TY - JOUR
T1 - H12-(ADP)-liposomes for hemorrhagic shock in thrombocytopenia
T2 - Mesenteric artery injury model in rabbits
AU - Hagisawa, Kohsuke
AU - Kinoshita, Manabu
AU - Takeoka, Shinji
AU - Ishida, Osamu
AU - Ichiki, Yayoi
AU - Saitoh, Daizoh
AU - Hotta, Morihiro
AU - Takikawa, Masato
AU - Torres Filho, Ivo P.
AU - Morimoto, Yuji
N1 - Funding Information:
This work was supported in part by JSPS (Japan Society for the Promotion of Science) KAKENHI Grant Number 19K07517 (K.H., M.K., S.T., and O.I.).
Publisher Copyright:
© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).
PY - 2022/2
Y1 - 2022/2
N2 - Background: Damage control resuscitation improves patient outcomes after severe hemorrhage and coagulopathy. However, effective hemostasis methods for these critical situations are lacking. Objective: 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. Methods: 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. Results: 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. Conclusion: H12-(ADP)-liposome treatment followed by RBC/PPP may be effective in lethal hemorrhage after mesenteric vessel injury in coagulopathic rabbits.
AB - Background: Damage control resuscitation improves patient outcomes after severe hemorrhage and coagulopathy. However, effective hemostasis methods for these critical situations are lacking. Objective: 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. Methods: 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. Results: 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. Conclusion: H12-(ADP)-liposome treatment followed by RBC/PPP may be effective in lethal hemorrhage after mesenteric vessel injury in coagulopathic rabbits.
KW - hemorrhagic shock
KW - mesenteric artery
KW - platelet transfusion
KW - resuscitation
KW - thrombocytopenia
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U2 - 10.1002/rth2.12659
DO - 10.1002/rth2.12659
M3 - Article
AN - SCOPUS:85127248935
SN - 2475-0379
VL - 6
JO - Research and Practice in Thrombosis and Haemostasis
JF - Research and Practice in Thrombosis and Haemostasis
IS - 2
M1 - e12659
ER -