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

ABSTRACT

INTRODUCTION: Oral 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 METHODS: Plasma fibrin clot permeability (K(s)) and efficiency of lysis, reflected by clot lysis time (CLT) and the rate of D-dimer release from clots (D-D(rate)) 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. RESULTS: OC discontinuation in FVL(+/-) women resulted in shortened CLT (-9%), and increased K(s) (+4%) and D-D(rate) (+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-D(max), along with lower D-D(rate) and K(s). Multiple regression analysis adjusted for fibrinogen and age, showed that PAI-1 antigen and TAFI activity independently predicted CLT in FVL(+/-) women on OC. CONCLUSION: FVL(+/-) 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.