Abstract 357: Treatment With Fibrinogen ?-chain Peptide-coated, Adenosine Diphosphate-encapsulated Liposomes as an Infusible Haemostatic Agent for Dilutional Coagulopathy

Abstract

Background: We developed a fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, adenosine-diphosphate (ADP)-encapsulated liposomes [H12-(ADP)-liposomes] that accumulate at bleeding site via interaction with activated platelets via GPIIb/IIIa and augment platelet aggregation by releasing ADP. Objective: To evaluate the haemostatic efficacy of H12-(ADP)-liposomes against active liver bleeding in dilutional thrombocytopenic rabbits following massive transfusion. Methods: Acute thrombocytopenia (platelets < 50 х 10 3 /μL) was induced in rabbits by repeated blood withdrawal and isovolemic transfusion of autologous washed red blood cells. In these thrombocytopenic rabbits, liver hemorrhage was made by penetrating liver injury. Subsequently, they received the astriction treatment against the liver hemorrhage for 5 min and were intravenously administered with H12-(ADP)-liposomes with platelet-poor plasma (PPP), platelet-rich plasma (PRP), PPP alone, H12-(PBS)-liposome/PPP or H12-(ADP)-liposomes/PPP + fibrinogen concentrate during the astriction. Results: Administration of H12-(ADP)-liposomes as well as PRP rescued 60% rabbits from the liver hemorrhage (PRP, 50%), although rabbits receiving PPP or H12-(PBS)-liposome/PPP showed 10 or 17% survival in the first 24 h, respectively. Administration of H12-(ADP)-liposomes as well as PRP potently reduced both bleeding volume and time from the liver injury site. H12-(ADP)-liposomes were observed at the bleeding site in the liver with thrombus formation, suggesting an induction of thrombi. Whereas, neither macro- nor micro-thrombi were detected in the lung, kidney or liver in rabbits treated with H12-(ADP)-liposomes. Supplementation of fibrinogen to H12-(ADP)-liposomes/PPP did not significantly improve rabbit survivals (40% survival). Conclusions: H12-(ADP)-liposomes may be a safe and effective therapeutic tool during damage control surgery for acute thrombocytopenic trauma patients with massive bleeding.