When is referral for ferritin testing recommended?

When to Refer for Ferritin Testing

Ferritin testing should be performed in all patients with suspected iron deficiency, with a cutoff of 45 ng/mL used to diagnose iron deficiency anemia rather than the traditional lower threshold of 15 ng/mL. 1

Primary Indications for Ferritin Testing

Suspected Iron Deficiency

• Patients with anemia (low hemoglobin)
• Patients with symptoms suggestive of iron deficiency (fatigue, weakness, poor concentration)
• Patients with risk factors for iron deficiency:
  • Women with heavy menstrual bleeding
  • Pregnant women
  • Patients with gastrointestinal blood loss
  • Patients with poor dietary iron intake
  • Patients with malabsorptive conditions

Monitoring Iron Status

• Patients receiving iron supplementation therapy
• Patients with chronic conditions requiring iron monitoring:
  • Chronic kidney disease
  • Inflammatory bowel disease
  • Sickle cell disease receiving chronic transfusions 1

Diagnostic Thresholds and Interpretation

The American Gastroenterological Association recommends using a ferritin cutoff of 45 ng/mL (rather than 15 ng/mL) when diagnosing iron deficiency anemia, as this provides higher sensitivity for detecting iron deficiency 1. This is supported by recent evidence suggesting that the physiologic ferritin "cutoff" should be around 50 ng/mL 2.

When interpreting ferritin results:

• <30 μg/L: Definitive iron deficiency 3
• 30-100 μg/L with transferrin saturation <20%: Possible iron deficiency, especially with inflammation 1, 3

• 100 μg/L with normal transferrin saturation: Iron deficiency unlikely 1

Remember that ferritin is an acute-phase reactant and may be falsely elevated in the presence of inflammation, infection, or liver disease 1, 3.

Special Populations Requiring Ferritin Testing

Pregnant Women

• Screen all pregnant women with serum ferritin in the first trimester 4
• Regular hemoglobin checks at least once per trimester 4

Patients with Chronic Disease

• Patients with inflammatory conditions may have functional iron deficiency despite normal or elevated ferritin levels
• Consider additional tests (transferrin saturation, serum iron, TIBC) when ferritin is between 46-99 ng/mL 5

Patients with Generalized Pruritus

• Full blood count and ferritin levels should be checked in all patients with chronic generalized pruritus without rash 1
• Iron deficiency is a common cause of generalized pruritus that responds to iron replacement 1

Patients with Sickle Cell Disease

• Patients receiving chronic transfusion therapy should have ferritin levels monitored
• Consider MRI for liver iron content every 1-2 years if ferritin >1000 ng/mL 1

Follow-up After Abnormal Ferritin Results

For Low Ferritin (<45 ng/mL):

1. Initiate iron supplementation (ferrous sulfate 200 mg once daily) 3
2. Investigate underlying cause:
   • In men and postmenopausal women: Refer for gastrointestinal evaluation (bidirectional endoscopy) 1
   • In premenopausal women: Consider trial of iron therapy with hemoglobin check at one month 5
   • Test for celiac disease with serology first, followed by small bowel biopsy only if positive 1

For Borderline Ferritin (45-100 ng/mL with low transferrin saturation):

1. Consider therapeutic trial of iron
2. Monitor response (hemoglobin should increase by 2 g/dL after 3-4 weeks) 3
3. If no response after 2-4 weeks, consider:
   • Poor compliance
   • Ongoing blood loss
   • Malabsorption
   • Incorrect diagnosis 3

Common Pitfalls to Avoid

1. Using outdated ferritin thresholds: Using the traditional cutoff of 15 ng/mL will miss many cases of iron deficiency 1, 2

2. Failing to account for inflammation: Ferritin is an acute-phase reactant and may be falsely elevated in inflammatory states 1, 3

3. Not investigating unexplained iron deficiency: In men and postmenopausal women, iron deficiency may be the first sign of gastrointestinal malignancy 1

4. Relying solely on ferritin in chronic disease: Consider additional tests like transferrin saturation or serum transferrin receptor in patients with chronic inflammatory conditions 6

5. Stopping iron therapy too soon: Continue iron supplementation for three months after correction of anemia to replenish iron stores 3