Von Willebrand disease and aging: An evolving phenotype

Y. V. Sanders, M. A. Giezenaar, B. A.P. Laros-van Gorkom, K. Meijer, J. G. van der Bom, M. H. Cnossen, M. R. Nijziel, P. F. Ypma, K. Fijnvandraat, J. Eikenboom, E. P. Mauser-Bunschoten, F. W.G. Leebeek, K. Fijnvandraat, S. Middeldorp, A. Kors, S. Zweegman, J. de Meris, M. H. Jonkers, N. Dors, M. R. NijzielK. Meijer, R. Y.J. Tamminga, P. W. van der Linden, P. F. Ypma, J. G. van der Bom, H. C.J. Eikenboom, F. J.W. Smiers, B. Granzen, K. Hamulyak, P. Brons, B. A.P. Laros-van Gorkom, M. H. Cnossen, Y. V. Sanders, E. P. Mauser-Bunschoten

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BACKGROUND: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. OBJECTIVES: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related differences in bleeding phenotype between elderly VWD patients and those <65 years. We also studied co-morbidity in elderly patients. PATIENTS/METHODS: We included VWD patients with VWF levels ≤ 30 U dL(-1) in the nationwide cross-sectional 'Willebrand in the Netherlands' (WiN-) study. Patients reported bleeding episodes and treatment of VWD in the year preceding inclusion and during life. This was compared between VWD patients older (n = 71) and younger (16-64 years, n = 593) than 65 years. In elderly patients, age-related changes in VWF and FVIII levels were studied longitudinally by including all historically measured levels. All medical records were examined for co-morbidity. RESULTS: In elderly type 1 patients, a decade age increase was associated with a 3.5 U dL(-1) (95% CI, -0.6 to 7.6) VWF:Ag increase and 7.1 U dL(-1) (95% CI, 0.7 to 13.4) FVIII:C increase. This increase was not observed in elderly type 2 patients. Elderly type 2 patients reported significantly more bleeding symptoms in the year preceding inclusion than younger patients (16/27, 59% vs. 87/221, 39%; P = 0.048), which was not observed in type 1 VWD. CONCLUSIONS: von Willebrand factor parameters and bleeding phenotype evolve with increasing age in VWD. VWF and FVIII levels increase with age in type 1 patients with no mitigation in bleeding phenotype. In type 2 patients VWF parameters do not increase with age and in these patients aging is accompanied by increased bleeding.
Original languageEnglish
Pages (from-to)1066-1075
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Issue number7
Publication statusPublished - 1 Jul 2014

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