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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
Author(s) -
Hagisawa Kohsuke,
Nishikawa Kahoko,
Yanagawa Rempei,
Kinoshita Manabu,
Doi Mami,
Suzuki Hidenori,
Iwaya Keiichi,
Saitoh Daizoh,
Seki Shuhji,
Takeoka Shinji,
Handa Makoto,
Nishida Yasuhiro
Publication year - 2015
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12829
Subject(s) - liposome , medicine , platelet , pharmacology , fibrinogen , thrombus , hemostasis , anesthesia , chemistry , biochemistry
Background We evaluated the hemostatic efficacy of H 12‐(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 × 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 H 12‐( ADP )‐liposomes with PLT ‐poor plasma ( PPP ), PLT ‐rich plasma ( PRP ), PPP alone, H 12‐(phosphate‐buffered saline [ PBS ])‐liposome/ PPP , or H 12‐( ADP )‐liposomes/ PPP plus fibrinogen concentrate during the tamponade. Results Administration of H 12‐( ADP )‐liposomes/ PPP rescued 60% of the rabbits from the liver hemorrhage; PRP administration rescued 50%. In contrast, rabbits receiving PPP or H 12‐( PBS )‐liposome/ PPP achieved only 10 or 17% survival, respectively, for the first 24 hours. H 12‐( 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 ( H 12‐( 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). H 12‐( 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 H 12‐( ADP )‐liposomes. Supplementation of fibrinogen to H 12‐( ADP )‐liposomes/PPP did not significantly improve rabbit survival. Conclusions H 12‐( ADP )‐liposomes might be a safe and effective therapeutic tool during damage control surgery for trauma patients with acute thrombocytopenia and massive bleeding.