Hemostasis and atherosclerosis.
Hemostatic factors play a crucial role in generating the occlusive thrombotic plug at sites of vascular damage (atherothrombosis). It remains uncertain, however, whether hemostatic factors contribute directly or indirectly to the pathogenesis of atherosclerosis. For example, 'hypercoagulable states' (eg, antithrombin deficiency, Factor VLeiden) generally predispose to venous thrombotic events, but not atherosclerosis. Further, 'hemophilic states' (eg, factor VIII deficiency, von Willebrand's disease) do not protect against atherosclerosis. Nevertheless, research has been stimulated by several clinical studies showing that an elevated fibrinogen level is a strong and independent risk factor for cardiovascular (arterial) thrombotic events. Moreover, basic investigations have demonstrated fibrin(ogen) antigens in evolving atherosclerotic plaques, and have suggested a smooth muscle mitogenic effect of fibrin. Other factors that may contribute to atherogenesis include platelets and platelet-derived microparticles, coagulation factor VII and lipoprotein (a) [Lp(a)]. Lp(a) is of particular interest since elevated levels of this lipoprotein particle are strongly linked to cardiovascular disease. Lp(a) appears to inhibit natural fibrinolysis, suggesting that this factor could represent an important link between thrombotic and lipid atherogenic mechanisms. Further work defining a role for the hemostatic system in atherogenesis is important because of the potential benefit of pharmacological manipulation of hemostatic risk factors, such as agents that lower fibrinogen levels.
Warkentin
T E
TE
Department of Laboratory Medicine, Hamilton Civic Hospitals, Ontario.
D000925:Anticoagulants / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology*; D001778:Blood Coagulation Disorders / Q000097:blood; D001779:Blood Coagulation Factors; D005167:Factor VII; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D010973:Platelet Adhesiveness; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology*; D014841:von Willebrand Factor / Q000032:analysis
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D017270:Lipoprotein(a); D014841:von Willebrand Factor; D005167:Factor VII; D005340:Fibrinogen