血管性血友病因子瑞斯托霉素辅因子活性与血管性血友病因子抗原水平之比用于诊断主动脉瓣狭窄所致获得性血管性血友病综合征
von Willebrand factor Ristocetin co-factor activity to von Willebrand factor antigen level ratio for diagnosis of acquired von Willebrand syndrome caused by aortic stenosis.
作者信息
Okubo Noriyuki, Sugawara Shingo, Fujiwara Tohru, Sakatsume Ko, Doman Tsuyoshi, Yamashita Mihoko, Goto Kota, Tateishi Masaki, Suzuki Misako, Shirakawa Ryutaro, Eura Yuka, Kokame Koichi, Hayakawa Masaki, Matsumoto Masanori, Kawate Yasunori, Miura Mizuki, Takiguchi Hiroshi, Soga Yoshimitsu, Shirai Shinichi, Ando Kenji, Arai Yoshio, Nakayoshi Takaharu, Fukumoto Yoshihiro, Takahama Hiroyuki, Yasuda Satoshi, Tamura Toshihiro, Watanabe Shin, Kimura Takeshi, Yaoita Nobuhiro, Shimokawa Hiroaki, Saiki Yoshikatsu, Kaikita Koichi, Tsujita Kenichi, Yoshii Shinji, Nakase Hiroshi, Fujimaki Shin-Ichi, Horiuchi Hisanori
机构信息
Department of Clinical Laboratory Medicine, Tohoku University Hospital, Sendai, Japan.
Department of Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan.
出版信息
Res Pract Thromb Haemost. 2023 Nov 30;8(1):102284. doi: 10.1016/j.rpth.2023.102284. eCollection 2024 Jan.
BACKGROUND
Severe aortic stenosis (AS) causes acquired von Willebrand syndrome by the excessive shear stress-dependent cleavage of high molecular weight multimers of von Willebrand factor (VWF). While the current standard diagnostic method is so-called VWF multimer analysis that is western blotting under nonreducing conditions, it remains unclear whether a ratio of VWF Ristocetin co-factor activity (VWF:RCo) to VWF antigen levels (VWF:Ag) of <0.7, which can be measured with an automated coagulation analyzer in clinical laboratories and is used for the diagnosis of hereditary von Willebrand disease.
OBJECTIVES
To evaluated whether the VWF:RCo/VWF:Ag is useful for the diagnosis of AS-induced acquired von Willebrand syndrome.
METHODS
VWF:RCo and VWF:Ag were evaluated with the VWF large multimer index as a reference, which represents the percentage of a patient's VWF high molecular weight multimer ratio to that of standard plasma in the VWF multimer analysis.
RESULTS
We analyzed 382 patients with AS having transaortic valve maximal pressure gradients of >30 mmHg, 27 patients with peripheral artery disease, and 46 control patients free of cardiovascular disease with osteoarthritis, diabetes, and so on. We assumed a large multimer index of <80% as loss of VWF large multimers since 59.0% of patients with severe AS had the indices of <80%, while no control patients or patients with peripheral artery disease, except for 2 patients, exhibited the indices of <80%. The VWF:RCo/VWF:Ag ratios, measured using an automated blood coagulation analyzer, were correlated with the indices (r = 0.470, < .001). When the ratio of <0.7 was used as a cut-off point, the sensitivity and specificity to VWF large multimer indices of <80% were 0.437 and 0.826, respectively.
CONCLUSION
VWF:RCo/VWF:Ag ratios of <0.7 may indicate loss of VWF large multimers with high specificity, but low sensitivity. VWF:RCo/VWF:Ag ratios in patients with AS having a ratio of <0.7 may be useful for monitoring the loss of VWF large multimers during their clinical courses.
背景
重度主动脉瓣狭窄（AS）通过对血管性血友病因子（VWF）高分子量多聚体的过度剪切应力依赖性裂解导致获得性血管性血友病综合征。虽然目前的标准诊断方法是所谓的VWF多聚体分析，即在非还原条件下进行蛋白质印迹，但目前尚不清楚VWF瑞斯托霉素辅因子活性（VWF:RCo）与VWF抗原水平（VWF:Ag）的比值<0.7是否可用于诊断遗传性血管性血友病，该比值可在临床实验室用自动凝血分析仪测量。
目的
评估VWF:RCo/VWF:Ag是否有助于诊断AS所致的获得性血管性血友病综合征。
方法
以VWF大多聚体指数作为参考评估VWF:RCo和VWF:Ag，VWF大多聚体指数代表患者VWF高分子量多聚体比例在VWF多聚体分析中相对于标准血浆的百分比。
结果
我们分析了382例经主动脉瓣最大压力梯度>30 mmHg的AS患者、27例外周动脉疾病患者以及46例无心血管疾病但患有骨关节炎、糖尿病等的对照患者。我们将大多聚体指数<80%视为VWF大多聚体丢失，因为59.0%的重度AS患者指数<80%，而除2例患者外，对照患者或外周动脉疾病患者均未表现出指数<80%。使用自动血液凝固分析仪测量的VWF:RCo/VWF:Ag比值与指数相关（r = 0.470，P <.001）。当以<0.7的比值作为切点时，对VWF大多聚体指数<80%的敏感性和特异性分别为0.437和0.826。
结论
VWF:RCo/VWF:Ag比值<0.7可能以高特异性但低敏感性表明VWF大多聚体丢失。AS患者中VWF:RCo/VWF:Ag比值<0.7可能有助于在其临床病程中监测VWF大多聚体的丢失。
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