Anticoagulant Therapy Part 1: Heparin

The Thrombotic Process and Its Complications Thrombi are composed of fibrin and blood cells and may form in any part of the cardiovascular system, including the veins, arteries, heart, and microcirculation. Because the relative proportions of cells and fibrin depend on hemodynamic factors, they differ in arterial and venous thrombi.12 Arterial thrombi form under conditions of high flow and are composed mainly of platelet aggregates bound together by thin fibrin strands.3-5 In contrast, venous thrombi form in areas of stasis and are composed mainly of red cells with a large amount of interspersed fibrin and relatively few platelets. Thrombi that form in regions of slow to moderate flow are composed of a mixture of red cells, platelets, and fibrin and are known as mixed platelet-fibrin thrombi.45 When a platelet-rich arterial thrombus becomes occlusive, stasis occurs and the thrombus can propagate as a red stasis thrombus. As thrombi age, they undergo progressive structural changes.6 Leukocytes are attracted by chemotactic factors released from aggregated platelets2 or proteolytic fragments of plasma proteins and become incorporated into the thrombi. The aggregated platelets swell and disintegrate and are gradually replaced by fibrin. Eventually the fibrin clot is digested by fibrinolytic enzymes released from endothelial cells and leukocytes or becomes organized by connective tissue. The complications of thrombosis are caused by the effects of local obstruction of the vessel, distant embolization of thrombotic material, or, less commonly, consumption of hemostatic elements by their participation in the thrombotic process. Arterial thrombi usually form either in regions of disturbed flow or at sites of rupture of atherosclerotic plaques. Plaque rupture exposes the thrombogenic subendothelium to platelets and coagulation proteins; it may also cause further narrowing due to hemorrhage into the plaque.7-1" Arterial thrombi may remain partially occlusive or they may embolize. Nonocclusive thrombi may become incorporated into the vessel wall and can accelerate the growth of atherosclerotic plaques.9"1213 When flow is slow, the degree of stenosis severe, or the thrombogenic stimulus intense, the thrombi may become totally occlusive. Arterial thrombi usually occur in association with preexisting vascular