title: 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.
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.
  
  
  METHODS
  Acute thrombocytopenia (platelet [PLT] count < 50 × 10(9) /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.
authors.affiliation: Department of Physiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Hagisawa
authors.forename: Kahoko
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Rempei
authors.initials: R
authors.lastname: Yanagawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Mami
authors.initials: M
authors.lastname: Doi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwaya
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.forename: Shuhji
authors.initials: S
authors.lastname: Seki
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Handa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishida
mesh_terms: D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D005340:Fibrinogen / Q000494:pharmacology*; D006470:Hemorrhage / Q000188:drug therapy*; D008081:Liposomes; D008099:Liver / Q000293:injuries*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013921:Thrombocytopenia / Q000188:drug therapy*
chemical_list: D008081:Liposomes; D010975:Platelet Aggregation Inhibitors; C027539:fibrinopeptides gamma; D000244:Adenosine Diphosphate; D005340:Fibrinogen