Type 2B von Willebrand Disease Evaluation with Normal VWF Levels
Type 2B von Willebrand disease cannot be completely excluded with a VWF antigen of 1.26 and activity of 1.18, despite these values appearing normal, as specialized testing is required for definitive diagnosis. 1
Analysis of Current Laboratory Values
- The patient's VWF antigen (1.26) and VWF activity (1.18) levels appear normal, but normal values do not definitively exclude type 2B VWD 1
- The VWF:RCo/VWF:Ag ratio is 0.94 (1.18/1.26), which is above the cutoff of <0.5-0.7 typically used to distinguish type 2 from type 1 VWD 2
- Recent surgical procedures (thyroidectomy with hemorrhage and colonoscopy) may have elevated the patient's VWF levels as an acute phase reaction, potentially masking underlying VWD 2, 1
Why Normal Values Don't Exclude Type 2B VWD
- VWF is an acute phase reactant that increases significantly following surgery, inflammation, or stress, which can temporarily normalize values in patients with underlying VWD 1
- The recent thyroidectomy with hemorrhage (5 weeks prior) and colonoscopy (1 week prior) likely triggered elevated VWF levels 2
- Some variants of type 2B VWD can present with normal VWF:RCo/VWF:Ag ratios despite having the characteristic molecular defect 3
- A study of genotypically confirmed type 2B VWD patients found that normal VWF:RCo/VWF:Ag ratios do not necessarily rule out type 2B VWD 3
Required Specialized Testing for Definitive Diagnosis
- VWF multimer analysis is essential to assess for the characteristic loss of high molecular weight multimers typically seen in type 2B VWD 2, 1
- Ristocetin-induced platelet aggregation (RIPA) at low concentrations of ristocetin (0.5 mg/mL) is the key diagnostic test for type 2B VWD, which typically shows enhanced aggregation 4
- Genetic sequencing of the VWF gene, particularly exon 28 which contains the A1 domain, is recommended to identify type 2B mutations 1, 5
Clinical Considerations
- The history of hemorrhage during thyroidectomy strongly suggests an underlying bleeding disorder 1
- Type 2B VWD accounts for fewer than 5% of all VWD patients but is clinically significant due to its unique management requirements 6
- Some type 2B VWD variants may present with intermittent thrombocytopenia, which should be evaluated in this patient 7
- Patients with type 2B VWD can have varied clinical manifestations even within the same family with identical mutations 7
Testing Recommendations and Pitfalls
- Testing should be repeated when the patient is at least 3 months post-surgery to minimize the impact of acute phase reactions 1
- Blood samples must be properly collected and processed at room temperature to prevent cryoprecipitation of VWF that could affect results 2
- Laboratory testing for VWD has high coefficients of variation (10-30%), especially for the VWF:RCo assay, which can impact diagnostic accuracy 2
- Multiple testing episodes may be necessary due to variability in VWF levels 1
Atypical Presentations of Type 2B VWD
- Some type 2B VWD variants may present with partial preservation of high molecular weight multimers despite enhanced VWF-platelet interaction 8
- Certain mutations (like p.R1308C) can present with absence of RIPA at 0.5 mg/mL despite being genetically confirmed type 2B VWD 3
- Patients with mutations p.P1266L and p.R1304V have been characterized as atypical type 2B VWD with different laboratory profiles 3