Treatment with fibrinogen γ-chain peptide-coated, adenosine 5′-diphosphate-encapsulated liposomes as an infusible hemostatic agent against active liver bleeding in rabbits with acute thrombocytopenia

Kohsuke Hagisawa, Kahoko Nishikawa, Rempei Yanagawa, Manabu Kinoshita, Mami Doi, Hidenori Suzuki, Keiichi Iwaya, Daizoh Saitoh, Shuhji Seki, Shinji Takeoka, Makoto Handa, Yasuhiro Nishida

Research output: Contribution to journalArticle

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Abstract

Background: We evaluated the hemostatic efficacy of H12-(adenosine 5′-diphosphate [ADP])-liposomes in the setting of active liver bleeding in rabbits with dilutional thrombocytopenia after massive transfusion. Study Design and Methods: Acute thrombocytopenia (platelet [PLT] count < 50 × 109/L) was induced in rabbits by repeated blood withdrawal and isovolemic transfusion of autologous washed red blood cells. Liver hemorrhage was initiated by a penetrating liver injury. Subsequently, the animals received tamponade treatment for the liver hemorrhage for 5 minutes and were intravenously administered H12-(ADP)-liposomes with PLT-poor plasma (PPP), PLT-rich plasma (PRP), PPP alone, H12-(phosphate-buffered saline [PBS])-liposome/PPP, or H12-(ADP)-liposomes/PPP plus fibrinogen concentrate during the tamponade. Results: Administration of H12-(ADP)-liposomes/PPP rescued 60% of the rabbits from the liver hemorrhage; PRP administration rescued 50%. In contrast, rabbits receiving PPP or H12-(PBS)-liposome/PPP achieved only 10 or 17% survival, respectively, for the first 24 hours. H12-(ADP)-liposomes/PPP as well as PRP consistently reduced bleeding volumes and shortened clotting times (CTs) in comparison to PPP administration. Specifically, bleeding volumes in the initial 5 minutes averaged 11 mL (H12-(ADP)-liposomes/PPP) and 17 mL (PRP) versus 30 mL (PPP; p < 0.05); CTs averaged 270 and 306 seconds versus 401 seconds (p < 0.05). H12-(ADP)-liposomes were observed at the bleeding site with thrombus formation, suggesting an induction of thrombi. Neither macro- nor microthrombi were detected in the lung, kidney, spleen, or liver in rabbits treated with H12-(ADP)-liposomes. Supplementation of fibrinogen to H12-(ADP)-liposomes/PPP did not significantly improve rabbit survival. Conclusions: H12-(ADP)-liposomes might be a safe and effective therapeutic tool during damage control surgery for trauma patients with acute thrombocytopenia and massive bleeding.

Original languageEnglish
Pages (from-to)314-325
Number of pages12
JournalTransfusion
Volume55
Issue number2
DOIs
Publication statusPublished - 2015 Feb 1

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Hemostatics
Liposomes
Thrombocytopenia
Adenosine Diphosphate
Fibrinogen
Hemorrhage
Rabbits
Peptides
Liver
Therapeutics
Thrombosis
Phosphates
Platelet-Rich Plasma
Wounds and Injuries
Platelet Count

ASJC Scopus subject areas

  • Hematology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Treatment with fibrinogen γ-chain peptide-coated, adenosine 5′-diphosphate-encapsulated liposomes as an infusible hemostatic agent against active liver bleeding in rabbits with acute thrombocytopenia. / Hagisawa, Kohsuke; Nishikawa, Kahoko; Yanagawa, Rempei; Kinoshita, Manabu; Doi, Mami; Suzuki, Hidenori; Iwaya, Keiichi; Saitoh, Daizoh; Seki, Shuhji; Takeoka, Shinji; Handa, Makoto; Nishida, Yasuhiro.

In: Transfusion, Vol. 55, No. 2, 01.02.2015, p. 314-325.

