What are the causes of a positive fecal globin (FG) test?

Causes of Positive Fecal Globin Test

A positive fecal globin test (FIT) is primarily caused by bleeding from colorectal cancer or large adenomatous polyps (>1-2 cm), but can also result from other gastrointestinal lesions, particularly those in the lower gastrointestinal tract. 1

Colorectal Causes of Positive FIT

Neoplastic Causes

• Colorectal cancer - The primary target of FIT screening, with sensitivity up to 65.8-94.1% depending on the specific test 1
• Advanced adenomatous polyps (>1-2 cm) - These precancerous lesions can bleed intermittently 1
• Other colorectal tumors - Less common neoplastic lesions of the colon 2

Non-Neoplastic Colorectal Causes

• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) 3
• Colitis (infectious, ischemic, radiation-induced) 3
• Vascular ectasias/angiodysplasias of the colon 4
• Hemorrhoids - Though often blamed for positive results, the US Multi-Society Task Force notes that hemorrhoids alone should not be assumed to be the cause of a positive FIT without colonoscopy 1
• Diverticular disease with active bleeding

Upper Gastrointestinal Causes

FIT tests are more specific for lower gastrointestinal bleeding than guaiac-based tests (gFOBT) because globin is degraded by digestive enzymes in the upper gastrointestinal tract 1. However, significant upper GI bleeding can still cause positive results, particularly with:

• Esophagitis 4
• Gastric ulcers 4
• Gastritis 4
• Duodenal ulcers 4

A study by Rockey et al. found that among patients with positive gFOBT tests (which are less specific than FIT), upper gastrointestinal lesions were actually identified more frequently than colonic lesions 4.

Small Bowel Causes

• Small bowel ulcers 2
• Small bowel tumors 2
• Small bowel vascular lesions 2

Medication-Related Causes

Unlike gFOBT, FIT results are generally not affected by medications. The US Multi-Society Task Force on Colorectal Cancer states: "There is no rationale to adjust diet or anticoagulation or antiplatelet agents when using FIT-based screening." 1

However, medications that can cause actual gastrointestinal bleeding may lead to true positive results:

• Anticoagulants (warfarin, direct oral anticoagulants)
• Antiplatelet agents (aspirin, clopidogrel)
• NSAIDs causing gastritis or ulceration

Studies have shown that sensitivity of FIT may actually be improved in patients on antiplatelet or anticoagulant therapy, with little decrease in specificity 1.

Technical and Practical Considerations

Several factors can affect FIT results:

• Sample return time - Studies show FIT results remain stable for up to 10 days, with hemoglobin degradation of approximately 5.88% per day 5
• Proper collection technique - Unlike gFOBT, FIT does not require dietary restrictions 1
• Laboratory processing - Quantitative FITs are preferred over qualitative tests due to improved quality control 1

Clinical Implications

When a positive FIT is detected:

1. Colonoscopy is the recommended follow-up test regardless of whether the patient has symptoms or is taking medications that might cause bleeding 1
2. Upper endoscopy is not routinely recommended after a positive FIT and negative colonoscopy unless there are signs/symptoms of upper GI pathology or iron deficiency anemia 1
3. Small bowel evaluation may be considered in patients with occult gastrointestinal bleeding when both colonoscopy and upper endoscopy are negative 2

Key Points to Remember

• Small polyps (<1 cm) typically do not bleed enough to cause a positive FIT 1
• Bleeding from cancers or large polyps is often intermittent, which is why annual testing is recommended 1
• A single sample FIT collected during digital rectal examination is not recommended due to very poor sensitivity 1, 6
• The positive predictive value of FIT for colorectal cancer and significant neoplasia is high, making follow-up colonoscopy essential 3