title: Impaired high-shear-stress-induced platelet aggregation in patients with chronic renal failure undergoing haemodialysis.
abstract: We investigated shear-induced platelet aggregation (SIPA) in 30 patients with chronic renal failure (CRF) undergoing haemodialysis. 26 patients showed a significant decrease in SIPA at high shear stress but no change in SIPA at low shear stress. The former reaction reflects the interaction between plasma von Willebrand factor (vWF) and its platelet receptors, glycoprotein (GP) Ib-IX and IIb/IIIa complex, whereas the latter is assumed to involve the binding of plasma fibrinogen to GP IIb/IIIa complex. These SIPA profiles in CRF patients after haemodialysis showed almost no change compared to those before haemodialysis. The ratio of ristocetin cofactor/vWF antigen in plasma was slightly lower in CRF patients than in controls (P < 0.01). However, the level of GPIb antigen in the platelets of these patients was significantly reduced (42.1 +/- 20.3% of normal platelets), with partial destruction of GPIb antigen. The number of vWF receptors on the GPIb molecule was quantitated using the GPIb-binding protein alboaggregin-B (AL-B), purified from the snake venom of Trimeresurus albolabris. AL-B bound to GPIb at a total of 48,760 +/- 9944 molecules per normal platelet and a Kd of 85.44 +/- 15.70 nM at saturation. In contrast, binding in CRF platelets was 22,980 +/- 6395 molecules per platelet and Kd was 50.08 +/- 13.83 nM. Taking these results together, we conclude that the impaired SIPA found in CRF patients is due to both abnormalities in plasma vWF and in its platelet GPIb receptor.
authors.affiliation: Department of Second Internal Medicine, Nara Medical University, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: I
authors.initials: I
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa
authors.forename: K
authors.initials: K
authors.lastname: Miyataka
authors.forename: M
authors.initials: M
authors.lastname: Oonuki
authors.forename: T
authors.initials: T
authors.lastname: Kawasaki
authors.forename: M
authors.initials: M
authors.lastname: Katayama
mesh_terms: D000328:Adult; D000368:Aged; D016824:Antigens, Human Platelet / Q000032:analysis; D015153:Blotting, Western; D003435:Crotalid Venoms / Q000494:pharmacology; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D006435:Renal Dialysis; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D016824:Antigens, Human Platelet; D003435:Crotalid Venoms; D010980:Platelet Membrane Glycoproteins; C029748:Trimeresurus venoms; D014841:von Willebrand Factor