ 60 years ( P = 0.004 ), NLR ( P = 0.025 ), history of previous thrombosis ( P < 0.001 ), and fibrinogen ( P = 0.042 ) were independent risk factors for the progression of future thrombotic events during follow-ups. The receiver operating characteristic curve (ROC curves) showed that NLR was more effective in predicting the progression of future thrombotic events than age ≥ 60 years, history of previous thrombosis, and fibrinogen. Kaplan-Meier survival analysis showed progression-free survival time of thrombotic events in the high NLR value group ( NLR ≥ 4.713 ) (median survival time 22.033 months, 95% CI: 4.226-35.840), which was significantly lower compared to the low NLR value group ( NLR < 4.713 ) (median overall survival time 66.000 months, 95% CI: 50.670-81.330); the observed difference was statistically significant ( P < 0.001 ). The 60-month progression-free survival in the low NLR value group was 58.8%, while it was 32.8% in the high NLR value group. Conclusion. Peripheral blood NLR levels in patients with PV resulted as an independent risk factor for the occurrence of thrombotic events at the time of initial diagnosis and for the progression of future thrombotic events during follow-ups. Peripheral blood NLR levels at the time of initial diagnosis and treatment had better diagnostic and predictive value for the progression of future thrombotic events in patients with PV than age ≥ 60 years, history of previous thrombosis, and fibrinogen.
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Heda, Pooja Prakash, and Ali Jafer Nejim Al-Hilly. "Thrombotic Events in Covid-19: Incidence and their Association with Lab Parameters, Vaccination Status and Mortality." Journal of the Bahrain Medical Society 34, no. 4 (2022): 1–10. http://dx.doi.org/10.26715/jbms.34_4_1.

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Background & Objectives: Major arterial or venous thrombotic complications occur frequently with COVID-19. This risk seems to be present despite no known underlying thrombophilia and even adequate anticoagulation does not diminish its risk. Whilst pulmonary embolism may seem to be the most common thrombotic complication, others may also occur. A vaccination link to thrombotic events in COVID-19 has not been studied to the best of our knowledge. Methods: In this retrospective cross-sectional study we determined the incidence of total thrombotic events, individual Venous Thromboembolisms (VTE) and Arterial Thromboembolisms (ATE) that occurred in patients requiring ICU admission for COVID-19 in one of Bahrain’s main COVID ICU facilities for a period of 6 months. We also aim to determine mortality rate in this group of patients, links with specific baseline characteristics, laboratory parameters and patient vaccination status. Results: We studied 1597 patients over 6 months, 6% of patients were found to have VTE or ATE with a cumulative incidence of 6.5% thrombotic events. Elevated D dimer >1 was associated with an increased risk of thrombosis and an increased risk of mortality. There was a higher risk of thrombotic events in unvaccinated individuals. All-cause mortality in COVID-19 patients complicated with thrombosis and mortality solely secondary to thrombotic event were both significantly higher in unvaccinated individuals. Conclusions: Based on the findings of this study, unvaccinated individuals are at significantly higher risk of developing thrombotic events. This will assist in enabling physicians to lower their threshold of diagnosing such events. The urgency of lab parameters the swift management of other risk factors and the importance of vaccination against COVID-19 can be further studied.
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Choudry, Qamar Un-Nisa, Raheel Iftikhar, Manzur Qadir, Tariq Mehmood Satti, Ghassan Omair, and Syed Kamran Mehmood. "HIGH ALTITUDE AND VENOUS THROMBOSIS: FREQUENCY AND RISK FACTORS." PAFMJ 71, no. 1 (February 24, 2021): 107–11. http://dx.doi.org/10.51253/pafmj.v71i1.3173.

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Objective: To determine the effect of high altitude on frequency and risk factors of venous thrombosis inindividuals ascending to high altitude Study Design: Cross-sectional analytical study. Place and Duration of Study: Armed Forces Bone Marrow Transplant Centre, Combined Military HospitalSkardu, from Apr 2015 to Aug 2018. Methodology: High Altitude was taken as height equal to or more than 8000 feet. Polycythemia as hemoglobin>16.5 g/dl OR hematocrit >49%. Medical records of all patients evacuated from high altitude through CombinedMilitary Hospital Skardu were analyzed retrospectively. A proforma was designed to include necessary variables. Results: We evaluated medical records of 539 individuals and found frequency of 86 (15.9%) for venous thromboembolism (VTE) at high altitude. Cerebral venous sinus thrombosis (CVST) was most common thrombotic complication seen in 39 patients (46%). Majority of thrombotic episodes occurred at >18000 feet (likelihood ratio (LR) 5.99, p-value 0.009). Majority of thrombotic episodes 34 (39%) occurred within first 45 days of ascent to high altitude. Thrombosis was linked to smoking 47 (55%) (likelihood ratio 21.3 and p-value <0.001) and use of melted snow as a source of drinking water 56 (65%) (likelihood ratio 57.6 and p-value <0.001). Conclusion: This study showed a very high frequency of thrombotic complications at high altitude. There isa need for a robust prospective study covering epidemiology, clinical information and diagnostics in order todevelop appropriate standard operating procedures and guidelines for prevention of thrombosis at HA
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Cohen, Kenneth Roy, David Anderson, Sheng Ren, and David J. Cook. "Contribution of the elevated thrombosis risk of males to the excess male mortality observed in COVID-19: an observational study." BMJ Open 12, no. 2 (February 2022): e051624. http://dx.doi.org/10.1136/bmjopen-2021-051624.

