Type 1 VWD classification revisited: novel insights from combined analysis of the LoVIC and WiN studies.

Autor:	Atiq F; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.; Department of Haematology, Erasmus University Medical Center-Erasmus MC, Rotterdam, The Netherlands., Blok R; Department of Haematology, Erasmus University Medical Center-Erasmus MC, Rotterdam, The Netherlands., van Kwawegen CB; Department of Haematology, Erasmus University Medical Center-Erasmus MC, Rotterdam, The Netherlands., Doherty D; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Lavin M; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.; National Coagulation Centre, St James's Hospital, Dublin, Ireland., van der Bom JG; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., O'Connell NM; National Coagulation Centre, St James's Hospital, Dublin, Ireland., de Meris J; Netherlands Hemophilia Society, Leiden, The Netherlands., Ryan K; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Schols SEM; Department of Hematology, Radboud University Medical Center, Nijmegen and Hemophilia Treatment Center, Nijmegen-Eindhoven-Maastricht, The Netherlands., Byrne M; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Heubel-Moenen FCJI; Department of Hematology, Maastricht University Medical Center, Maastricht, The Netherlands., van Galen KPM; Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Preston RJS; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland., Cnossen MH; Department of Pediatric Hematology and Oncology, Erasmus MC, University Medical Center-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands., Fijnvandraat K; Department of Pediatric Hematology, Emma Children's Hospital, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands., Baker RI; Western Australia Centre for Thrombosis and Haemostasis, Perth Blood Institute, Murdoch University, Perth, WA, Australia.; Irish-Australian Blood Collaborative Network, Dublin, Ireland., Meijer K; Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands., James P; Department of Medicine, Queen's University, Kingston, ON, Canada., Di Paola J; Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO., Eikenboom J; Department of Internal Medicine, Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands., Leebeek FWG; Department of Haematology, Erasmus University Medical Center-Erasmus MC, Rotterdam, The Netherlands., O'Donnell JS; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.; National Coagulation Centre, St James's Hospital, Dublin, Ireland.; Irish-Australian Blood Collaborative Network, Dublin, Ireland.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Apr 04; Vol. 143 (14), pp. 1414-1424.
DOI:	10.1182/blood.2023022457
Abstrakt:	Abstract: There is significant ongoing debate regarding type 1 von Willebrand disease (VWD) defintion. Previous guidelines recommended patients with von Willebrand factor (VWF) levels <30 IU/dL be diagnosed type 1 VWD, whereas patients with significant bleeding and VWF levels from 30 to 50 IU/dL be diagnosed with low VWF. To elucidate the relationship between type 1 VWD and low VWF in the context of age-induced increases in VWF levels, we combined data sets from 2 national cohort studies: 162 patients with low VWF from the Low VWF in Ireland Cohort (LoVIC) and 403 patients with type 1 VWD from the Willebrand in The Netherlands (WiN) studies. In 47% of type 1 VWD participants, VWF levels remained <30 IU/dL despite increasing age. Conversely, VWF levels increased to the low VWF range (30-50 IU/dL) in 30% and normalized (>50 IU/dL) in 23% of type 1 VWD cases. Crucially, absolute VWF antigen (VWF:Ag) levels and increase of VWF:Ag per year overlapped between low VWF and normalized type 1 VWD participants. Moreover, multiple regression analysis demonstrated that VWF:Ag levels in low VWF and normalized type 1 VWD patients would not have been different had they been diagnosed at the same age (β = 0.00; 95% confidence interval, -0.03 to 0.04). Consistently, no difference was found in the prevalence of VWF sequence variants; factor VIII activity/VWF:Ag or VWF propeptide/VWF:Ag ratios; or desmopressin responses between low VWF and normalized type 1 VWD patients. In conclusion, our findings demonstrate that low VWF does not constitute a discrete clinical or pathological entity. Rather, it is part of an age-dependent type 1 VWD evolving phenotype. Collectively, these data have important implications for future VWD classification criteria. (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu