Infusible platelet membranes retain partial functionality of the platelet GPIb/IX/V receptor complex.
Infusible platelet membranes (IPMs) prepared from fresh or outdated human platelets have been shown to correct prolonged bleeding times in thrombocytopenic rabbits. In previous trials, IPMs did not seem to be immunogenic and lacked dose-limiting toxicity. The present study was undertaken to explore whether the platelet glycoprotein (GP) Ib/IX/V complex might retain functionality in the IPM preparation. IPMs did not spontaneously bind von Willebrand factor (vWF), but saturable binding could be induced by ristocetin, with a dissociation constant (Kd) of 0.31 +/- 0.03 microgram/mL at 1.0 mg/mL of ristocetin. Of 4 anti-GPIb-alpha monoclonal antibodies tested, AN-51 inhibited vWF binding 67.8% +/- 5.8%, whereas AS-2, AS-7, and SZ-2 were ineffective. Maximal vWF binding induced by botrocetin was only 10% to 15% of that observed with ristocetin. Retention of partial functionality of the GPIb/IX/V receptor allowing vWF binding in a modulated manner seems to represent a critical mechanism by which IPMs may provide hemostatic efficacy.
Graham
S S
SS
Department of Pathology, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY 13210, USA.
Gonchoroff
N J
NJ
Miller
J L
JL
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003435:Crotalid Venoms / Q000494:pharmacology; D006801:Humans; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology / Q000378:metabolism*; D017713:Platelet Transfusion; D012310:Ristocetin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003435:Crotalid Venoms; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D012310:Ristocetin; C030961:botrocetin