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, Shinji Takeoka, M. Handa

    Research output: Contribution to journalArticle

    17 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

    Fingerprint

    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, Shinji; 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, Shinji ; 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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    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.",
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    TY - JOUR

    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, Shinji

    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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