How do I determine if a significant drop in platelet count is disproportionate in a patient with suspected von Willebrand's disease?

Determining Disproportionate Platelet Drop in Suspected von Willebrand Disease

In suspected von Willebrand disease (VWD), a disproportionate platelet drop is identified by a VWF:RCo/VWF:Ag ratio <0.5-0.7, particularly in Type 2B VWD, along with loss of high molecular weight multimers and enhanced ristocetin-induced platelet aggregation at low doses. 1

Diagnostic Approach for Platelet Drop in VWD

Initial Laboratory Assessment

• Complete a core VWF panel including:
  • VWF antigen (VWF:Ag)
  • VWF ristocetin cofactor activity (VWF:RCo)
  • Factor VIII coagulant activity (FVIII:C)
  • Calculate VWF:RCo/VWF:Ag ratio 1

Key Indicators of Disproportionate Platelet Drop

1. VWF:RCo/VWF:Ag ratio <0.5-0.7 - This is the primary indicator of qualitative VWF defects 1
2. Enhanced ristocetin-induced platelet aggregation (RIPA) at low doses - Particularly characteristic of Type 2B VWD 1
3. Loss of high molecular weight VWF multimers - Seen in electrophoretic analysis 1
4. Platelet count reduction that correlates with VWF abnormalities 2

Specific Testing for Type 2B VWD (Most Associated with Platelet Drops)

• Light transmission aggregometry (LTA) with ristocetin 2
• Flow cytometry to assess platelet surface glycoproteins 2
• Genetic testing of GP1BA gene for platelet-type VWD 3

Differentiating Between VWD Types with Platelet Abnormalities

VWD Type	Laboratory Findings	Platelet Characteristics
Type 2A	• VWF:RCo <30 IU/dL • VWF:Ag 30-200 IU/dL • VWF:RCo/VWF:Ag <0.5-0.7 • Loss of high & intermediate MW multimers	Moderate platelet drop
Type 2B	• VWF:RCo <30 IU/dL • VWF:Ag 30-200 IU/dL • VWF:RCo/VWF:Ag <0.5-0.7 • Loss of high MW multimers	Disproportionate platelet drop Enhanced RIPA at low doses
Platelet-type VWD	• Similar to Type 2B • GP1BA gene mutation	Disproportionate platelet drop Enhanced RIPA with mixing studies

Clinical Pearls and Pitfalls

• Pitfall: Relying solely on VWF antigen and activity levels without calculating the ratio can miss Type 2 VWD 1
• Pitfall: Failing to perform RIPA testing can miss Type 2B and platelet-type VWD 3
• Important: A mildly reduced platelet count should not exclude further testing for inherited platelet function disorders 2
• Caution: Desmopressin should be avoided in Type 2B VWD as it may worsen thrombocytopenia 4

Management Considerations

• For Type 2B VWD with disproportionate platelet drops, VWF-containing factor concentrates are the treatment of choice, not desmopressin 1, 4
• Platelet transfusions may be necessary in platelet-type VWD with significant thrombocytopenia 3
• Target VWF:RCo levels of ≥80-100 IU/dL for major procedures 1

By systematically evaluating the VWF:RCo/VWF:Ag ratio, RIPA response, multimer pattern, and platelet count, you can accurately identify disproportionate platelet drops in suspected VWD and distinguish between the different subtypes that affect platelets.