Research output: Contribution to journalArticle

Hagisawa, K, Nishikawa, K, Yanagawa, R, Kinoshita, M, Doi, M, Suzuki, H, Iwaya, K, Saitoh, D, Seki, S, Takeoka, S, Handa, M & Nishida, Y 2015, 'Treatment with fibrinogen γ-chain peptide-coated, adenosine 5′-diphosphate-encapsulated liposomes as an infusible hemostatic agent against active liver bleeding in rabbits with acute thrombocytopenia', Transfusion, vol. 55, no. 2, pp. 314-325. https://doi.org/10.1111/trf.12829
Hagisawa, Kohsuke ; Nishikawa, Kahoko ; Yanagawa, Rempei ; Kinoshita, Manabu ; Doi, Mami ; Suzuki, Hidenori ; Iwaya, Keiichi ; Saitoh, Daizoh ; Seki, Shuhji ; Takeoka, Shinji ; Handa, Makoto ; Nishida, Yasuhiro. / Treatment with fibrinogen γ-chain peptide-coated, adenosine 5′-diphosphate-encapsulated liposomes as an infusible hemostatic agent against active liver bleeding in rabbits with acute thrombocytopenia. In: Transfusion. 2015 ; Vol. 55, No. 2. pp. 314-325.
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abstract = "Background: We evaluated the hemostatic efficacy of H12-(adenosine 5′-diphosphate [ADP])-liposomes in the setting of active liver bleeding in rabbits with dilutional thrombocytopenia after massive transfusion. Study Design and Methods: Acute thrombocytopenia (platelet [PLT] count < 50 × 109/L) was induced in rabbits by repeated blood withdrawal and isovolemic transfusion of autologous washed red blood cells. Liver hemorrhage was initiated by a penetrating liver injury. Subsequently, the animals received tamponade treatment for the liver hemorrhage for 5 minutes and were intravenously administered H12-(ADP)-liposomes with PLT-poor plasma (PPP), PLT-rich plasma (PRP), PPP alone, H12-(phosphate-buffered saline [PBS])-liposome/PPP, or H12-(ADP)-liposomes/PPP plus fibrinogen concentrate during the tamponade. Results: Administration of H12-(ADP)-liposomes/PPP rescued 60{\%} of the rabbits from the liver hemorrhage; PRP administration rescued 50{\%}. In contrast, rabbits receiving PPP or H12-(PBS)-liposome/PPP achieved only 10 or 17{\%} survival, respectively, for the first 24 hours. H12-(ADP)-liposomes/PPP as well as PRP consistently reduced bleeding volumes and shortened clotting times (CTs) in comparison to PPP administration. Specifically, bleeding volumes in the initial 5 minutes averaged 11 mL (H12-(ADP)-liposomes/PPP) and 17 mL (PRP) versus 30 mL (PPP; p < 0.05); CTs averaged 270 and 306 seconds versus 401 seconds (p < 0.05). H12-(ADP)-liposomes were observed at the bleeding site with thrombus formation, suggesting an induction of thrombi. Neither macro- nor microthrombi were detected in the lung, kidney, spleen, or liver in rabbits treated with H12-(ADP)-liposomes. Supplementation of fibrinogen to H12-(ADP)-liposomes/PPP did not significantly improve rabbit survival. Conclusions: H12-(ADP)-liposomes might be a safe and effective therapeutic tool during damage control surgery for trauma patients with acute thrombocytopenia and massive bleeding.",
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T1 - Treatment with fibrinogen γ-chain peptide-coated, adenosine 5′-diphosphate-encapsulated liposomes as an infusible hemostatic agent against active liver bleeding in rabbits with acute thrombocytopenia

AU - Hagisawa, Kohsuke

AU - Nishikawa, Kahoko

AU - Yanagawa, Rempei

AU - Kinoshita, Manabu

AU - Doi, Mami

AU - Suzuki, Hidenori

AU - Iwaya, Keiichi

AU - Saitoh, Daizoh

AU - Seki, Shuhji

AU - Takeoka, Shinji

AU - Handa, Makoto

AU - Nishida, Yasuhiro

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Background: We evaluated the hemostatic efficacy of H12-(adenosine 5′-diphosphate [ADP])-liposomes in the setting of active liver bleeding in rabbits with dilutional thrombocytopenia after massive transfusion. Study Design and Methods: Acute thrombocytopenia (platelet [PLT] count < 50 × 109/L) was induced in rabbits by repeated blood withdrawal and isovolemic transfusion of autologous washed red blood cells. Liver hemorrhage was initiated by a penetrating liver injury. Subsequently, the animals received tamponade treatment for the liver hemorrhage for 5 minutes and were intravenously administered H12-(ADP)-liposomes with PLT-poor plasma (PPP), PLT-rich plasma (PRP), PPP alone, H12-(phosphate-buffered saline [PBS])-liposome/PPP, or H12-(ADP)-liposomes/PPP plus fibrinogen concentrate during the tamponade. Results: Administration of H12-(ADP)-liposomes/PPP rescued 60% of the rabbits from the liver hemorrhage; PRP administration rescued 50%. In contrast, rabbits receiving PPP or H12-(PBS)-liposome/PPP achieved only 10 or 17% survival, respectively, for the first 24 hours. H12-(ADP)-liposomes/PPP as well as PRP consistently reduced bleeding volumes and shortened clotting times (CTs) in comparison to PPP administration. Specifically, bleeding volumes in the initial 5 minutes averaged 11 mL (H12-(ADP)-liposomes/PPP) and 17 mL (PRP) versus 30 mL (PPP; p < 0.05); CTs averaged 270 and 306 seconds versus 401 seconds (p < 0.05). H12-(ADP)-liposomes were observed at the bleeding site with thrombus formation, suggesting an induction of thrombi. Neither macro- nor microthrombi were detected in the lung, kidney, spleen, or liver in rabbits treated with H12-(ADP)-liposomes. Supplementation of fibrinogen to H12-(ADP)-liposomes/PPP did not significantly improve rabbit survival. Conclusions: H12-(ADP)-liposomes might be a safe and effective therapeutic tool during damage control surgery for trauma patients with acute thrombocytopenia and massive bleeding.

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