How do you differentiate quantitative von Willebrand factor deficiency from qualitative defects?

• A. Measure ristocetin cofactor activity alone.
• B. Compare vWF antigen (quantity) with ristocetin cofactor activity (function); type 2 defects have reduced function with relatively preserved antigen.
• C. Assess platelet aggregation with ADP.
• D. Evaluate vWF multimers by gel electrophoresis.

Answer: (B)

Distinguishing quantitative from qualitative VWF defects hinges on comparing how much VWF is present with how well it works. The vWF antigen test measures the amount of VWF, while the ristocetin cofactor activity test measures its function in supporting platelet agglutination in the presence of ristocetin. If the amount and the function decline together (the function tracks the amount), this points to a quantitative deficiency (fewer VWF molecules, and those present work relatively normally). If the amount is preserved or only mildly reduced, but the function is disproportionately low, that indicates a qualitative defect where the VWF protein is present but dysfunctional.

In practice, a reduced ristocetin cofactor activity that is out of proportion to a normal or near-normal vWF antigen level suggests a type 2 (qualitative) defect. Conversely, parallel decreases in both antigen and function support a type 1 or more severe quantitative deficiency. To further classify type 2 subtypes, additional testing like vWF multimer analysis or other specialized assays can be used, but the essential distinction comes from assessing both quantity and function and interpreting their relationship.