Should a patient with a family history of von Willebrand's disease be tested for the condition?

Testing for von Willebrand Disease in Patients with Family History

Patients with a family history of von Willebrand disease should be tested for the condition, especially if they report any bleeding symptoms or are planning to undergo surgery or invasive procedures. 1

Rationale for Testing

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, characterized by quantitative or qualitative defects in von Willebrand factor (VWF). Family history is a crucial clinical consideration when assessing for bleeding disorders, with 98% of clinicians including it in their initial bleeding assessment 2.

Initial Clinical Evaluation

When a patient presents with a family history of VWD, follow this approach:

1. Conduct a detailed bleeding history assessment using these questions:

   • Have you ever had prolonged bleeding after surgery, dental procedures, or trauma?
   • Do you bruise easily or develop large bruises with minor trauma?
   • Have you experienced frequent nosebleeds, gum bleeding, or heavy menstrual bleeding?

2. Perform a targeted physical examination looking for:

   • Ecchymoses, hematomas, petechiae
   • Evidence of recent bleeding
   • Signs of other conditions that may cause increased bleeding

Laboratory Testing Algorithm

If family history of VWD is present, proceed with laboratory testing:

Initial Tests:

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

VWD-Specific Tests (all three are required):

• VWF antigen (VWF:Ag)
• VWF ristocetin cofactor activity (VWF:RCo)
• Factor VIII coagulant activity (FVIII)

Interpretation of Results:

• Abnormal findings: One or more test results below normal range and/or VWF:RCo to VWF:Ag ratio below 0.5-0.7
• If abnormal: Additional specialized testing is needed for VWD subtyping

Important Considerations

• Test timing: VWF levels can be affected by various conditions including stress, exercise, pregnancy, and inflammation. Testing should ideally be performed when the patient is in their baseline state 1.

• Test limitations: No single laboratory test can screen for VWD. The combination of the three initial VWD tests is essential for proper diagnosis 1.

• Newer assays: The International Society on Thrombosis and Haemostasis recognizes newer assays with improved performance for diagnosing VWD, including VWF:GPIbR, VWF:GPIbM, and VWF:Ab 2.

Special Considerations

• Mild cases: Even patients with mildly decreased VWF (30-50% or IU/dL) should be evaluated if family history is present 1.

• Acquired von Willebrand syndrome: Consider this possibility in patients with abnormal VWF test results and bleeding symptoms but without a family history consistent with hereditary VWD 1.

• Preoperative screening: Testing is particularly important before surgical or invasive procedures to assess bleeding risk 1.

Common Pitfalls to Avoid

1. Relying on a single test: VWD diagnosis requires multiple tests and clinical correlation.

2. Ignoring borderline results: Mild VWD may present with borderline laboratory values but still cause significant bleeding.

3. Overlooking pre-analytical variables: Sample collection, processing, and storage can affect test results.

4. Failing to consider VWD subtypes: Different VWD types have different clinical implications and treatment approaches.

By following this structured approach, you can appropriately evaluate patients with a family history of VWD and determine whether they have inherited the condition.