埼玉医科大学雑誌 第42巻 第1号 (2015年8月) 1-6頁◇論文(図表を含む全文)は,PDFファイルとなっています

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第IX因子複合体およびフィブリノゲンが希釈血液の線溶亢進状態に及ぼす作用

山家 陽児1)*,川崎 潤1),小山 薫1),田中 健一2)
1) 埼玉医科大学 総合医療センター 麻酔科
2) 米国メリーランド州立大学 麻酔科

〔平成26年10月24日 受付 / 平成27年3月26日 受理〕


Effects of prothrombin complex concentrates and fibrinogen on the profibrinolytic state of diluted blood
Youji Yanbe1)*, Jun Kawasaki1),Kaoru Koyama1), Kenichi A. Tanaka2)
1) Department of Anesthesiology, Saitama Medical Center, Saitama Medical University
2) Department of Anesthesiology, University of Maryland, USA

【Background】Fluid replacement therapy using crystalloids and colloids without transfusion of blood or fresh-frozen plasma after massive haemorrhage may result in a profibrinolytic state. We tested the effects of prothrombin complex concentrates (PCC) and fibrinogen (Fib) on the profibrinolytic state in hemodilution, using thrombelastography (TEG®) and a plasmin-plasmin inhibitor complex (PIC) assay.

【Method】 After approval from the ethical committee of the Saitama Medical Center and obtaining informed consent, a six-channel TEG® (n=15) was performed using blood samples from healthy individuals. The normal blood was diluted by 40% using normal saline (NS), then a six-channel TEG® was performed in 320 μL of recalcified, Intem®-activated whole blood as follows; normal blood + NS, diluted blood + NS, diluted blood + PCC (final concentration 0.2 IU/ml), diluted blood + PCC (0.4 IU/ml), diluted blood + Fib (1.5 g/L), diluted blood + {Fib (1.5 g/L) + PCC (0.2 IU (/ml)}Experiment 1). Furthermore, a six-channel TEG® (n=15) was performed using blood samples collected from patients at the time of anesthetic induction and at the time when more than 2L of fluid was administered and the amount of bleeding was more than 400 mL. The TEG® was performed with recalcified, Intem®-activated whole blood spiked with tPA (final conc. 0.15 μg/ml) and the same additives as each TEG® channel in Experiment 1. Apart from the TEG® testing, PCC, Fib and tPA, etc. were added to 0.9 ml of each blood sample in the same proportion as in the TEG®. Thirty minutes later, clotting reactions were stopped by 0.1 ml of 3.2% citric acid. The PIC was determined in plasma obtained by centrifugation (Experiment 2).

【Results】Fibrinolytic tendency was significantly enhanced after haemodilution with saline (Experiment 1) and with fluid replacement therapy after bleeding and fluid replacement (Experiment 2). The PCC and Fib could, in a concentration dependent manner, mitigate the profibrinolytic state enhanced by haemodilution, which was most effectively controlled with the simultaneous addition of PCC and Fib. Decreased maximum amplitude (MA) values after hemodilution were lowered futher by PCC, while they were increased by adding Fib.

【Conclusion】The combination of PCC and Fib was most effective in mitigating a tPA-induced profibrinolytic state after hemodilution compared to adding PCC or Fib per se. PCC might increase thrombin generation whereas Fib increases the mass of the clot.

J Saitama Medical University 2015; 42(1): 1-6
(Received October 24, 2014 / Accepted March 26, 2015)

Keywords: hemodilution, profibrinolytic state, prothrombin complex concentrates, fibrinogen, thrombelastography, plasmin-plasmin inhibitor complex


(C) 2015 The Medical Society of Saitama Medical University