What is the appropriate management for a patient with a von Willebrand factor antigen level of 1.33 and activity level of 0.93, and a clear bleeding phenotype, suspected to have von Willebrand disease?

Management of Patient with Normal VWF Levels but Clear Bleeding Phenotype

For a patient with normal von Willebrand factor levels (antigen 1.33, activity 0.93) but a clear bleeding phenotype, the most appropriate approach is to consider a diagnosis of bleeding disorder of unknown cause (BDUC) and manage symptomatically with hemostatic agents appropriate for the specific bleeding manifestations. 1

Diagnostic Considerations

When evaluating this patient, several key points should be noted:

• The VWF:Ag level of 1.33 and VWF activity of 0.93 are both within normal range
• The VWF:RCo/VWF:Ag ratio is approximately 0.7, which is at the borderline of normal (ratios below 0.5-0.7 suggest Type 2 VWD) 2
• Despite normal laboratory values, the patient has a clear bleeding phenotype

This presentation represents a diagnostic challenge that is increasingly recognized in clinical practice. Up to 60-70% of patients investigated for mild-moderate bleeding disorders with mucocutaneous bleeding may be categorized as having BDUC 1.

Key Differential Diagnoses to Consider:

• Bleeding Disorder of Unknown Cause (BDUC) - most likely diagnosis given normal laboratory tests with clear bleeding phenotype
• Type 1 VWD with variable expression - though less likely with normal VWF levels
• Platelet function disorder - not excluded by the tests mentioned
• Other coagulation factor deficiencies
• Connective tissue disorders (e.g., Ehlers-Danlos syndrome)

Management Approach

1. Document bleeding history thoroughly

   • Use a standardized bleeding assessment tool (BAT) to objectively quantify bleeding severity 1
   • Document frequency and severity of bleeding episodes 2
   • Assess for signs of ecchymoses, hematomas, petechiae, joint and skin laxity 2

2. Additional laboratory testing

   • Complete blood count to assess for thrombocytopenia
   • Prothrombin time (PT) and activated partial thromboplastin time (PTT)
   • Consider platelet function testing
   • Evaluate for other potential causes of bleeding

3. Treatment options based on bleeding manifestations:

   • For minor bleeding episodes:

     • Antifibrinolytics (e.g., tranexamic acid)
     • Local hemostatic measures

   • For significant bleeding or surgical procedures:

     • Consider trial of desmopressin (DDAVP) with monitoring of response
     • For severe bleeding unresponsive to desmopressin, consider VWF-containing factor concentrates 2

   • For recurrent severe bleeding:

     • Consider prophylactic treatment similar to approaches used in VWD 3

Important Considerations and Pitfalls

• Pitfall #1: Dismissing bleeding symptoms due to normal laboratory values. The International Society on Thrombosis and Haemostasis recognizes BDUC as a real clinical entity requiring management despite normal standard hemostatic tests 1.

• Pitfall #2: Failing to repeat testing. VWF levels can vary, and testing may need to be repeated up to 3 times to ensure reliable results 2.

• Pitfall #3: Not considering medication effects. Document use of anticoagulants, NSAIDs, and certain supplements that can affect test results 2.

• Pitfall #4: Missing associated conditions. Evaluate for conditions like Ehlers-Danlos syndrome or arteriovenous malformations that may contribute to bleeding 2.

Treatment Monitoring

• Document response to interventions to guide future management
• For surgical procedures, aim for VWF activity levels ≥50 IU/dL 2
• Balance hemostasis with thrombosis risk, especially in older patients 2
• Consider consultation with a hematologist experienced in bleeding disorders 2

This approach acknowledges the reality that not all bleeding disorders fit neatly into established diagnostic categories, while still providing practical management strategies for patients with clear bleeding symptoms despite normal laboratory values.