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- Title
Treatment with fibrinogen γ-chain peptide-coated, adenosine 5'-diphosphate–encapsulated liposomes as an infusible hemostatic agent against active liver bleeding in rabbits with acute thrombocytopenia.
- Authors
Hagisawa, Kohsuke; Nishikawa, Kahoko; Yanagawa, Rempei; Kinoshita, Manabu; Doi, Mami; Suzuki, Hidenori; Iwaya, Keiichi; Saitoh, Daizoh; Seki, Shuhji; Takeoka, Shinji; Handa, Makoto; Nishida, Yasuhiro
- Abstract
BACKGROUND: We evaluated the hemostatic efficacy of H12-(adenosine 5'-diphosphate [ADP])-liposomes in the setting of active liver bleeding in rabbits with dilutional thrombocytopenia after massive transfusion. STUDY DESIGN AND METHODS: Acute thrombocytopenia (platelet [PLT] count < 50 × 109/L) was induced in rabbits by repeated blood withdrawal and isovolemic transfusion of autologous washed red blood cells. Liver hemorrhage was initiated by a penetrating liver injury. Subsequently, the animals received tamponade treatment for the liver hemorrhage for 5 minutes and were intravenously administered H12-(ADP)-liposomes with PLT-poor plasma (PPP), PLT-rich plasma (PRP), PPP alone, H12-(phosphate-buffered saline [PBS])-liposome/ PPP, or H12-(ADP)-liposomes/PPP plus fibrinogen concentrate during the tamponade. RESULTS: Administration of H12-(ADP)-liposomes/PPP rescued 60% of the rabbits from the liver hemorrhage; PRP administration rescued 50%. In contrast, rabbits receiving PPP or H12-(PBS)-liposome/PPP achieved only 10 or 17% survival, respectively, for the first 24 hours. H12-(ADP)-liposomes/PPP as well as PRP consistently reduced bleeding volumes and shortened clotting times (CTs) in comparison to PPP administration. Specifically, bleeding volumes in the initial 5 minutes averaged 11 mL (H12-(ADP)-liposomes/PPP) and 17 mL (PRP) versus 30 mL (PPP; p < 0.05); CTs averaged 270 and 306 seconds versus 401 seconds (p < 0.05). H12-(ADP)-liposomes were observed at the bleeding site with thrombus formation, suggesting an induction of thrombi. Neither macro- nor microthrombi were detected in the lung, kidney, spleen, or liver in rabbits treated with H12-(ADP)-liposomes. Supplementation of fibrinogen to H12-(ADP)-liposomes/PPP did not significantly improve rabbit survival. CONCLUSIONS: H12-(ADP)-liposomes might be a safe and effective therapeutic tool during damage control surgery for trauma patients with acute thrombocytopenia and massive bleeding.
- Subjects
THROMBOCYTOPENIA treatment; LIVER injuries; HEMOSTATICS; PYROPHOSPHATES; LABORATORY rabbits; FIBRINOGEN
- Publication
Transfusion, 2015, Vol 55, Issue 2, p314
- ISSN
0041-1132
- Publication type
Article
- DOI
10.1111/trf.12829