Potential role of activated factor VIII (FVIIIa) in FVIIa/tissue factor-dependent FXa generation in initiation phase of blood coagulation.

• Material Type: 博士論文
• Title: Potential role of activated factor VIII (FVIIIa) in FVIIa/tissue factor-dependent FXa generation in initiation phase of blood coagulation.
• Author/Editor: Furukawa, Shoko; Nogami, Keiji; Ogiwara, Kenichi; Shima, Midori
• Author Heading: Furukawa, Shoko; Nogami, Keiji; Ogiwara, Kenichi; Shima, Midori
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2019-04
• Publication Date (W3CDTF): 2019-04
• Alternative Title: 凝固初期相における活性型凝固第Ⅶ因子/組織因子依存性の活性型凝固第Ⅹ因子生成に対する活性型凝固第Ⅷ因子の働き
• Periodical title: International journal of hematology Vol. No. p. (2019 Apr)
• No. or year of volume/issue: 109 4
• Volume: 109
• Issue: 4
• Pages: 390-401
• ISSN (Periodical Title): ISSN : 0925-5710
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2019-06-26
• Dissertation Number: 乙第1429号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: FVIIa; Tissue factor; FVIII; FXa generation; Initiation phase
• Target Audience: 一般
• Note (General): type:Article; Factor VIIa/tissue factor (FVIIa/TF) initiates blood coagulation by promoting FXa generation (extrinsic-Xa). Subsequent generation of intrinsic FXa (intrinsic-Xa) amplifies thrombin formation. Previous studies suggested that FVIIa/TF activates FVIII rapidly in immediate coagulation reactions, and FVIIa/TF/FXa activates FVIII prior to thrombin-dependent feedback. We investigated FVIII/FVIIa/TF/FXa relationships in early coagulation mechanisms. Total FXa generated by FVIIa/TF and FVIIa/TF-activated FVIII (FVIIIaVIIa/TF) was 22.6 ± 1.7 nM (1 min); total FXa with FVIIa-inhibitor was 3.4 ± 0.7 nM, whereas FXa generated by FVIIa/TF or FVIII/TF was 10.4 ± 1.1 or 0.74 ± 0.14 nM, respectively. Little Xa was generated by FVIII alone, suggesting that intrinsic-Xa mechanisms were mediated by FVIIIaVIIa/TF and FVIII/TF in the initiation phase. Intrinsic-Xa was delayed somewhat by von Willebrand factor (VWF). FVIII activation by FXa with FVIIa/TF was comparable to activation with Glu-Gly-Arg-inactivated-FVIIa/TF. TF counteracted the inhibitory effects of VWF on FXa-induced FVIII activation mediated by Arg372 cleavage. The FVIII-C2 domain bound to cytoplasmic domain-deleted TF (TF¹⁻²⁴³), and VWF blocked this binding by > 80%, indicating an overlap between VWF- and TF1-243-binding site(s) on C2. Overall, these data suggest that FVIII-associated intrinsic-Xa, governed by both FVIIa/TF-induced and FXa-induced FVIII activation mediated by FVIII-TF interactions, together with FVIIa-dependent extrinsic-Xa mechanisms, may be central to the initiation phase of coagulation.; 博士（医学）・乙第1429号・令和元年6月26日; © Japanese Society of Hematology 2019; This is a post-peer-review, pre-copyedit version of an article published in International journal of hematology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12185-019-02611-3.; identifier:International journal of hematology Vol.109 No.4 p.390-401 (2019 Apr); identifier:09255710; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3591; identifier:International journal of hematology Vol. No. p. (2019 Apr), 109(4): 390-401
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3591/1/01%e4%b9%991429%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3591/2/02%e4%b9%991429%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3591/6/03%e4%b9%991429%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1007/s12185-019-02611-3
• Periodical Title (NCID): AA10797094; https://ci.nii.ac.jp/ncid/AA10797094
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU