Activated partial thromboplastin time‑based clot waveform analysis enables measurement of very low levels of factor IX activity in patients with severe hemophilia B

• Material Type: 博士論文
• Title: Activated partial thromboplastin time‑based clot waveform analysis enables measurement of very low levels of factor IX activity in patients with severe hemophilia B
• Author/Editor: Nishiyama, Atsuko; Ogiwara, Kenichi; Mizumachi, Kuniyoshi; Hashimoto, Naoki; Takeyama, Masahiro; Nogami, Keiji
• Author Heading: Nishiyama, Atsuko; Ogiwara, Kenichi; Mizumachi, Kuniyoshi; Hashimoto, Naoki; Takeyama, Masahiro; Nogami, Keiji
• Publication, Distribution, etc.: Springer
• Publication Date: 2022-11
• Publication Date (W3CDTF): 2022-11
• Periodical title: International journal of hematology
• No. or year of volume/issue: 116 5
• Volume: 116
• Issue: 5
• Pages: 778-786
• ISSN (Periodical Title): ISSN : 0925-5710
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2022-12-22
• Dissertation Number: 乙第1528号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Hemophilia B; Factor IX; Severity; Clot waveform analysis; Activity
• Target Audience: 一般
• Note (General): type:Thesis; The precise measurement of very low levels of factor IX activity (FIX:C < 1 IU/dL) is essential for understanding clinical severity and risk of inhibitor development in patients with severe hemophilia B (Pw-SHB). However, such measurement sensitivity has not yet been achieved. We aimed to establish a measurement method using clot waveform analysis (CWA). Residual FIX:C by adding anti-FIX monoclonal antibody, FIX:C by adding recombinant (r)FIX to the commercial Pw-SHB plasmas, and FIX:C in our Pw-SHB were determined by CS-2000i™/CS-2400™, followed by analysis of CWA parameters. The presence of anti-FIX antibody in the commercial Pw-SHB plasmas significantly decreased coagulation potential compared to its absence. The addition of rFIX to these innate plasma samples produced significant changes in three parameters upon adding FIX:C at 0.1–1 IU/dL, supporting the presence of trace FIX:C in Pw-SHB. Therefore, appropriate FIX-depleted plasma containing minimum residual FIX:C was chosen from reference curves of FIX:C (0.01–1 IU/dL). Among patients with untreated Pw-SHB, two had FIX:C 0.6–0.7 IU/dL and two had lower than detectable levels using FIX-depleted plasma. One of the latter had detectable trough levels post-rFIX administration. In conclusion, CWA enabled measurement of very low levels of FIX:C using appropriate FIX-deficient plasma.; 博士（医学）・乙第1528号・令和4年12月22日; identifier:International journal of hematology,Vol.116 No.5 p.778-786 (2022); identifier:09255710; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4094; identifier:International journal of hematology, 116(5): 778-786
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4094/1/01%e4%b9%991528%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4094/6/02%e4%b9%991528%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4094/7/03%e4%b9%991528%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1007/s12185-022-03419-4
• 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