Bleeding symptoms in patients diagnosed as type 3 von Willebrand disease: Results from 3WINTERS-IPS, an international and collaborative cross-sectional study

Research output: Contribution to journalArticle


Background: Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. Aims: To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. Methods: We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM-1VWD bleeding questionnaire in patients enrolled in the 3WINTERS-IPS and MCMDM-1VWD studies. Results: In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five-fold over-represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels < 20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. Conclusions: In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.


  • Alberto Tosetto
  • Zahra Badiee
  • Mohammad Reza Baghaipour
  • Luciano Baronciani
  • Javier Battle
  • Imre Bodó
  • Ulrich Budde
  • Giancarlo Castaman
  • Jeroen C.J. Eikenboom
  • Peyman Eshghi
  • Cosimo Ettorre
  • Anne Goodeve
  • Jenny Goudemand
  • Charles Richard Morris Hay
  • Hamid Hoorfar
  • Mehran Karimi
  • Bijan Keikhaei
  • Riitta Lassila
  • Frank W.G. Leebeek
  • Maria Fernanda Lopez Fernandez
  • Pier Mannuccio Mannucci
  • Maria Gabriella Mazzucconi
  • Massimo Morfini
  • Johannes Oldenburg
  • Ian Peake
  • Rafael Parra Lòpez
  • Flora Peyvandi
  • Reinhard Schneppenheim
  • Andreas Tiede
  • Gholamreza Toogeh
  • Marc Trossaert
  • Omidreza Zekavat
  • Augusto B. Federici
External organisations
  • Ospedale San Bortolo
  • Mashhad University of Medical Sciences
  • Iranian Hemophilia Comprehensive Treatment Centre
  • Maggiore Hospital Policlinico
  • University of A Coruña
  • Skåne University Hospital
  • Semmelweis University
  • MEDILYS Labor Gesellschaft
  • Careggi University Hospital
  • Leiden University Medical Centre
  • Shahid Beheshti University of Medical Sciences
  • Bari University Hospital
  • University of Sheffield
  • University of Lille
  • Manchester Royal Infirmary
  • Isfahan University of Medical Sciences
  • Ahvaz Jundishapur University of Medical Sciences
  • Helsinki University Central Hospital
  • Erasmus University Medical Center
  • Sapienza University of Rome
  • University of Bonn
  • Vall d'Hebron University Hospital
  • University of Milan
  • University Medical Center Hamburg-Eppendorf
  • Hannover Medical School
  • Thrombosis Hemostasis Research Center
  • Centre Régional de Traitement de l’Hémophilie—Laboratoire d’Hématologie
  • Luigi Sacco University Hospital
  • Shiraz University of Medical Sciences
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology


  • type 1 epidemiology hemorrhage blood coagulation disorders, type 3 von Willebrand disease, von Willebrand disease
Original languageEnglish
Pages (from-to)2145-2154
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Issue number9
Publication statusPublished - 2020 Sep 1
Publication categoryResearch
Externally publishedYes