An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets. Its influence on glycoprotein IIb-IIIa complex function.

Abstract

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.

• Authors: P Nurden, P Savi, E Heilmann, C Bihour, J M Herbert, J P Maffrand, A Nurden
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 95 Issue 4 Pg. 1612-22 (Apr 1995) ISSN: 0021-9738 [Print] United States
• PMID: 7706468 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Platelet Membrane Glycoproteins
• Receptors, Purinergic P2
• Thionucleotides
• methylthio-ADP
• Adenosine Diphosphate
• Fibrinogen
• Cyclic AMP
• Alprostadil
• Epinephrine

Topics

• Adenosine Diphosphate (analogs & derivatives, metabolism, pharmacology)
• Alprostadil (pharmacology)
• Blood Coagulation Disorders (genetics, metabolism)
• Blood Platelets (drug effects, metabolism, ultrastructure)
• Cyclic AMP (metabolism)
• Cytoplasmic Granules
• Epinephrine (pharmacology)
• Fibrinogen (metabolism)
• Flow Cytometry
• Humans
• Male
• Middle Aged
• Platelet Aggregation
• Platelet Membrane Glycoproteins (metabolism)
• Receptors, Purinergic P2 (metabolism)
• Thionucleotides (metabolism)
• White People