Therapeutic potential of fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes as a haemostatic adjuvant for post-cardiopulmonary bypass coagulopathy
Therapeutic potential of fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes as a haemostatic adjuvant for post-cardiopulmonary bypass coagulopathy
复制标题
纤维蛋白原 γ 链肽包被、ADP 封装的脂质体作为心肺旁路术后凝血病止血佐剂的治疗潜力
DOI：
10.1038/s41598-020-68307-5
复制
发表时间：
2020
影响因子：
4.6
通讯作者：
Kinoshita Manabu
中科院分区：
文献类型：
--
作者：
Ishida Osamu;Hagisawa Kohsuke;Yamanaka Nozomu;Tsutsumi Koji;Suzuki Hidenori;Takikawa Masato;Takeoka Shinji;Kinoshita Manabu
纤维蛋白原γ链肽包被的5′-二磷酸腺苷（ADP）脂质体（H12-ADP-liposomes）是一种有效的促血小板血栓形成的止血佐剂。这些脂质体是涂有血小板GPIIb/IIIa特异性结合位点并包裹ADP的脂质颗粒。它们在出血部位起作用，通过促进活化血小板聚集和释放ADP以强烈活化血小板来促进止血。在这项研究中，我们研究了H12-ADP-脂质体在临床前环境中对心肺转流（CPB）后凝血病的治疗潜力。我们使用雄性新西兰白色兔（体重，3 kg）建立了CPB后凝血病模型。CPB后1h，分别静脉注射H12-ADP-脂质体和富血小板血浆（PRP）（H12-ADP-脂质体/PRP组，n = 8）或单纯PRP（PRP组，n = 8）。与PRP组（441 ± 108 s，p < 0.001）相比，H12-ADP-脂质体/PRP组（263 ± 111 s）的耳出血时间大大减少。电子显微镜检查显示H12-ADP-脂质体/PRP组出血部位有含脂质体的血小板血栓。然而，在H12-ADP-脂质体给药后，在终末器官中未观察到此类脂质体参与的血小板血栓。这些结果表明，H12-ADP-脂质体可以帮助有效和安全地巩固CPB后凝血障碍的血小板止血，并可能减少CPB心血管手术后的出血并发症。
Fibrinogen γ-chain peptide-coated, adenosine 5′-diphosphate (ADP)-encapsulated liposomes (H12-ADP-liposomes) are a potent haemostatic adjuvant to promote platelet thrombi. These liposomes are lipid particles coated with specific binding sites for platelet GPIIb/IIIa and encapsulating ADP. They work at bleeding sites, facilitating haemostasis by promoting aggregation of activated platelets and releasing ADP to strongly activate platelets. In this study, we investigated the therapeutic potential of H12-ADP-liposomes on post-cardiopulmonary bypass (CPB) coagulopathy in a preclinical setting. We created a post-CPB coagulopathy model using male New Zealand White rabbits (body weight, 3 kg). One hour after CPB, subject rabbits were intravenously administered H12-ADP-liposomes with platelet-rich plasma (PRP) collected from donor rabbits (H12-ADP-liposome/PRP group, n = 8) or PRP alone (PRP group, n = 8). Ear bleeding time was greatly reduced for the H12-ADP-liposome/PRP group (263 ± 111 s) compared with the PRP group (441 ± 108 s, p < 0.001). Electron microscopy showed platelet thrombus containing liposomes at the bleeding site in the H12-ADP-liposome/PRP group. However, such liposome-involved platelet thrombi were not observed in the end organs after H12-ADP-liposome administration. These findings suggest that H12-ADP-liposomes could help effectively and safely consolidate platelet haemostasis in post-CPB coagulopathy and may have potential for reducing bleeding complications after cardiovascular surgery with CPB.
登录
查看更多内容
影响因子：
10.4
作者：
Okamura, Y.;Takeoka, S.;Handa, M.
通讯作者：
Handa, M.
影响因子：
5.7
作者：
Ortmann, Erik;Klein, Andrew A.;Besser, Martin W.
通讯作者：
Besser, Martin W.
IL-1α响应急性血小板需求，通过巨核细胞破裂诱导血小板生成
DOI：
10.1084/jem.2125oia27
发表时间：
2015
期刊：
Pediatric Rheumatology Online Journal
影响因子：
--
作者：
S. Nishimura;M. Nagasaki;S. Kunishima;A. Sawaguchi;A. Sakata;Hiroyasu Sakaguchi;T. Ohmori;I. Manabe;J. Italiano;T. Ryu;N. Takayama;I. Komuro;T. Kadowaki;K. Eto;R. Nagai
通讯作者：
R. Nagai
超越离体血小板生物发生
DOI：
--
发表时间：
2019
期刊：
影响因子：
--
作者：
王 崑陽;小野寺 真―;齋藤光代;奥田 昇;Koji Eto
通讯作者：
Koji Eto
影响因子：
4.7
作者：
Y. Okamura;Ippei Maekawa;Y. Teramura;H. Maruyama;M. Handa;Y. Ikeda;S. Takeoka
通讯作者：
Y. Okamura;Ippei Maekawa;Y. Teramura;H. Maruyama;M. Handa;Y. Ikeda;S. Takeoka