Laboratory Pattern Interpretation: Type 1 von Willebrand Disease
When all three tests—factor VIII activity, VWF antigen (VWF:Ag), and VWF activity (VWF:RCo)—are positive (present but proportionately reduced together), this pattern is characteristic of Type 1 von Willebrand disease. 1
Diagnostic Laboratory Pattern
Type 1 VWD demonstrates a quantitative deficiency where all VWF parameters decrease proportionately: 1, 2
- VWF:Ag: Reduced (typically 30-50% of normal)
- VWF:RCo (activity): Reduced proportionately to VWF:Ag
- Factor VIII activity: Reduced proportionately (since VWF carries FVIII in plasma)
- VWF:RCo/VWF:Ag ratio: Normal (>0.5-0.7), distinguishing it from Type 2 variants 1
Key Distinguishing Features from Other VWD Types
Type 1 differs from Type 2 variants by maintaining a normal ratio between VWF activity and antigen: 1, 3
- Type 2 VWD shows disproportionately low VWF:RCo compared to VWF:Ag (ratio <0.5-0.7), indicating qualitative dysfunction 1
- Type 2 variants have abnormal VWF multimer patterns, while Type 1 shows all multimers present (just reduced in quantity) 3, 4
Type 1 differs from Type 3 by having detectable (though reduced) VWF levels: 3
- Type 3 VWD shows absent or nearly absent (<3%) VWF:Ag, VWF:RCo, and very low FVIII 3
Critical Diagnostic Pitfalls to Avoid
VWF is an acute phase reactant, so levels can be falsely elevated during: 5, 6
- Stress, inflammation, or recent surgery
- Pregnancy or estrogen use
- This can mask underlying Type 1 VWD, requiring repeat testing when the patient is at baseline 5, 6
High test variability (coefficient of variation 10-30% for VWF:RCo) means: 5, 6
- Borderline results require repeat testing up to 3 times 5
- Single normal results do not exclude VWD if clinical bleeding history is strong 5
Sample handling is critical: 1, 6
- Process samples at room temperature to prevent cryoprecipitation of VWF 1
- Improper collection can yield falsely abnormal results 6
When to Consider Type 1 Subtypes
Some Type 1 VWD patients have specific mechanisms requiring specialized testing: 7, 3
- Type 1C (Vicenza): Rapid VWF clearance with unusually large multimers present; identified by elevated VWFpp/VWF:Ag ratio >10 7, 3
- Type 1/2E: Multimerization defect with clearance issues; VWFpp/VWF:Ag ratio 3.2-4.7 3
- These subtypes may respond differently to DDAVP (good initial response but rapid clearance) 3, 8