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- Title
Combination therapy using fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes and hemoglobin vesicles for trauma-induced massive hemorrhage in thrombocytopenic rabbits.
- Authors
Hagisawa, Kohsuke; Kinoshita, Manabu; Takikawa, Masato; Takeoka, Shinji; Saitoh, Daizoh; Seki, Shuhji; Sakai, Hiromi
- Abstract
<bold>Background: </bold>We previously developed substitutes for red blood cells (RBCs) and platelets (PLTs) for transfusion. These substitutes included hemoglobin vesicles (HbVs) and fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, adenosine diphosphate (ADP)-encapsulated liposomes [H12-(ADP)-liposomes]. Here, we examined the efficacy of combination therapy using these substitutes instead of RBC and PLT transfusion in a rabbit model with trauma-induced massive hemorrhage with coagulopathy.<bold>Study Design and Methods: </bold>Thrombocytopenia (PLT count approximately 40,000/μL) was induced in rabbits by repeated blood withdrawal and isovolemic transfusion with autologous RBCs. Thereafter, lethal hemorrhage was induced in rabbits by noncompressible penetrating liver injury. Subsequently, H12-(ADP)-liposomes with platelet-poor plasma (PPP), platelet-rich plasma (PRP), or PPP alone were administered to stop bleeding. Once achieving hemostasis, HbVs, allogenic RBCs, or 5% albumin were transfused into rabbits to rescue them from fatal anemia following massive hemorrhage.<bold>Results: </bold>Administration of H12-(ADP)-liposomes/PPP as well as PRP (but not PPP) effectively stopped liver bleeding (100% hemostasis). The subsequent administration with HbVs as well as RBCs after hemostasis markedly rescued rabbits from fatal anemia (75% and 70% survivals for 24 hr, respectively). In contrast, 5% albumin administration rescued none of the rabbits.<bold>Conclusion: </bold>Combination therapy with H12-(ADP)-liposomes and HbVs may be effective for damage control resuscitation of trauma-induced massive hemorrhage.
- Publication
Transfusion, 2019, Vol 59, Issue 7, pN.PAG
- ISSN
0041-1132
- Publication type
journal article
- DOI
10.1111/trf.15427