What to do in a patient with recurrent Gastrointestinal (GI) bleeding and negative initial diagnostic tests, including Esophagogastroduodenoscopy (EGD), colonoscopy, and capsule endoscopy?

Management of Recurrent GI Bleeding with Negative Initial Diagnostic Tests

For patients with recurrent gastrointestinal bleeding and negative initial diagnostic tests (EGD, colonoscopy, and capsule endoscopy), multiphase CT enterography (CTE) should be performed as the next diagnostic step to identify potential small bowel bleeding sources. 1

Diagnostic Algorithm for Recurrent GI Bleeding

Step 1: Repeat Endoscopic Evaluation

• Consider repeat upper and lower endoscopy with special attention to:
  • Commonly overlooked lesions in upper GI tract: Cameron's erosions in hiatal hernias, fundic varices, Dieulafoy's lesion, and gastric antral vascular ectasia 1
  • Use cap-fitted endoscopy to examine blind areas (high lesser curve, under incisura angularis, posterior wall of duodenal bulb) 1
  • Obtain random duodenal biopsies to rule out celiac disease 1
  • Carefully examine the terminal ileum during colonoscopy (blood in terminal ileum strongly predicts small bowel bleeding source) 2

Step 2: Advanced Imaging

• Perform multiphase CT enterography (CTE) for hemodynamically stable patients 1

  • Should include at least arterial and enteric/portal venous phases
  • Use neutral enteric contrast administered in divided doses beginning 1 hour before CTE
  • Particularly valuable for patients >40 years where vascular lesions are common causes of bleeding

• If hemodynamically unstable with active bleeding: Perform CT angiography (CTA) instead of CTE 1

Step 3: Additional Interventions Based on CTE Results

• If CTE is positive: Proceed with targeted therapy based on findings
• If CTE is negative: Consider the following options:
  • Repeat capsule endoscopy (diagnostic yield increases with second study) 1
  • Device-assisted enteroscopy (balloon enteroscopy) for direct visualization and potential intervention 1
  • Meckel scan in younger patients, especially children and adolescents 1
  • Catheter angiography if suspicion for vascular lesion remains high 1

Special Considerations

Age-Based Approach

• Patients <40 years: More aggressive investigation as small bowel tumors are the most common cause of obscure bleeding 1
• Patients >40 years: Focus on vascular lesions (angiectasias account for up to 80% of causes) 1

Timing of Repeat Studies

• Development of overt bleeding and hemoglobin decrease ≥4 g/dL are significant predictors for positive findings on repeat capsule endoscopy 1
• Patients with angiodysplasia on initial capsule, bleeding duration >3 months, and ongoing anticoagulant use have higher risk of rebleeding 1

Common Pitfalls to Avoid

1. Don't stop after negative capsule endoscopy - diagnostic yield increases with repeated studies in patients with recurrent bleeding 1
2. Don't overlook the terminal ileum - blood in the terminal ileum is strongly associated with small bowel bleeding source 2
3. Don't use single-phase CT - multiphase technique is essential for detecting vascular lesions in patients >40 years 1
4. Don't forget about commonly missed lesions - review previous endoscopic studies for potentially overlooked sources 1

When to Consider Interventional Procedures

• Catheter angiography: For patients with documented extravasation on CTE/CTA or when bleeding site has been localized but requires intervention 1
• Superselective embolization: When possible, perform in distal to proximal fashion to reduce risk of rebleeding through collaterals 1
• Surgical intervention: Consider when other modalities fail to identify or treat the bleeding source, particularly for suspected small bowel tumors in younger patients 1

By following this systematic approach, most causes of recurrent GI bleeding can be identified and appropriately managed, reducing morbidity and mortality associated with ongoing blood loss.