Does a patient with a family history of type 2B von Willebrand disease and a bleeding score of six require further testing and treatment?

Further Testing is Required for a Patient with Family History of Type 2B VWD and Elevated Bleeding Score

A patient with a bleeding score of six and multiple family members with type 2B von Willebrand disease should undergo multimer analysis and genetic testing despite normal initial laboratory results. 1, 2

Why Further Testing is Necessary

Strong Clinical Indicators Present

• Bleeding score of 6 (clinically significant)
• Strong family history (mother, sister, niece, and uncle with type 2B VWD)
• Autosomal dominant inheritance pattern of type 2B VWD

Limitations of Initial Testing

• Initial VWD testing can be normal even in patients with type 2 variants
• According to the NHLBI guidelines, when bleeding history is strong but initial tests are normal, specialized VWD studies should be considered 1
• Type 2B VWD accounts for fewer than 5% of all VWD cases, making it easily missed on routine testing 3

Recommended Additional Testing

1. Multimer Analysis

   • Essential for detecting the characteristic loss of high molecular weight multimers seen in type 2B VWD 2
   • Can reveal abnormalities even when standard VWF antigen and activity tests appear normal

2. Ristocetin-Induced Platelet Aggregation (RIPA)

   • Type 2B VWD typically shows enhanced RIPA at low ristocetin concentrations 2
   • Critical for distinguishing between VWD subtypes

3. Genetic Testing

   • Sequence analysis of VWF gene (particularly exon 28) to identify type 2B mutations 4
   • 84.2% of type 2B variants are found in exon 28 of the VWF gene 4
   • Can confirm diagnosis when laboratory findings are ambiguous

Clinical Implications of Missed Diagnosis

• Treatment Considerations: Type 2B VWD requires specific management approaches
• Medication Risks: Desmopressin can worsen thrombocytopenia in type 2B VWD and should be used with caution 5, 3
• Surgical Planning: Patients require VWF replacement therapy rather than desmopressin for surgical procedures 6
• Pregnancy Management: Type 2B VWD can cause worsening thrombocytopenia during pregnancy, requiring specialized care 7

Management Recommendations if Diagnosis Confirmed

• VWF-containing factor concentrates are the mainstay of therapy for type 2B VWD 2, 3
• Avoid or use desmopressin with extreme caution due to risk of worsening thrombocytopenia 5, 6
• Monitor platelet counts regularly, especially during physiologic stressors like pregnancy 7
• Consult with a hematologist experienced in bleeding disorders 2

Important Caveats

• Type 2B VWD can show significant clinical heterogeneity even among family members with identical mutations 8
• Platelet counts may fluctuate over time, with some patients showing intermittent rather than persistent thrombocytopenia 7
• Recent research shows that specific genetic variants (particularly p.Arg1306Trp) are strongly associated with thrombocytopenia risk 7

The pathologist's conclusion that the patient is normal and doesn't need multimer or genetic testing is not supported by current guidelines, which recommend specialized testing when there is a strong family history and elevated bleeding score, even with normal initial test results 1, 2.