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BackgroundThe mortality rate of COVID-19 is elevated in males compared with females.ObjectiveDetermine the extent that the elevated thrombotic risk in males relative to females contributes to excess COVID-19 mortality in males.DesignObservational study.SettingData sourced from electronic medical records from over 200 US hospital systems.Participants60 877 patients aged 18 years and older hospitalised with COVID-19.ExposureExposure variable: biological sex; key variable of interest: thrombosis.Primary outcome measuresPrimary outcome was COVID-19 mortality. We measured: (1) mortality rate of males relative to females, (2) rate of thrombotic diagnoses occurring during hospitalisation for COVID-19 in both sexes and (3) mortality rate when evidence of thrombosis was present.ResultsThe COVID-19 mortality rate of males was 29.9% higher than that of females. Males had a 35.8% higher rate of receiving a thrombotic diagnosis compared with females. The mortality rate of all patients with a thrombotic diagnosis was 40.0%—over twice that of patients with COVID-19 without a thrombotic diagnosis (adjusted OR 2.50 (2.37 to 2.64), p<0.001). When defining thrombosis as either a documented thrombotic diagnosis or a D-dimer level ≥3.0 µg/mL, 16.4% of the excess mortality in male patients could be explained by increased thrombotic risk.ConclusionsOur findings suggest the higher COVID-19 mortality rate in males may be significantly accounted for by the elevated risk of thrombosis among males. Understanding the mechanisms that underlie increased male thrombotic risk may allow for the advancement of effective anticoagulation strategies that reduce COVID-19 mortality in males.
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Mirrakhimov, Aibek E., Alaa M. Ali, Aram Barbaryan, Suartcha Prueksaritanond, and Nasir Hussain. "Primary Nephrotic Syndrome in Adults as a Risk Factor for Pulmonary Embolism: An Up-to-Date Review of the Literature." International Journal of Nephrology 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/916760.

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Patients with nephrotic syndrome are at an increased risk for thrombotic events; deep venous thrombosis, renal vein thrombosis, and pulmonary embolism are quite common in patients with nephrotic syndrome. It is important to note that nephrotic syndrome secondary to membranous nephropathy may impose a greater thrombotic risk for unclear reasons. Increased platelet activation, enhanced red blood cell aggregation, and an imbalance between procoagulant and anticoagulant factors are thought to underlie the excessive thrombotic risk in patients with nephrotic syndrome. The current scientific literature suggests that patients with low serum albumin levels and membranous nephropathy may benefit from primary prophylactic anticoagulation. A thorough approach which includes accounting for all additional thrombotic risk factors is, therefore, essential. Patient counseling regarding the pros and cons of anticoagulation is of paramount importance. Future prospective randomized studies should address the question regarding the utility of primary thromboprophylaxis in patients with nephrotic syndrome.
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27

Palacios-Acedo, Ana-Luisa, Mélanie Langiu, Lydie Crescence, Diane Mège, Christophe Dubois, and Laurence Panicot-Dubois. "Platelet and Cancer-Cell Interactions Modulate Cancer-Associated Thrombosis Risk in Different Cancer Types." Cancers 14, no. 3 (January 30, 2022): 730. http://dx.doi.org/10.3390/cancers14030730.

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The first cause of death in cancer patients, after tumoral progression itself, is thrombo-embolic disease. This cancer-associated hypercoagulability state is known as Trousseau’s syndrome, and the risk for developing thrombotic events differs according to cancer type and stage, as well as within patients. Massive platelet activation by tumor cells is the key mediator of thrombus formation in Trousseau’s syndrome. In this literature review, we aimed to compare the interactions between cancer cells and platelets in three different cancer types, with low, medium and high thrombotic risk. We chose oral squamous cell carcinoma for the low-thrombotic-risk, colorectal adenocarcinoma for the medium-thrombotic-risk, and pancreatic carcinoma for the high-thrombotic-risk cancer type. We showcase that understanding these interactions is of the highest importance to find new biomarkers and therapeutic targets for cancer-associated thrombosis.
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28

Cedrone, Michele, Barbara Anaclerico, Francesca Paoloni, Roberto Latagliata, Marco Montanaro, Francesca Spirito, Sabrina Leonetti Crescenzi, et al. "Application of the International Prognostic Score of Thrombosis for Essential Thrombocytemia(ET) (IPSET-Thrombosis) in a Cohort of ET Patients: Experience from Gruppo Laziale for Myeloproliferative Ph Negative Neoplasms." Blood 126, no. 23 (December 3, 2015): 2821. http://dx.doi.org/10.1182/blood.v126.23.2821.2821.

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Abstract INTRODUCTION: Essential Thrombocytemia (ET) is the most common of the myeloproliferative neoplasms, vascular complications contribute mostly to both morbidity and mortality. The ability to identify thrombotic risk of the individual patient is necessary for a correct therapeutic management. Traditionally, risk stratification for thrombosis in ET pts was based on the respective absence and/or presence of either age >60 years or history of thrombosis. Recently, the IPSET score (International Prognostic Score Of Thrombosis for ET) was developed to better predict the occurrence of thrombotic events in ET patients. Risk factors included in the new score were: age, cardiovascular risk factors, previous thrombosis, presence of JAK 2 V617F mutation. AIM: to evaluate the validity of IPSET-thrombosis score in a cohort of ET patients from "Gruppo Laziale for Myeloproliferative Ph negative Neoplasms" in predicting thrombosis incidence. METHODS: from January 1978 to December 2011 we observed 1249 ET patients, median follow up was 105 months (range 12.1-417.7). We were able to retrospectively evaluate all the IPSET risk factors in 680 ET patients and estimated the clinical implication of the IPSET-thrombosis score system. According to the score 27.3 %, 19.1% and 53.5% of pts were stratified in low, intermediate and high risk group respectively. RESULTS: median age at the time of diagnosis was 61.8 yrs (range 19.9 -94; 64% females), median hemoglobin was 14 g/dl (range 6-20); median leukocyte count was 8.8 x 109/L (range 1,2-57); median platelets count was 812x 109/L (range 108-3582). We observed, during a median follow-up of 200 months, 82 thrombotic events (total incidence 17,89 %). According IPSET-thrombosis risk, in our ET population was documented a statistically different thrombosis free survival (TFS) (Gray test 0.1316): 85%, 78%, 77% in low,intermediate and high risk group respectively. During all the observation period the intermediate and high risk group showed a similar probability of thrombotic events. CONCLUSIONS: in our retrospective study the IPSET score was able to differentiate the rate of thrombosis events in low-risk (0-1 risk factors) from that of intermediate (>= 2 risk factors) and high risk (>= 3 risk factors) ET pts. Unfortunately the intermediate and high risk groups show a similar incidence of thrombotic events during the whole observation period. We were not able to verify the clinical benefit resulting from the different treatment strategies. Because treatment options in ET pts are tailored according to thrombotic risk, and since we have specified therapeutic indications for patients with low and high risk, it is necessary to validate the score IPSET in a large prospective, long term study to discriminate a true "intermediate" subset of patients for which there are no currently defined therapeutic guidelines. Disclosures No relevant conflicts of interest to declare.
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Kharlamova, E. N., T. M. Reshetnyak, and G. M. Tarasova. "Thrombosis risk factors in ANCA-associated vasculitis." Modern Rheumatology Journal 17, no. 2 (April 22, 2023): 93–99. http://dx.doi.org/10.14412/1996-7012-2023-2-93-99.

