Screening of the protein C pathway abnormality-related thrombophilia by using thrombomodulin-mediated tissue factor-triggered clot waveform analysis.

• Material Type: 博士論文
• Title: Screening of the protein C pathway abnormality-related thrombophilia by using thrombomodulin-mediated tissue factor-triggered clot waveform analysis.
• Author/Editor: Hashimoto, Naoki; Ogiwara, Kenichi; Shimonishi, Naruto; Nakagawa, Takashi; Nakajima, Yuto; Furukawa, Shoko; Takeyama, Masahiro; Nogami, Keiji
• Author Heading: Hashimoto, Naoki; Ogiwara, Kenichi; Shimonishi, Naruto; Nakagawa, Takashi; Nakajima, Yuto; Furukawa, Shoko; Takeyama, Masahiro; Nogami, Keiji
• Publication, Distribution, etc.: Wiley
• Publication Date: 2022-07
• Publication Date (W3CDTF): 2022-07
• Alternative Title: 組織因子惹起-トロンボモジュリン添加凝固波形解析を用いたプロテインC経路異常を伴う血栓性素因のスクリーニング法
• Periodical title: European journal of haematology
• No. or year of volume/issue: 109 1
• Volume: 109
• Issue: 1
• Pages: 100-108
• ISSN (Periodical Title): ISSN : 0902-4441
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2022-09-28
• Dissertation Number: 乙第1527号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: clot waveform analysis; factor V; protein C pathway; thrombomodulin; thrombophilia
• Target Audience: 一般
• Note (General): type:Thesis; Objectives: Absolute or relative protein (P)C pathway abnormalities (PC deficiency, PS deficiency, antiphospholipid syndrome (APS), factor (F)V-abnormality, and high FVIII level) cause thrombophilia. Although screening assays for these thrombophilias are available, one utilizing clot waveform analysis (CWA) remains unknown. We aimed to establish a CWA-based screening assay to distinguish PC pathway abnormality-related thrombophilia. Methods: Samples were reacted with tissue factor (TF)/phospholipids and recombinant thrombomodulin (rTM; optimal 20 nM), followed by CWA measurement. The peak ratio (with/without rTM) of the first derivative curve of clot waveform was calculated. Results: The peak ratio in healthy plasmas (n = 35) was 0.36 ± 0.13; hence, the cutoff value was set to 0.49. The peak ratios in plasmas with PC deficiency, PS deficiency, high-FVIII (spiked 300 IU/dl), and APS were higher than the cutoff values (0.79/0.97/0.50/0.93, respectively). PC-deficient plasma or PS-deficient plasma mixed with normal plasma (25%/50%/75%/100% PC or PS level) showed dose-dependent decreases in the peak ratios (PC deficient: 0.85/0.64/0.44/0.28; PS deficient: 0.69/0.53/0.40/0.25), suggesting that the peak ratio at ≤50% of PC or PS level exceeded the cutoff value. The peak ratio in FV deficiency with FV ≤25% was higher than the cutoff value. FV-deficient plasma spiked with 40 IU/dl rFV-R506Q (FVLeiden ) or rFV-W1920R (FVNara ) showed >90% peak ratios. Conclusions: rTM-mediated TF-triggered CWA might be useful for screening PC pathway abnormality-related thrombophilia.; 博士（医学）・乙第1527号・令和4年9月28日; © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.; This is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/10.1111/ejh.13777], which has been published in final form at [https://doi.org/10.1111/ejh.13777]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.; 発行元が定める登録猶予期間終了の後、本文を登録予定（2023.07）; identifier:European journal of haematology Vol.109 No.1 p.100-108 (2022 Jul); identifier:09024441; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4081; identifier:European journal of haematology, 109(1): 100-108
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1111/ejh.13777
• 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

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