Fibrin clot properties in women heterozygous for factor V Leiden mutation: Effects of oral contraceptives

Abstract

IntroductionOral contraceptives (OC) in the presence of factor V Leiden mutation (FVL) markedly increase the risk of venous thromboembolism (VTE). Little is known about the OC and FVL-related alterations in fibrin clot properties. Subjects and MethodsPlasma fibrin clot permeability (Ks) and efficiency of lysis, reflected by clot lysis time (CLT) and the rate of D-dimer release from clots (D-Drate) induced by recombinant tissue plasminogen activator (tPA) were determined in 25 women with a family history of VTE who were heterozygous for FVL [FVL(+/−) – twice, on third-generation OC and after their discontinuation. Female non-carriers of FVL, matched for demographics, using OC and after their discontinuation served as controls (n=25). All participants had no personal history of VTE. ResultsOC discontinuation in FVL(+/−) women resulted in shortened CLT (−9%), and increased Ks (+4%) and D-Drate (+1.4%; all p<0.01). Alterations in fibrin clot properties were associated with decreased prothrombin fragments 1+2 (F1+2) (−8%), plasminogen activator inhibitor-1 (PAI-1) antigen (−11%), and thrombin activatable fibrinolysis inhibitor (TAFI) activity (−20%; all p<0.01). During OC use FVL(+/−) carriers compared with non-carriers had higher platelet count, activity of PAI-1, TAFI, and tPA, as well as prolonged CLT and higher D-Dmax, along with lower D-Drate and Ks. Multiple regression analysis adjusted for fibrinogen and age, showed that PAI-1 antigen and TAFI activity independently predicted CLT in FVL(+/−) women on OC. ConclusionFVL(+/−) is associated with hypofibrinolysis in apparently healthy women and third-generation OC administration unfavorably alters plasma clot characteristics in female FVL(+/−) carriers with a family history of thrombotic events.