What is the most likely cause of a false-positive fecal occult blood test (FOBT)?

Causes of False-Positive Fecal Occult Blood Tests

Aspirin therapy is most likely to cause a false-positive fecal occult blood test among the listed options. 1, 2

Mechanism of False-Positive Results in gFOBT

Guaiac-based fecal occult blood tests (gFOBT) detect blood in stool through the pseudoperoxidase activity of heme or hemoglobin. Several factors can interfere with this process:

• Medications that can cause false-positive results:

  • Aspirin - Even at low doses can cause gastric irritation and microbleeding, leading to false-positive results 2
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) - Similar to aspirin, can cause gastric irritation 1, 2
  • Anticoagulants like Coumadin (warfarin) - May increase bleeding tendency but less commonly cause false positives than aspirin 1

• Dietary factors affecting test results:

  • Red meat, poultry, fish - Contain animal hemoglobin with peroxidase activity 1, 2
  • Some raw vegetables - May contain peroxidases 1, 2
  • Dietary peroxidases - While they can cause false positives, their effect is less pronounced than medications like aspirin 2

• Other factors:

  • Vitamin C (ascorbic acid) - Actually causes false-negative results by inhibiting the peroxidase reaction 3
  • Iron supplements - Can interfere with test results but are less likely to cause false positives than aspirin 2, 4

Comparative Analysis of Options

1. Oral iron therapy - While iron supplements can interfere with test results, studies indicate they tend to lower both false-positive and false-negative reactions 4. Iron is not the most likely cause of false positives among the options.

2. Coumadin therapy - Anticoagulants like warfarin can increase bleeding tendency, but modern FIT testing shows little decrease in specificity with anticoagulant use 1.

3. Aspirin therapy - Guidelines specifically recommend avoiding aspirin for 7 days prior to gFOBT testing due to its significant effect on false-positive rates 1, 2.

4. Nonsteroidal anti-inflammatory medications - Like aspirin, NSAIDs can cause false positives, but aspirin has been more extensively documented as problematic 1, 2.

5. Dietary peroxidases - While these can cause false positives, their effect is less significant than medications, especially when test development is delayed 2, 5.

Clinical Implications

• Patients should avoid aspirin (more than one adult aspirin per day) for 7 days prior to testing unless they are on a cardioprotective regimen 1
• Dietary restrictions (avoiding red meat, poultry, fish) for 3 days before testing can help reduce false-positive results 1, 2
• Using fecal immunochemical tests (FIT) instead of guaiac-based tests can eliminate concerns about dietary peroxidases and reduce false positives from medications 1
• Proper collection of 3 stool samples from consecutive bowel movements at home is essential for accurate results 1, 2

Common Pitfalls to Avoid

• Single stool sample collection after digital rectal examination in the office has unacceptably low sensitivity (4.9% for advanced neoplasia) and higher risk of false positives 1, 2
• Rehydration of gFOBT slides substantially increases the false-positive rate and is not recommended 1, 2
• Failing to follow up positive tests with colonoscopy - approximately one-third of physicians incorrectly follow up with repeat gFOBT 1
• Using FOBT for inappropriate indications in hospital settings rather than for its validated purpose of colorectal cancer screening 6