Should a patient with suspected von Willebrand disease (VWD) be tested after experiencing a gastrointestinal (GI) bleed following intense physical activity, such as running 22 kilometers?

Testing for von Willebrand Disease After GI Bleeding Following Intense Exercise

Yes, a patient with suspected von Willebrand disease (VWD) who experiences a GI bleed after running 22 km should be tested for VWD, as this represents a significant bleeding event that warrants diagnostic evaluation. 1, 2

Rationale for Testing

• GI bleeding is a recognized manifestation of VWD and can occur in all types of VWD, particularly in more severe forms 1, 3
• Exercise-induced gastrointestinal syndrome (EIGS) from intense physical activity like running 22 km can cause splanchnic hypoperfusion and gastrointestinal ischemia 1
• While exercise can trigger GI symptoms in healthy individuals, the presence of a significant GI bleed after exercise in someone with suspected VWD represents a potential diagnostic opportunity when the patient is symptomatic

Diagnostic Approach

1. Initial Laboratory Evaluation:

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

   These three tests are considered the cornerstone of VWD diagnosis according to the American Society of Hematology 2

2. Additional Testing Based on Initial Results:

   • If VWF:RCo/VWF:Ag ratio is <0.5-0.7, perform:
     • Ristocetin-induced platelet aggregation (RIPA)
     • VWF multimer analysis
   • These tests help differentiate between VWD subtypes 2

Interpretation of Results

VWD classification based on laboratory values 2:

Type	VWF:RCo (UI/dL)	VWF:Ag (UI/dL)	FVIII	VWF:RCo/VWF:Ag Ratio
Type 1	<30	<30	↓ or Normal	>0.5-0.7
Type 2A	<30	<30-200	↓ or Normal	<0.5-0.7
Type 2B	<30	<30-200	↓ or Normal	Generally <0.5-0.7
Type 2M	<30	<30-200	↓ or Normal	<0.5-0.7
Type 2N	30-200	30-200	↓↓	>0.5-0.7
Type 3	<3	<3	↓↓↓ (<10 UI/dL)	-

Important Considerations

• Timing of Testing: Ideally, testing should be performed when the patient is not actively bleeding and not receiving treatment that could affect results
• Potential Confounders: Stress, exercise, inflammation, and hormonal factors can temporarily increase VWF levels, potentially masking VWD 4, 5
• Repeat Testing: A single normal result does not exclude VWD; repeat testing may be necessary due to variability in VWF levels 2

Clinical Implications

• GI bleeding in VWD patients can be recurrent and difficult to manage 3
• Proper diagnosis allows for appropriate treatment planning, including consideration of prophylaxis for those with severe or recurrent bleeding 6
• Patients with VWD and GI bleeding may require combination therapy with VWF concentrates, antifibrinolytics, and other treatments 3

Common Pitfalls to Avoid

• Delayed Testing: Waiting too long after a bleeding episode may miss the diagnostic window
• Inadequate Testing Panel: Performing only partial testing (e.g., only VWF:Ag without activity assays)
• Misinterpreting Exercise Effects: Exercise can cause both GI symptoms and temporary increases in VWF levels
• Failure to Consider VWD Subtypes: Different VWD types require different diagnostic approaches and treatments

Testing for VWD in this clinical scenario is essential for proper diagnosis, classification, and subsequent management of this common but often underdiagnosed bleeding disorder.