演題詳細

ポスター / Poster

ポスター 38 (Poster 38) :血栓症・その他 (Thrombosis and Others)

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日程
2013年10月11日(金)
時間
16:50 - 17:50
会場
ポスター会場 / Poster (ロイトン札幌 3F ロイトンホールABCD)
座長・司会
小嶋 哲人 (Tetsuhito Kojima):1
1:名古屋大学大学院医学系研究科
 
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Evaluation of antithrombin resistance in the prothrombin mutants at R596

演題番号 : PS-1-284

高木 夕希 (Yuki Takagi):1、高木 明 (Akira Takagi):1、鈴木 敦夫 (Atsuo Suzuki):1、奥山 恵理子 (Eriko Okuyama):1、村田 萌 (Moe Murata):1、安藤 裕実 (Yumi Ando):1、加藤 衣央 (Io Kato):1、中村 友紀 (Yuki Nakamura):1、松下 正 (Tadashi Matsushita):2、齋藤 英彦 (Hidehiko Saito):3、小嶋 哲人 (Tetsuhito Kojima):1

1:Nagoya University Graduate School of Medicine , Nagoya , Japan、2:Division of Transfusion Medicine , Nagoya University Hospital , Nagoya , Japan、3:National Hospital Organization-Nagoya Medicine Center , Nagoya , Japan

 

Aim: Previously, we have reported antithrombin (AT) resistance in the prothrombin (FII) Yukuhashi (p.R596L) associated with hereditary thrombophilia. The mutant thrombin (IIa) showed a low clotting activity, but a severely impaired inactivation by AT. Here, we evaluated effects of the other mutations at R596 of FII caused by single base substitution.
Methods: We prepared recombinant FIIs (rFIIs: 596R, L, P, Q, W, G). After activation of rFIIs by Oxyuranus scutellatus venom, we incubated them with sufficient human AT for various time periods. We then added S-2238, measured changes in delta A/min at 405 nm, and calculated relative residual IIa activities. We measured TAT complex formations by using ELISA kit, and also performed IIa-generation assay (TGA) for reconstituted plasmas added rFIIs to FII-deficient plasma.
Results: The secretion level of 596P rFII was markedly lower than those of the other mutants. In the chromogenic assay, relative activities of the mutant IIas were substantially low compared with that of the wild-type. After 30 min inactivation by AT, relative residual IIa activities of the mutants were apparently high compared with that of the wild-type. TAT derived from the wild-type IIa increased in a time-dependent manner, but those from mutants were almost negligible during first 40 min. In the TGA, the 596Q mutant showed a decreased Peak, but an extension of time to Start Tail, resulting in increased endogenous IIa potential.
Conclusion: The missense mutant FIIs at R596 were all AT-resistant in vitro, although their secretion depended on the mutation.

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