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Uremic platelets have a functional defect affecting the interaction of von
Willebrand factor with glycoprotein IIb-IIIa
G Escolar, A Cases, E Bastida, M Garrido, J Lopez, L Revert, R Castillo and A Ordinas
Servicio de Hemoterapia y Hemostasia, Hospital Clinic i Provincial,
Barcelona, Spain.
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.
Volume 76,
Issue 7,
pp. 1336-1340,
10/01/1990
Copyright © 1990 by The American Society of Hematology
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