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
Noriyuki Okubo, Shingo Sugawara, Tohru Fujiwara, Ko Sakatsume, Tsuyoshi Doman, Mihoko Yamashita, Kota Goto, Masaki Tateishi, Misako Suzuki, Ryutaro Shirakawa, Yuka Eura, Koichi Kokame, Masaki Hayakawa, Masanori Matsumoto, Y. Kawate, Mizuki Miura, Hiroshi Takiguchi, Yoshimitsu Soga, Shinichi Shirai, Kenji Andò, Yoshio Arai, Takaharu Nakayoshi, Yoshihiro Fukumoto, Hiroyuki Takahama, Satoshi Yasuda, Toshihiro Tamura, Shin Watanabe, Takeshi Kimura, Nobuhiro Yaoita, Hiroaki Shimokawa, Yoshikatsu Saiki, Koichi Kaikita, Kenichi Tsujita, Shinji Yoshii, Hiroshi Nakase, Shinichi Fujimaki, Hisanori Horiuchi
Abstract
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: < .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.