Fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes rescue thrombocytopenic rabbits from non-compressible liver hemorrhage

K. Nishikawa, K. Hagisawa, M. Kinoshita, S. Shono, S. Katsuno, M. Doi, R. Yanagawa, H. Suzuki, K. Iwaya, D. Saitoh, T. Sakamoto, S. Seki, S. Takeoka, M. Handa

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: We developed a fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV [H12])-coated, ADP-encapsulated liposome (H12-[ADP]-liposome) that accumulates at bleeding sites via interaction with activated platelets via glycoprotein IIb-IIIa and augments platelet aggregation by releasing ADP. Objective: To evaluate the efficacy of H12-(ADP)-liposomes for treating liver hemorrhage in rabbits with acute thrombocytopenia. Methods: Thrombocytopenia (platelets<50000μL-1) was induced in rabbits by repeated blood withdrawal (100mLkg-1 in total) and isovolemic transfusion of autologous washed red blood cells. H12-(ADP)-liposomes with platelet-poor plasma (PPP), platelet-rich plasma (PRP), PPP, ADP liposomes with PPP or H12-(PBS)-liposomes/PPP, were administered to the thrombocytopenic rabbits, and liver hemorrhage was induced by penetrating liver injury. Results: Administration of H12-(ADP)-liposomes and of PRP rescued all thrombocytopenic rabbits from liver hemorrhage as a result of potent hemostasis at the liver bleeding site, although rabbits receiving PPP or ADP liposomes showed 20% survival in the first 24h. Administration of H12-(ADP)-liposomes and of PRP suppressed both bleeding volume and time from the site of liver injury. H12-(phosphate-buffered saline)-liposomes lacking ADP also improved rabbit survival after liver hemorrhage, although their hemostatic effect was weaker. In rabbits with severe thrombocytopenia (25000 plateletsμL-1), the hemostatic effects of H12-(ADP)-liposomes tended to be attenuated as compared with those of PRP treatment. Histologic examination revealed that H12-(ADP)-liposomes accumulated at the bleeding site in the liver. Notably, neither macrothombi nor microthrombi were detected in the lung, kidney or liver in rabbits treated with H12-(ADP)-liposomes. Conclusions: H12-(ADP)-liposomes appear to be a safe and effective therapeutic tool for acute thrombocytopenic trauma patients with massive bleeding.

Original languageEnglish
Pages (from-to)2137-2148
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume10
Issue number10
DOIs
Publication statusPublished - 2012 Oct

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Liposomes
Adenosine Diphosphate
Fibrinogen
Hemorrhage
Rabbits
Peptides
Liver
Platelet-Rich Plasma
Blood Platelets
Thrombocytopenia
Hemostatics
Wounds and Injuries
Platelet Membrane Glycoproteins
Platelet Glycoprotein GPIIb-IIIa Complex
Bleeding Time
Hemostasis
Platelet Aggregation
Erythrocytes
Phosphates
Kidney

Keywords

  • Hemostasis
  • Liver hemorrhage
  • Nanotechnology
  • Platelet substitute
  • Rabbits
  • Thrombocytopenia

ASJC Scopus subject areas

  • Hematology

Cite this

Fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes rescue thrombocytopenic rabbits from non-compressible liver hemorrhage. / Nishikawa, K.; Hagisawa, K.; Kinoshita, M.; Shono, S.; Katsuno, S.; Doi, M.; Yanagawa, R.; Suzuki, H.; Iwaya, K.; Saitoh, D.; Sakamoto, T.; Seki, S.; Takeoka, S.; Handa, M.

In: Journal of Thrombosis and Haemostasis, Vol. 10, No. 10, 10.2012, p. 2137-2148.

Research output: Contribution to journalArticle

Nishikawa, K, Hagisawa, K, Kinoshita, M, Shono, S, Katsuno, S, Doi, M, Yanagawa, R, Suzuki, H, Iwaya, K, Saitoh, D, Sakamoto, T, Seki, S, Takeoka, S & Handa, M 2012, 'Fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes rescue thrombocytopenic rabbits from non-compressible liver hemorrhage', Journal of Thrombosis and Haemostasis, vol. 10, no. 10, pp. 2137-2148. https://doi.org/10.1111/j.1538-7836.2012.04889.x
Nishikawa, K. ; Hagisawa, K. ; Kinoshita, M. ; Shono, S. ; Katsuno, S. ; Doi, M. ; Yanagawa, R. ; Suzuki, H. ; Iwaya, K. ; Saitoh, D. ; Sakamoto, T. ; Seki, S. ; Takeoka, S. ; Handa, M. / Fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes rescue thrombocytopenic rabbits from non-compressible liver hemorrhage. In: Journal of Thrombosis and Haemostasis. 2012 ; Vol. 10, No. 10. pp. 2137-2148.
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T1 - Fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes rescue thrombocytopenic rabbits from non-compressible liver hemorrhage

AU - Nishikawa, K.

