H12-(ADP)-liposomes for hemorrhagic shock in thrombocytopenia: Mesenteric artery injury model in rabbits.
H12-(ADP)-liposomes for hemorrhagic shock in thrombocytopenia: Mesenteric artery injury model in rabbits.
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DOI：
10.1002/rth2.12659
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发表时间：
2022-03
影响因子：
4.6
通讯作者：
Morimoto Y
中科院分区：
文献类型：
--
作者：
Hagisawa K;Kinoshita M;Takeoka S;Ishida O;Ichiki Y;Saitoh D;Hotta M;Takikawa M;Torres Filho IP;Morimoto Y
损伤控制复苏可改善严重出血和凝血障碍患者的预后。然而，缺乏针对这些危急情况的有效止血方法。我们评价了纤维蛋白原γ链（HHLGGAKQAGDV，H12）包被的二磷酸腺苷（ADP）脂质体（H12-[ADP]-脂质体）在失血性休克失血性休克家兔中的止血效果。在同时接受肠系膜血管损伤的家兔中诱导急性血小板减少症（80%），导致失血性休克。损伤后5分钟，受试者接受静脉推注H12-（ADP）-脂质体（20 mg/kg），然后每5分钟输注一次储存的红细胞（RBC）/贫血小板血浆（PPP）（RBC：PPP = 1：1 [vol/vol]）或乳酸林格氏液以补偿失血。一组接受H12-（磷酸盐缓冲盐水[PBS]）脂质体，随后接受RBC/PPP。其他组接受RBC/富血小板血浆（PRP）（RBC：PRP = 1：1 [vol/vol]）、RBC/PPP、单独PPP或乳酸林格氏液等容输注。H12-（ADP）-脂质体治疗后，RBC/PPP输注和RBC/PRP输注可有效止血。相比之下，用RBC/PPP处理的10只兔中有3只止血失败，并且没有接受乳酸林格氏液的兔止血或存活。出血后24小时，接受H12-（ADP）-脂质体然后输注RBC/PPP的家兔有80%存活，接受RBC/PRP输注的家兔也有70%存活，尽管输注RBC/PPP的家兔存活率为40%。接受H12-（ADP）-脂质体和乳酸林格氏溶液的家兔显示出短暂的止血潜力，但未能存活。H12-（PBS）-脂质体显示对止血无有益作用。PPP组和乳酸林格氏液组均未存活。H12-（ADP）-脂质体处理后RBC/PPP可能对凝血病家兔肠系膜血管损伤后的致死性出血有效。
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.
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