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Infusible platelet membranes improve hemostasis in thrombocytopenic blood: experimental studies under flow conditions
A M Galán1, J Bozzo, M R Hernández
1Hemotherapy and Hemostasis Service, Hospital Clínic, Barcelona, Spain. agalan@clinic.ub.es
Background:
The potential hemostatic effect of infusible platelet membranes (IPM; Cyplex, Cypress Bioscience) prepared from outdated human platelets is investigated.
Study Design And Methods:
Increasing concentrations of IPM were added to blood samples anticoagulated with low-molecular-weight heparin, in which platelets and WBC counts had been experimentally reduced by a filtration procedure. Thrombocytopenic blood with IPM was circulated in a perfusion chamber at various shear rates (300, 600, and 1200/sec(-1)), and platelet and fibrin deposition on the surface of a damaged vessel was measured. Prothrombin fragments 1 and 2 (F1+2) levels were also monitored.
Results:
Under conditions of severe thrombocytopenia (<6000 platelets/microL) IPM did not increase platelet deposition. However, a dose-dependent increase in fibrin deposition was observed with concentrations of IPM ranging from 0.5 to 2 mg per kg in perfusions at 300 and 600 per sec(-1) (p<0.05 vs. thrombocytopenic blood). Experimental studies performed under conditions of moderate thrombocytopenia and higher shear rates (25, 000-30,000 platelets/microL; 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 +/- 12.8%, respectively, vs. 22.7 +/- 5.2% in controls) and also promoted a moderate increase in platelet deposition, with a concomitant significant increase in the size of platelet aggregates (p<0.05). Exposure of thrombocytopenic 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 always similar to levels in untreated controls.
Conclusion:
IPM promotes local procoagulant activity at sites of vascular damage under conditions of severe and moderate thrombocytopenia. IPM also appears to facilitate platelet cohesive functions under conditions of moderate thrombocytopenia.