Type 2B von Willebrand Disease Can Present with Normal VWF Antigen Levels
Yes, type 2B von Willebrand disease can present with normal von Willebrand factor antigen (VWF:Ag) levels, as indicated in the 2008 NHLBI/NIH guidelines. 1
Laboratory Characteristics of Type 2B VWD
- Type 2B VWD is characterized by increased VWF affinity for platelet glycoprotein Ib (GP Ib) and may be associated with decreased platelet numbers 1
- According to the NHLBI/NIH guidelines, VWF:Ag levels in type 2B VWD typically range from <30 to 200 IU/dL, which includes the normal range 1
- The VWF ristocetin cofactor activity (VWF:RCo) is typically <30 IU/dL 1
- The VWF:RCo/VWF:Ag ratio is usually <0.5-0.7, which helps distinguish type 2 from type 1 VWD 1
Diagnostic Challenges with Normal VWF:Ag Levels
- Cases with normal VWF:Ag levels have been documented, including a report of patients with type 2B VWD who had "normal plasma vWF antigen and ristocetin cofactor activity" 2
- Laboratory testing for VWD has high coefficients of variation (10-30%), especially for the VWF:RCo assay, which can impact diagnostic accuracy 1
- VWF is an acute phase reactant, and levels can be elevated in response to stress, inflammation, pregnancy, or estrogen use, potentially masking underlying abnormalities 1
- Repeat testing may be necessary as exceptions to prototypical laboratory values occur 1, 3
Key Diagnostic Features Despite Normal VWF:Ag
- Enhanced ristocetin-induced platelet aggregation (RIPA) at low concentrations of ristocetin is a hallmark of type 2B VWD, even when VWF:Ag levels are normal 3, 2
- Loss of high molecular weight VWF multimers is typically present but may be partially preserved in some unusual type 2B phenotypes 2
- Intermittent thrombocytopenia is a characteristic feature that may help identify type 2B VWD even when VWF:Ag levels are normal 3, 4
- Genetic testing can identify mutations in the A1 domain of VWF, particularly in exon 28, which are diagnostic for type 2B VWD regardless of VWF:Ag levels 3, 5
Clinical Implications and Management
- The diagnosis of type 2B VWD should not be excluded based solely on normal VWF:Ag levels 3, 2
- Specialized testing including VWF multimer analysis, RIPA at low concentrations, and genetic sequencing is recommended when clinical suspicion is high despite normal VWF:Ag levels 3
- Treatment with factor VIII/VWF concentrates remains the most effective approach for prevention and treatment of bleeding in type 2B VWD 6
- Desmopressin should be used with caution as it may exacerbate thrombocytopenia in type 2B VWD 5
Pitfalls to Avoid
- Relying solely on VWF:Ag levels to rule out type 2B VWD can lead to misdiagnosis 3, 2
- Failing to calculate the VWF:RCo/VWF:Ag ratio, which may be abnormal even when VWF:Ag is normal 1
- Not considering the effects of acute phase reactions, stress, or medications on VWF levels 1
- Inadequate sample collection and processing can affect test results (samples should be processed at room temperature to prevent cryoprecipitation of VWF) 1