Introduction: We developed a Hemoglobin vesicle (HbV) and a fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, adenosine-diphosphate (ADP)-encapsulated liposomes [H12-(ADP)-liposomes], which are artificial substitute for Red blood cells (RBCs) and platelet, respectively.
Hypothesis: To evaluate the efficacy of HbV and H12-(ADP)-liposomes for alternative treatment instead of massive transfusion protocol (MTP) in rabbits with hemorrhagic shock and trauma-induced coagulopathy.
Methods: Thrombocytopenia was induced in rabbits by repeated blood withdrawal and isovolemic transfusion of autologous washed red blood cells. Subsequent penetrating liver injury caused uncontrolled hemorrhage, resulting in exacerbation of thrombocytopenia and hemorrhagic shock. H12-(ADP)-liposomes with platelet-poor plasma (PPP) (n=20) or platelet-rich plasma (PRP, n=16) was administered to the thrombocytopenic rabbits during liver hemorrhage. After achieving hemostasis, the subject animals receiving H12-(ADP)-liposomes/PPP were administered HbV (n=10) or allogenic RBCs transfusion (n=10). Also, the subjects receiving PRP were administered RBC (n=10) or 5% albumin (n=6).
Results: In anemic and thrombocytopenic rabbits (Hb < 6.0 g/dl, platelet count < 40,000 /μL), administration with HbV and H12-(ADP)-liposomes as well as transfusion with RBCs concentrate and PRP rescued 60-70 % animals from liver hemorrhage because of potent hemostasis in the liver bleeding site and improvement of severe hypohemogloblinemia, although rabbits receiving 5% albumin showed no survival in the first 24 hours.
Conclusions: Combination therapy with HbV and H12-(ADP)-liposomes may be effective instead of standard MTP with RBCs, platelets and plasma for acute hemorrhagic shock and trauma-induced coagulopathy.