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The article presents a review of current data on arteriovenous thrombosis risk factors in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Thrombotic complications are among the most frequent prognostically unfavorable factors in AAV. In general, patients with AAV are at greater risk of mortality from cardiovascular events compared with the general population and patients with other forms of systemic vasculitis. Understanding the mechanisms of thrombosis, as well as pathogenic factors that cause an increased risk of arterial and venous thrombosis in AAV, can improve the quality of management of these patients. Therefore, the question of the need for primary and secondary prevention of thrombosis in AAV is of great practical importance. The presented data show the need to estimate the probability of thrombosis in patients with AAV, taking into account risk factors, as well as the influence of the disease itself and ongoing therapy. Assessment of the risk of thrombosis (both venous and arterial) is necessary for the timely administration of adequate preventive treatment of thrombotic complications in AAV.
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30

Seck, Moussa, Elimane Seydi Bousso, Sokhna Aissatou Touré, Abibatou Sall, Maryama Ndao, Sérigne Mourtalla Guèye, Blaise Félix Faye, et al. "Thrombotic Events and Risk Factors for Thrombosis in Polycythemia in Senegal, West Africa." Journal of Clinical Haematology 4, no. 1 (June 5, 2023): 1–8. http://dx.doi.org/10.33696/haematology.4.052.

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Objectives: We aim to identify thrombotic events and risk factors for thrombosis (RFT) comparing polycythemia vera (PV) and secondary polycythemia (SP) patients. Methods: We carried out a retrospective study of a cohort of 59 patients with PV (n=34) and SP (n=25) followed for a period of 14 years. Variables studied were the frequency and type of thrombosis, sociodemographic, clinical, and biological RFT. Statistical analysis was performed using SPSS software version 18. Multivariate analysis was performed to identify RFT. Results: Mean age in PV was 53 years (33 - 79) and 44.5 years (5 - 78) in SP (p=0.74). The sex ratio in PV was 1.12 and 2.57 in PS (p=0.52). Sixteen patients had thrombotic events (27.1%) including 12 PV (35.3%) versus 4 SP (16%) (p=0.09). Twenty-two thrombotic events were identified; 14 (63.7%) of arterial thrombosis and 8 (36.3%) of venous thrombosis. There were 18 thrombotic events (81.8%) in PV versus 4 (18.2%) in SP (p=0.02). Arterial thrombosis was more frequent in PV (55.6%). Thrombosis events were more frequent in female patients (59.1%). RFT in PV were age (40-59 years), hematocrit >45% and thrombocytosis ≥ 600 G/L and in SP, RFT were hematocrit >45% and hypercholesterolemia. After multivariate analysis, hematocrit >45% was the only RFT independently associated with thrombosis occurrence. Conclusion: We show through this study, a frequent occurrence of arterial thrombosis in polycythemia. Main RFT is the high hematocrit level (>45%). We insist on the interest of therapeutic bloodletting, sometimes associated with cytoreductive treatment in order to maintain a hematocrit level <45%.
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Kahn, Susan R. "The post-thrombotic syndrome." Hematology 2016, no. 1 (December 2, 2016): 413–18. http://dx.doi.org/10.1182/asheducation-2016.1.413.

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Abstract The post-thrombotic syndrome (PTS) is a frequent, sometimes disabling complication of deep vein thrombosis (DVT) that reduces quality of life and is costly. This article discusses risk factors for PTS after DVT and available means to prevent and treat PTS, with a focus on new information in the field. After DVT, PTS will develop in 20% to 50% of patients, and severe PTS, including venous ulcers, will develop in 5% to 10%. The principal risk factors for PTS are anatomically extensive DVT, recurrent ipsilateral DVT, persistent leg symptoms 1 month after acute DVT, obesity, and older age. By preventing the initial DVT and ipsilateral DVT recurrence, primary and secondary prophylaxes of DVT will prevent cases of PTS. Based on recent evidence from a large multicenter trial, routine use of elastic compression stockings (ECS) after DVT to prevent PTS is not advocated, but in patients with DVT-related leg swelling that is bothersome, a trial of ECS is reasonable. Selecting DVT patients for catheter-directed thrombolytic treatment as a means of preventing PTS should be done on a case-by-case basis, with a focus on patients with extensive thrombosis, recent symptoms onset, and low bleeding risk. For patients with established PTS, daily use of ECS may help to relieve symptoms and edema. Intermittent compression devices can be tried in patients with moderate-to-severe PTS whose symptoms are inadequately controlled with ECS alone. A supervised exercise training program may improve PTS symptoms. Management of post-thrombotic ulcers should ideally involve a multidisciplinary approach. Important areas for future research are summarized.
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Ruffatti, A., T. Del Ross, M. Ciprian, M. Nuzzo, M. Rampudda, M. T. Bertero, R. Bergia, et al. "Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study." Annals of the Rheumatic Diseases 68, no. 3 (September 23, 2008): 397–99. http://dx.doi.org/10.1136/ard.2008.096669.

