Bleeding symptoms in patients diagnosed as type 3 Von Willebrand Disease: results from 3WINTERS-IPS, an international and collaborative cross-sectional study

Authors: Tosetto, A., Badiee, Z., Baghaipour, M. R., Baronciani, L., Battle, J., Berntorp, E., Bodo, I., Budde, U., Castaman, G., Eikenboom, J. C. J., Eshghi, P., Ettorre, C., Goodeve, A., Goudemand, J., Charles Richard, Morris H., Hoorfar, H., Karimi, M., Keikhaei, B., Lassila, R., Leebeek, F. W. G., Lopez Fernandez, M. F., Mannucci, P. M., Mazzucconi, M. G., Morfini, M., Oldenburg, J., Peake, I., Parra, Lopez R., Peyvandi, F., Schneppenheim, R., Tiede, A., Toogeh, G., Trossaert, M., Zekavat, O., Zetterberg, E. M. K., and Federici, A. B.

Publication: J Thromb Haemost; May 2020

Affiliations: Hemophilia and Thrombosis Center, Hematology Department, San Bortolo Hospital, Vicenza, Italy; Hemophilia-Thalassemia Center, Mashhad University of Medical Science, Mashad, Islamic Republic of Iran; Iranian Hemophilia Comprehensive Treatment Centre, Tehran, Islamic Republic of Iran; Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy Complejo Hospitalario Universitario de A Coruna – Servicio de Hematologia y Hemoterapia, A Coruna, Spain; Skane University Hospital, Malmo, Sweden; St. Istvan & St. Laszlo Hospital of Budapest – Hematology and Stem Cell Transplantation, Budapest, Hungary; MEDILYS Labor Gesellschaft, Hamburg, Germany (…)

Abstract: 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. vs. 6.0 and 5 vs. 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 VWF:Ag 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.