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 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.
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
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース(IRDB)(機関リポジトリ)
提供元機関・データベース奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU