Platelet Activation in Unstable Coronary Disease

TLDR

Platelets are implicated in unstable angina and myocardial infarction, yet their activation during episodic ischemia remains unclear. The study aimed to quantify thromboxane and prostacyclin biosynthesis as platelet activation markers in stable versus unstable coronary disease and to assess the therapeutic potential of targeting thromboxane A₂. Researchers measured plasma and urine thromboxane and prostacyclin metabolites using physicochemical analysis to index platelet activation. Elevated prostacyclin and thromboxane synthesis were observed during unstable angina episodes—84 % of chest pain events and 50 % of silent ischemia—indicating platelet activation, while thromboxane inhibitors would likely be ineffective in stable angina.

Abstract

Pathological and clinical studies have suggested that platelets have a role in the pathogenesis of unstable angina and myocardial infarction. However, the relation of platelet activation to episodic ischemia in patients with unstable angina is unknown. We assessed the biosynthesis of thromboxane and prostacyclin as indexes of platelet activation in patients with stable and unstable coronary disease by physicochemical analysis of metabolites in plasma and urine. Prostacyclin biosynthesis was markedly elevated in patients with acute myocardial infarction and correlated with plasma creatine kinase (r = 0.795; P less than 0.001). The largest rise in thromboxane synthesis was observed in patients with unstable angina, in whom 84 percent of the episodes of chest pain were associated with phasic increases in the excretion of thromboxane and prostacyclin metabolites. However, 50 percent of such increases were not associated with chest pain, possibly reflecting silent myocardial ischemia. These data indicate that platelet activation occurs during spontaneous ischemia in patients with unstable angina. The increment in prostacyclin biosynthesis during such episodes may be a compensatory response of vascular endothelium that limits the degree or effects of platelet activation. If so, biochemically selective inhibition of the synthesis or action of thromboxane A2 would be desirable in the treatment of unstable angina. In contrast, thromboxane inhibitors or antagonists would not be expected to be effective in patients with chronic stable angina, in whom there was no increase in the formation of thromboxane A2.