Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis\ud

Background: Inherited thrombophilia is only weakly associated with recurrence in patients with a first venous thrombosis (VT). In spite of this, thrombophilia testing is often performed in these patients. Positive results may influence patient management such as prolonged anticoagulant treatment or intensified prophylaxis in high-risk situations. Objective: To investigate whether thrombophilia testing reduces the risk of recurrent VT by virtue of these management alterations. Methods: From a large case–control study of patients (MEGA study), aged 18–70 years, with a first VT between 1999 and 2004, we selected 197 patients who had had a recurrence during follow-up. We compared the incidence of thrombophilia testing to that of a control cohort of 324 patients. We calculated the odds ratio (OR) for recurrent thrombosis in tested vs. non-tested patients. Only patients who were tested before recurrence were regarded as tested. All first and recurrent thrombotic events were objectively confirmed. Results: Thrombophilia tests were performed in 35% of cases and in 30% of controls. The OR for recurrence was 1.2 [95% confidence interval (CI) 0.9–1.8] for tested vs. non-tested patients. After correction for age, sex, family history, geographic region, presence of clinical risk factors, and year of first VT, the OR remained unchanged. Discussion: Thrombophilia testing in patients with a first VT does not reduce the incidence of recurrence in clinical practice.\u

More on 'universal' versus 'selected' screening for thrombophilia: the hidden costs of false-positive diagnosis - response to Favaloro and Keeling

Abstract not availabl

Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study

Combined oral contraceptives,oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women.The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47).Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users

Antiphosphatidylserine antibody as a cause of multiple dural venous sinus thromboses and ST-elevation myocardial infarction

Objective: Rare disease Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antibodies directed against phos-pholipids on plasma membranes. Through unclear mechanisms, APS confers hypercoagulability. APS may cause recurrent thromboses in the arterial and venous vasculature. We report a case of primary APS resulting in cerebral venous thrombosis and ST-elevation myocardial infarction (STEMI) for which only antiphosphatidylserine (aPS) IgM antibody was positive after extensive investigation. Case Report: A 48-year-old male was admitted after a witnessed generalized seizure with subsequent confusion. Imaging demonstrated thrombosis of multiple central nervous system (CNS) sinuses, including the superior sagittal sinus and bilateral transverse sinuses. The patient was heparinized with aggressive hydration, which proved inadequate, prompting endovascular thrombectomy. Three months later, despite anticoagulation therapy, the patient developed a STEMI when International Normalized Ratio (INR) was 1.8. Echocardiogram (ECHO) and PAN CT scan were normal. Initial coagulation studies demonstrated normal anticardiolipin antibody, prothrombin time, partial thromboplastin time, and platelet count. Outpatient coagulation studies revealed normal an-tithrombin III, protein C/S, hemoglobin electrophoresis, homocysteine, anti-b2 glycoprotein 1 antibodies, and D-Dimer. Factor V Leiden, JAK 2 mutation, prothrombin gene mutation, and tests for paroxysmal nocturnal he-moglobinuria (PNH) were negative. A positive phosphatidylserine IgM was detected. The patient was continued on warfarin (10 mg daily) with a target INR of 3.0–3.5 and clopidogrel (75 mg daily). Conclusions: Despite extensive investigation, this patient only showed evidence of elevated aPS IgM antibodies, likely contributing to his CNS venous sinus thromboses and STEMI. It is important to screen for antiphosphatidylserine antibodies in cases of unprovoked thrombosis when standard thrombophilia analysis is unrevealing. This will assist in identifying pathogenicity and help prevent recurrence of subsequent thromboses. © Am J Case Rep, 2018

Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period

Some women are at risk of forming blood clots in a deep vein during pregnancy, after a caesarean birth, or during the first few weeks after childbirth. If part of the clot breaks off and lodges in a blood vessel in the lungs, it can be life-threatening. Preventive treatments include blood-thinning drugs to prevent clots, support stockings, and exercise soon after the birth to keep circulation moving. However, some drugs might cause problems such as increased blood loss after the birth. Drugs used include heparin, low molecular weight heparin and aspirin. We included 16 randomised controlled studies in the review but only 13 trials with 1774 women contributed data for the outcomes of interest. We did not find enough evidence from the trials to be sure about the effects of these different preventive treatments.This means there is not enough evidence to show which are the best ways to prevent deep vein thrombosis (DVT) during or following pregnancy, or after a caesarean birth

Thrombophilia Impact on Treatment Decisions, Subsequent Venous or Arterial Thrombosis and Pregnancy-Related Morbidity: A Retrospective Single-Center Cohort Study.

