Iron Studies: Initial Steps and Treatment Options
The initial approach to iron studies should include measurement of transferrin saturation (TSAT) and serum ferritin to assess iron status, with treatment decisions based on these values. 1
Diagnostic Approach
Initial Laboratory Evaluation
- Measure transferrin saturation (TSAT) and serum ferritin as first-line tests
- TSAT is calculated by dividing serum iron by total iron binding capacity (TIBC)
- Obtain samples in the morning after overnight fast, avoiding iron supplements for 24 hours before testing 1
Interpretation of Iron Studies
- Absolute Iron Deficiency Anemia (AIDA):
- TSAT < 20% and ferritin < 30 ng/mL 1
- Functional Iron Deficiency Anemia (FIDA):
- TSAT 20-50% and ferritin 30-800 ng/mL 1
- Iron Overload (Hemochromatosis):
- Elevated TSAT > 45% and elevated ferritin 1
Additional Testing When Results Are Equivocal
- If ferritin is between 46-99 ng/mL, consider additional tests 2:
- RET-He < 30.7 pg suggests iron deficiency with 68.2% sensitivity and 69.7% specificity 3
Treatment Algorithm
1. For Absolute Iron Deficiency (TSAT < 20%, ferritin < 30 ng/mL)
- First-line: Oral iron supplementation
- Ferrous sulfate 200 mg once daily in the morning with vitamin C 4
- Provides approximately 65 mg of elemental iron
- Continue for 3 months to replenish stores
2. For Functional Iron Deficiency (TSAT 20-50%, ferritin 30-800 ng/mL)
- Consider underlying cause (inflammation, chronic disease)
- Treat with oral iron if no contraindications
- Consider IV iron if:
- Oral iron is not tolerated
- Poor response to oral therapy after 1 month
- Ongoing blood loss exceeds oral iron absorption capacity 1
3. For Iron Deficiency with Anemia (Hb < 10 g/dL)
- For severe anemia (Hb < 10 g/dL): Consider IV iron formulations 1
4. For Iron Overload (Hemochromatosis)
- Phlebotomy therapy if TSAT > 45% and elevated ferritin 1
- Do not administer iron supplements
Monitoring Response to Treatment
Oral Iron Therapy
- Check hemoglobin after 3-4 weeks of treatment
- Expected response: 1-2 g/dL increase in hemoglobin within 4-8 weeks 1, 2
- If no response (< 1 g/dL increase after 1 month), consider:
- Poor compliance
- Ongoing blood loss
- Malabsorption
- Need for IV iron therapy 2
IV Iron Therapy
- Check CBC and iron studies 4-8 weeks after last infusion
- Do not check iron studies within 4 weeks of IV iron administration (falsely elevated results) 1
- Target ferritin ≥ 50 ng/mL in absence of inflammation 1
Special Considerations
Cancer-Related Anemia
- Assess iron studies in all cancer patients with Hb < 10 g/dL and symptomatic patients with Hb 10-12 g/dL 1
- Consider IV iron with or without erythropoiesis-stimulating agents (ESAs) 1
Chronic Kidney Disease
- Different thresholds may apply: consider iron therapy if TSAT ≤ 30% and ferritin ≤ 500 ng/mL 1
Restless Legs Syndrome
- Consider iron supplementation if ferritin ≤ 75 ng/mL or TSAT < 20% 1
- Use IV iron if ferritin is between 75-100 ng/mL 1
Common Pitfalls to Avoid
- Checking iron studies too soon after IV iron administration (wait at least 4 weeks)
- Ignoring functional iron deficiency in inflammatory states (ferritin may be normal/elevated despite iron deficiency)
- Premature discontinuation of iron therapy before stores are replenished
- Failing to investigate underlying cause of iron deficiency, especially in men and postmenopausal women 2
- Overlooking that serum ferritin can be elevated in inflammatory conditions despite iron deficiency 4
By following this systematic approach to iron studies, clinicians can accurately diagnose iron status disorders and implement appropriate treatment strategies to improve patient outcomes.