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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/4113

Title: Increased cleavage of von Willebrand factor by ADAMTS13 may contribute strongly to acquired von Willebrand syndrome development in patients with essential thrombocythemia
Other Titles: 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。
Authors: Kubo, Masayuki
Sakai, Kazuya
Hayakawa, Masaki
Kashiwagi, Hirokazu
Yagi, Hideo
Seki, Yoshinobu
Hasegawa, Atsushi
Tanaka, Haruyuki
Amano, Itsuto
Tomiyama, Yoshiaki
Matsumoto, Masanori
Keywords: ADAMTS13 protein
essential thrombocythemia
hemorrhage
von Willebrand disease
von Willebrand factor
Issue Date: Jul-2022
Publisher: Blackwell Pub
Citation: Journal of thrombosis and haemostasis Vol.20 No.7 p.1589-1598 (2022 Jul)
Abstract: Background: Patients with essential thrombocythemia (ET) often experience bleeding associated with acquired von Willebrand syndrome (AVWS) when the platelet count is markedly increased. Objective: We investigated whether von Willebrand factor (VWF) degradation is enhanced in patients with ET. Methods: Seventy patients with ET underwent VWF multimer (VWFM) analysis and measurement of VWF-related parameters. We calculated the VWFM index, defined as the ratio of intensities of a patient's molecular weight-categorized VWFMs, and those of a healthy subject's, using densitometric analysis. VWF degradation product (DP) was measured via ELISA using a monoclonal antibody that specifically recognizes Y1605 at the C-terminal boundary, which is exposed following ADAMTS13-mediated cleavage of the Y1605-M1606 bond of the VWF A2 domain. Results: Patients with higher platelet counts had a significantly reduced high molecular weight (HMW)-VWFM index and an increased VWF-DP: VWF antigen (Ag) ratio compared to those with lower platelet counts. On multivariate analysis, the VWF-DP/ VWF:Ag ratio was an independent predictor of the HMW-VWFM index. Patients who underwent cytoreductive therapy had a significantly higher HMW-VWFM index and lower VWF-DP/ VWF:Ag ratio than those who did not. Among individual patients, there was also a significant increase in the HMW-VWFM index and a decrease in the VWF-DP/ VWF:Ag ratio after cytoreductive therapy compared to pre-therapy values. Conclusion: In patients with ET, an increased platelet count is associated with enhanced cleavage of VWF at the Y1605-M1606 bond, primarily by ADAMTS13, leading to AVWS. Cytoreductive therapy reduces the platelet count, prevents excessive VWF cleavage, and improves VWFM distributions.
Description: 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.
URI: http://hdl.handle.net/10564/4113
ISSN: 15387933
DOI: https://doi.org/10.1111/jth.15717
Academic Degrees and number: 24601甲第881号
Degree-granting date: 2023-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2022年度

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