(1) Background: Thrombophilia testing utility has remained controversial since its clinical introduction, because data on its influence on treatment decisions are limited. (2) Methods: We conducted a single-center retrospective cohort study of 3550 unselected patients referred for thrombophilia consultation at the Bern University Hospital in Switzerland from January 2010 to October 2020. We studied the influence of thrombophilia testing results on treatment decisions and evaluated the association between thrombophilia and thromboembolic and pregnancy-related morbidity events after testing up to 03/2021. (3) Results: In 1192/3550 patients (34%), at least one case of thrombophilia was found and 366 (10%) had high-risk thrombophilia. A total of 211/3550 (6%) work-ups (111/826 (13%) with low-risk thrombophilia and 100/366 (27%) with high-risk thrombophilia) led to an appropriate decision to extend or initiate anticoagulation, and 189 (5%) negative results led to the withholding of anticoagulation therapy inappropriately. A total of 2492 patients (69%) were followed up for >30 days, with a median follow-up of 49 months (range, 1-183 months). Patients with high-risk thrombophilia had a higher risk of subsequent venous thromboembolic events and pregnancy-related morbidity compared to those without thrombophilia. (4) Conclusions: Our study demonstrated the limited usefulness of thrombophilia work-up in clinical decision-making. High-risk thrombophilia was associated with subsequent venous thromboembolism and pregnancy-related morbidity

Significant correlation of angiotensin converting enzyme and glycoprotein IIIa genes polymorphisms with unexplained recurrent pregnancy loss in north of Iran

Background: Spontaneous abortion is considered as the most complex problem during pregnancy. Thrombophilia is resumed as a cause of recurrent pregnancy loss (RPL). Glycoprotein IIIa (GPIIIa) gene is involved in thrombosis and abortion. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II and is involved in thrombosis. The most common polymorphism in this gene is the insertion/deletion (I/D). Objective: In this study, we analyzed the association between ACE I/D and GPIIIa c.98C >T polymorphisms in women with unexplained RPL from the north of Iran. Materials and Methods: Sample population consisted of 100 women with unexplained RPL and 100 controls. The ACE I/D and GPIIIa c.98C>T polymorphisms were genotyped by TETRA-ARMS PCR. The association between genotypes frequency and RPL were analyzed using χP2P and exact fisher tests. Associated risk with double genotype combinations was also investigated by binary logistic regression. Results: There was significant association between ACE DD genotype and RPL (OR=2.04; 95% CI=0.94-4.44; p=0.036). ACE D Allele was also significantly associated with the RPL (OR=1.59; 95% CI=1.05-2.41; p=0.013). No significant association was observed between GPIIIa c.98C>T polymorphism and RPL. Conclusion: ACE I/D polymorphism may probably be a prognostic factor in female family members of women with the history of recurrent abortion. © 2016, Research and Clinical Center for Infertitlity. All Rights Reserved

Extensive Pulmonary Embolism in late pregnancy associated with Anticardiolipin Antibodies

The leading cause of morbidity and mortality during pregnancy and the puerperium is venous thromboembolism. Though uncommon, the risk is five times higher in a pregnant woman than in a non-pregnant woman of similar age.1,2 In pregnancy, all three underlying factors for venous thrombosis are present: hypercoagulability, venous stasis and vascular damage (Virchow's triad). Of these, the most constant predisposing factor is increasing venous stasis due to the pressure of the gravid uterus on the pelvic vasculature. In addition the presence of a thrombophilia, (congenital or acquired) will increase this risk substantially. During pregnancy hypercoagulability is a physiological preparation for the haemostatic challenge of delivery. There are increases in procoagulant factors, such as von Willebrand factor, factor VIII, factor V, and fibrinogen together with an acquired resistance to activated protein C and a reduction in protein S. Increases in plasminogen activator inhibitors impair fibrinolysis. The third factor of this triad, vascular damage, is a possible complication of trophoblastic invasion of the uterine spiral arterioles or of delivery.peer-reviewe