Hereditary defect of the platelet ADP receptor(s)

Four patients with a previously unrecognized congenital disorder of platelet function have recently been described. Their platelets aggregate very poorly to exogenous ADP. The abnormality is likely due to a severe defect of the platelet ADP receptor that is coupled to adenylate cyclase, as suggested by the following findings: 1) ADP does not normally lower cAMP levels of PGE1-treated platelets; 2) platelet shape change induced by ADP is normal; 3) the binding of [radiolabelled]ADP to formalin-fixed platelets or of the ADP analogue [radiolabelled]2-MeS-ADP to fresh platelets is severely defective. Since all patients that have been described were born from consanguineous parents, the condition seems to be inherited as an autosomal recessive trait. Platelets of an obligate heterozygote have intermediate binding sites for 2-M eS-ADP, undergo a normal primary wave of aggregation induced by exogenous ADP, but do not normally secrete the content of their granules when stimulated by release-inducing agonists. Studies of normal platelets treated with acetylsalycilic acid revealed that ADP potentiates platelet secretion directly, and that the full complement of its platelet receptors appears to be necessary for this function.