AN INHERITED BLEEDING DISORDER LINKED TO A DEFECTIVE INTERACTION BETWEEN ADP AND ITS RECEPTOR ON PLATELETS - ITS INFLUENCE ON GLYCOPROTEIN IIB-IIIA COMPLEX FUNCTION

Much discussion has concerned the central role of ADP in platelet aggr egation, We now describe a patient (M. L.) with an inherited bleeding disorder whose specific feature is that ADP induces a limited and rapi dly reversible platelet aggregation even at high doses, Platelet shape change and other hemostatic parameters were unmodified, A receptor de fect was indicated, for, while epinephrine normally lowered cAMP level s of PGE(1)-treated (M. L.) platelets, ADP was without effect, The bin ding of [H-3]2-methylthio-ADP decreased from 836+/-126 molecules/plate let for normals to 30+/-17 molecules/platelet for the patient, Flow cy tometry confirmed that ADP induced a much lower fibrinogen binding to (M. L.) platelets, Nonetheless, the binding in whole blood of activati on-dependent monoclonal antibodies showed that some activation of GP I Ib-IIIa complexes by ADP was occurring, Platelets of a patient with ty pe I Glanzmann's thrombasthenia bound [H-3]2-methylthio-ADP and respon ded normally to ADP in the presence of PGE(1). Electron microscopy sho wed that ADP-induced aggregates of (M. L.) platelets were composed of loosely bound shape-changed platelets with few contact points, Thus th is receptor defect has a direct influence on the capacity of platelets to bind to each other in response to ADP.