The term "hypercoagulability" is used to describe patients who are at increased risk for thrombosis because of inherited defects in their anticoagulant pathways or because of various predisposing causes. About one in five patients of European descent who present with venous thromboembolism have a specific genetic defect in their anticoagulant pathway. In these patients, anticoagulant prophylaxis is indicated at times of high risk, such as after surgery. Prolonged anticoagulant therapy may be required in patients with recurrent or life-threatening thromboemboli, but decisions about this are best made on an individual basis. Patients who present with arterial thrombosis usually develop their disease as a complication of atherosclerosis. However, these patients also have a form of hypercoagulability, manifested primarily by high fibrinogen levels and elevated factor VII activity. Evidence increasingly indicates that these and other hemostatic markers may help in the assessment of patients at risk for coronary heart disease.

Hypercoagulability in Venous and Arterial Thrombosis

https://www.nejm.org/doi/pdf/10.1056/NEJMra072753

Acute pulmonary embolism.

Purpose: Venous thromboembolism (VTE) is of particular concern in women receiving tamoxifen in a chemopreventive setting. We investigate the association between acquired and inherited risk factors for VTE in the International Breast Cancer Intervention Study (IBIS-I) trial of tamoxifen prophylaxis for women at increased risk of breast cancer. Methods: We used a nested case-control study design to investigate the role of tamoxifen and acquired risk factors in the risk of developing a VTE. Results: Tamoxifen was associated with a significantly increased risk of developing a major VTE (odds ratio [OR], 2.1; 95% CI, 1.1 to 4.1). Women who had surgery, immobilization, or fracture in the previous month had a greatly increased risk of developing a major VTE (OR, 4.7; 95% CI, 2.2 to 10.1). Prothrombin and factor V Leiden mutations were found exclusively among control women: factor V Leiden in eight of 159 control women (5.0%) and the prothrombin mutation in three control women (1.9%). Thirty-five women with a VTE...

Inherited and Acquired Risk Factors for Venous Thromboembolic Disease Among Women Taking Tamoxifen to Prevent Breast Cancer

MEDLINE searches identified epidemiologic, experimental, and clinical studies on the genetics of cerebrovascular disease and stroke, including the following topics: genetic epidemiology of stroke; genetics of systemic disorders that cause ischemic stroke, including coagulation disorders, connective tissue disorders, vasculopathies, metabolic disorders, and disorders of unknown etiology; and genetics of systemic disorders that cause hemorrhagic stroke. Recent discoveries in stroke genetics involve the genetic basis of monogenic disorders such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and sickle cell disease. Reproducing similar advances in other forms of cerebrovascular disease and stroke will be more difficult because their inheritance is complex, multigenic, and heterogeneous. However, the future is promising with the application of molecular genetic approaches such as linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses as well as the transmission/disequilibrium test--a statistical method for detection of linkage between a marker and a disease-susceptibility locus.

Advances in the genetics of cerebrovascular disease and stroke

INTRODUCTION To evaluate the pregnancy-associated risk of venous thromboembolism and the risk of stillbirth and miscarriage a multicenter, retrospective and controlled study was conducted in women carrying the homozygous factor V Leiden mutation and in an agematched control group of women from the normal population. PATIENTS AND METHODS In 64 homozygous (median age 44 years, range 21-75 years) and in 52 control women from five different centers data on venous thromboembolism and pregnancy outcome were obtained. RESULTS The 64 homozygous women had in total 212 pregnancies, the 52 control women had 118 pregnancies. In homozygous women 65% of pregnancies ended with delivery of a viable infant, 15% with fetal loss (3.3% stillbirth, 12% miscarriage) and 20% by pregnancy termination. In the control women 75% of pregnancies ended with delivery of a viable infant, 12% with fetal loss (1.7% stillbirth, 10% miscarriage) and 13% by pregnancy termination. The differences were statistically not significant. Venous thromboembolism occurred significantly more often in the homozygous women, in 4.2% (9/212) during pregnancy and in 4.7% (10/212) after delivery or pregnancy termination. None of the control women had a thromboembolic episode. CONCLUSION Our data indicate that women with homozygous factor V Leiden have a high probability for a favorable pregnancy outcome. The increased risk for venous thromboembolism during pregnancy and after delivery would favor heparin prophylaxis during and after pregnancy in women homozygous for factor V Leiden.

Pregnancy-associated risk for venous thromboembolism and pregnancy outcome in women homozygous for factor V Leiden.

Risk of thrombosis in patients homozygous for factor V Leiden [letter; comment]

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Risk of thrombosis in patients homozygous for factor V Leiden [letter; comment]