Unexpectedly high prevalence of acquired von Willebrand syndrome in patients with severe aortic stenosis as evaluated with a novel large multimer index

Toshihiro Tamura, Hisanori Horiuchi, Masao Imai, Tomohisa Tada, Hiroki Shiomi, Maiko Kuroda, Shunsuke Nishimura, Yusuke Takahashi, Yusuke Yoshikawa, Akira Tsujimura, Masashi Amano, Yukiko Hayama, Sari Imamura, Naoaki Onishi, Yodo Tamaki, Soichiro Enomoto, Makoto Miyake, Hirokazu Kondo, Kazuaki Kaitani, Chisato IzumiTakeshi Kimura, Yoshihisa Nakagawa

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Aim: Severe gastrointestinal bleeding sometimes occurs in patients with aortic stenosis (AS), known as Heyde’s syndrome. This syndrome is thought to be caused by acquired von Willebrand syndrome and is characterized by reduced large von Willebrand factor (vWF) multimers. However, the relationship between the severity of AS and loss of large vWF multimers is unclear. Methods: We examined 31 consecutive patients with severe AS. Quantitative evaluation for loss of large vWF multimers was performed using the conventional large vWF ratio and novel large vWF multimer index. This novel index was defined as the ratio of large multimers of patients to those of controls. Results: Loss of large vWF multimers, defined as the large vWF multimer index <80%, was detected in 21 patients (67.7%). The large vWF multimer ratio and the large vWF multimer index were inversely correlated with the peak aortic gradient (R =−0.58, p=0.0007, and R=−0.64, p<0.0001, respectively). Anemia defined as hemoglobin <9.0 g/dl was observed in 12 patients (38.7%), who were regarded as Heyde’s syndrome. Aortic valve replacement was performed in 7 of these patients, resulting in the improvement of anemia in all patients from a hemoglobin concentration of 7.5±1.0 g/dl preoperatively to 12.4±1.3 g/dl postoperatively (p<0.0001). Conclusions: Acquired von Willebrand syndrome may be a differential diagnosis in patients with AS with anemia. The prevalence of AS-associated acquired von Willebrand syndrome is higher than anticipated.

Original languageEnglish
Pages (from-to)1115-1123
Number of pages9
JournalJournal of atherosclerosis and thrombosis
Issue number11
Publication statusPublished - 2015 Nov 2


  • Acquired von Willebrand syndrome
  • Aortic stenosis
  • Gastrointestinal bleeding
  • Heyde’s syndrome
  • Large vWF multimer index

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical


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