Coagulation activation-induced fibrinolysis biomarker changes depend on thrombophilic risk factors and their clinical phenotype: an interventional in vivo study

Abstract

BackgroundRecently we have shown alterations in the anticoagulant response to recombinant activated factor VII (rFVIIa)-induced coagulation activation in patients with thrombophilia. ObjectivesHere we extended this in vivo model to study fibrinolysis biomarkers. MethodsThe study population included 56 patients with thrombophilia and a history of venous thromboembolism (VTE+), 38 asymptomatic patients with thrombophilia (VTE-) and 35 healthy controls. Plasma levels of D-dimer, plasmin-2-antiplasmin complex (PAP), and plasminogen activator inhibitor-1 (PAI-1) were monitored over 8 hours after rFVIIa infusion (15 {micro}g/kg) along with thrombin activation markers and activated protein C (APC). ResultsIn all cohorts, PAP increased (PA carriers or patients with unexplained familial thrombophilia. ConclusionrFVIIa-induced thrombin formation is associated with fibrinolysis parameter changes outlasting the concomitant anticoagulant response. Both correlate with thrombosis history in FVL and might help to explain its variable clinical expressivity. EssentialsO_LIImpairment of fibrinolysis might result in increased risk of thrombosis. C_LIO_LIWe studied fibrinolytic biomarkers after coagulation activation by recombinant factor VIIa. C_LIO_LIHereby induced alterations in fibrinolytic biomarkers outlast concomitant anticoagulant changes. C_LIO_LIFactor V Leiden carriers with or without thrombosis showed distinct fibrinolytic changes. C_LI