Vascular thrombotic disorders are the leading causes of mortality in the Western world. It is interesting to note that most, if not all of these disorders, although consisting of a systemic imbalance in hemostasis, are characterized by the development of focal thrombotic lesions (Tables 101–1 and 101–2). For example, microangiopathic hemolytic anemia (e.g., hemolytic uremia syndrome and thrombotic thrombocytopenia purpura) affect every microvascular bed with the notable exception of the liver and lung (see Chapter 146). The congenital hypercoagulable states, as exemplified by the factor V Leidenmutation, are associated with systemic changes in clotting factor level and/or activity, yet generally predispose patients to an increased risk of venous, and not arterial, thrombosis (1,2). In patients with warfarin-induced skin necrosis (a rare complication of coumarin treatment), a systemic imbalance occurs in vitamin K–dependent clotting factors (circulating protein C is disproportionately low compared with circulating factors II, VII, IX, and X). Remarkably, fibrin deposition is limited to postcapillary venules of the dermis (3,4). In the final analysis, very few, if any, thrombotic diseases affect the entire vasculature (2). This observation is supported by genetic mouse models, in which the deletion of one or another natural anticoagulant mechanisms results in vascular bed–specific fibrin deposition and thrombosis (5). An important question that arises from these clinical and animal studies is how a systemic imbalance in hemostasis is ultimately manifested by local rather than diffuse vasculopathic lesions. As discussed herein, the endothelium provides an important clue to the answer.

CLASSIFICATIONS IN HEMOSTASIS

Hemostasis is strictly defined as the arrest of bleeding. Coagulation is the transformation of a liquid into a semisolid or solid, coherent mass.