ORIGINAL ARTICLESEnhancement of fibrinolytic potential in vitro by anticoagulant drugs targeting activated factor X, but not by those inhibiting thrombin or tissue factorLisman, Tona,b; Adelmeijer, Jellea,b; Nieuwenhuis, H Karela; de Groot, Philip Ga,bAuthor Information aThrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre, Utrecht and bInstitute of Biomembranes, Utrecht University, Utrecht, The Netherlands. Sponsorship: This study was sponsored in part by an unrestricted educational grant from Novo Nordisk. Correspondence and requests for reprints to Ton Lisman, Thrombosis and Haemostasis Laboratory, Department of Haematology, G.03.647, University Medical Centre, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Tel: +31 30 2506513; fax: +31 30 2511893; e-mail: email@example.com Received 21 January 2003 Revised 4 March 2003 Accepted 10 March 2003 Blood Coagulation & Fibrinolysis: September 2003 - Volume 14 - Issue 6 - p 557-562 Buy Abstract Tissue factor-induced coagulation leads to the generation of a small amount of thrombin, resulting in the formation of a fibrin clot. After clot formation, thrombin generation continues resulting in the activation of thrombin activatable fibrinolysis inhibitor, leading to downregulation of fibrinolysis. In this study, the effect of anticoagulant drugs targeting different steps in the coagulation cascade on clot formation and subsequent breakdown was investigated using a plasma-based clot lysis assay. All drugs tested significantly delayed clot formation; only those drugs targeting activated factor X (FXa) (tissue factor pathway inhibitor, fondaparinux, and low molecular weight heparin) accelerated fibrinolysis. Anticoagulant drugs targeting tissue factor (active site-inactivated recombinant activated factor VII) or thrombin (hirudin and d-phenylalanyl-l-prolyl-l-arginyl chloromethyl ketone) did not affect clot lysis time. In accordance with these findings, it was shown that total thrombin generation, as quantified by the endogenous thrombin potential, was only affected by anticoagulant drugs targeting FXa when all drugs were used in a concentration resulting in doubling of clotting time. Induction of hyperfibrinolysis by anticoagulant drugs directed against FXa might be beneficial as increased clot breakdown might facilitate thrombolysis or prevent re-occlusion. On the other hand, the induction of hyperfibrinolysis by these compounds might increase the risk of bleeding complications. © 2003 Lippincott Williams & Wilkins, Inc.