What is the recommended approach for screening Von Willebrand (VWD) disease?

Screening for Von Willebrand Disease

Screening for Von Willebrand disease requires initial clinical evaluation followed by specific laboratory tests including VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII). 1

Clinical Evaluation

Initial Screening Questions

The screening process begins with a thorough clinical assessment:

• For asymptomatic patients undergoing surgery or invasive procedures, ask these three questions:

  1. Have you or a blood relative ever needed medical attention for a bleeding problem?
  2. Have you ever had prolonged bleeding after surgery or dental procedures?
  3. Have you ever had bruising with minimal or no apparent trauma?

• For patients with suspected bleeding disorders, use the expanded nine-question assessment that evaluates:

  • Epistaxis frequency and severity
  • Bruising patterns
  • Bleeding after minor wounds
  • Oral cavity bleeding
  • Gastrointestinal bleeding
  • Post-surgical bleeding
  • Menorrhagia
  • Family history of bleeding disorders
  • Previous blood product transfusions 1

• Use of a standardized bleeding assessment tool (BAT) is recommended to objectively quantify bleeding history 2

Physical Examination

Look specifically for:

• Ecchymoses, hematomas, petechiae
• Evidence of liver disease (jaundice)
• Splenomegaly
• Joint and skin laxity (Ehlers-Danlos syndrome)
• Telangiectasia
• Signs of anemia
• Anatomic lesions on gynecologic examination 1

Laboratory Testing Algorithm

Initial Hemostasis Tests

If clinical evaluation suggests a bleeding disorder:

• Complete blood count (CBC)
• Prothrombin time (PT)
• Activated partial thromboplastin time (PTT) 1

Initial VWD-Specific Tests

When mucocutaneous bleeding history is strong, order these three core tests:

1. VWF antigen (VWF:Ag)
2. VWF ristocetin cofactor activity (VWF:RCo)
3. Factor VIII coagulant activity (FVIII) 1, 2

Interpretation of Initial Results

• Diagnosis of VWD is made when:
  • VWF levels are under 30 IU/dL, or
  • VWF levels are between 30-50 IU/dL with a positive bleeding history 3
• Calculate VWF:RCo to VWF:Ag ratio - a ratio below 0.5-0.7 suggests qualitative VWD (Type 2) 1

Advanced Testing

If initial tests are abnormal or clinical suspicion remains high despite normal initial tests:

• VWF multimer analysis (not for initial screening)
• Ristocetin-induced platelet aggregation (RIPA)
• VWF collagen binding assay
• VWF:FVIII binding assay (for Type 2N)
• Genetic testing 2, 4

Important Considerations and Pitfalls

• Repeat testing may be necessary: VWF levels can fluctuate, and up to 3 tests may be needed for reliable results 2

• Timing of testing: Test when patient's health is at baseline level, as VWF levels can be affected by:

  • Stress from acute bleeding
  • Anemia
  • Pregnancy
  • Medications
  • Inflammation 3

• Blood group influence: VWF levels are typically lower in individuals with blood group O 5

• False negatives: Initial VWD testing can be normal even in patients with Type 2 variants, highlighting the need for specialized studies in certain cases 2

• Type 2M VWD is often misdiagnosed as Type 2A or Type 1 VWD - specific test patterns using collagen binding vs. glycoprotein Ib binding assays can help differentiate 4

• Acquired von Willebrand syndrome: Consider this in persons with abnormal VWF test results and bleeding symptoms without personal/family history consistent with hereditary VWD 1

By following this structured approach to screening, clinicians can effectively identify patients with VWD and ensure appropriate classification, which is essential for proper treatment and counseling.