HIT/HITT and alternative anticoagulation: current concepts.

Heparin is a widely used anticoagulant for the treatment and prevention of thromboembolic disorders in medical and surgical patients. Its importance as an anticoagulant has been well established by its effectiveness, rapid onset of action, ease of laboratory monitoring and cost. Heparin is a member of the heterogeneous family of glycosaminoglycans, which range in size from 3000 to 30 000 Da. The non-branching, negatively charged chain structure of heparin consists of repeating disaccharide units. Heparin is an anticoagulant released by mast cells and basophils in the process of clot formation, as well as a drug that is administered to the same effect. Standard unfractioned heparin is usually derived from porcine intestinal mucosa or bovine lung. Heparin plays many roles in human physiology, such as: (i) binding to antithrombin III and increasing the ef®cacy of antithrombin III as an inhibitor of the activation of thrombin and certain clotting factors; (ii) inhibiting platelet formation; (iii) increasing the permeability of vessel walls; (iv) inhibiting the proliferation of vascular smooth muscle cells; and (v) playing a role in the regulation of angiogenesis. In clinical use heparin has numerous activities, but the most important is its anticoagulant property (Table 1). It is also used as a thrombolytic, a fat-clearing anti-atherosclerotic and as a potentially effective anti-in ̄ammatory agent. Heparin inhibits reactions that lead to clotting of blood and formation of ®brin clots both in vitro and in vivo. It acts at multiple sites in the normal coagulation system. It binds to antithrombin III (heparin cofactor), causing a conformational change in the structure of antithrombin III. This conformational change converts antithrombin III from a slowto a fast-acting inhibitor of thrombin activation. The complex has a further inhibitory effect on other clotting factors, such as factors IX, X, XI and XII and kallikrein, and on the conversion of prothrombin to thrombin. 62 Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of ®brinogen to ®brin. Heparin also prevents the formation of a stable ®brin clot by inhibiting the activation of the ®brin-stabilizing factor.