ABSTRACT
Traditionally, the coagulation pathways are divided into the intrinsic or contact pathway and the extrinsic pathway (Fig. 12.1). Activation of these serine protease cascades results in the creation of the tenase and prothrombinase complexes, which form on platelet surface membranes, and the subsequent generation of thrombin (Fig. 12.2), and platelet thrombi (Fig. 12.3). To control these procoagulant cascades, there are a series of natural anticoagulants, including antithrombin, heparin cofactor II, proteins S and C, and tissue factor pathway inhibitor (TFPI). Antithrombin, a serine protease inhibitor, formerly termed antithrombin III, is the major natural anticoagulant that not only inhibits thrombin but also factors Xa, IXa, XIa, XIIa, and kallikrein. Heparin cofactor II also inhibits thrombin. Protein C inactivates factors Va and Villa in reactions catalyzed by protein S. Similarly, there is a natural inhibitor for the extrinsic system, tissue factor pathway inhibitor (TFPI), which is mainly produced by the endothelium, and its release is stimulated by heparin.1
