In a patient with a normal von Willebrand factor multimer pattern, VWF antigen ~19 %, ristocetin cofactor activity ~12 % (VWF:RCo/VWF:Ag ratio ≈0.6) and factor VIII level ~47 %, what type of von Willebrand disease is most likely?

Type 1 von Willebrand Disease

In a patient with normal VWF multimers, VWF:Ag ~19%, VWF:RCo ~12%, a VWF:RCo/VWF:Ag ratio of approximately 0.6, and Factor VIII ~47%, the most likely diagnosis is Type 1 von Willebrand disease. 1

Diagnostic Reasoning

The key to classification lies in interpreting the VWF:RCo/VWF:Ag ratio alongside the multimer pattern:

• The ratio of 0.6 falls at or above the typical 0.5–0.7 cutoff used to distinguish Type 2 from Type 1 VWD, making Type 2 less likely 1
• Normal multimer analysis effectively excludes Type 2 variants (2A, 2B, 2M), which characteristically show loss or abnormalities of high molecular weight multimers 1, 2
• Both VWF:Ag and VWF:RCo are proportionally reduced, consistent with a quantitative rather than qualitative defect 3

Important Technical Considerations

Several factors complicate the interpretation of these borderline values:

• The VWF:RCo assay has limited reliability at low concentrations (10–20 IU/dL detection limit) with coefficients of variation of 10–30%, making precise ratio calculations less dependable when VWF:RCo is ~12% 1
• VWF is an acute-phase reactant that can be falsely elevated during inflammation or stress, potentially masking the true severity of deficiency 4, 1
• Repeat testing is recommended after any acute illness resolves, ideally up to 3 times if clinical suspicion remains high, given the inherent variability in VWF measurements 4

Why Not Type 2?

Type 2 VWD subtypes are excluded by the following:

• Type 2A and 2B show absent high molecular weight multimers on gel electrophoresis, which this patient does not have 2
• Type 2M typically shows VWF:RCo/VWF:Ag ratios well below 0.5 with selectively decreased platelet-dependent function but normal VWF:CB 2
• Type 2B would demonstrate enhanced RIPA at low ristocetin concentrations and often presents with intermittent thrombocytopenia, neither of which is mentioned 5, 2

Clinical Pitfalls to Avoid

• Do not rely solely on a single VWF:RCo/VWF:Ag ratio when the value is borderline (0.5–0.7 range), as assay variability can shift classification 4
• Failing to obtain multimer analysis when the ratio is equivocal can lead to misclassification between Type 1 and Type 2 1
• Testing during acute illness or recent procedures may artificially elevate VWF levels and obscure the diagnosis 4

Confirmatory Testing if Needed

If clinical bleeding severity seems disproportionate to these laboratory findings:

• Genetic testing of the VWF gene can identify specific mutations confirming Type 1 VWD or revealing unexpected Type 2 variants 1, 5
• VWF propeptide (VWFpp) to VWF:Ag ratio can distinguish clearance defects (elevated ratio >3) from synthesis/secretion defects (normal ratio) within Type 1 VWD 2