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Inhibitors of Factor Xa

  • Chapter
Antithrombotics

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 132))

Abstract

Thrombin occupies a central position in thrombus formation and recently has been a target for the development of anticoagulant agents. As is well known, blood coagulation operates as a cascade or multiple enzymatic amplification process. In the classical intrinsic pathway, factor (f) IXa in the presence of fVIIIa, Ca2+ and phospholipid converts fX to fXa, while in the classical extrinsic pathway, fX is activated by fVIIa in the presence of tissue factor. In turn, fXa activates prothrombin to generate thrombin. More recently, the coagulation cascade has been divided into two stages, rather than distinct pathways (CAMERER et al . 1996). A small amount of thrombin is generated in the “initiation stage” by activation of the fVIIa/tissue factor complex. The amount of thrombin generated by the tissue factor pathway is limited by tissue factor pathway inhibitor, but enough thrombin is generated to activate factors V, VIII and XI. Recruitment of these additional factors begins the “augmentation stage” which can provide large amounts of additional thrombin that plays a dominant role in subsequent thrombus formation. In both the classical coagulation cascade and the more current tissue factor dependent stages, fXa plays a pivotal role by controlling activation of prothrombin to thrombin.

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  1. S. Kunitada
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  2. T. Nagahara
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  3. T. Hara
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  1. Drug Development, Parke-Davis Pharmaceutical Research Division, Warner-lambert Company, 2800 Plymouth Road, Ann Arbor, MI, 48105, USA

    Andrew C. G. Uprichard M.D. (Vice President) (Vice President)

  2. Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI, 48105, USA

    Kim P. Gallagher Ph.D.

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Kunitada, S., Nagahara, T., Hara, T. (1999). Inhibitors of Factor Xa. In: Uprichard, A.C.G., Gallagher, K.P. (eds) Antithrombotics. Handbook of Experimental Pharmacology, vol 132. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59942-2_14

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