Combination therapy using fibrinogen γ‐chain peptide‐coated, ADP‐encapsulated liposomes and hemoglobin vesicles for trauma‐induced massive hemorrhage in thrombocytopenic rabbits

BACKGROUND 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. STUDY DESIGN AND METHODS 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. RESULTS 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. CONCLUSION Combination therapy with H12‐(ADP)‐liposomes and HbVs may be effective for damage control resuscitation of trauma‐induced massive hemorrhage.