Platelet resistance to prostaglandin D2 in patients with myeloproliferative disorders

Abstract

We investigated the effect of prostaglandin D2 (PGD2) on platelet adenylate cyclase activity in 23 patients with myeloproliferative disorders, including eight patients with polycythemia vera, seven with myeloid metaplasia, four with chronic myelogenous leukemia, and four with essential thrombocythemia. In 20 of these patients there was less activation of platelet adenylate cyclase at all concentrations of PGD2 studied when compared to normal controls. In 5 of these patients we also studied the effect of PGD, on platelet aggregation and the release of 14C-serotonin. Each of these patients required ten fold higher than normal concentrations of PGD2 to inhibit collagen-induced 14C-serotonin release. This diminished response was specific for PGD2; the stimulation of adenylate cyclase by PGE1 and PGI2 was normal in these patients’ platelets, as was the inhibition of 14C-serotonin release by PGE1. Aspirin therapy in 5 patients and anticoagulation with sodium warfarin in 1 patient did not correct this platelet abnormality. Five subjects with reactive thrombocytosis who were studied had a normal platelet adenylate cyclase response to PGD2. Since sufficient PGD2 is synthesized by platelets to inhibit aggregation, the resistance of these platelets to physiologic concentrations of PGD2 could contribute to the high incidence of thrombosis in patients with myeloproliferative disorders.