Alberto Tosetto1, Zahra Badiee2, Mohammad-Reza Baghaipour3, Luciano Baronciani4, Javier Battle5, Erik Berntorp6, Imre Bodó7, Ulrich Budde8, Giancarlo Castaman9, Jeroen C J Eikenboom10, Peyman Eshghi11, Cosimo Ettorre12, Anne Goodeve13, Jenny Goudemand14, Charles Richard Morris Hay15, Hamid Hoorfar16, Mehran Karimi17, Bijan Keikhaei18, Riitta Lassila19, Frank W G Leebeek20, Maria Fernanda Lopez Fernandez5, Pier Mannuccio Mannucci4, Maria Gabriella Mazzucconi21, Massimo Morfini9, Johannes Oldenburg22, Ian Peake13, Rafael Parra Lòpez23, Flora Peyvandi4,24, Reinhard Schneppenheim25, Andreas Tiede26, Gholamreza Toogeh27, Marc Trossaert28, Omidreza Zekavat29, Eva M K Zetterberg6, Augusto B Federici30. 1. Hemophilia and Thrombosis Center, Hematology Department, San Bortolo Hospital, Vicenza, Italy. 2. Hemophilia-Thalassemia Center, Mashhad University of Medical Science, Mashad, Islamic Republic of Iran. 3. Iranian Hemophilia Comprehensive Treatment Centre, Tehran, Islamic Republic of Iran. 4. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Fondazione Luigi Villa, Milan, Italy. 5. Complejo Hospitalario Universitario de A Coruña-Servicio de Hematología y Hemoterapia, A Coruña, Spain. 6. Skane University Hospital, Malmo, Sweden. 7. Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary. 8. MEDILYS Labor Gesellschaft, Hamburg, Germany. 9. Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy. 10. Division of Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands. 11. Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran. 12. Hemostasis and Thrombosis Center, Azienda Ospedaliera Policlinico Consorziale, Bari, Italy. 13. University of Sheffield, Sheffield, UK. 14. Department of Haematology Transfusion, University Lille-CRMW, CHRU Lille, Lille, France. 15. Manchester Royal Infirmary, Manchester, UK. 16. Hemophilia Center-Esfahan University of Medical Science, Esfahan, Islamic Republic of Iran. 17. Hematology Research Center, Nemazee Hospital, Shiraz University of Medical Science, Shiraz, Islamic Republic of Iran. 18. Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 19. Coagulation Disorders, Helsinki University Central Hospital, Helsinki, Finland. 20. Erasmus Medical Center, Rotterdam, the Netherlands. 21. Hemophilia and Thrombosis Center-University of Rome, Rome, Italy. 22. Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany. 23. Unidad de Hemofilia-Hospital Universitari General Vall d'Hebron, Barcelona, Spain. 24. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. 25. Department of Pediatric Hematology and Oncology, University Medical Centre, Hamburg, Germany. 26. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. 27. Thrombosis Hemostasis Research Center-Vali-Asr Hospital-Emam Khameini Complex Hospital, Tehran University of Medical Science, Tehran, Islamic Republic of Iran. 28. Centre Régional de Traitement de l'Hémophilie-Laboratoire d'Hématologie, Nantes, France. 29. Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran. 30. Hematology and Transfusion Medicine, Department of Oncology and Oncohematology, L. Sacco University Hospital, University of Milan, Milano, Italy.
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 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.
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 VWDpatients 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 VWDpatients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWDpatients (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 VWDpatients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.
Authors: Nathan T Connell; Veronica H Flood; Romina Brignardello-Petersen; Rezan Abdul-Kadir; Alice Arapshian; Susie Couper; Jean M Grow; Peter Kouides; Michael Laffan; Michelle Lavin; Frank W G Leebeek; Sarah H O'Brien; Margareth C Ozelo; Alberto Tosetto; Angela C Weyand; Paula D James; Mohamad A Kalot; Nedaa Husainat; Reem A Mustafa Journal: Blood Adv Date: 2021-01-12
Authors: Dominique P M S M Maas; Ferdows Atiq; Nicole M A Blijlevens; Paul P T Brons; Sandy Krouwel; Britta A P Laros-van Gorkom; Frank W G Leebeek; Laurens Nieuwenhuizen; Selene C M Schoormans; Annet Simons; Daniëlle Meijer; Waander L van Heerde; Saskia E M Schols Journal: J Thromb Haemost Date: 2021-11-21 Impact factor: 16.036
Authors: Jonathan C Roberts; Lynn M Malec; Imrran Halari; Sarah A Hale; Abiola Oladapo; Robert F Sidonio Journal: Haemophilia Date: 2021-11-10 Impact factor: 4.263
Authors: Erik Berntorp; Sonata S Trakymienė; Augusto B Federici; Katharina Holstein; Fernando F Corrales-Medina; Glenn F Pierce; Alok Srivastava; Mario von Depka Prondzinski; Jill M Johnsen; Irena P Zupan; Susan Halimeh; Vuokko Nummi; Jonathan C Roberts Journal: Haemophilia Date: 2022-07 Impact factor: 4.263
Authors: Luciano Baronciani; Ian Peake; Reinhard Schneppenheim; Anne Goodeve; Minoo Ahmadinejad; Zahra Badiee; Mohammad-Reza Baghaipour; Olga Benitez; Imre Bodó; Ulrich Budde; Andrea Cairo; Giancarlo Castaman; Peyman Eshghi; Jenny Goudemand; Wolf Hassenpflug; Hamid Hoorfar; Mehran Karimi; Bijan Keikhaei; Riitta Lassila; Frank W G Leebeek; Maria Fernanda Lopez Fernandez; Pier Mannuccio Mannucci; Renato Marino; Nikolas Nikšić; Florian Oyen; Cristina Santoro; Andreas Tiede; Gholamreza Toogeh; Alberto Tosetto; Marc Trossaert; Eva M K Zetterberg; Jeroen Eikenboom; Augusto B Federici; Flora Peyvandi Journal: Blood Adv Date: 2021-08-10