title: Thromboregulation: multicellular modulation of platelet reactivity in hemostasis and thrombosis.
abstract: Blood platelets represent the first line of host defense when normal vessels are injured. Platelet adhesion to subendothelium, aggregation, and further platelet recruitment culminate in hemostatic plug formation, which is accompanied by the consolidating effect of fibrin deposition on and between platelets. The process is multicellular in that erythrocytes promote and neutrophils inhibit platelet plug formation. Endothelial cells in proximity possess three protective mechanisms (thrombo-regulators) for limiting the size of the hemostatic plug-ADPase, eicosanoids, endothelium-dependent relaxing factor/NO. We propose that in advanced atherosclerotic blood vessels such as coronary arteries, an ulcer or fissure in the fibrous cap of the atheroma serves as an agonist that transforms the platelet into a major prothrombotic offender. Induction of excessive platelet activation overcomes the normal thromboregulatory mechanisms. Erythrocytes further activate platelets, even in the presence of aspirin, and neutrophil blockage of platelet reactivity is insufficient to prevent impending vascular occlusion. Appreciating that multiple cell types and metabolic pathways are involved in modulation of platelet reactivity in vascular occlusion is a relatively recent concept. Strategies designed to restore processes such as thromboregulation may serve to improve therapeusis in thrombosis, which at present is far from optimal.
authors: Department of Medicine, Department of Veterans Affairs Medical Center, New York, New York 10010.
authors: A J
authors: AJ
authors: Marcus
authors: L B
authors: LB
authors: Safier
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology; D006487:Hemostasis; D006801:Humans; D009504:Neutrophils / Q000502:physiology; D013927:Thrombosis / Q000097:blood*