What is the workup for von Willebrand (vWD) disease?

Workup for von Willebrand Disease

Clinical Evaluation

Begin with structured bleeding history screening using three initial questions to identify bleeding risk, followed by nine additional detailed questions if initial screening is positive. 1, 2

Bleeding History Assessment

• Ask about excessive bleeding from minor wounds, dental procedures, or surgeries 1
• Inquire about mucocutaneous bleeding symptoms including epistaxis, easy bruising, menorrhagia, and gingival bleeding 1, 2
• Document family history of bleeding disorders or symptoms 1, 2
• The likelihood of VWD increases proportionally with the number of positive responses to screening questions 2

Physical Examination

• Examine for ecchymoses, hematomas, petechiae, and other evidence of recent bleeding 1
• Assess for alternative causes: jaundice or splenomegaly (liver disease), joint and skin laxity (Ehlers-Danlos syndrome), telangiectasia (hereditary hemorrhagic telangiectasia), signs of anemia 1
• Perform gynecologic examination in females to identify anatomic lesions that may cause bleeding 1, 2

Laboratory Testing Algorithm

Initial Hemostasis Tests (Optional First Step)

• Order CBC, PT, and aPTT if the clinical presentation is unclear to rule out thrombocytopenia, thrombocytosis, or other coagulation factor deficiencies 1, 2
• If mucocutaneous bleeding history is strong, skip directly to VWD-specific testing 2

Core VWD Testing Panel (Primary Diagnostic Tests)

Order all three of the following tests simultaneously as the initial VWD evaluation panel: 1, 2

• VWF antigen (VWF:Ag) - measures the quantity of von Willebrand factor protein in plasma 2
• VWF ristocetin cofactor activity (VWF:RCo) - assesses the functional ability of VWF to bind to platelets 2
• Factor VIII coagulant activity (FVIII) - evaluates factor VIII levels, which are carried and protected by VWF 2

These three tests together establish the diagnosis and suggest VWD type and severity 1, 2

Interpretation of Initial Results

• Abnormal results requiring reflex testing include: 1, 2
  • Any test result that is abnormally low
  • VWF:RCo to VWF:Ag ratio below 0.5-0.7

Specialized Testing (Only After Abnormal Initial Results)

Do not order VWF multimer analysis as part of initial screening - reserve this complex test for reflex testing when initial results are abnormal 1, 2

• VWF multimer analysis visualizes the distribution of plasma VWF multimers and helps determine VWD subtype 1
• Additional specialized tests may include collagen binding assay (VWF:CB) and ristocetin-induced platelet aggregation (RIPA) 2

Critical Testing Considerations

Factors That Affect Test Results

• Physiological elevations of VWF occur with: stress, exercise, inflammation, pregnancy, or estrogen therapy - these can falsely normalize VWF levels and mask the diagnosis 2
• ABO blood group O has 25% lower VWF levels than other blood groups 2
• Test ideally when patient is not acutely ill, stressed, or pregnant 2

Sample Handling Requirements

• Transport samples at room temperature 2
• Separate plasma promptly 2
• Freeze at or below -40°C if not tested within 2 hours 2
• Laboratory variability can significantly affect results, so proper specimen collection, processing, transportation, and storage are essential 2

Common Pitfalls to Avoid

• Do not rely on bleeding time or PFA-100 tests - these have conflicting data regarding sensitivity and specificity and are not recommended for routine screening 2, 3
• Do not order only one or two of the core VWD tests - no single laboratory test can screen for all forms of VWD; all three tests (VWF:Ag, VWF:RCo, FVIII) are necessary 2
• Do not order VWF multimer analysis initially - this should only be performed after abnormal initial test results 1, 2
• Do not rely solely on PT and aPTT - normal results do not exclude VWD 3

Next Steps After Testing

• Consult hematology or hemostasis specialist if initial test results are abnormal for further evaluation, subtype determination, and management planning 2
• Repeat testing may be necessary if initial results are borderline or if testing was performed during conditions that elevate VWF levels 2