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Objectives:To asses risk factors for a first thrombotic event in antiphospholipid antibody (aPL) positive carriers and evaluate the efficacy of prophylactic treatments.Methods:Recruitment criteria were age 18–65 years, no history of thrombosis, positivity for lupus anticoagulant and/or IgG/IgM anticardiolipin antibody (aCL) on ⩾2 occasions at least 6 weeks apart. Demographic, laboratory and clinical parameters were collected at enrolment and at the time of the thrombotic event.Results:370 patients/subjects (mean (SD) age 34 (9.9) years) were analysed retrospectively for a mean (SD) follow-up of 59.3 (45.5) months. Thirty patients (8.1%) developed a first thrombotic event during follow-up. Hypertension and medium/high levels of IgG aCL were identified by multivariate logistic regression analysis as independent risk factors for thrombosis. Thromboprophylaxis during high-risk and long-term periods was significantly protective.Conclusions:Hypertension or medium/high titres of IgG aCL are risk factors for a first thrombotic event in asymptomatic aPL carriers and primary prophylaxis is protective.
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Chaireti, Roza, and Hareth Nahi. "Risk Factors and Risk Stratification of Thromboembolic Risk in Patients with Multiple Myeloma." Hemato 3, no. 3 (August 29, 2022): 518–26. http://dx.doi.org/10.3390/hemato3030036.

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Multiple myeloma (MM) is a hematological malignancy characterized by a high risk for thrombotic episodes, mainly venous thromboembolism (VTE). This risk is accentuated by cancer treatments such as immunomodulatory drugs (IMiDs). Cancer-associated thrombosis is one of the leading causes of mortality and morbidity, and the prevention of thrombosis is, therefore, of paramount significance. To this day, it is unclear which type of thromboprophylaxis is the most effective. This is partly due to the multifactorial etiology behind thrombosis since the compound of patient-, disease- and treatment-associated factors characterizing each patient with MM is unique. Additionally, the established risk scores are not reliable in patients with MM. The scope of this review is to summarize the factors contributing to increased thrombosis risk in MM, as well as the risk scores and thromboprophylaxis regimes available.
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Mancini, Mariangela, Gianmarco Randazzo, Gregory Piazza, and Fabrizio Dal Moro. "Arterial Thrombotic Complications in COVID-19: A Case of Renal Infarction." Biomedicines 10, no. 10 (September 21, 2022): 2354. http://dx.doi.org/10.3390/biomedicines10102354.

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COVID-19 infection has been associated with thrombotic complications, especially venous thromboembolism. Although arterial thrombotic complications are rarely seen in these patients, we report the case of a 43-year-old patient who developed thrombosis of the main branch of the left renal artery, causing partial infarction of the left kidney associated with severe pain. He had no risk factors for thrombosis except for COVID-19 infection. We excluded any possible condition usually associated with renal artery thrombosis/embolism (i.e., cardiovascular, oncological, hematological, or rheumatic). The thrombosis resolved after a combination of anticoagulant and anti-platelet therapy. This case highlights the importance of the risk of recurrence of thrombosis in patients with a recent history of COVID-19, even after hospital discharge, improvement of the initial thrombotic event, and clearance of SARS-CoV-2 infection.
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Zhang, Xueya, Xuerong Cai, and Jingxin Pan. "Correlation Between PAI-1 Gene 4G/5G Polymorphism and the Risk of Thrombosis in Ph Chromosome-Negative Myeloproliferative Neoplasms." Clinical and Applied Thrombosis/Hemostasis 26 (January 1, 2020): 107602962093520. http://dx.doi.org/10.1177/1076029620935207.

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Thrombosis has been recognized as one of the most significant risk factors of high mortality and disability in patients with Philadelphia (Ph) chromosome negative myeloproliferative neoplasms (MPNs). However, the risk factors of thrombotic events in these patients have not been completely understood. In this study, the clinical data of 58 patients with Ph-MPNs were obtained and analyzed, including 34 cases of essential thrombocytopenia (ET), 23 thrombotic events happened in 21 (36%) patients, among which 60% (14 of 23) with cerebral infarction, 17% (4 of 23) with coronary heart disease and 23% (5 of 23) with venous thrombosis. There were no significant differences in age, sex, and blood cell count between polycythemia vera (PV) and ET patients who have experienced thrombotic events and those who have not. In ET patients, the incidence of thrombotic events in plasminogen activator inhibitor-1 (PAI-1) genotype 4G4G was significantly higher than that in genotype 4G5G and genotype 5G5G ( P < .05). The incidence of thrombotic events in PV and ET patients with infection was higher than those without infection ( P < .05). Using logistic regression analysis, we found that PAI-1 genotype 4G4G and infection were associated with thrombotic events (odds ratio 6.744, 95% CI: 1.195-38.056 and 15.641 95% CI: 3.327-73.522). The 4G/4G polymorphism of PAI-1 gene and infection are independent risk factors of thrombotic events in patients with Ph-MPNs. PAI-1 gene 4G4G and infection in ET and PV patients with Janus kinase 2 (JAK2) V617F mutation were shown to be high risk of thrombotic events. Therefore, clinical doctors should put more attention on PAI-1 genotype 4G4G and infection in JAK2 V617F mutated patients with Ph-MPNs to prevent the thrombosis.
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Buxhofer-Ausch, Veronika, Heinz Gisslinger, Juergen Thiele, Bettina Gisslinger, Hans-Michael Kvasnicka, Leonhard Müllauer, Sophie Frantal, et al. "Risk Factors for Thrombosis in WHO-Defined Early/Prefibrotic Myelofibrosis: An International Study of 264 Patients,." Blood 118, no. 21 (November 18, 2011): 3846. http://dx.doi.org/10.1182/blood.v118.21.3846.3846.

