Hagisawa Kohsuke, Kinoshita Manabu, Takeoka Shinji, Ishida Osamu, Ichiki Yayoi, Saitoh Daizoh, Hotta Morihiro, Takikawa Masato, Torres Filho Ivo P, Morimoto Yuji
Department of Physiology National Defense Medical College Tokorozawa Japan.
Department of Immunology and Microbiology National Defense Medical College Tokorozawa Japan.
Res Pract Thromb Haemost. 2022 Feb 15;6(2):e12659. doi: 10.1002/rth2.12659. eCollection 2022 Feb.
Damage control resuscitation improves patient outcomes after severe hemorrhage and coagulopathy. However, effective hemostasis methods for these critical situations are lacking.
We evaluated the hemostatic efficacy of fibrinogen γ-chain (HHLGGAKQAGDV, H12)-coated, adenosine-diphosphate (ADP)-encapsulated liposomes (H12-[ADP]-liposomes) in thrombocytopenic rabbits with hemorrhagic shock.
Acute thrombocytopenia (80%) was induced in rabbits that also received mesenteric vessel injury, leading to hemorrhagic shock. Five minutes after injury, subjects received intravenous bolus injection with H12-(ADP)-liposomes (20 mg/kg), followed by isovolemic transfusion with stored red blood cells (RBCs)/platelet poor plasma (PPP) (RBC:PPP = 1:1 [vol/vol]), or lactated Ringer solution every 5 min to compensate blood loss. One group received H12-(phosphate buffered saline [PBS]) liposomes followed by RBC/PPP. Additional groups were received isovolemic transfusion with RBC/platelet rich plasma (PRP) (RBC:PRP = 1:1 [vol/vol]), RBC/PPP, PPP alone, or lactated Ringer solution.
Treatment with H12-(ADP)-liposomes followed by RBC/PPP transfusion and RBC/PRP transfusion effectively stopped bleeding in all thrombocytopenic rabbits. In contrast, three of 10 rabbits treated with RBC/PPP failed hemostasis, and no rabbits receiving lactated Ringer solution stopped bleeding or survived. Twenty-four hours after hemorrhage, 80% of rabbits receiving H12-(ADP)-liposome followed by RBC/PPP transfusion survived and 70% of rabbits receiving RBC/PRP transfusion also survived, although RBC/PPP-transfused rabbits showed 40% survival. Rabbits receiving H12-(ADP)-liposomes followed by lactated Ringer solution showed a transient hemostatic potential but failed to survive. H12-(PBS)-liposomes showed no beneficial effect on hemostasis. Neither the PPP group nor the lactated Ringer group survived.
H12-(ADP)-liposome treatment followed by RBC/PPP may be effective in lethal hemorrhage after mesenteric vessel injury in coagulopathic rabbits.
损伤控制复苏可改善严重出血和凝血病患者的预后。然而，针对这些危急情况缺乏有效的止血方法。
我们评估了纤维蛋白原γ链（HHLGGAKQAGDV，H12）包被、二磷酸腺苷（ADP）封装的脂质体（H12-[ADP]-脂质体）对血小板减少性出血性休克兔的止血效果。
诱导兔急性血小板减少（80%），同时造成肠系膜血管损伤，导致出血性休克。损伤后5分钟，受试动物静脉推注H12-(ADP)-脂质体（20 mg/kg），随后每隔5分钟等量输注储存红细胞（RBC）/少血小板血浆（PPP）（RBC:PPP = 1:1[体积/体积]）或乳酸林格液以补偿失血。一组接受H12-(磷酸盐缓冲液[PBS])脂质体，随后输注RBC/PPP。其他组分别接受等量输注RBC/富含血小板血浆（PRP）（RBC:PRP = 1:1[体积/体积]）、RBC/PPP、单纯PPP或乳酸林格液。
先给予H12-(ADP)-脂质体治疗，随后输注RBC/PPP和RBC/PRP可有效止住所有血小板减少性兔的出血。相比之下，10只接受RBC/PPP治疗的兔中有3只止血失败，接受乳酸林格液治疗的兔均未止血或存活。出血后24小时，先接受H12-(ADP)-脂质体治疗随后输注RBC/PPP的兔中80%存活，接受RBC/PRP治疗的兔中70%存活，不过接受RBC/PPP输注的兔存活率为40%。先接受H12-(ADP)-脂质体治疗随后接受乳酸林格液治疗的兔显示出短暂的止血潜能，但未能存活。H12-(PBS)-脂质体对止血无有益作用。PPP组和乳酸林格液组均未存活。
先给予H12-(ADP)-脂质体治疗随后输注RBC/PPP可能对凝血病兔肠系膜血管损伤后的致命性出血有效。
