• Kohsuke Hagisawa, Manabu Kinoshita, Bonpei Takase, Kenichi Hashimoto, Daizoh Saitoh, Shuhji Seki, Yasuhiro Nishida, and Hiromi Sakai.
• Department of Physiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
• Shock. 2018 Sep 1; 50 (3): 324-330.

IntroductionWe have developed hemoglobin vesicles (HbVs) as a substitute for red blood cells (RBCs). We investigated the efficacy of HbV transfusion in the treatment of massive hemorrhage in rabbits in the setting of thrombocytopenic coagulopathy, focusing on the efficacy of hemostasis by subsequent platelet transfusion.MethodsThrombocytopenic coagulopathy was induced in rabbits by repeated blood withdrawal and isovolemic retransfusion of autologous RBC (platelet counts <45,000/μL). A penetrating liver injury was then made. For 30 min, bleeding volume was measured every 10 min, after which subjects were transfused with an equivalent volume of stored RBC, HbV, or platelet poor plasma (PPP) to compensate for blood loss, simulating initial prehospital resuscitation. Thereafter, we transfused platelet rich plasma (PRP) to stop bleeding, which simulated inhospital resuscitation.ResultsDuring the initial resuscitation, the HbV group was similar to the RBC group (but not the PPP group) in their hemodynamics and tissue circulation/oxygenation as assessed by plasma lactate levels. All rabbits showed similar bleeding volumes (20-30 mL) in this period. HbV-transfused rabbits sustained hemoglobin levels, but showed lower hematocrit levels compared with RBC-transfused rabbits. Subsequent PRP transfusion effectively stopped bleeding in all RBC-transfused rabbits (6/6) and most HbV-transfused rabbits (7/8) but not PPP-transfused rabbits (2/8). In addition, 83% of RBC-transfused rabbits and 75% of HbV-transfused rabbits survived for 24 h, although no PPP-transfused rabbits survived. HbV transfusion did not scavenge nitric oxide in rabbits.ConclusionsHbV transfusion effectively rescued rabbits from severe hemorrhage with coagulopathy, without disturbing hemostasis after the platelet transfusion. HbV transfusion may be practical and useful in prehospital resuscitation.

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