PREPARATIONS OF SYNTHETIC PHOSPHOLIPIDS PROMOTE PROCOAGULANT ACTIVITYON DAMAGED VESSELS - STUDIES UNDER FLOW CONDITIONS

BACKGROUND: The possibility of developing synthetic platelet substitut es that could promote hemostasis with prolonged shelf-life and increas ed safety is an appealing one. STUDY DESIGN AND METHODS: Preparations containing synthetic phospholipids were incorporated into blood sample s (1. 15 mg/mL) in which platelets and white cell counts had been expe rimentally reduced by a filtration procedure. Vesicles containing phos phatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserin e (PS), phosphatidylinositol (PI), or combinations of PC and PE and of PC and PS were tested in this system. Blood was recirculated (10 min; shear rate, 250/sec) through a perfusion chamber containing Vascular segments. The ability of the various phospholipid preparations to prom ote fibrin formation on the damaged subendothelium was evaluated morph ometrically and expressed as the percentage of fibrin coverage. Genera tion of thrombin in the system was monitored through the measurement o f prothrombin fragments 1 and 2. RESULTS: Vesicles containing PG, PI, PE:PC (I:1), or PS:PC (1:3) increased fibrin deposition on the subendo thelium (64.5 +/- 9.8%, 32.7 +/- 6.3%, 58.3 +/- 6.5%, and 46.6 +/- 15. 2%, respectively; p<0.01 vs. 11.5 +/- 1.2% in thrombocytopenic blood). Vesicles containing PE, PS, or PS:PC (3:1) did not show procoagulant effect. CONCLUSION: Synthetic phospholipid preparations promote a loca l procoagulant activity at sites of vascular damage when they are inco rporated into thrombocytopenic blood maintained under flow conditions.