Platelet activation by a novel solid-phase agonist: effects of VWF immobilized on polystyrene beads.
The interaction between platelets stirred in suspension and VWF immobilized on polystyrene beads was studied. Platelets aggregated and released ATP in response to stirring with VWF beads. Closer examination of the interaction using transmission electron microscopy revealed that the platelets did not simply aggregate with one another but initially adhered to the beads and spread. Platelets in suspension then bound to the bead-adherent platelets forming layers of platelets associated with each bead. The VWF bead-induced platelet activation was completely inhibited by addition of monoclonal antibody (mAb) to GPIb or GPIIb/IIIa. In addition, the activation response was inhibited in the presence of aspirin, indomethacin or the thromboxane receptor antagonist BM13.177, demonstrating a dependence on an intact cyclo-oxygenase pathway. Platelet function studies were carried out on 30 patients with a history of mild bleeding using conventional optical aggregation and VWF bead-induced platelet activation. 12 patients were abnormal by conventional optical aggregometry, whereas 27 patients showed depressed ATP release in response to VWF beads. The results suggest that easily-bruised patients may have a platelet function defect rather than a vascular-based abnormality and that VWF bead-induced platelet activation is a more sensitive test for detecting platelet dysfunction.
Stewart
M W
MW
Department of Laboratory Medicine and Pathology, University of Alberta Hospitals, Edmonton, Canada.
Etches
W S
WS
Boshkov
L K
LK
Mant
M J
MJ
Gordon
P A
PA
Shaw
A R
AR
D001241:Aspirin / Q000494:pharmacology; D001778:Blood Coagulation Disorders / Q000097:blood; D003288:Contusions / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D015539:Platelet Activation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D014841:von Willebrand Factor / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D013449:Sulfonamides; D014841:von Willebrand Factor; C040624:sulotroban; D001241:Aspirin; D007213:Indomethacin