Abstract
The use of hormonal contraception is associated with an increased risk of venous thromboembolism (VTE). Unfavorably altered fibrin clot phenotype has been reported in patients following unprovoked VTE who are at risk of recurrences. It remains unknown whether fibrin clot characteristics in women with contraception-related VTE differ from those in unprovoked VTE. We studied three age-matched groups of women: (1) after contraception-related VTE, (n = 48) (2) after unprovoked VTE (n = 48), and (3) controls (n = 48). Plasma fibrin clot permeability (Ks), turbidity of clot formation, efficiency of fibrinolysis using clot lysis time (CLT), and rate of increase in D-dimer during lytic clot degradation (D-Drate), along with thrombin generation and fibrinolysis proteins were determined. Compared with the controls, patients following contraception-related and unprovoked VTE formed faster (lag phase, -8.8% and -20.4%, respectively) fibrin clots of increased density (Ks, -8.6% and -13.4%, respectively) displaying impaired fibrinolysis as evidenced by prolonged CLT (+11.5% and +14.5%, respectively) and lower D-Drate (-7.1% and -5.6%, respectively), accompanied with higher plasminogen activator inhibitor-1 (PAI-1, +14.9% and +17.8%, respectively) and elevated peak thrombin generation (+63.8% and +36.7%, respectively). The only differences between women with unprovoked and contraception-related VTE were lower fibrin mass in plasma clots (D-Dmax, -8.6%), along with higher peak thrombin generation (+19.8%) and shorter lag phase (-6.8%) in the latter group. This study suggests that women after contraception-related VTE, similar to those following unprovoked VTE, have denser fibrin clot formation and impaired clot lysis. These findings might imply higher risk of VTE recurrence in women with the prothrombotic clot phenotype.
Highlights
Venous thromboembolism (VTE), including both pulmonary embolism (PE) and deep vein thrombosis (DVT), is a rare complication of combined hormonal contraceptives (CHCs) with the annual incidence of 7-12 events per 10,000 women [1, 2]
The current study shows that women who experienced the first contraception-related episode of VTE, compared with controls, demonstrate increased thrombin generation and prothrombotic plasma fibrin clot phenotype, evidenced by faster formation of denser fiber networks and reduced clot susceptibility to lysis
We found no differences in most prothrombotic variables between women following VTE related to hormonal contraception and those after unprovoked VTE, apart from slightly lower maximum D-dimer levels measured during lytic clot degradation and higher peak thrombin generation and longer lag phase in the first group
Summary
Venous thromboembolism (VTE), including both pulmonary embolism (PE) and deep vein thrombosis (DVT), is a rare complication of combined hormonal contraceptives (CHCs) with the annual incidence of 7-12 events per 10,000 women [1, 2]. The risk of VTE may vary depending on estrogen dose, formula, and types of progestogens [3, 4]. Both hormones lead to a procoagulant risk profile associated with higher plasma D-dimer, tissue plasminogen activator (tPA), and coagulation factors II, VII, and X [5, 6]. CHCs diminish levels of the natural anticoagulants such as protein C and antithrombin and may lead to the resistance to activated protein C [4]. Altered fibrin clot properties have been shown to increase the risk of unprovoked VTE and recurrent PE as well as DVT [8,9,10]
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