Reversible activation defect of the platelet glycoprotein IIb-IIIa complex in patients with uremia.
Patients with chronic renal failure may experience a bleeding tendency and blood loss after surgical procedures or trauma. Altered platelet function has been indicated as the major cause of uremic bleeding, but its pathogenesis remains to be clarified. In two groups of patients with chronic renal disease of various etiology, the receptor function of glycoprotein (GP) Ib and GP IIb-IIIa complex was studied. Glycoprotein Ib was assessed with both 125I-von Willebrand factor (vWF) and 125I-asialo-vWF binding to platelets. Activation-dependent receptor function of the GP IIb-IIIa complex was studied with 125I-fibrinogen and 125I-vWF binding to washed platelets stimulated with adenosine diphosphate plus epinephrine (10 mumol/L each). Flow cytometric analyses on resting and stimulated platelets were performed using an activation-dependent, anti-GP IIb-IIIa monoclonal antibody (PAC1) as well as an activation-independent antibody (LJ-P1). Binding of PAC1 also was assessed in washed and stimulated platelets and in platelet-rich plasma before and after dialysis. We found that the activation-dependent receptor function of the GP IIb-IIIa complex is defective in uremia, as shown by decreased binding of both vWF and fibrinogen to stimulated platelets. Moreover, binding of the activation-dependent anti-GP IIb-IIIa monoclonal antibody, PAC1, was significantly decreased in uremia compared with that of the activation-independent antibody, LJ-P1. Thus, the number of GP IIb-IIIa receptors expressed on the platelet membrane is normal, but their activation is impaired. In contrast to the functional abnormality of GP IIb-IIIa, the vWF-binding activity of GP Ib was normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Benigni
A
A
Mario Negri Institute for Pharmacological Research, Laboratori Negri Bergamo, Italy.
Boccardo
P
P
Galbusera
M
M
Monteagudo
J
J
De Marco
L
L
Remuzzi
G
G
Ruggeri
Z M
ZM
D000328:Adult; D000368:Aged; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood* / Q000628:therapy; D014841:von Willebrand Factor / Q000378:metabolism
D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D005340:Fibrinogen