Identification of a new congenital defect of platelet function characterized by severe impairment of platelet responses to adenosine diphosphate.
This study characterizes a congenital hemorrhagic disorder caused by a platelet function defect with the following features: (1) severely impaired platelet aggregation and fibrinogen or von Willebrand factor (vWF) binding induced by adenosine diphosphate (ADP); (2) defective aggregation, release reaction, and fibrinogen or vWF binding induced by other agonists; (3) normal aggregation and release reaction induced by high concentrations of thrombin or collagen; (4) no further inhibition by ADP scavengers of aggregation, release reaction, and fibrinogen or vWF binding, comparable with those observed for normal platelets in the presence of ADP scavengers; (5) normal membrane glycoprotein (GP) composition and normal binding of the anti-GP IIb/IIIa monoclonal antibody 10E5; (6) no acceleration by ADP of binding of the anti-GP IIb/IIIa monoclonal antibody 7E3; (7) normal platelet-fibrin clot retraction if induced by thrombin or reptilase plus epinephrine, absent if induced by reptilase plus ADP; (8) no inhibition by ADP of the prostaglandin E1-induced increase in platelet cyclic adenosine monophosphate, but normal inhibition by epinephrine; (9) defective mobilization of cytoplasmic Ca2+ by ADP; (10) normal binding of 14C-ADP to fresh platelets, but defective binding of [2-3H]-ADP to formalin-fixed platelets. This congenital platelet function defect is characterized by selective impairment of platelet responses to ADP, caused by either decreased number of platelet ADP receptors or abnormalities of the signal-transduction pathway of platelet activation by ADP.
Cattaneo
M
M
A. Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Milan, Italy.
Lecchi
A
A
Randi
A M
AM
McGregor
J L
JL
Mannucci
P M
PM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000097:blood / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000097:blood; D003018:Clot Retraction; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D004837:Epinephrine / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D006470:Hemorrhage / Q000097:blood* / Q000235:genetics; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012016:Reference Values; D013917:Thrombin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005340:Fibrinogen; D003094:Collagen; D000242:Cyclic AMP; D013917:Thrombin; D002118:Calcium; D007213:Indomethacin; D004837:Epinephrine