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Abstract Abstract 3846 INTRODUCTION There is strong evidence indicating that the clear-cut separation of prefibrotic primary myelofibrosis (PMF) from essential thrombocythemia (ET) by consequent application of the World Health Organization (WHO) 2008 criteria is reflected in different, well defined clinical pictures and divergent prognoses (Barbui et al, JCO 2011,Thiele et al, Blood 2011). Very recently the specific risk profile for arterial and venous thrombosis in WHO- diagnosed ET was published (Carobbio et al, Blood 2011). In PMF so far all published data on vascular events were exclusively based on overt disease manifestations until now there are no data available regarding prefibrotic stages. Consequently, we aimed to evaluate the corresponding risk profile of patients with WHO-diagnosed prefibrotic PMF. METHODS A total number of 264 patients with WHO-defined prefibrotic PMF derived from either the Medical University of Vienna or an International Database (Barbui et al, JCO 2011) were studied. Nonfatal thrombotic events considered in this study were reported as rates per 100 patient-years and included transient ischemic attacks, thrombotic cerebrovascular accidents, coronary artery disease, myocardial infarction, peripheral arterial disease, deep vein thrombosis of peripheral vasculature, pulmonary embolism, and abdominal large vein thrombosis. Cardiovascular risks factors considered, comprised of arterial hypertension, diabetes mellitus and tobacco use. To evaluate risk factors for total thrombosis and for arterial and venous events in particular multivariate Cox- regression analysis including the co-variables sex, age, previous thrombotic event, laboratory parameters measured at diagnosis and need for cytoreductive and/or antiplatelet therapy during follow-up was calculated. P values less than 0.05 were considered as statistically significant. RESULTS After a median follow- up of 5.8 years (range0.0 – 27.2), the total rate of non fatal thrombotic events was 2.1% patient-years (95% CI, 1.5–2.8); the incidence of arterial events was higher (1.7% patient- years) than of venous events (0.6% patient-years).Considering thrombosis in general a higher white blood cell (WBC) count enhances the risk significantly (p=0.005; HR 1.15). This is also true in arterial events in particular (p=0.047; HR 1.12). A lower platelet count is associated with a higher risk for thrombotic events; for thrombosis in general this association is of borderline significance (p=0.056; HR 0.99), for arterial thrombosis in particular of significance (p= 0.042; HR 0.99). A lower hemoglobin level is associated with a higher risk for venous thrombosis (p=0.007; HR 0.59). CONCLUSION Leukocytosis appears as a risk factor for thrombosis in general and also for arterial thrombosis in particular in WHO-diagnosed prefibrotic PMF. Moreover, higher platelet counts seem to decrease significantly the risk for thrombotic events in general and arterial thrombosis in particular. Anemia is associated with a higher risk for venous thrombosis. These observations are partly in line with recently published findings in WHO-diagnosed ET (Carobbio et al,2011) and might indicate the existence of a specific risk profile for thrombotic events in prefibrotic PMF. This is the first study reporting data on the risk profile for thrombosis in WHO-diagnosed prefibrotic PMF. Certainly these findings ask for validation in a larger patient population. Disclosures: Gisslinger: Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau; AOP-Orphan Pharmaceuticals AG: Speakers Bureau. Vannucchi:Novartis: Honoraria.
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Grover, Steven P., Yohei M. Hisada, Raj S. Kasthuri, Brandi N. Reeves, and Nigel Mackman. "Cancer Therapy–Associated Thrombosis." Arteriosclerosis, Thrombosis, and Vascular Biology 41, no. 4 (April 2021): 1291–305. http://dx.doi.org/10.1161/atvbaha.120.314378.

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Patients with cancer have an increased risk of both arterial and venous thrombotic events compared with the general population. Both the site and stage of cancer are known to contribute to the increased risk of thrombotic events. In addition, several treatment-related factors enhance the risk of thrombosis, including hospitalization, surgery, central venous catheters, radiation, and anticancer agents. Chemotherapy serves as a mainstay treatment for a broad range of malignancies. Chemotherapeutic agents typically exert antineoplastic effects through either direct cytotoxicity or inhibition of cellular processes necessary for the proliferation of malignant cells. Unfortunately, in addition to targeting malignant cells, chemotherapeutic agents are also cytotoxic to nonmalignant cells. Chemotherapeutic agents have been associated with an increased risk of arterial and venous thrombosis. More recently, targeted agents have been developed that offer improved selectivity towards malignant cells. However, some of these agents are also associated with an increased risk of both arterial and venous thrombosis. Here, we review the association between specific anticancer agents and thrombotic events in patients with cancer. Despite an established association in most cases, the mechanism by which these agents increase thrombosis is poorly understood. Anticancer agents may damage the endothelium, decrease anticoagulants or increase procoagulants leading to activation of coagulation, or activate platelets. An improved understanding of the mechanisms that drive the increased risk of thrombotic events associated with anticancer agents will enable treatment strategies that mitigate this risk.
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Srisuwananukorn, Andrew, Rasha Raslan, Xu Zhang, Binal N. Shah, Jin Han, Michel Gowhari, Robert E. Molokie, Victor R. Gordeuk, and Santosh L. Saraf. "Clinical, laboratory, and genetic risk factors for thrombosis in sickle cell disease." Blood Advances 4, no. 9 (May 8, 2020): 1978–86. http://dx.doi.org/10.1182/bloodadvances.2019001384.

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Abstract Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ0-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ0-genotype patients (P &lt; .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ0 genotype, and higher white blood cell (WBC) counts and Hb (P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD.
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Vera, Rodrigo Hernández, Gemma Vilahur, and Lina Badimon. "Obesity with insulin resistance increase thrombosis in wild-type and bone marrow-transplanted Zucker fatty rats." Thrombosis and Haemostasis 109, no. 02 (2013): 319–27. http://dx.doi.org/10.1160/th12-09-0696.

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SummaryObesity induces metabolic and inflammatory alterations that contribute to the presentation of cardiovascular events. Although obesity is a risk factor for atherosclerosis and vascular disease, its role on thrombosis has not been directly explored. Therefore, we aimed to investigate the mechanisms by which obesity affects thrombosis. Thrombus formation was monitored by real-time intravital microscopy in Zucker Fatty rats (ZF) and lean controls (ZC). Crossed bone marrow (BM) transplants between ZF and ZC were performed. Intravital microscopy showed that ZF had significantly shorter occlusion times (OTs) than ZC, reflecting a three-fold higher thrombotic risk. Transplantation of ZC-BM to ZF recipients significantly reduced thrombosis, reducing their thrombotic risk to one third of that observed in non-transplanted ZF. Wild-type ZF showed increased platelet counts and increased platelet size compared to wild-type ZC and platelet number remained unaltered after transplantation. However, ZF-BM produced a significant increase in platelet size in ZC recipients. Thrombotic risk was found to be inversely correlated with both weight and insulin levels and directly correlated to HOMA-IR, while platelet number and size were directly correlated with weight. Thus, our data shows that obesity with insulin resistance significantly increases thrombosis and that alterations in BM-derived cells significantly contribute to this prothrombotic behaviour. Importantly, the reduction of insulin resistance was associated with reduced thrombotic risk even in the presence of obesity.
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Pósfai, Éva, Imelda Marton, Attila Nemes, and Zita Borbényi. "Thrombotic events and importance of IPSET thrombosis risk evaluation score in essential thrombocythaemia." Orvosi Hetilap 156, no. 14 (April 2015): 558–63. http://dx.doi.org/10.1556/oh.2015.30117.

