In a patient with von Willebrand factor antigen ~19 % and factor VIII ~47 %, does a ristocetin cofactor of 12 % indicate type III von Willebrand disease?

Von Willebrand Disease Type 3 Classification

No, these laboratory values do not indicate Type 3 von Willebrand disease; they are more consistent with Type 1 or possibly Type 2 VWD. Type 3 VWD requires virtually absent VWF levels (typically <3-5%), and this patient has detectable VWF antigen at 19% and ristocetin cofactor at 12%. 1, 2

Why This Is Not Type 3 VWD

Type 3 VWD is characterized by:

• Complete or near-complete absence of VWF protein (VWF:Ag typically <3% or undetectable) 1, 2
• Absent ristocetin cofactor activity (VWF:RCo <1% or undetectable) 1, 2
• Severely reduced Factor VIII (typically <10%, often <5%) due to lack of VWF protection 1, 2
• Caused by homozygosity or compound heterozygosity for null mutations (nonsense mutations) 1, 2

Your patient has:

• VWF:Ag of ~19% (detectable, not absent)
• VWF:RCo of 12% (detectable, not absent)
• Factor VIII of ~47% (relatively preserved, not severely reduced)

Most Likely Classification

This pattern suggests Type 1 VWD or possibly a Type 2 variant:

Type 1 VWD Features Present:

• Proportional reduction in both VWF:Ag (19%) and VWF:RCo (12%) 3, 1
• VWF:RCo/VWF:Ag ratio of 0.63 (12/19), which is borderline but not definitively reduced below the typical 0.5-0.7 cutoff used to distinguish Type 2 from Type 1 4, 5
• Factor VIII relatively preserved at 47%, which is typical for Type 1 VWD where FVIII is usually >30% 3, 1

Important Technical Consideration:

• The VWF:RCo assay has poor sensitivity at low levels, with a limit of detection around 10-20 IU/dL and high coefficient of variation (10-30%) 6
• At a level of 12%, the VWF:RCo measurement is at the lower limit of reliable detection, making precise ratio calculations less reliable 6

Recommended Next Steps

To definitively classify this patient's VWD:

1. Repeat testing when not acutely ill, as VWF is an acute phase reactant that can be falsely elevated 4

2. VWF multimer analysis to assess for loss of high molecular weight multimers, which would indicate Type 2 VWD 4, 3

3. Consider genetic testing if multimer analysis shows abnormalities or if clinical bleeding severity seems disproportionate to laboratory findings 4, 5

4. DDAVP challenge test can help differentiate between Type 1 and Type 2 variants based on response patterns 3, 1

Critical Pitfall to Avoid

Do not diagnose Type 3 VWD when VWF is detectable. Type 3 is a severe, recessive disorder with virtually absent VWF protein and severe Factor VIII deficiency, presenting with severe bleeding from early childhood including hemarthroses and muscle hematomas similar to severe hemophilia A. 1, 2 Your patient's laboratory values, particularly the preserved Factor VIII at 47%, are incompatible with this diagnosis.