IMPAIRED HIGH-SHEAR-STRESS-INDUCED PLATELET-AGGREGATION IN PATIENTS WITH CHRONIC-RENAL-FAILURE UNDERGOING HEMODIALYSIS

We investigated shear-induced platelet aggregation (SIPA) in 30 patien ts with chronic renal failure (CRF) undergoing haemodialysis. 26 patie nts showed a significant decrease in SIPA at high shear stress but no change in SIPA at low shear stress. The former reaction reflects the i nteraction between plasma non Willebrand factor (vWF) and its platelet receptors, glycoprotein (GP) Ib-M and IIb/IIIa complex, whereas the l atter 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 ra tio of ristocetin cofactor/vWF antigen in plasma was slightly lower in CRF patients than in controls (P<0.01). However, the level of GPIb an tigen in the platelets of these patients was significantly reduced (42 .1+/-20.3% of normal platelets), with partial destruction of GPIb anti gen, The number of VWF receptors on the GPIb molecule was quantitated using the GPIb-binding protein alboaggregin-B (AL-B), purified from th e snake venom of Trimeresurus albolabris. AL-B bound to GPIb at a tota l of 48 760+/-9944 molecules per normal platelet and a K-d Of 85.44+/- 15.70 nm at saturation. In contrast, binding in CRF platelets was 22 9 80+/-6395 molecules per platelet and K-d was 50.08+/-13.83 nm. Taking these results together, we conclude that the impaired SIPA found in CR F patients is due to both abnormalities in plasma vWF and in its plate let GPIb receptor.