Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa.
Uremic patients have an impaired platelet function that has been related to membrane glycoprotein (GP) abnormalities. Using a perfusion system, we have studied the interaction of normal and uremic platelets with vessel subendothelium (SE) under flow conditions. Reconstituted blood containing washed platelets, purified von Willebrand factor (vWF) (1 U/mL), and normal washed red blood cells was exposed to de-endothelialized rabbit segments for 10 minutes at two different shear rates (800 and 1,600 seconds-1). In some experiments a monoclonal antibody to the GPIIb-IIIa complex (EDU3) was added to the perfusates. With normal platelets, the percentage of the vessel covered by platelets (%CS) was 23.1% +/- 3.7% at 800 seconds-1 and 30% +/- 4.3% at 1,600 seconds-1. Platelets were observed in contact or forming monolayers on vessel SE. EDU3 inhibited the spreading of normal platelets. The %CS (11.1% +/- 3.3%) was statistically decreased (P less than .01) and most of the platelets were observed in contact with the vessel surface. These data indicate that, under flow conditions, the interaction of vWF with GPIIb-IIIa can support the spreading of normal platelets in the absence of exogenous fibrinogen. Under the same experimental conditions, the interaction of uremic platelets with SE was markedly impaired at both shear rates studied (P less than .01 v normal platelets). The presence of EDU3 did not modify the interaction of uremic platelets. These results confirm the impairment of the platelet adhesion observed in uremic patients. Furthermore, they indicate the presence of a functional defect in the interaction of vWF with GPIIb-IIIa. The fact that perfusions with normal and uremic platelets in the presence of an antibody to the GPIIb-IIIa complex did not show any differences gives indirect evidence on a functionally normal interaction vWF/GPIb in uremic patients.
Servicio de Hemoterapia y Hemostasia, Hospital Clínic i Provincial, Barcelona, Spain.
G
G
Escolar
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A
Cases
E
E
Bastida
M
M
Garrido
J
J
López
L
L
Revert
R
R
Castillo
A
A
Ordinas
D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D014511:Uremia / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology; D014841:von Willebrand Factor / Q000378:metabolism* / Q000502:physiology
D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor