Fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes rescue thrombocytopenic rabbits from non-compressible liver hemorrhage
Article first published online: 1 OCT 2012
© 2012 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 10, Issue 10, pages 2137–2148, October 2012
How to Cite
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. and HANDA, M. (2012), Fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes rescue thrombocytopenic rabbits from non-compressible liver hemorrhage. Journal of Thrombosis and Haemostasis, 10: 2137–2148. doi: 10.1111/j.1538-7836.2012.04889.x
- Issue published online: 1 OCT 2012
- Article first published online: 1 OCT 2012
- Accepted manuscript online: 20 AUG 2012 10:20AM EST
- Received 9 March 2012, accepted 30 July 2012
- liver hemorrhage;
- platelet substitute;
Summary. 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 < 50 000 μL−1) was induced in rabbits by repeated blood withdrawal (100 mL kg−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 24 h. 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 (25 000 platelets μL−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.