Pathophysiology and therapeutic modification of thrombin generation in patients with coronary artery disease

Thrombin plays a central role in thrombogenesis: it activates platelets, co nverts fibrinogen to fibrin, and activates factor XIII, which then crosslin ks and stabilizes the fibrin clot, In addition, thrombin amplifies coagulat ion by activating factors VIII and V, key cofactors in the generation of ac tivated factor X and thrombin, respectively. Even platelet function is infl uenced by thrombin. Hence, thrombin generation is most important both in th e chronic progression of coronary atherosclerotic disease and in its conver sion to acute events. To date, various therapeutic approaches capitalize on this knowledge by targeting specific thrombin-related pathways. Among the succesful and carefully documented pharmacologic strategies in acute or chr onic coronary heart disease are the use of unfractioned heparin, low-molecu lar-weight heparin, thrombolysis. hirudin, and/or inhibition of thrombin ge neration by glycoprotein IIb/IIIa antagonists most often utilized on top of antiplatelet theraphy (e.g., with acetylsalicylic acid) and/or vitamin K a ntagonism. The present review provides insights into the pathophysiology of thrombin generation in coronary atherosclerosis and gives an overview over the above mentioned therapeutic thrombin modifications. (C) 2000 Elsevier Science B.V. All rights reserved.