What happens to von Willebrand's factor secretion in the elderly?

Von Willebrand Factor Secretion in the Elderly

Von Willebrand factor (VWF) levels increase with age in type 1 von Willebrand disease patients, but this increase is not observed in type 2 patients, leading to different bleeding risk profiles in elderly patients based on their VWD subtype. 1

Age-Related Changes in VWF Levels

• VWF is a multimeric plasma glycoprotein that mediates platelet adhesion and aggregation at sites of vascular injury and carries/stabilizes coagulation factor VIII (FVIII) in circulation 2

• In elderly patients with type 1 VWD (partial quantitative deficiency), a decade increase in age is associated with a 3.5 U/dL increase in VWF:Ag levels and a 7.1 U/dL increase in FVIII:C levels 1

• This age-related increase in VWF levels is not observed in elderly patients with type 2 VWD (qualitative deficiency) 1

• The increase in VWF levels with age in the general population and in type 1 VWD patients may be related to various physiological changes associated with aging 3

Impact on Bleeding Symptoms

• Despite the increase in VWF levels in type 1 VWD patients with age, there is no significant mitigation in bleeding phenotype observed 1

• Conversely, elderly type 2 VWD patients report significantly more bleeding symptoms compared to younger patients (59% vs. 39%, p=0.048) 1

• Some studies suggest an inverse association between age and bleeding score in type 1 VWD patients, with older patients experiencing fewer bleeding symptoms 4

Clinical Implications for Elderly VWD Patients

• The evolving VWF parameters and bleeding phenotype with increasing age necessitate regular monitoring and potential adjustment of treatment strategies in elderly VWD patients 1

• Age-related comorbidities can complicate the management of VWD in elderly patients, including:

  • Cardiovascular disease and the need for antiplatelet therapy 3, 5
  • Venous thromboembolism risk 3
  • Malignancies 5

• Specific bleeding challenges in elderly VWD patients include:

  • Gastrointestinal bleeding 3
  • Hematuria 3

Acquired von Willebrand Syndrome in the Elderly

• Elderly patients are at increased risk of developing acquired von Willebrand syndrome (AVWS) due to age-related conditions 5

• AVWS can be associated with:

  • Malignancies 5
  • Hypothyroidism 5
  • Cardiovascular diseases 5
  • Cardiac replacement devices 5

Treatment Considerations

• Medications used to treat VWD should be used with special precaution in older patients, including:

  • Desmopressin (DDAVP) 3
  • VWF-containing factor concentrates 3

• Treatment decisions for elderly VWD patients should consider:

  • The patient's VWD subtype (type 1 vs. type 2) 1
  • Current VWF levels 6
  • Bleeding history and recent bleeding symptoms 1
  • Presence of comorbidities that may affect bleeding risk 5

Research Gaps

• Current literature is limited by a lack of older patients in clinical trials 5

• There is a need for larger studies to determine if age-related comorbidities affect VWD patients at different frequencies than the general elderly population 5

• Registry-based studies are needed to evaluate many age-related comorbidities in VWD patients 5