Infusible platelet membranes improve hemostasis in thrombocytopenic blood:experimental studies under flow conditions

BACKGROUND: The potential hemostatic effect of infusible platelet membranes (IPM; Cyplex, Cypress Bioscience) prepared from outdated human platelets i s investigated. STUDY DESIGN AND METHODS: Increasing concentrations of IPM were added to bl ood samples anticoagulated with low-molecular-weight heparin, in which plat elets and WBC counts had been experimentally reduced by a filtration proced ure, Thrombocytopenic blood with IPM was circulated in a perfusion chamber at various shear rates (300, 600, and 1200/sec(-1)), and platelet and fibri n deposition on the surface of a damaged vessel was measured. Prothrombin f ragments 1 and 2 (F1+2) levels were also monitored. RESULTS: Under conditions of severe thrombocytopenia (<6000 platelets/mu L) IPM did not increase platelet deposition. However, a dose-dependent increa se in fibrin deposition was observed with concentrations of IPM ranging fro m 0.5 to 2 mg per kg in perfusions at 300 and 600 per sec(-1) (p<0.05 vs. t hrombocytopenic blood). Experimental studies performed under conditions of moderate thrombocytopenia and higher shear rates (25,000-30,000 platelets/m u L; at 600 and 1200/sec(-1)) showed that IPM concentrations equivalent to 0.5 or 1 mg per kg improved fibrin deposition (33.5 +/- 9.5% and 37.7 +/- 1 2.8%, respectively, vs. 22.7 +/- 5.2% in controls) and also promoted a mode rate increase in platelet deposition, with a concomitant significant increa se in the size of platelet aggregates (p<0.05). Exposure of thrombocytopeni c blood to a damaged vessel resulted in an increase of F1+2 levels from 0.8 +/- 0.15 to 1.7 +/- 0.22 nM at 300 per sec(-1) and 1.94 +/- 0.46 nM at 600 per sec(-1). Postperfusion levels of F1+2 after the addition of IPM were a lways similar to levels in untreated controls. CONCLUSION: IPM promotes local procoagulant activity at sites of vascular d amage under conditions of severe and moderate thrombocytopenia. IPM also ap pears to facilitate platelet cohesive functions under conditions of moderat e thrombocytopenia.