Do I need to check von Willebrand (vW) antigen in addition to factor VIII antigen?

Von Willebrand Factor Antigen vs Factor VIII Antigen Testing

Yes, you need to check von Willebrand factor antigen (VWF:Ag) in addition to factor VIII activity, as they are different tests measuring distinct components that are critical for proper diagnosis of von Willebrand disease. 1

Differences Between VWF:Ag and Factor VIII Antigen

• VWF:Ag measures the quantity of von Willebrand factor protein in plasma, while factor VIII activity (FVIII) measures the clotting activity of factor VIII 1
• These are separate proteins that circulate together as a complex in plasma but have distinct functions and can be independently affected in different bleeding disorders 2
• VWF:Ag is specifically used to quantify the amount of VWF protein present, regardless of its functionality 3
• Factor VIII activity testing evaluates the procoagulant function of factor VIII, which is different from measuring factor VIII antigen 4

Standard Testing Panel for VWD Diagnosis

The 2008 NHLBI/NIH guidelines recommend three initial tests for VWD evaluation:

1. VWF antigen (VWF:Ag) - measures the quantity of VWF protein 1
2. VWF ristocetin cofactor activity (VWF:RCo) - measures VWF function 1
3. Factor VIII coagulant activity (FVIII) - measures factor VIII function 1

Clinical Importance of Testing Both

• Testing both VWF:Ag and factor VIII activity is essential because their relationship helps differentiate between VWD subtypes 1
• Type 2N VWD specifically affects the binding between VWF and factor VIII, making both measurements crucial for diagnosis 5
• The ratio of VWF:RCo to VWF:Ag (normally >0.5-0.7) is important for distinguishing Type 1 from Type 2 variants 1
• In Type 2N VWD, factor VIII levels are markedly decreased while VWF:Ag may be normal, highlighting the need for both tests 1

Testing Considerations

• Sample collection and handling are critical for accurate results - blood should be transported at room temperature and processed promptly 1
• Both tests have relatively high coefficients of variation (10-30%), so results should be interpreted carefully 1
• Patient factors like stress, inflammation, pregnancy, and ABO blood type can affect VWF and factor VIII levels 1
• Newer assays like VWF:GPIbM may provide more precise measurements than traditional VWF:RCo testing 1

Diagnostic Algorithm

1. Obtain all three initial tests: VWF:Ag, VWF:RCo, and FVIII activity 1
2. Calculate the VWF:RCo/VWF:Ag ratio to help determine VWD subtype 1
3. If results are abnormal or inconsistent with clinical presentation, consider specialized testing:
   • VWF multimer analysis for Type 2A, 2B, or 2M 1
   • VWF:FVIIIB (VWF-factor VIII binding) for suspected Type 2N 5
   • RIPA (ristocetin-induced platelet aggregation) for Type 2B 6

Common Pitfalls to Avoid

• Relying on a single test for diagnosis - all three initial tests are needed 1
• Failing to consider pre-analytical variables that can affect test results 1
• Not repeating abnormal tests to confirm findings, as there is high variability in testing 1
• Overlooking the need for specialized testing when initial results are inconclusive 1
• Misinterpreting normal factor VIII levels as excluding VWD (particularly in Type 2 variants) 1