What are the causes of a positive fecal occult blood test (FOBT)?

Causes of Positive FOBT

A positive fecal occult blood test results from either true gastrointestinal bleeding (from colorectal cancer, adenomas, upper GI lesions, or other bleeding sources) or false-positive results (from dietary factors, medications, or procedural issues with guaiac-based tests). 1

True Positive Results: Actual Gastrointestinal Bleeding

Colorectal Sources

• Colorectal cancer is the primary target lesion that FOBT is designed to detect, with guaiac-based tests showing 83% sensitivity for cancer detection 1
• Large adenomatous polyps (≥1-2 cm) can cause intermittent bleeding, though small polyps typically do not bleed 2, 1
• Colitis (inflammatory bowel disease or infectious) can produce positive results 3
• Vascular ectasia in the colon represents another bleeding source 3

Upper Gastrointestinal Sources

• Upper GI lesions are identified as frequently or more frequently than colonic lesions in patients with positive FOBT, particularly when iron-deficiency anemia and active bleeding are excluded 3
• Esophagitis is the most common upper GI cause (23 patients in one prospective study) 3
• Gastric ulcers (14 patients) and gastritis (12 patients) are frequent causes 3
• Duodenal ulcers account for additional upper GI bleeding sources (10 patients) 3
• Guaiac-based tests detect upper GI bleeding through the pseudoperoxidase activity of heme, while FIT is more specific to lower GI sources 1

Other Bleeding Sources

• Any bleeding lesion anywhere in the gastrointestinal tract can cause a positive guaiac-based test result 3
• Bleeding from cancers or large polyps is intermittent and may not be detectable in every stool sample, which is why proper 3-day collection protocols are essential 2, 1

False Positive Results

Dietary Factors (Guaiac-Based Tests Only)

• Recent consumption of red meat strongly causes false positives due to pseudoperoxidase activity of animal hemoglobin 1
• Poultry, fish, and some raw vegetables may also contribute to false-positive results 1
• Manufacturers recommend avoiding these foods for 3 days before testing to reduce false positivity 1
• Vitamin C in excess of 250 mg can actually cause false-negative results and should be avoided 1, 4
• FIT tests do not require dietary restrictions as they react specifically to human globin, eliminating dietary interference 2, 1

Medication-Related False Positives

• NSAIDs (ibuprofen, naproxen) should be avoided for 7 days prior to guaiac-based testing 1, 4
• Aspirin at doses higher than one adult aspirin per day increases false-positive rates 1
• Iron supplements can interfere with test results 1
• However, for FIT testing, there is no need to adjust anticoagulation or antiplatelet agents, as two high-quality prospective studies showed no negative impact on test characteristics with aspirin, NSAIDs, warfarin, or clopidogrel use 2

Procedural and Collection Issues

• Digital rectal examination immediately before collecting stool samples can cause trauma-related bleeding, leading to false positives 1
• Single-stool sample FOBT collected after digital rectal exam in the office has extremely poor sensitivity (only 4.9% for advanced neoplasia) and higher risk of false positives 1, 4
• Rehydration of guaiac-based FOBT slides substantially increases the false-positive rate and is not recommended 1
• Laboratory variation in test interpretation can affect results, emphasizing the need for standardized procedures 1

Critical Context for Interpretation

Proper Testing Protocol

• Proper collection requires 2 samples from each of 3 consecutive bowel movements at home, as test sensitivity improves with each additional sample 2, 1
• 85.2% of hospitalized patients are taking medications that could result in false-positive results, yet only 8.7% had medications modified and 9.2% had diet modified before testing 5

Common Pitfalls

• FOBT is validated only for colorectal cancer screening in asymptomatic outpatients, not for diagnosis of active GI bleeding in hospitalized patients 6, 5
• In symptomatic patients with iron-deficiency anemia, FOBT has poor sensitivity (58%) and 42% of patients with identifiable causes had false-negative results 7
• Long-term users of aspirin, ethanol, or NSAIDs accounted for 30 of 71 patients with upper GI lesions in one prospective study 3

Follow-Up Requirements

• Any positive result requires colonoscopy to examine the entire colon, not repeat FOBT 2, 4
• Colonoscopy should be performed within 60 days of a positive result to minimize risk of disease progression 4