What is the appropriate management for a patient with normal von Willebrand factor antigen and activity levels suspected of having Type 2B von Willebrand disease?

Management of Suspected Type 2B von Willebrand Disease with Normal VWF Levels

Additional specialized testing is required for a patient with normal von Willebrand factor antigen (1.33) and activity (0.93) levels who is suspected of having Type 2B von Willebrand disease, as these normal values do not rule out the diagnosis.

Diagnostic Considerations

• Normal VWF:Ag and VWF:RCo levels do not exclude Type 2B VWD, as demonstrated in studies showing that some patients with genetically confirmed Type 2B VWD can present with normal laboratory values 1
• The VWF:RCo/VWF:Ag ratio (0.93/1.33 = 0.70) is at the borderline of normal, which could still be consistent with Type 2B VWD 2
• Type 2B VWD is characterized by increased affinity of VWF for platelet GP Ib, which may not always be reflected in standard VWF assays 2, 1

Recommended Additional Testing

• Ristocetin-induced platelet aggregation (RIPA) at low concentrations (0.5 mg/mL) - enhanced RIPA is the hallmark laboratory finding in Type 2B VWD 3, 1
• VWF multimer analysis - to assess for selective deficiency of high-molecular-weight multimers, which is commonly seen in Type 2B VWD 2, 4
• Platelet count monitoring - thrombocytopenia may be intermittent or stress-induced in Type 2B VWD 3
• Genetic testing for mutations in the A1 domain of the VWF gene - definitive for diagnosis of Type 2B VWD 5, 1

Management Algorithm

1. For mild bleeding episodes or prophylaxis:

   • Consider desmopressin (DDAVP) challenge test under controlled conditions 3
   • Monitor platelet count closely as DDAVP may exacerbate thrombocytopenia in Type 2B VWD 3

2. For moderate to severe bleeding episodes:

   • VWF replacement therapy with VWF-containing concentrates is the mainstay of treatment 2, 3
   • Avoid DDAVP if thrombocytopenia is present or worsens after administration 3

3. For surgical procedures:

   • VWF replacement therapy to achieve target VWF:RCo levels appropriate for the procedure 2
   • Monitor platelet count throughout the perioperative period 2, 3

4. Adjunctive therapies:

   • Antifibrinolytic agents (e.g., tranexamic acid) for mucosal bleeding 3
   • Cryoprecipitate should be used only if specific VWF/FVIII concentrates are unavailable 2

Important Caveats

• Some Type 2B VWD variants (particularly p.R1308C) may show absence of enhanced RIPA at 0.5 mg/mL despite genetic confirmation of Type 2B VWD 1
• Blood group O is overrepresented in VWD patients (70.5% in one study), which may affect interpretation of VWF levels 1
• Laboratory testing for VWD has high coefficients of variation (10-30%), especially the VWF:RCo assay, which may affect diagnostic accuracy 2
• Sample handling is critical - blood samples should be transported at room temperature and plasma separated promptly to avoid artifactual results 2

Special Considerations

• Pregnancy and other physiologic stressors may exacerbate thrombocytopenia in Type 2B VWD patients 3
• Family studies are important as Type 2B VWD has complete penetrance but variable expressivity 1
• De novo mutations can occur, so absence of family history does not rule out Type 2B VWD 1