AU - Hagisawa, K.

AU - Kinoshita, M.

AU - Shono, S.

AU - Katsuno, S.

AU - Doi, M.

AU - Yanagawa, R.

AU - Suzuki, H.

AU - Iwaya, K.

AU - Saitoh, D.

AU - Sakamoto, T.

AU - Seki, S.

AU - Takeoka, S.

AU - Handa, M.

PY - 2012/10

Y1 - 2012/10

N2 - Background: We developed a fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV [H12])-coated, ADP-encapsulated liposome (H12-[ADP]-liposome) that accumulates at bleeding sites via interaction with activated platelets via glycoprotein IIb-IIIa and augments platelet aggregation by releasing ADP. Objective: To evaluate the efficacy of H12-(ADP)-liposomes for treating liver hemorrhage in rabbits with acute thrombocytopenia. Methods: Thrombocytopenia (platelets<50000μL-1) was induced in rabbits by repeated blood withdrawal (100mLkg-1 in total) and isovolemic transfusion of autologous washed red blood cells. H12-(ADP)-liposomes with platelet-poor plasma (PPP), platelet-rich plasma (PRP), PPP, ADP liposomes with PPP or H12-(PBS)-liposomes/PPP, were administered to the thrombocytopenic rabbits, and liver hemorrhage was induced by penetrating liver injury. Results: Administration of H12-(ADP)-liposomes and of PRP rescued all thrombocytopenic rabbits from liver hemorrhage as a result of potent hemostasis at the liver bleeding site, although rabbits receiving PPP or ADP liposomes showed 20% survival in the first 24h. Administration of H12-(ADP)-liposomes and of PRP suppressed both bleeding volume and time from the site of liver injury. H12-(phosphate-buffered saline)-liposomes lacking ADP also improved rabbit survival after liver hemorrhage, although their hemostatic effect was weaker. In rabbits with severe thrombocytopenia (25000 plateletsμL-1), the hemostatic effects of H12-(ADP)-liposomes tended to be attenuated as compared with those of PRP treatment. Histologic examination revealed that H12-(ADP)-liposomes accumulated at the bleeding site in the liver. Notably, neither macrothombi nor microthrombi were detected in the lung, kidney or liver in rabbits treated with H12-(ADP)-liposomes. Conclusions: H12-(ADP)-liposomes appear to be a safe and effective therapeutic tool for acute thrombocytopenic trauma patients with massive bleeding.

AB - Background: We developed a fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV [H12])-coated, ADP-encapsulated liposome (H12-[ADP]-liposome) that accumulates at bleeding sites via interaction with activated platelets via glycoprotein IIb-IIIa and augments platelet aggregation by releasing ADP. Objective: To evaluate the efficacy of H12-(ADP)-liposomes for treating liver hemorrhage in rabbits with acute thrombocytopenia. Methods: Thrombocytopenia (platelets<50000μL-1) was induced in rabbits by repeated blood withdrawal (100mLkg-1 in total) and isovolemic transfusion of autologous washed red blood cells. H12-(ADP)-liposomes with platelet-poor plasma (PPP), platelet-rich plasma (PRP), PPP, ADP liposomes with PPP or H12-(PBS)-liposomes/PPP, were administered to the thrombocytopenic rabbits, and liver hemorrhage was induced by penetrating liver injury. Results: Administration of H12-(ADP)-liposomes and of PRP rescued all thrombocytopenic rabbits from liver hemorrhage as a result of potent hemostasis at the liver bleeding site, although rabbits receiving PPP or ADP liposomes showed 20% survival in the first 24h. Administration of H12-(ADP)-liposomes and of PRP suppressed both bleeding volume and time from the site of liver injury. H12-(phosphate-buffered saline)-liposomes lacking ADP also improved rabbit survival after liver hemorrhage, although their hemostatic effect was weaker. In rabbits with severe thrombocytopenia (25000 plateletsμL-1), the hemostatic effects of H12-(ADP)-liposomes tended to be attenuated as compared with those of PRP treatment. Histologic examination revealed that H12-(ADP)-liposomes accumulated at the bleeding site in the liver. Notably, neither macrothombi nor microthrombi were detected in the lung, kidney or liver in rabbits treated with H12-(ADP)-liposomes. Conclusions: H12-(ADP)-liposomes appear to be a safe and effective therapeutic tool for acute thrombocytopenic trauma patients with massive bleeding.

KW - Hemostasis

KW - Liver hemorrhage

KW - Nanotechnology

KW - Platelet substitute

KW - Rabbits

KW - Thrombocytopenia

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