Could a patient with a history of continuous bleeding, thrombocytopenia, low ferritin levels, and a family history of bleeding problems, presenting with low von Willebrand factor (VWF) activity and von Willebrand antigen, have Type 2B von Willebrand disease?

Type 2B von Willebrand Disease Evaluation in a Patient with Normal VWF Levels

This patient likely has Type 2B von Willebrand disease despite normal VWF antigen levels, and should undergo specialized VWF testing including VWF multimer analysis, ristocetin-induced platelet aggregation (RIPA), and genetic testing to confirm the diagnosis. 1, 2

Clinical Presentation Supporting Type 2B VWD

• History of continuous bleeding following procedures (gum graft, thyroidectomy) strongly suggests an underlying bleeding disorder 1
• Intermittent thrombocytopenia is a hallmark feature of Type 2B VWD, as abnormal VWF spontaneously binds to platelets leading to their clearance 1, 3
• Low ferritin levels likely reflect chronic blood loss due to the bleeding disorder 1
• Strong family history of bleeding problems across multiple generations (mother, uncle, grandmother, daughter) supports an inherited bleeding disorder 1, 4

Laboratory Findings Analysis

• The patient's VWF antigen of 1.33 (133 IU/dL) and activity of 0.93 (93 IU/dL) appear normal but require careful interpretation 1, 2
• VWF:RCo/VWF:Ag ratio is 0.70 (0.93/1.33), which is borderline for distinguishing Type 1 from Type 2 VWD (cutoff typically <0.5-0.7) 1, 5
• Normal or elevated VWF levels do not exclude Type 2B VWD, especially when measured during periods of stress, inflammation, or when thrombocytopenia is severe 2, 3

Why Normal VWF Levels Don't Rule Out Type 2B VWD

• VWF is an acute phase reactant and levels can be falsely elevated during stress, inflammation, or other conditions 1, 2
• In Type 2B VWD with severe thrombocytopenia, high molecular weight multimers (HMWM) may temporarily normalize as platelet clearance mechanisms become saturated 3
• Laboratory testing for VWF has high coefficients of variation (10-30%), especially for VWF:RCo assay, affecting diagnostic accuracy 1, 2
• Some Type 2B VWD variants can present with atypical laboratory findings, including normal VWF:RCo/VWF:Ag ratios 6

Recommended Specialized Testing

• VWF multimer analysis to assess distribution of high molecular weight multimers 1
• Ristocetin-induced platelet aggregation (RIPA) at low concentrations of ristocetin (0.5 mg/mL) to detect enhanced VWF-platelet binding 1, 4
• Platelet VWF studies to evaluate platelet-VWF interactions 1
• Genetic sequencing of VWF gene, particularly exon 28 which contains most Type 2B mutations 1, 7

Testing Considerations and Pitfalls

• Repeat testing during different clinical states is crucial, as VWF levels and multimer patterns may fluctuate with platelet count 3, 4
• Blood samples for VWF assays must be properly collected and processed at room temperature to prevent cryoprecipitation of VWF 1
• Some Type 2B variants may have normal RIPA at standard low ristocetin concentrations, requiring additional specialized testing 6
• Testing should be performed when the patient is not taking medications that affect platelet function 1

Clinical Management Implications

• Diagnosis of Type 2B VWD would explain the patient's bleeding history and guide appropriate treatment for future procedures 1, 4
• Desmopressin (DDAVP) may worsen thrombocytopenia in Type 2B VWD and should be used cautiously if at all 7
• Family members should be evaluated given the autosomal dominant inheritance pattern and variable expressivity of Type 2B VWD 4, 6