title: von Willebrand disease and aging: an evolving phenotype.
abstract: BACKGROUND
  Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Y V
authors.initials: YV
authors.lastname: Sanders
authors.forename: M A
authors.initials: MA
authors.lastname: Giezenaar
authors.forename: B A P
authors.initials: BA
authors.lastname: Laros-van Gorkom
authors.forename: K
authors.initials: K
authors.lastname: Meijer
authors.forename: J G
authors.initials: JG
authors.lastname: van der Bom
authors.forename: M H
authors.initials: MH
authors.lastname: Cnossen
authors.forename: M R
authors.initials: MR
authors.lastname: Nijziel
authors.forename: P F
authors.initials: PF
authors.lastname: Ypma
authors.forename: K
authors.initials: K
authors.lastname: Fijnvandraat
authors.forename: J
authors.initials: J
authors.lastname: Eikenboom
authors.forename: E P
authors.initials: EP
authors.lastname: Mauser-Bunschoten
authors.forename: F W G
authors.initials: FW
authors.lastname: Leebeek
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D003430:Cross-Sectional Studies; D005260:Female; D006470:Hemorrhage; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D055815:Young Adult; D014842:von Willebrand Diseases / Q000503:physiopathology* / Q000628:therapy*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor
keywords: aging; factor VIII; hemorrhage; von Willebrand disease; von Willebrand factor