von Willebrand disease and aging: an evolving phenotype

Area of Science:

• Hematology
• Gerontology
• Internal Medicine

Background:

• The increasing prevalence of elderly patients with von Willebrand disease (VWD) necessitates understanding age-related pathophysiological changes.
• Aging may influence von Willebrand factor (VWF) and factor VIII (FVIII) levels and bleeding phenotypes in VWD patients.

Purpose of the Study:

• To evaluate age-related alterations in VWF and FVIII levels.
• To compare bleeding phenotypes between elderly and younger VWD patients.
• To investigate co-morbidities in elderly VWD patients.

Main Methods:

• A nationwide cross-sectional study ('Willebrand in the Netherlands' - WiN) included VWD patients with VWF levels ≤30 U/dL.
• Bleeding episodes and VWD treatment were compared between elderly (≥65 years, n=71) and younger (<65 years, n=593) VWD patients.
• Longitudinal analysis of historical VWF and FVIII levels and examination of medical records for co-morbidities were performed in elderly patients.

Main Results:

• In elderly type 1 VWD patients, a 10-year increase in age correlated with a 3.5 U/dL increase in VWF:Ag and a 7.1 U/dL increase in FVIII:C.
• These age-related increases in VWF and FVIII were not observed in elderly type 2 VWD patients.
• Elderly type 2 VWD patients reported significantly more bleeding symptoms in the preceding year compared to younger patients (59% vs. 39%, P=0.048).

Conclusions:

• Von Willebrand factor parameters and bleeding phenotypes change with age in VWD patients.
• In type 1 VWD, aging is associated with increased VWF and FVIII levels, without a reduction in bleeding phenotype.
• In type 2 VWD, VWF parameters do not increase with age, and aging is linked to an increased bleeding tendency.