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Introduction: Thrombo-haemorrhagic complications contribute to both morbidity and mortality in patients with essential thrombocythaemia. Aim: The aim of the authors was to estimate the incidence of thrombotic events and to examine the clinical utility of IPSET thrombosis risk evaluation score against conventional two-categorical (low and high) risk assessment. Method: A retrospective analysis was carried out on 155 patients with essential thrombocythaemia (106 females; median age, 61 years) in a period between 1999 and 2014. Results: The analysis revealed 55 (35.5%) major thrombotic events before and 25 (16.1%) major thrombotic complications after establishment of the haematologic diagnosis. Significant differences were observed in thrombosis-free survival between the different IPSET groups (p = 0.002). Conclusions: The IPSET model was first examined in this cohort of patients with essential thrombocythaemia diagnosed in a single Hungarian haematologic centre. The results suggest that this score may provide more information than the conventional thrombosis risk assessment. Orv. Hetil., 2015, 156(14), 558–563.
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Mishcheniuk, O. Y., O. M. Kostiukevych, L. K. Benkovska, and A. N. Kravchenko. "THE CONTRIBUTION OF CARRIER THE ALLELIC VARIANT G1691A OF THE GENE V OF COAGULATION FACTOR TO THE DEVELOPMENT OF THROMBOTIC COMPLICATIONS DEPENDING ON THE PRESENCE OF CARDIOVASCULAR RISK FACTORS IN INDIVIDUALS WITH SECONDARY LEUKOCYTOSIS, THROMBOCYTOSIS A." Клінічна та профілактична медицина 4, no. 9-10 (October 17, 2019): 61–67. http://dx.doi.org/10.31612/2616-4868.3(9).2019.08.

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Introduction. In addition to the "Classical" Risk Factors (RF) for Arterial and Venous Thrombosis, some authors, as triggers for the development of the latter, refer to reactive changes in Peripheral Blood (PB) counts and markers of Hereditary Thrombophilia. The results of most studies indicate that the "Classical" Risk Factors (RF) for Vascular Thrombotic Episodes are strong triggers of their development, the presence of which eliminates the Pro-thrombogenic potential of carrier of the Hereditary Thrombophilia and reactive changes in Peripheral Blood (PB) (RChPB). However, to date, there is no data regarding the assessment of contribution of the Leiden Mutation in the cohort with both reactive changes in Peripheral Blood (PB) and Risk Factors (RF) for Thrombotic Complications (ThC). Results. In patients with reactive changes in the Peripheral Blood (PB), the Leiden Mutation occurs in 5,92% of cases (9 carriers). In individuals with Thrombotic Complications (ThC), the Allele G1691A of the Proaccelerin Gene is determined more often than in a cohort without them (5 out of 31 vs 4 out of 121; p=0,030). In the general cohort of individuals with reactive changes in Peripheral Blood (PB), carriage of the Leiden Mutation increased the risk of Thrombotic Complications (ThC) by 3,05 times (Relative Risk (RR) = 3,05; 95% Confidence Interval (CI) = 1,54-6,03). In patients without Risk Factors (RF) and people under 60 years of age, Thrombosis occurred more often with the Nucleotide Variant of Allele G1691A of the Gene V of Coagulation Factor than with the Allele of wild-type (3 out of 6 vs 4 out of 75; p=0,007 and 4 out of 6 vs 8 out of 107; p=0,010, respectively). The probability of developing of Thrombosis with carriage the Allele G1691A of the Proaccelerin Gene in patients with Thrombotic Complications (ThC) without Risk Factors (RF) and in younger patients was 10,57 (95% Confidence Interval (CI) = 2,60-42,87) and 16,83 times (95% Confidence Interval =3,43-82,41), respectively. The risk of Thrombotic events in people without Risk Factors (RF) younger than 60 years is 16,75 times (Relative Risk (RR) = 16,75; 95% Confidence Interval (CI) = 3,44-81,50). However, the frequency and risk of Thrombosis did not increase in individuals with Risk Factors (RF), in patients over 60 years of age or in a cohort with Risk Factors over 60 years of age. Conclusion. Carriage the Allele G1691A of the Gene V of Coagulation Factor in patients with reactive Thrombocytosis, Leukocytosis and Secondary Polycythemia increases the risk of Thrombosis primarily due to patients without Risk Factors (RF) younger than 60 years.
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Alabyad, Darwish, Srikant Rangaraju, Michael Liu, Rajeel Imran, Christine L. Kempton, Milad Sharifpour, Sara C. Auld, et al. "Validation of an admission coagulation panel for risk stratification of COVID-19 patients." PLOS ONE 16, no. 3 (March 19, 2021): e0248230. http://dx.doi.org/10.1371/journal.pone.0248230.

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Background There is limited data on the markers of coagulation and hemostatic activation (MOCHA) profile in Coronavirus disease 2019 (COVID-19) and its ability to identify COVID-19 patients at risk for thrombotic events and other complications. Methods Hospitalized patients with confirmed SARS-COV-2 from four Atlanta hospitals were included in this observational cohort study and underwent admission testing of MOCHA parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer). Clinical outcomes included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, access line thrombosis, ICU admission, intubation and mortality. Main results Of 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American), 45 (16%) had a thrombotic endpoint. Each MOCHA parameter was independently associated with a thrombotic event (p<0.05) and ≥ 2 abnormalities was associated with thrombotic endpoints (OR 3.3, 95% CI 1.2–8.8) as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5–6.6) and ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6–7.9). However, only ≥ 2 MOCHA abnormalities were associated with ICU admission (OR 3.0, 95% CI 1.7–5.2) and intubation (OR 3.2, 95% CI 1.6–6.4). MOCHA and D-dimer cutoffs were not associated with mortality. MOCHA with <2 abnormalities (26% of the cohort) had 89% sensitivity and 93% negative predictive value for a thrombotic endpoint. Conclusions An admission MOCHA profile is useful to risk-stratify COVID-19 patients for thrombotic complications and more effective than isolated d-dimer for predicting risk of ICU admission and intubation.
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Cattaneo, Marco. "Hyperhomocysteinemia, Atherosclerosis and Thrombosis." Thrombosis and Haemostasis 81, no. 02 (1999): 165–76. http://dx.doi.org/10.1055/s-0037-1614438.

