One, Two, Three or More Pathways for Platelet Aggregation

The presently available knowledge on three mechanisms of platelet aggregation, including release of ADP, formation of thromboxane A2, and a third process in which PAF appears to be centrally involved are summarized.

Abstract

ABSTRACT. Platelet aggregation is a complex event, and no single pathway for release and/or activity of mediators can be postulated. Three mechanisms at least operate for aggregation: release of ADP, formation of thromboxane A 2 , and a third process in which PAF appears to be centrally involved. In every case the adenylate cyclase system is likely to control aggregation, after appropriate stimuli have been provided and potential aggregating substances have been released. Any approach which involves inhibiting the release of the mediators must be based on a knowledge of the mechanism of this release. Phospholipase A 2 appears to be a reasonably critical point at which to attempt inhibition of platelet aggregation and activation in general, particularly since doing so should at the same time reduce the synthesis of thromboxane A 2 (which is dependent upon the availability of AA hydro‐lysed from phospholipids) and also that of PAF. Platelet aggregation is essential for arterial thrombosis. Even though the insidious vascular lesion precedes the platelet alteration, and thus appears to be the critical step where prophylaxis against coronary thrombosis should be applied, attempts to inhibit platelet responsiveness during acute myocardial infarction or during the post‐infarction stages appear justified. This is true for two reasons, first precisely because of the insidious and relatively uncontrolled nature of the vascular disease, and secondly because the clinician has to deal with established atherosclerotic patients who are statistically likely to undergo myocardial reinfarction. The understanding of the mechanisms of platelet aggregation is thus important for the biologist, as well as for the physiopathologist and the clinician. This paper attempts to summarize the presently available knowledge on these mechanisms.