What blood tests are needed to diagnose von Willebrand disease?

Blood Tests Required for von Willebrand Disease Diagnosis

The diagnosis of von Willebrand disease requires three essential initial blood tests: VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII). 1

Initial Laboratory Evaluation

First-line Tests

• Complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (PTT) should be ordered if a bleeding disorder is suspected, though these do not specifically diagnose VWD 1
• The three essential VWD-specific tests that should always be performed include:
  • VWF antigen (VWF:Ag) - measures the quantity of VWF protein 1
  • VWF ristocetin cofactor activity (VWF:RCo) - measures VWF function 1
  • Factor VIII coagulant activity (FVIII) - measures FVIII levels which are often affected in VWD 1

Interpretation of Initial Tests

• VWF:RCo/VWF:Ag ratio below 0.5-0.7 suggests qualitative VWD (Type 2) rather than quantitative deficiency (Type 1) 1, 2
• Normal ranges for these tests are typically 50-200 IU/dL for VWF:Ag, VWF:RCo, and FVIII 1
• A definitive diagnosis of VWD is typically made when VWF:RCo is <30 IU/dL 1

Specialized Testing

Second-line Tests

• VWF multimer analysis should be performed if initial testing reveals abnormal results or if clinical suspicion remains high despite normal initial tests 1
• This test visualizes the distribution of VWF multimers and is crucial for determining VWD subtype, but is technically complex and not recommended for initial screening 1, 3

Additional Tests

• Some laboratories may offer VWF collagen binding assay (VWF:CB) which can help distinguish between VWD subtypes, particularly Type 2M 4, 5
• Newer assays like the INNOVANCE assay (VWF:Ac) may be used as alternatives to VWF:RCo in some laboratories 4, 6

Important Considerations for Testing

Sample Collection and Processing

• Blood samples for VWF assays must be transported to the laboratory at room temperature 1
• Plasma should be separated from blood cells promptly at room temperature 1
• If testing will be delayed beyond 2 hours, samples must be frozen at or below -40°C 1

Factors Affecting Test Results

• Patient factors that can elevate VWF and FVIII levels include stress, recent exercise, inflammatory illness, pregnancy, and oral contraceptives 7
• The VWF:RCo assay has high coefficient of variation (10-30%), which may affect result interpretation 1
• Repeat testing may be necessary due to variability in test results 1, 7

Diagnostic Pitfalls

• Relying solely on a single test can lead to misdiagnosis - all three initial tests are required 7
• Failure to consider ABO blood type when interpreting results (type O is associated with lower VWF levels) 1
• Improper sample handling can significantly affect test results, potentially leading to false negatives or positives 1, 7
• Patients with VWF:RCo between 30-50 IU/dL may still have VWD if there is supporting clinical or family evidence 1