Does type 1 von Willebrand disease (VWD) improve with age as von Willebrand factor (VWF) levels increase, but not type 2 due to defective VWF?

Von Willebrand Disease Type 1 vs Type 2: Age-Related Changes

Type 1 von Willebrand disease (VWD) can improve with age as von Willebrand factor (VWF) levels naturally increase, but Type 2 VWD typically does not improve because the underlying defect is qualitative rather than quantitative. 1

Understanding VWD Types and Their Characteristics

• Type 1 VWD is characterized by a partial quantitative deficiency of VWF, with VWF levels typically <30 IU/dL but with functionally normal VWF (VWF:RCo/VWF:Ag ratio >0.5-0.7) 1
• Type 2 VWD involves qualitative defects in VWF structure or function, with subtypes including:
  • Type 2A: Decreased VWF-dependent platelet adhesion with selective deficiency of high-molecular-weight VWF multimers 1
  • Type 2B: Increased VWF affinity for platelet GP Ib 1
  • Type 2M: Decreased VWF-dependent platelet adhesion without selective deficiency of high-molecular-weight VWF multimers 1
  • Type 2N: Markedly decreased VWF binding affinity for FVIII 1

Age-Related Changes in VWD

• In Type 1 VWD, VWF levels can increase with advancing age, potentially leading to improvement in bleeding symptoms 2
• This improvement occurs because VWF is an acute phase reactant that naturally increases with age in the general population 2
• In Type 2 VWD, despite potential increases in VWF quantity with age, the underlying qualitative defect in VWF structure or function persists 2
• The defective VWF in Type 2 remains dysfunctional regardless of its concentration, explaining why symptoms typically do not improve with age 1, 2

Clinical Implications

• Patients with Type 1 VWD may experience decreased bleeding tendency as they age due to increasing VWF levels 2, 3
• Type 2 VWD patients generally require continued monitoring and treatment throughout life as their qualitative VWF defect remains unchanged 4
• The VWF:RCo/VWF:Ag ratio remains a critical diagnostic parameter:
  • In Type 1: Ratio typically >0.5-0.7 (normal functional activity relative to antigen levels) 1
  • In Type 2 (A, B, M): Ratio typically <0.5-0.7 (reduced functional activity relative to antigen levels) 1

Diagnostic Considerations

• Diagnosis of VWD requires three criteria: positive bleeding history since childhood, reduced VWF activity in plasma, and appropriate inheritance pattern 5
• Laboratory testing should include VWF:RCo, VWF:Ag, and FVIII levels to distinguish between VWD types 1
• Repeat testing may be necessary due to variability in VWF levels influenced by external factors 1
• The diagnostic cutoff for VWD is typically <30 IU/dL for VWF:RCo, though patients with levels between 30-50 IU/dL may still have clinically significant disease 1, 4

Treatment Implications

• For Type 1 VWD patients, treatment needs may decrease with age as VWF levels naturally rise 4, 2
• For Type 2 VWD patients, treatment approaches must continue to address the qualitative defect regardless of age 4
• Desmopressin is often effective for Type 1 VWD but less useful for Type 2 variants where VWF concentrates may be required 4

Common Pitfalls and Caveats

• Misdiagnosis of Type 1 VWD is common due to overlap with normal variation, especially in those with blood type O who naturally have lower VWF levels 6
• Aging-related increases in VWF may mask underlying Type 1 VWD in older patients, potentially leading to underdiagnosis 2
• In Type 2 VWD, increased VWF quantity with age may create false reassurance if only quantitative (not functional) assays are performed 1
• The VWF:RCo/VWF:Ag ratio should always be assessed to distinguish between Type 1 and Type 2 VWD, especially in older patients 1