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 PGE1-treated (M.L.) platelets, ADP was without effect. The binding of [3H]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 [3H]2-methylthio-ADP and responded normally to ADP in the presence of PGE1. 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.
Nurden
P
P
Unité de Recherche Associée 1464 Centre National de la Recherche Scientifique, Hôpital Cardiologique, Pessac, France.
Savi
P
P
Heilmann
E
E
Bihour
C
C
Herbert
J M
JM
Maffrand
J P
JP
Nurden
A
A
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D001778:Blood Coagulation Disorders / Q000235:genetics / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000242:Cyclic AMP / Q000378:metabolism; D003594:Cytoplasmic Granules; D004837:Epinephrine / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013873:Thionucleotides / Q000378:metabolism; D044465:White People
D010980:Platelet Membrane Glycoproteins; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; C002480:methylthio-ADP; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000242:Cyclic AMP; D000527:Alprostadil; D004837:Epinephrine