Thrombolysis [antikvár]

CHAPTER 1 Biology and chemistry of thrombosis Marc Verstraete Thrombosis is a multifactorial phenomenon to which plasmatic, vascular, and cellular elements contribute. The pathogenesis of thrombosis may vary considerably, depending on the vascular district involved (venous, arterial, cardiac, and microvascular thrombosis). However, platelets invariably appear to play a role. This role is most prominent in the arterial system, where flow rates are high and vascular lesions are common, but it is alsó evident in the first steps of the process leading to venous thrombosis, where a small platelet clump is usually seen at the site of the origin of such thrombi, most frequently within a valve pocket. The difference between arterial and venous thromboses is morphological (red versus white thrombus) but otherwise more quantitative than qualitative. Activation of the coagulation factors proceeds in an explosive fashion by a series of consecutive enzymatic reactions with multiple positive feedback loops. This results in conversion of prothrombin to the enzyme thrombin, which finally converts fibrinogen to a fibrin gel. BLOOD COAGULATION The coagulation of blood is an autocatalytic and self-limiting process in which the formation of thrombin occupies a central and pivotal position. As soon as this enzyme is förmed in sufficient concentration to overcome the effect of circulating antithrombins and other serine protease inhibitors (called serpins), it rapidly converts soluble fibrinogen into a gel of fibrin, the ultimate and visible effect of the coagulation system. However, this is not the only function of thrombin; it is alsó involved in platelet activation and aggregation, as well as in activating factors V, X, VII, VIII, and XIII (a transglutaminase that stabilizes the polymeric fibrin meshwork by covalent cross-linkage of the polymers) and protein C (a vitamin K-dependent proteinase that inactivates factors Va and VIIIJ. (Activated factors are identified by an "a" added as a suffix to their Román identification number.) Thrombin is förmed as a result of reactions involving a sequential transformation of coagulation factors, which are present in plasma in an inactive form or as zymogens.