Historical overview of the role of platelets in hemostasis and thrombosis

Abstract

Platelets were discovered by G. Bizzozero in 1882 and rediscovered in the 1960s after many decades of oblivion. Interestingly enough, their role was initially more clearly associated with thrombosis than with hemostasis. For many years a serious unresolved problem was that the clotting time was normal even in severe thrombocytopenia. The concept of coagulation as an enzymatic cascade had not yet been elaborated. During the 1960s, the interest of many experts moved from the interaction of platelets with the process of blood coagulation to the interaction of these cells with the vascular wall (adhesion) and each other (aggregation). The discovery of the role of ADP as the principle of platelet aggregation stimuli was rapidly followed by other important discoveries such as the aggregating properties of collagen and thrombin, the release reaction, the metabolism of arachidonic acid, and the inhibitory effect of aspirin. The use of aspirin as a potential antithrombotic drug has made the history of clinical trials in the last 30 years. The last two decades have been characterized by an explosion of cell and molecular biology approaches. There are presently people who study platelet signal transduction or platelet-leukocyte interactions but who know almost nothing about hemostasis or thrombosis! This is due not only to the intrinsic limitations of the biological approach but also to the progressive recognition of the role of platelets in other physiopathologic and clinical conditions such as inflammation, cancer growth and dissemination, and organ transplant rejection. Overlooked for more than two centuries after the microscope was made available to hematologists, considered as an artifact or a Cinderella, the platelet has mainly been considered in the past 30 years as a dangerous cell to be inhibited by (ever more expensive) drugs. But the taming of the shrew is far from being achieved.