Reports from A.G.G. Turpie et al highlight recent research in coagulation
2009 AUG 3 - (NewsRx.com) -- "Long-available anticoagulants including unfractionated and low-molecular-weight heparins (UFH and LMWHs, respectively) and vitamin K antagonists (VKAs), as well as the more recently introduced synthetic pentasaccharide, fondaparinux, have demonstrated efficacy in preventing thromboembolic events. However, all of them have a number of practical limitations," researchers in Hamilton, Canada report. "UFH, LMWHs, and fondaparinux must be administered parenterally, making them less attractive for long-term prophylaxis, and heparins are associated with immune-mediated thrombocytopenia. Until recently, VKAs such as warfarin were the only approved oral anticoagulants, but they have a narrow therapeutic window and require routine laboratory monitoring of the international normalized ratio. In addition, VKAs have multiple food and drug interactions. scheduled for operation need to stop VKA treatment and may require ''bridging'' anticoagulant therapy with UFH or LMWH before and after surgery. Heparins and VKAs have multiple targets in the coagulation cascade and are indirect inhibitors of thrombin. The various limitations of these anticoagulants have provided the impetus for the development of new drugs for the prevention and treatment of both venous (VTE) and arterial thromboembolism. Such development has focused on small molecules that target a single factor which is part of the final common pathway in the coagulation cascade. Numerous agents that specifically target factor IIa (thrombin) or factor Xa (FXa), are currently in development. Dabigatran, an orally administered direct thrombin inhibitor, was recently launched in Europe and Canada for VTE prevention in patients undergoing elective total hip and knee replacement (THR and TKR, respectively). Another promising group of novel anticoagulants are the direct FXa inhibitors. These bind directly to FXa, inhibiting its procoagulant activity. Proof-of-concept for targeted FXa inhibition was provided by fondaparinux, the parenteral indirect inhibitor. FXa is an ideal target for an anticoagulant because it is positioned at the start of the common pathway of coagulation. Direct FXa inhibitors currently being evaluated in clinical trials are YM150, DU-176b, betrixaban, apixaban, and rivaroxaban. YM150, DU-176b, and betrixaban are at an earlier stage of development than apixaban and rivaroxaban, and are being investigated in phase II studies for VTE prevention in orthopedic surgery. Major orthopedic surgery is often used as a development model because it provides relatively fast validation of efficacy and safety, in an established indication requiring prophylaxis for only 2-5 weeks. Such validation can then provide support for development in other indications," wrote A.G.G. Turpie and colleagues. The researchers concluded: "Apixaban and rivaroxaban are the most advanced in development, and rivaroxaban was recently approved in Canada and the EU for preventing VTE in patients undergoing elective THR or TKR.." Turpie and colleagues published their study in Thrombosis and Haemostasis (New approaches to anticoagulation: Oral factor Xa inhibitors. Thrombosis and Haemostasis, 2009;101(6):16-20). For additional information, contact A.G.G. Turpie, Hamilton Health Science Corp., Dept. of Medical, Hamilton Health Science General Division, 237 Barton St. E, Hamilton, ON L8L 2X2, Canada. Publisher contact information for the journal Thrombosis and Haemostasis is: Schattauer GmbH-Verlag Medizin Naturwissenschaften, Holderlinstrasse 3, D-70174 Stuttgart, Germany. Keywords: Canada, Hamilton, Coagulation, Angiology, Anticoagulant, Coumarin and Indandione Derivative, Drug Development, Haemostasis, Hematology, Rodenticide, Surgery, Therapy, Thrombocytopenia, Thromboembolism, Thrombosis, Treatment, Warfarin. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
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