newer anticoagulants

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Dear Members, The main initiator of blood coagulation in vivo is the tissue factor (TF)-factor VIIa pathway. Tissue factor is a transmembrane protein ubiquitously expressed outside the vasculature, but not normally expressed in an active form within vessels. The exposure of TF on damaged endothelium or to blood that has extravasated into tissue binds TF to factor VIIa. This complex, in turn, activates factors X and IX. Factor Xa along with factor Va forms the prothrombinase complex on activated cell surfaces, which catalyzes the conversion of prothrombin (factor II) to thrombin (factor IIa). Thrombin, in turn, activates upstream clotting factors, primarily factors V, VIII, and XI, resulting in amplification of thrombin generation. The TF-factor VIIa-catalyzed activation of factor Xa is regulated by tissue factor pathway inhibitor (TFPI). Thus after initial activation of factor X to Xa by TF-VIIa, further propagation of the clot is by feedback amplification of thrombin through the intrinsic pathway factors VIII and IX (this provides an explanation of why patients with deficiency of factor VIII or IX—hemophilia A and hemophilia B, respectively—have a severe bleeding disorder). Regards,Dr. Vijaya Chaudhari.JR-3,Dept. of Pharmacology,Government Medical College, Nagpur.