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SummaryHigh plasma levels of homocysteine are the results of the interplay between congenital and environmental factors. In the last two decades, a growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor of thromboembolic diseases. Case-control and cross-sectional studies clearly indicated that mild-to-moderate hyperhomocysteinemia is associated with heightened risk of both arterial and venous thrombosis. On the other hand, prospective studies did not unequivocally show that hyperhomocysteinemia is associated with a high thrombotic risk. Therefore, additional studies are needed to define whether hyperhomocysteinemia is a risk factor for thrombosis, especially of the venous circulation. Among these, prospective cohort studies will clarify better the temporal relationship between high homocysteine levels and the thrombotic event. Most importantly, however, randomized, placebo-controlled, double-blind trials of the effects of homocysteine-lowering vitamins on the thrombotic risk are urgently needed. Not only will they help in defining whether the relationship between hyperhomocysteinemia and thrombosis is causal, they will also have a potential dramatic impact in the prevention of thromboembolic events.
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Franchini, Massimo. "Thrombotic complications in patients with hereditary bleeding disorders." Thrombosis and Haemostasis 92, no. 08 (2004): 298–304. http://dx.doi.org/10.1160/th04-03-0148.

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SummaryThromboses in patients with hereditary bleeding disorders are uncommon. However, in some cases, the co-existence of prothrombotic risk factors may increase the likelihood of developing thrombotic complications in such patients. This review summarizes the cases of thrombosis reported in the literature and analyzes the most important risk factors for thrombosis in patients with a congenital bleeding tendency. In particular we focus on central venous catheter (CVC)-associated thrombosis, on the thrombotic complications of coagulation factor concentrate therapy and on the presence of prothrom-botic gene mutations. Data were identified by searches of the published literature, including PubMed, references from reviews and abstracts from the most important meetings on this topic. In conclusion, there is increasing evidence that thrombotic complications in patients with hereditary bleeding disorders have a multifactorial pathogenesis, depending on exogenous (coagulation factor replacement therapy, CVC, HIV infection) and/or endogenous (prothrombotic gene mutations) risk factors.
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DeRoo, Scott, K. Barry Deatrick, and Peter Henke. "The vessel wall: A forgotten player in post thrombotic syndrome." Thrombosis and Haemostasis 104, no. 10 (2010): 681–92. http://dx.doi.org/10.1160/th10-03-0183.

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SummaryMuch research in venous thrombotic diseases focuses on the acute thrombotic process such as anticoagulation and risk factors. Deep-vein thrombosis directly leads to post thrombotic syndrome, and this can cause significant patient disability. Little research has focused on the vein wall injury response to the thrombotic inflammatory insult. Herein, we review what is currently known about this process with emphasis on the matrix, mediators, and vascular medial smooth muscle response after thrombotic injury. Translational therapies and potential future agents are reviewed.
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Cortelazzo, S., P. Viero, G. Finazzi, A. D'Emilio, F. Rodeghiero, and T. Barbui. "Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia." Journal of Clinical Oncology 8, no. 3 (March 1990): 556–62. http://dx.doi.org/10.1200/jco.1990.8.3.556.

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The purpose of this study was to determine which factors were associated with an increased risk of thrombo-hemorrhagic complications in a historical cohort of 100 consecutive and unselected patients with essential thrombocythemia (ET) in whom busulfan treatment was given when platelets were more than 1,000 x 10(9)/L and/or a major thrombotic or hemorrhagic event occurred. The incidence of major hemorrhagic complications was very low (0.33%/person-time at risk [pt-yr]) in comparison with that of thrombotic episodes (6.6%/pt-yr). In an adequate and appropriate control historical group of 200 patients, no severe hemorrhages were recorded and the incidence of thrombotic events was 1.2% pt-yr. Thus, the analysis of risk factors was restricted to this latter group of events. Age, a previous thrombotic event, and long duration of thrombocytosis were identified as major risk factors for thrombosis, while smoking, diabetes mellitus, hyperlipidemia, and hypertension did not influence the rate of thrombotic episodes.
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Zapletal, Ondrej, Jan Blatny, and Eva Janousova. "Inherited Pro-Thrombotic Risk Factors in Children of South Moravia Region, Czech Republic." Blood 120, no. 21 (November 16, 2012): 5136. http://dx.doi.org/10.1182/blood.v120.21.5136.5136.

