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Understanding of the pathophysiology of thrombosis, both venous and arterial, has increased dramatically over the past 50 years. A rapidly increasing number of inherited and acquired conditions predisposing patients to venous thromboembolism and/or arterial thrombosis or embolus are being discovered. Virchow’s triad of hypercoagulability, venous stasis, and endothelial injury continues to be a useful model for the interplay of genetic factors and environmental triggers leading to inappropriate thrombosis. Most patients develop venous thromboembolism after some inciting event, such as trauma, surgery, or prolonged immobilization. However, a patient with a disorder causing hypercoagulability can develop a serious thrombotic event with little or no inciting factor. This has led some researchers to postulate that risk from various factors is additive; and when a patient’s risk reaches a “thrombosis threshold,” inappropriate thrombus develops. In fact, some researchers believe that all patients with thrombosis have a hypercoagulable tendency that is yet to be discovered. The initial ED approach is similar for most common inherited and acquired conditions causing hypercoagulable states (Table 229-1).

Table 229-1 Hypercoagulable States

Several physiologic systems are in place to ensure that blood clots do not extend beyond the area in which they are needed. The two most clinically important pathways involve protein C and antithrombin (Figure 229-1 and Table 229-2). Antithrombin (previously known as antithrombin III) is a plasma-based protein that inhibits the function of several activated coagulation factors, primarily thrombin, Factor Xa, and Factor IXa. Both unfractionated heparin and low-molecular-weight heparin possess anticoagulant activity by increasing the rate by which antithrombin inhibits these factors; approximately 2000- to 4000-fold for thrombin, about 500- to 1000-fold for Factor Xa, and about a million-fold for Factor IXa. Protein C is a vitamin K–dependent plasma protein that binds to the endothelial cell surface and is activated by thrombin. Activated protein C cleaves both Factor Va and Factor VIIIa, inhibiting both the common pathway and the intrinsic pathway. Protein S, another vitamin K–dependent plasma protein, is a cofactor that increases the inhibitory action of activated protein C by about 20-fold.

Figure 229-1.

Simplified depiction of the common pathway of coagulation and the actions of antithrombin and activated protein C. Coagulation is triggered by either the intrinsic and extrinsic pathways that meet at the common pathway to activate Factor X. Factor Xa complexes with Factor Va, phospholipid (PL) and calcium ion [Ca++] to convert prothrombin (Factor II) to thrombin. One of thrombin’s many actions is to convert fibrinogen into fibrin, which is a major component of ...

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