A dominant role of thromboxane formation in secondary aggregation of platelets

Abstract

Aggregation of human platelets in vitro can occur in two phases—primary and secondary aggregation¹. Primary aggregation is due to the direct interaction of the aggregating agent with its receptor^2,3, whereas secondary aggregation is associated with both the secretion of dense granule constituents, including the aggregating agents, serotonin and ADP (ref. 4) and the activation of a pathway for the conversion of arachidonic acid to prostaglandins (PGs)⁵. Both secondary aggregation and the associated secretion of dense granule constituents are contingent on the formation of PGG₂ and PGH₂ which can, in part, be transformed into thromboxane (TX) A₂ (refs 1,3,6,7). TXA₂ is a potent aggregating agent and apparently the functionally active compound in the arachidonate pathway^8–10. However, the precise role of TXA₂ in mediating secondary aggregation is a matter of controversy as it is not clear whether secondary aggregation can occur independently of secretion. We report here that platelets from cats with the Chediak–Higashi (CH) syndrome¹¹ aggregate with arachidonate in a cyclooxygenase-dependent manner and that biphasic aggregation produced by serotonin is accompanied by TXB₂ formation without detectable ADP secretion. These results demonstrate that secondary platelet aggregation can be mediated through thromboxane formation without participation of secreted ADP.