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Abstract Abstract 5136 Introduction: Pro-thrombotic risk factors are associated with increased risk of thrombosis. Some of them are inherited, but clinical manifestation of thrombosis in childhood is rare. It is most likely to appear in the adulthood. When leading to thrombosis during childhood, risk factors must be either very strong (e. g. homozygous deficiency of natural coagulation inhibitors), or must act together with other, usually acquired factors. Aims: - To analyse data of children referred for thrombophilia screening to Thrombosis Haemostasis centre, Dpt. of Paediatric Haematology University Hospital Brno, Czech Republic in years 2005–09. - To specify the characteristics of that cohort and identify the reasons for referral. -To determine prevalence of respective risk factors (RF) in children within study cohort. -To analyse possible correlation between related RF findings (ProC Global and FV Leiden, Protein C, Protein S; homocystein and MTHFR C677T polymorphism). Methods: We have collected data of all consecutive children aged from 0 to 18 years referred to our out-patient clinic for assessment of inherited thrombophilia in years 2005–2009 for any reason. Data recorded for each patient were as follows: age, gender, reason for assessment, thrombotic event and its type (if applicable) and vascular anomalies. Laboratory examinations done: FV Leiden mutation, Prothrombin gene mutation G20210A, MTHFR C677T polymorphism, protein C, protein S and Antithrombin levels, coagulation activity of F VIII, ProC Global test, homocystein and lipoprotein (a) level. Data were statistically analyzed to reach the aims of the study. Results: Data of 849 Caucasian children aged 0–18 years were available for analysis, 475 girls (55. 9 %) and 374 boys (44. 1 %). Median age was 11 years at the time of referral, boys 10 years, girls 13 years. Reasons for thrombophilia screening were as follows: family history of thrombosis/thrombophilia (70. 6 %), vascular anomaly (10. 8 %), thrombotic event (8 %) and others (10. 6 %). Thrombophilia screening was in more than 70 % of children performed before 15 years of age. Thrombotic event has been recorded in 79 patients (9. 3 %), both arterial (37. 6 %) and venous (63. 3 %). Adolescent patients had significantly more thrombotic events than younger children. Most of them were venous thromboses. Ischemic strokes and other arterial events were relatively more frequent in younger children. Frequency of “positive” laboratory findings in the studied cohort were as follows: MTHFR 60. 3 %, positive ProC Global test findings 58. 1 %, FV Leiden (heterozygous)37 %, hyperlipoproteinemia (a) 28. 5 %, protein S deficiency 11. 3 %, high FVIII activity 9. 4 %, Prothrombin gene mutation (heterozygous) 7. 7 %, Antithrombin deficiency 2. 7 %, elevation of homocystein 1. 6 % and protein C deficiency 1 %. Findings have confirmed high sensitivity of ProC Global test to the pathology in protein C pathway, particularly to FV Leiden mutation (sensitivity 98. 4 %). There was no statistically significant relation between homocystein level and MTHFR polymorphism status. Prevalence of RF in study cohort was found to be similar to the literature data. Deficiencies of natural coagulation inhibitors (AT, PC and PS) were rare, pro-thrombotic mutations were more frequent. Data suggest, that role of inherited pro-thrombotic risk factors in the development of thrombotic event in children is not the major one. It is very likely, that more potent risk factors, often acquired ones, are often important for development of thrombotic event during childhood. Conclusions: In our centre, we assessed proximately 170 children referred for thrombophilia screening per year. The incidence is thus 8 children per 10000. During 2005–09the main reason for referral was positive family history, but children were often referred in younger age, than recommended. The evidence available to date suggests that it is neither necessary nor useful to examine asymptomatic children before they reach puberty. Finding of inherited thrombophilia, and thus possibility to use measures preventing eventual thrombotic event, are more important in adolescence and adulthood rather than in younger age. In children with thrombotic event, however, it is recommended to screen for inherited risks. Diagnosis and treatment of thrombotic event in children requires a specialised care and relevant expertise of the Paediatric Thrombosis Haemostasis centre. Disclosures: No relevant conflicts of interest to declare.
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Lugacheva, Yu G., I. V. Kulagina, I. A. Kovalev, Ye V. Krivoschekov, O. S. Yanulevich, and T. E. Suslova. "Risk factors of thrombotic complications in patients with single functional ventricle." Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) 64, no. 2 (May 15, 2019): 68–74. http://dx.doi.org/10.21508/1027-4065-2019-64-2-68-74.

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Objective: to analyze the parameters of the hemostasis system and the results of molecular genetic testing in patients with a single functional ventricle. The study included 102 patients. All the patients underwent a staged surgical hemodynamic correction of a single functional ventricle. The authors performed a retrospective analysis of patient records in order to identify the episodes of thrombosis. The incidence of thrombotic complications at different stages of hemodynamic correction in the examined patients with a single functional ventricle was 12.7%. The indicators of plasma link hemostasis in the observed patients have been characterized by a balance of hemostatic reactions in the group of children with thrombosis and without. The results of a molecular genetic study demonstrated that the carrier of the heterozygous genotype of 20210GA factor II gene in patients with a single functional ventricle increased the risk of thrombotic complications 16 times (15.4% in patients with thrombosis versus 1.1% in the group without thrombosis; odds ratio 16.0; 95% confidence interval 1.34–191.24; p=0.028). All patients with thrombosis in the history revealed a homozygous condition according to variant 10976GG factor VII gene (p=0.017). Conclusion: molecular genetic analysis of polymorphic variants of the hemostatic system in patients with a single functional ventricle is required to predict the risk, timely prevention and correction of thrombotic complications during the surgical treatment of congenital heart disease.
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Capecchi, Marco, Alessandro Ciavarella, Andrea Artoni, Maria Abbattista, and Ida Martinelli. "Thrombotic Complications in Patients with Immune-Mediated Hemolysis." Journal of Clinical Medicine 10, no. 8 (April 18, 2021): 1764. http://dx.doi.org/10.3390/jcm10081764.

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Autoimmune hemolytic anemias are rare and heterogeneous disorders characterized by hemolysis, which is a well-recognized risk factor for thrombosis. The most common immune-mediated anemias are represented by autoimmune hemolytic anemia and paroxysmal nocturnal hemoglobinuria, both associated with a high rate of thrombosis. Multiple pathophysiological mechanisms for thrombosis have been proposed, involving hemolysis itself and additional effects of the immune system. Despite the increasing awareness of the thrombotic risk in these conditions, evidence-based guidance on prevention and management of thrombotic events is lacking. We herein report available evidence on epidemiological data on thrombosis and thrombophilia in immune-mediated hemolysis, together with possible underlying pathophysiological mechanisms. In addition, we summarize current recommendations for treatment of thrombosis in immune-mediated hemolysis. In particular, we address the issue of thrombotic complications treatment and prophylaxis by proposing a therapeutic algorithm, focusing on specific situations such as splenectomy and pregnancy.
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LINDQVIST, PELLE, BJÖRN DAHLBÄCK, and KAREL MARŜÁL. "Thrombotic Risk During Pregnancy." Obstetrics & Gynecology 94, no. 4 (October 1999): 595–99. http://dx.doi.org/10.1097/00006250-199910000-00021.

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