並列タイトル等ADAMTS13によるvon Willebrand因子の切断増加は、本態性血小板血症患者における後天性von Willebrand症候群の発症に強く寄与する。
タイトル（掲載誌）Journal of thrombosis and haemostasis
一般注記type:Thesis
Background: Patients with essential thrombocythemia (ET) often experience bleedingassociated with acquired von Willebrand syndrome (AVWS) when the plateletcount is markedly increased.Objective: We investigated whether von Willebrand factor (VWF) degradation is enhancedin patients with ET.Methods: Seventy patients with ET underwent VWF multimer (VWFM) analysis andmeasurement of VWF-relatedparameters. We calculated the VWFM index, definedas the ratio of intensities of a patient's molecular weight-categorizedVWFMs, andthose of a healthy subject's, using densitometric analysis. VWF degradation product(DP) was measured via ELISA using a monoclonal antibody that specifically recognizesY1605 at the C-terminalboundary, which is exposed following ADAMTS13-mediatedcleavage of the Y1605-M1606bond of the VWF A2 domain.Results: Patients with higher platelet counts had a significantly reduced high molecularweight (HMW)-VWFMindex and an increased VWF-DP:VWF antigen (Ag) ratiocompared to those with lower platelet counts. On multivariate analysis, the VWF-DP/VWF:Ag ratio was an independent predictor of the HMW-VWFMindex. Patients whounderwent cytoreductive therapy had a significantly higher HMW-VWFMindex andlower VWF-DP/VWF:Ag ratio than those who did not. Among individual patients,there was also a significant increase in the HMW-VWFMindex and a decrease in theVWF-DP/VWF:Ag ratio after cytoreductive therapy compared to pre-therapyvalues.Conclusion: In patients with ET, an increased platelet count is associated with enhancedcleavage of VWF at the Y1605-M1606bond, primarily by ADAMTS13, leadingto AVWS. Cytoreductive therapy reduces the platelet count, prevents excessive VWFcleavage, and improves VWFM distributions.
博士（医学）・甲第881号・令和5年3月15日
This is the peer reviewed version of the following article: [Masayuki Kubo et al. Increased cleavage of von Willebrand factor by ADAMTS13 may contribute strongly to acquired von Willebrand syndrome development in patients with essential thrombocythemia. Journal of Thrombosis and Haemostasis. 2022, 20(7), p.1589-1598.], which has been published in final form at [https://doi.org/10.1111/jth.15717]. 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.
identifier:Journal of thrombosis and haemostasis Vol.20 No.7 p.1589-1598 (2022 Jul)
identifier:15387933
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4113
identifier:Journal of thrombosis and haemostasis, 20(7): 1589-1598
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