The Plasma Coagulation Cascade: Potential Targets for Novel Anticoagulants in Major Lower Limb Surgery

Elizabeth      O. Johnson; Maria      Konstandi; George      C. Babis; Mara      Piagkou; Panayotis      N. Soucacos

Abstract

Strategies for prevention of venous thromboembolism in orthopaedic patients undergoing major lower limb surgery include pharmacological prophylaxis. Over the last three decades, the search for new safe and effective approaches for the prevention of venous thromboembolism in these patients has continued. Increased understanding of the haemostatic process has led to a clearer appreciation of the mechanisms of action of antithrombotic drugs already in use as well as the identification of new targets for novel drug development. As a result, the development of new anticoagulants has advanced rapidly over recent years. The molecular targets of several novel anticoagulants, and their effectiveness in early Phase II and Phase III trials are reviewed.

Keywords: Anticoagulants, venous thromboembolism, pulmonary embolism, haemostasis, thromboprophylaxis, antithrombotic drugs, prophylaxis, fibrinolytic mechanism, intravascular thrombosis, ticlopidine, vasoconstriction, Von Willebrand factor, serotonin, prostaglandins, factor X, antithrombin, auto-regulation, tissue factor pathway inhibitor (TFPI), Heparin, penta-saccharide, Thrombomodulin, tissue-type plasminogen, urokinase-type plasminogen activator (uPA), plasmin (via alpha2-antiplasmin), hemorhelogy, vascular bifurcations, atheromatous, Virchow's triad, sequelae, Varicose veins, pulmonary emboli, fatal pulmonary emboli, (hirudin), specific factor Xa inhibitors (fondaparinux), oral warfarin sodium, haematophagous organisms, Tifacogin, FVIIai, NAPc2, Fondaparinux, Idraparinux, DX9065a, LY 517717, Razaxaban, Rivaroxaban (BAY59-7939), SSR12517E, SSR123781A, Otamixaben, Apixaban, Ximelagatran, Dabigatran etexilate