Platelet activation in thrombotic disorders

Abstract

Recent advances have resulted in the elucidation of the principal molecular pathways of platelet function. Parallel studies have led to the identification of glycoprotein antigens whose presence at the platelet surface indicates an activated state. Such markers include GMP-140 and other glycoproteins of intracellular membranes whose translocation requires secretion and fusion of granule membranes with those joined to the surface. Other markers include activation-dependent epitopes on the GP IIb-IIIa complex and adhesive proteins bound to the activated GP IIb-IIIa receptor. Such epitopes can be detected by specific monoclonal antibodies. Quantification of their binding by flow cytometry allows an estimation of epitope expression within the whole platelet population. Our studies are designed to answer the question of whether measuring these epitopes is useful for predicting thrombosis in patients with acute cardiovascular disease. For this, we have examined three states where platelet function may be modified and where the risk of thrombosis and/or bleeding is increased. These include (i) patients with severe burns, (ii) patients who have undergone coronary angioplasty, and (iii) patients receiving fibrinolytic therapy following myocardial infarction. Our results show that activated platelets can be detected in the circulation and that their level reflects the degree of the lesion. Nonetheless, we have as yet failed to show a direct correlation between their presence and a future pathological event.