von Willebrand disease and aging: an evolving phenotype.

YV Sanders, M A Giezenaar, BAP Laros-van Gorkom, K Meijer, JG van der Bom, MH Cnossen, MR Nijziel, PF Ypma, K Fijnvandraat, J Eikenboom, EP Mauser-Bunschoten, FWG Leebeek*

*Corresponding author for this work

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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)1066-75
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Issue number7
Publication statusPublished - 2014


  • 80 and over
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aging
  • Cross-Sectional Studies
  • Female
  • Hemorrhage
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Phenotype
  • Young Adult
  • von Willebrand Diseases
  • von Willebrand Diseases: physiopathology
  • von Willebrand Diseases: therapy
  • von Willebrand Factor
  • von Willebrand Factor: metabolism

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