Would you expect von Willebrand factor (VWF) levels to be higher in a 62-year-old woman with type 2B von Willebrand disease compared to a younger woman?

Von Willebrand Factor Levels in Type 2B von Willebrand Disease in a 62-Year-Old Woman

In a 62-year-old woman with type 2B von Willebrand disease, you would expect von Willebrand factor (VWF) levels to be higher compared to her younger years, but this increase is likely less significant than what would be observed in a healthy woman of the same age or in patients with type 1 VWD.

Age-Related Changes in VWF Levels by VWD Type

Type 2B VWD Patients

• Unlike type 1 VWD, patients with type 2B VWD do not show significant increases in VWF activity with advancing age 1
• Type 2B VWD is characterized by gain-of-function mutations in the A1 domain causing increased binding to platelet GPIbα receptors 2
• These patients have reduced VWF survival regardless of multimer representation, with significantly shorter half-life (approximately 4.5 hours vs normal 15.5 hours) 3

Type 1 VWD vs Type 2 VWD Age-Related Changes

• In type 1 VWD patients, a decade increase in age after 40 years is associated with:
  • 3.5 U/dL increase in VWF:Ag (95% CI, -0.6 to 7.6)
  • 7.1 U/dL increase in FVIII:C (95% CI, 0.7 to 13.4) 1
• In contrast, type 2 VWD patients (including 2B) do not show this age-related increase in VWF parameters 1

Clinical Implications for Older Type 2B Patients

Bleeding Risk

• Elderly type 2 VWD patients (>65 years) report significantly more bleeding symptoms compared to younger patients (59% vs 39%, P=0.048) 1
• This increased bleeding tendency occurs despite the general trend of VWF levels rising with age in the general population

Pathophysiological Mechanisms

• The lack of age-related VWF increase in type 2B patients is likely due to:
  1. Persistently increased clearance of VWF from circulation 3
  2. Continued preferential loss of high molecular weight VWF multimers 2
  3. Increased platelet binding and subsequent clearance 2

Management Considerations for Older Type 2B Patients

• Replacement therapy with factor VIII/VWF concentrates remains the most effective approach for prevention and treatment of bleeding 2
• Desmopressin should be used with caution as it may cause transient thrombocytopenia and increased bleeding risk 2
• Platelet transfusions may provide suboptimal results since transfused platelets can be aggregated by the abnormal VWF 2
• Careful assessment of bleeding risk is needed when considering antiplatelet or anticoagulant therapy 4

Conclusion

While VWF levels generally increase with age in the general population and in type 1 VWD, patients with type 2B VWD do not experience this age-related increase. Therefore, a 62-year-old woman with type 2B VWD would not be expected to have significantly higher VWF levels than her younger counterparts with the same condition, despite her advanced age. This lack of age-related VWF increase may contribute to the observed higher bleeding tendency in elderly type 2 VWD patients.