Clinical Significance of Faecal Haemoglobin Quantitative <6 μg/g
A faecal haemoglobin concentration below 6 μg/g is considered normal and effectively rules out significant bowel disease, including colorectal cancer, higher-risk adenoma, and inflammatory bowel disease with very high negative predictive value (>96%).
Interpretation of Low Faecal Haemoglobin Results
Normal Range and Clinical Implications
- Faecal haemoglobin (f-Hb) <50 μg/g is generally considered within normal range 1
- Values <6 μg/g represent an even lower level that is well below established clinical thresholds
- The negative predictive value for significant bowel disease at undetectable levels approaches 100% for colorectal cancer, 97.8% for higher-risk adenoma, and 98.4% for inflammatory bowel disease 2
Threshold Considerations
- Most guidelines recommend using cut-off values between 10-20 μg/g for optimal sensitivity and specificity in detecting colorectal cancer 3
- The US Multi-Society Task Force on Colorectal Cancer favors a lower threshold cut-off (≤20 μg/g) to define a positive test 3
- A meta-analysis showed that cut-off values <20 μg/g had the best combination of sensitivity (86%) and specificity (91%) for colorectal cancer 3
Clinical Decision-Making Algorithm
When f-Hb <6 μg/g is Reassuring (No Further Testing Required):
- Patients with non-specific lower GI symptoms without alarm features
- Patients with suspected irritable bowel syndrome
- Low-risk patients (younger age, no family history of colorectal cancer)
- Patients without rectal bleeding, weight loss, or iron deficiency anemia
When f-Hb <6 μg/g Requires Further Investigation Despite Result:
- Presence of alarm symptoms (rectal bleeding, change in bowel habits with weight loss)
- Iron deficiency anemia
- Age >50 years with new GI symptoms 1
- Bloody diarrhea (requires endoscopic assessment regardless of f-Hb) 3
- Strong clinical suspicion of colorectal cancer based on other factors
Important Considerations and Caveats
Pre-analytical Factors
- Sample stability is a concern - f-Hb concentration can decline rapidly within a day of storage at room temperature 4
- For accurate results, samples should be transferred rapidly into specialized collection devices 4
- Different collection methods may yield different results - patient self-collection versus laboratory transfer 4
Test Performance
- Quantitative FITs have advantages over qualitative tests, including automated reading and ability to adjust cut-off concentrations 3
- The limit of detection varies between different FIT assays 5
- A value <6 μg/g may be below the limit of detection for some assays, representing essentially undetectable haemoglobin
Risk Stratification
- In symptomatic patients, undetectable f-Hb is an excellent "rule-out" test for significant bowel disease 2
- The FAST score (combining f-Hb, age, and sex) has been proposed to improve risk stratification, but evidence suggests f-Hb alone may be sufficient for initial assessment 6
Conclusion
A faecal haemoglobin result <6 μg/g provides strong reassurance against significant colorectal pathology in most clinical scenarios, particularly in the absence of alarm symptoms. However, clinical judgment should prevail when alarm features are present, as these warrant further investigation regardless of f-Hb results.