Serum albumin enhances the impairment of platelet aggregation with thromboxane synthase inhibition by increasing the formation of prostaglandin D2

Dazoxiben, a thromboxane synthase inhibitor, inhibits arachidonic acid induced aggregation in platelet-rich plasma from some donors only (“responders”). We have studied the effect of dazoxiben in vitro on platelet aggregation and prostaglandin (PG) metabolism and the influence of the incubation period and of exogenously added serum albumin (SA). SA, which increases the production of anti-aggregatory PGD₂ from cyclic endoperoxides, induced “non-responder” human platelets to respond. With rabbit platelets, however, that are insensitive to PGD₂, exogenous SA failed to potentiate dazoxiben-induced inhibition. The ratio between PGD₂ and TXB₂ + PGE₂ formed was crucial in determining the response of human platelets to dazoxiben: whenever this ratio was high, platelet aggregation was inhibited. SQ 22536, an adenylate cyclase inhibitor, and NO164, a PGD₂ antagonist, reversed the inhibition by dazoxiben in human platelet-rich plasma, stressing the importance of a PGD₂ mediated rise of cyclic AMP for the effectiveness of a thromboxane synthase inhibitor.