Is type 2 von Willebrand disease (VWD) totally excluded in a patient with a von Willebrand antigen level of 1.52 and von Willebrand activity level of 1.14?

Type 2 von Willebrand Disease is Not Excluded in This Patient

Type 2 von Willebrand disease cannot be excluded based solely on the von Willebrand antigen level of 1.52 and activity level of 1.14, and additional testing is necessary for definitive diagnosis. 1, 2

Interpretation of Current Laboratory Values

The patient's laboratory results show:

• VWF antigen: 1.52 (normal range 0.50-2.00 IU/dL)
• VWF activity: 1.14 (normal range 0.50-2.00 IU/dL)
• VWF:RCo/VWF:Ag ratio: 0.75 (calculated from provided values)

While these values appear normal in isolation, they must be interpreted in the context of:

1. The patient's advanced age (90 years old)
2. History of bleeding
3. Significant platelet drops

Key considerations:

• VWF levels typically increase with age, so "normal" values in an elderly patient may actually represent relative deficiency 2
• The VWF:RCo/VWF:Ag ratio of 0.75 is borderline normal (cutoff <0.5-0.7 for type 2 VWD) 1
• Some type 2 variants can present with normal or elevated VWF antigen levels 3

Additional Testing Required

To definitively exclude or confirm type 2 VWD, the following tests are necessary:

1. VWF multimer analysis: Critical for detecting qualitative defects in type 2 VWD, especially to identify loss of high molecular weight multimers seen in types 2A and 2B 2, 3

2. Ristocetin-induced platelet aggregation (RIPA): To differentiate between type 2B (enhanced response at low-dose ristocetin) and other subtypes 2

3. VWF collagen binding assay (VWF:CB): May reveal disproportionately low binding compared to antigen levels in type 2 variants 3, 4

4. VWF propeptide (VWFpp) to VWF:Ag ratio: Can help identify variants with increased clearance 3

5. FVIII binding assay: To exclude type 2N VWD, which presents with normal VWF levels but reduced FVIII binding 2, 5

Diagnostic Algorithm for Type 2 VWD

1. Initial assessment:

   • Calculate VWF:RCo/VWF:Ag ratio (borderline in this case at 0.75)
   • Evaluate FVIII:C levels

2. Further testing based on initial results:

   • Perform multimer analysis to detect structural abnormalities
   • Conduct RIPA testing at both low and high ristocetin concentrations
   • Assess VWF:CB and VWF:CB/VWF:Ag ratio

3. Specialized testing if indicated:

   • VWF propeptide assay
   • FVIII binding assay
   • Genetic testing for mutations in specific domains of VWF gene

Important Clinical Considerations

• The patient's history of bleeding with platelet drops strongly suggests an underlying hemostatic disorder, even with apparently normal VWF levels 6

• Type 2M VWD can present with normal multimer patterns but decreased platelet-dependent function 5, 3

• Type 2B VWD can cause thrombocytopenia, which aligns with the patient's history of platelet drops 2, 5

• Advanced age increases baseline VWF levels, potentially masking relative deficiencies 3

• Some type 2 variants (particularly 2M and some 2B) may have normal or near-normal VWF:RCo/VWF:Ag ratios but still demonstrate functional defects 6, 3

Common Pitfalls to Avoid

• Do not exclude type 2 VWD based solely on normal VWF levels in elderly patients, as age-related increases in VWF can mask relative deficiencies

• Do not rely exclusively on VWF:RCo/VWF:Ag ratio without multimer analysis and specialized testing

• Do not overlook type 2B VWD in patients with thrombocytopenia, as this variant specifically can cause platelet consumption

• Do not dismiss borderline normal ratios (like 0.75 in this case), as they may still indicate subtle qualitative defects

In conclusion, this 90-year-old patient with bleeding history and platelet drops requires comprehensive VWD testing, including multimer analysis, RIPA, and other specialized assays to definitively exclude type 2 VWD, despite apparently normal VWF levels.