our results showed that estrogen plus progestin did not increase the risk of thrombosis to a larger degree among older or obese women, age and body mass index were the primary determinants of increased absolute risk of thrombosis," said Mary Cushman, M.D., of the University of Vermont, Burlington, Vt., lead investigator of this study. "Researchers have known that the use of hormones both birth control pills and estrogen increase a woman's risk of venous thrombosis, however in this study, we were able to identify the compounding risk factors that put women at an even greater risk."
In a nested case control study on venous thrombosis in this E+P trial, the WHI researchers reported the associations of genetic variants with thrombosis risk. They identified 147 women in the WHI study who developed thrombosis, and compared them to 513 controls. Factor V Leiden was associated with thrombosis risk, and appeared to lead to a further increased risk in combination with E+P; the prevalence of Factor V Leiden among cases and controls was 13.8 percent and 4.6 percent, respectively. Compared to women without Factor V Leiden and assigned to placebo, women with Factor V Leiden assigned to E+P had a 6.7-fold increased risk of thrombosis (95 percent CI 3.1 14.5). The prothrombin 20210A variant was not common enough to draw conclusions; prevalences were 3.6 percent and 4.2 percent for E+P and placebo, respectively. Factor V Leiden is characterized by a poor anticoagulant response to activated protein C (APC) and an increased risk of venous thromboembolism. Factor V Leiden, inactivated at a rate approximately ten times slower than normal factor V, increases a woman's risk for venous thrombosis. Prothrombin 20210A is associated with elevated prothrombin levels (plasma protein produced in the liver in the presence of vitamin K and converted into thrombin by the action of various activators in the clotting of blood) and an increased risk for venous thrombosis.
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American Society of Hematology
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