{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:02:52Z","timestamp":1791576172450,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>We previously developed substitutes for red blood cells (RBCs) and platelets (PLTs) for transfusion. These substitutes included hemoglobin vesicles (HbVs) and fibrinogen \u03b3\u2010chain (dodecapeptide HHLGGAKQAGDV, H12)\u2013coated, adenosine diphosphate (ADP)\u2010encapsulated liposomes [H12\u2010(ADP)\u2010liposomes]. Here, we examined the efficacy of combination therapy using these substitutes instead of RBC and PLT transfusion in a rabbit model with trauma\u2010induced massive hemorrhage with coagulopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>Thrombocytopenia (PLT count approximately 40,000\/\u03bcL) 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\u2010(ADP)\u2010liposomes with platelet\u2010poor plasma (PPP), platelet\u2010rich 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Administration of H12\u2010(ADP)\u2010liposomes\/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\u2009hr, respectively). In contrast, 5% albumin administration rescued none of the rabbits.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Combination therapy with H12\u2010(ADP)\u2010liposomes and HbVs may be effective for damage control resuscitation of trauma\u2010induced massive hemorrhage.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.15427","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T09:00:58Z","timestamp":1561971658000},"page":"3186-3196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Combination therapy using fibrinogen \u03b3\u2010chain peptide\u2010coated, ADP\u2010encapsulated liposomes and hemoglobin vesicles for trauma\u2010induced massive hemorrhage in thrombocytopenic rabbits"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-4570","authenticated-orcid":false,"given":"Kohsuke","family":"Hagisawa","sequence":"first","affiliation":[{"name":"Departments of Physiology National Defense Medical College  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology National Defense Medical College  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Takikawa","sequence":"additional","affiliation":[{"name":"Departments of Advanced Science and Engineering Graduate School of Advanced Science and Engineering, Waseda University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Takeoka","sequence":"additional","affiliation":[{"name":"Departments of Life Science and Medical Bioscience Graduate School of Advanced Science and Engineering, Waseda University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daizoh","family":"Saitoh","sequence":"additional","affiliation":[{"name":"Division of Traumatology National Defense Medical College Research Institute  Tokorozawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhji","family":"Seki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology National Defense Medical College  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Chemistry Nara Medical University  Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wem.2016.12.007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aes389"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ta.0000199549.80731.e6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200607000-00030"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e318185a9ad"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14972"},{"key":"e_1_2_9_8_1","unstructured":"Multifunctional Resuscitation Fluid: Office of Naval Research Broad Agency Announcement # 10\u2010008. 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