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


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).


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.
Galán
Ana M
AM
Servicio de Hemoterapia y Hemostasia, Hospital Clinic, Villarroel 170, 08036-Barcelona, Spain. agalan@clinic.ub.es
Casals
Elisenda
E
Estelrich
Joan
J
Hernández
M Rosa
MR
Bozzo
Jordi
J
Reverter
Joan
J
Mazzara
Roberto
R
Ordinas
Antonio
A
Escolara
Ginés
G
D000818:Animals; D001011:Aorta; D001775:Blood Circulation / Q000187:drug effects; D001791:Blood Platelet Disorders / Q000628:therapy; D004730:Endothelium, Vascular / Q000378:metabolism; D005337:Fibrin / Q000187:drug effects / Q000378:metabolism; D006490:Hemostatics / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D008955:Models, Cardiovascular; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology; D010976:Platelet Count; D011817:Rabbits; D013921:Thrombocytopenia / Q000628:therapy
D006490:Hemostatics; D008081:Liposomes; D010743:Phospholipids; D005337:Fibrin