What if a patient's platelet count fluctuates and a subsequent test shows thrombocytopenia (low platelet count), should von Willebrand's disease be considered?

Considering von Willebrand Disease in Patients with Fluctuating Platelet Counts

Yes, von Willebrand Disease (VWD) should be considered in patients with fluctuating platelet counts, especially when a subsequent test shows thrombocytopenia, as certain VWD subtypes (particularly Type 2B) can present with intermittent thrombocytopenia.

Understanding the Relationship Between VWD and Platelet Counts

VWD is a common bleeding disorder that requires comprehensive testing for diagnosis. While most VWD types don't typically affect platelet counts, certain subtypes can present with thrombocytopenia:

• Type 2B VWD specifically can present with thrombocytopenia due to enhanced binding of abnormal von Willebrand factor (VWF) to platelets, leading to their clearance from circulation 1
• Platelet counts may fluctuate in Type 2B VWD, with normal counts at some times and thrombocytopenia at others
• The International Society on Thrombosis and Haemostasis notes that Type 2B VWD should be considered in patients with unexplained thrombocytopenia 2

Diagnostic Approach for Suspected VWD

When a patient presents with fluctuating platelet counts and potential thrombocytopenia, the following testing should be performed:

1. Initial laboratory evaluation:

   • Complete blood count with platelet count and assessment of platelet size
   • Prothrombin time (PT)
   • Activated partial thromboplastin time (aPTT)
   • Clauss fibrinogen
   • VWF screening panel:
     • VWF antigen (VWF:Ag)
     • VWF activity assays (VWF:RCo or newer assays like VWF:GPIbM)
     • Factor VIII coagulant activity (FVIII:C)
     • VWF:RCo/VWF:Ag ratio (ratio <0.5-0.7 suggests Type 2 VWD) 1

2. Specialized testing:

   • Ristocetin-induced platelet aggregation (RIPA) with mixing studies
     • Enhanced RIPA at low-dose ristocetin is characteristic of Type 2B VWD 1
   • VWF multimer analysis to distinguish between VWD subtypes
     • Type 2B shows loss of high molecular weight multimers 1
   • Genetic testing of GP1BA gene for platelet-type VWD 2

Important Considerations

1. Repeat testing may be necessary:

   • VWF is an acute phase reactant and levels can vary in response to clinical status
   • Testing may need to be repeated up to 3 times to ensure reliable results 3
   • Fluctuations in platelet count should be documented with serial measurements

2. Diagnostic pitfalls to avoid:

   • Don't dismiss VWD based on a single normal platelet count
   • Normal VWF levels don't exclude all VWD subtypes, particularly Type 2 variants
   • Thrombocytopenia in VWD patients may be misattributed to other causes

3. When to suspect Type 2B VWD:

   • Intermittent thrombocytopenia with large platelets
   • Enhanced RIPA at low ristocetin concentrations
   • Decreased VWF:RCo with normal or slightly decreased VWF:Ag
   • VWF:RCo/VWF:Ag ratio <0.5-0.7
   • Loss of high molecular weight VWF multimers 1, 4

Management Implications

If VWD is confirmed in a patient with fluctuating platelet counts:

• For Type 2B VWD:

  • Desmopressin is generally contraindicated as it may worsen thrombocytopenia 5
  • VWF-containing concentrates are the treatment of choice 1
  • Platelet transfusions may be needed in cases of severe thrombocytopenia with bleeding 2

• For other VWD types:

  • Treatment depends on subtype and severity
  • Desmopressin may be effective for Type 1 VWD with factor VIII levels >5% 5
  • VWF-containing concentrates for more severe cases or types not responsive to desmopressin 1

Conclusion

Fluctuating platelet counts with episodes of thrombocytopenia should prompt consideration of VWD, particularly Type 2B. Comprehensive testing including VWF levels, activity assays, multimer analysis, and RIPA studies is essential for accurate diagnosis. Misdiagnosis is common, with studies showing that 25% of historically diagnosed VWD patients may have normal VWF levels on repeat testing 6, highlighting the importance of thorough evaluation.