Possible hemostatic effect of synthetic liposomes in experimental studies under flow conditions

Abstract

BACKGROUND AND OBJECTIVES: The possibility of developing synthetic platelet substitutes is a subject of current interest. We explored the possible hemostatic effect of synthetic phospholipid incorporated in multilamellar vesicles (MLVs) or intermediate unilamellar vesicles (IUVs) using a well-characterized experimental system with circulating human thrombocytopenic blood (10 min, 250 s(-1)). DESIGN AND METHODS: The ability of the liposomes containing different combinations of dipalmitoylphosphatidylcholine (DPPC), phosphatidylethanolamine (PE) and dipalmitoylphosphatidylserine (DPPS) to promote fibrin formation (%F) on the damaged subendothelium was morphometrically evaluated. Generation of thrombin in the system was monitored through prothrombin fragment F1+2 determination. RESULTS: IUV liposomes containing DPPC, 1DPPS:9DPPC, 1DPPS:3DPPC, 1PE:1DPPC increased fibrin deposition on the subendothelium (53.87 +/- 11.0%; 39.76 +/- 6.75%; 40.69 +/- 10.54% and 32.22 +/- 7.35%, respectively vs. thrombocytopenic blood 11.5 +/- 1.2%; p<0.05), while 9PE:1DPPS IUV liposome failed to promote a procoagulant effect. MLV liposomes containing DPPC alone, 1DPPS:3DPPC and 1PE:1DPPC showed a positive effect on fibrin deposition (85.50 +/- 5.95%, 59.86 +/- 11.55% and 43.73 +/- 7.84% respectively; p<0.05). However, no effect was observed in those experiments performed with liposomes containing 3DPPS:1DPPC. After perfusion experiments, the coagulation system became activated, but differences were not statistically significant vs. control experiments, except for MLV liposomes containing DPPC alone (p<0.05). INTERPRETATION AND CONCLUSIONS: These results confirm that, at an experimental level, liposomes containing phospholipids could potentially be used to improve hemostasis in patients with quantitative or qualitative platelet disorders.