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 aggregation, We now describe a patient (M. L.) with an inherited bleeding disorder whose specific feature is that ADP induces a limited and rapidly reversible platelet aggregation even at high doses, Platelet shape change and other hemostatic parameters were unmodified, A receptor defect was indicated, for, while epinephrine normally lowered cAMP levels of PGE(1)-treated (M. L.) platelets, ADP was without effect, The binding of [H-3]2-methylthio-ADP decreased from 836+/-126 molecules/platelet for normals to 30+/-17 molecules/platelet for the patient, Flow cytometry confirmed that ADP induced a much lower fibrinogen binding to (M. L.) platelets, Nonetheless, the binding in whole blood of activation-dependent monoclonal antibodies showed that some activation of GP IIb-IIIa complexes by ADP was occurring, Platelets of a patient with type I Glanzmann's thrombasthenia bound [H-3]2-methylthio-ADP and responded normally to ADP in the presence of PGE(1). Electron microscopy showed that ADP-induced aggregates of (M. L.) platelets were composed of loosely bound shape-changed platelets with few contact points, Thus this receptor defect has a direct influence on the capacity of platelets to bind to each other in response to ADP.