Infusible platelet membranes retain partial functionality of the platelet GPIb/IX/V receptor complex

Infusible platelet membranes (IPMs) prepared from fresh or outdated human p latelets have been shown to correct prolonged bleeding times in thrombocyto penic rabbits.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 functio nality in the IPM preparation. IPMs did not spontaneously bind von Willebra nd factor (VWF), but saturable binding could be induced by ristocetin, with a dissociation constant (Kd) of 0.31 +/- 0.03 mug/mL at 1.0 mg/mL of risto cetin. Of 4 anti-GPlb-alpha monoclonal antibodies tested, AN-51 inhibited v WF binding 67.8% +/- 5.8%, whereas AS-2, AS-7, and SZ-2 were ineffective. M aximal VWF binding induced by botrocetin was only 10% to 15% of that observ ed with ristocetin. Retention of partial functionality of the GPIb/IX/V rec eptor allowing vWF binding in a modulated manner seems to represent a criti cal mechanism by which IPMs may provide hemostatic efficacy.