MECHANISMS OF BLOOD COAGULATION
The vascular endothelial cell layer lining blood vessels has an anti-coagulant phenotype, and circulating blood platelets and clotting factors do not normally adhere to it to an appreciable extent. In the setting of vascular injury, the endothelial cell layer rapidly under-goes a series of changes resulting in a more procoagulant pheno-type. Injury exposes reactive subendothelial matrix proteins such as collagen and von Willebrand factor, which results in platelet adher-ence and activation, and secretion and synthesis of vasoconstrictors and platelet-recruiting and activating molecules. Thus, thromboxaneA2 (TXA2) is synthesized from arachidonic acid within plateletsand is a platelet activator and potent vasoconstrictor. Products secreted from platelet granules include adenosine diphosphate(ADP), a powerful inducer of platelet aggregation, and serotonin (5-HT), which stimulates aggregation and vasoconstriction.Activation of platelets results in a conformational change in the αIIbβIIIintegrin (IIb/IIIa) receptor, enabling it to bind fibrinogen,which cross-links adjacent platelets, resulting in aggregation and formation of a platelet plug (Figure 34–1). Simultaneously, the coagulation system cascade is activated, resulting in thrombin gen-eration and a fibrin clot, which stabilizes the platelet plug . Knowledge of the hemostatic mechanism is important for diagnosis of bleeding disorders. Patients with defects in the forma-tion of the primary platelet plug (defects in primary hemostasis, eg, platelet function defects, von Willebrand disease) typically bleed from surface sites (gingiva, skin, heavy menses) with injury. In contrast, patients with defects in the clotting mechanism (second-ary hemostasis, eg, hemophilia A) tend to bleed into deep tissues (joints, muscle, retroperitoneum), often with no apparent inciting event, and bleeding may recur unpredictably.
Platelet-rich thrombi (white thrombi) form in the high flow rate and high shear force environment of arteries. Occlusive arterial thrombi cause serious disease by producing downstream ischemia of extremities or vital organs, and can result in limb
amputation or organ failure. Venous clots tend to be more fibrin-rich, contain large numbers of trapped red blood cells, and are recognized pathologically as red thrombi. Venous thrombi can cause severe swelling and pain of the affected extremity, but the most feared consequence is pulmonary embolism. This occurs when part or all of the clot breaks off from its location in the deep venous system and travels as an embolus through the right side of the heart and into the pulmonary arterial circulation. Sudden occlusion of a large pulmonary artery can cause acute right heart failure and sudden death. In addition lung ischemia or infarction will occur distal to the occluded pulmonary arterial segment. Such emboli usually arise from the deep venous system of the proximal lower extremities or pelvis. Although all thrombi are mixed, the platelet nidus dominates the arterial thrombus and the fibrin tail dominates the venous thrombus.