Hematology Consults

Iron Deficiency

A resident-focused guide to diagnosis, ferritin and TSAT interpretation, identifying the cause, oral and intravenous repletion, CKD and heart-failure considerations, and treatment response.

Audience: internal medicine residents Last reviewed: July 2026
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Quick interpretation Diagnostic thresholds Laboratory patterns Calculators Find the cause Oral iron IV iron Monitoring CKD Heart failure Questions References

Quick interpretation

Start here

Ferritin <30 ng/mL Strongly supports depleted iron stores. [1] [3]
Ferritin <45 ng/mL AGA diagnostic cutoff for iron deficiency in an adult with anemia. [2]
TSAT <20% Supports reduced circulating iron availability, especially when ferritin may be altered by inflammation. [1]
TSAT <15% More strongly supports iron deficiency in the appropriate context. [3]
Normal MCV Does not exclude early iron deficiency or mixed anemia. [1]
Normal or high ferritin Does not reliably exclude deficiency during inflammation, CKD, liver disease, malignancy, infection, or recent IV iron. [1] [3]

1. Diagnostic thresholds

Clinical context Practical criteria Interpretation
General adult with anemia Ferritin <45 ng/mL AGA threshold selected to improve sensitivity when diagnosing iron deficiency in patients with anemia. [2]
Classic absolute deficiency Ferritin <30 ng/mL, usually with low TSAT Strong evidence of depleted storage iron. [1] [3]
Possible deficiency with inflammation Often TSAT <20% with ferritin that is not clearly low Consider mixed absolute deficiency and inflammatory iron restriction. Ferritin alone may be misleading. [1]
Heart-failure trial definition Ferritin <100 ng/mL, or ferritin 100–299 ng/mL with TSAT <20% Disease-specific construct used in major heart-failure trials and guidelines; do not apply it indiscriminately to all adults. [5]
CKD not receiving hemodialysis Ferritin <100 ng/mL with TSAT <40%, or ferritin 100–300 ng/mL with TSAT <25% KDIGO 2026 suggested thresholds for initiating iron in a patient with anemia and CKD not receiving hemodialysis. [4]
CKD G5 receiving hemodialysis Ferritin ≤500 ng/mL and TSAT ≤30% KDIGO 2026 suggested threshold for initiating iron. [4]
During iron treatment in CKD Ferritin >700 ng/mL or TSAT ≥40% KDIGO considers it reasonable to withhold routine iron and reassess the overall clinical picture. [4]
Resident pearl: Serum iron alone is not diagnostic. Classic iron deficiency tends to produce low ferritin, low TSAT, and increased TIBC. Inflammation tends to produce low serum iron with low or normal TIBC and normal or increased ferritin.

2. Iron deficiency versus inflammation

Finding Iron deficiency anemia Anemia of inflammation Iron deficiency with inflammation
MCV Often <80 fL; may be normal early Usually normal; may become mildly low Normal or low
Serum iron Low Low Low
TIBC / transferrin Usually increased Usually low or normal Often low or normal
TSAT Usually <20%; often <15% Often low Usually low
Ferritin Usually <30 ng/mL Normal or elevated Variable; may be below 100 ng/mL or considerably higher
Soluble transferrin receptor Usually increased Usually normal Often increased
Reticulocyte response Inappropriately low before treatment Inappropriately low Inappropriately low
Stainable marrow iron Absent Present Absent

Soluble transferrin receptor and reticulocyte hemoglobin measurements may help when ferritin and TSAT are discordant, although availability, local reference ranges, and assay variation limit universal use. [1]

Interactive tools

Iron calculators

These tools perform arithmetic estimates only. They do not replace clinical assessment, local protocols, pharmacy review, or formulation-specific prescribing information.

TSAT calculator

Enter the serum iron and TIBC.

TSAT (%) = serum iron ÷ TIBC × 100.

Ganzoni iron-deficit estimate

Enter the weight and hemoglobin values.

Estimate = weight × (target Hb − current Hb) × 2.4 + storage allowance. Product dosing may differ substantially.

3. Confirm the diagnosis and identify the cause

Initial evaluation

  • CBC with MCV, MCH, and RDW
  • Absolute reticulocyte count or corrected reticulocyte response
  • Ferritin
  • Serum iron
  • TIBC or transferrin
  • TSAT
  • Peripheral smear when the diagnosis is unclear
  • Creatinine and estimated GFR
  • CRP or ESR when inflammation may affect interpretation
  • Vitamin B12 and folate when mixed deficiency is possible
  • Celiac testing when clinically appropriate

Blood loss

  • Heavy menstrual bleeding
  • Occult or overt gastrointestinal bleeding
  • Frequent blood donation
  • Repeated diagnostic phlebotomy
  • Recent surgery or trauma
  • Hematuria
  • Anticoagulant-associated bleeding

Reduced absorption

  • Celiac disease
  • Inflammatory bowel disease
  • Bariatric or gastric surgery
  • Small-bowel resection
  • Autoimmune or atrophic gastritis
  • Helicobacter pylori-associated disease

Increased requirement

  • Pregnancy and lactation
  • Growth
  • Recovery after substantial blood loss
  • Erythropoiesis-stimulating therapy

Inflammatory iron restriction

  • Chronic kidney disease
  • Heart failure
  • Chronic infection
  • Autoimmune or inflammatory disease
  • Active malignancy

Gastrointestinal evaluation

Men and postmenopausal women with unexplained iron-deficiency anemia generally require evaluation for gastrointestinal blood loss. Premenopausal women require individualized assessment based on menstrual loss, severity, recurrence, gastrointestinal symptoms, age, family history, and other risk factors. [2]

Heavy menstrual bleeding does not automatically exclude a concurrent gastrointestinal source, especially when anemia is severe, recurrent, disproportionate, or accompanied by concerning symptoms.

4. Oral iron repletion

Practical starting regimen

A common starting regimen is ferrous sulfate 325 mg, which contains approximately 65 mg elemental iron, taken once daily or every other day. [1] [2] [3]

AGA best-practice advice recommends oral iron no more than once daily. Every-other-day dosing may be better tolerated while maintaining useful absorption for many patients. [2]

Preparation Approximate elemental iron Practical considerations
Ferrous sulfate 325 mg Approximately 65 mg Common first choice because of availability, cost, and established use.
Ferrous gluconate 325 mg Approximately 35–38 mg Lower elemental dose per tablet; may be useful when a smaller dose is desired.
Ferrous fumarate 325 mg Approximately 106 mg Higher elemental dose; gastrointestinal tolerance may still limit adherence.
Slow- or enteric-release preparations Varies May release iron distal to the main sites of absorption and are not routinely preferred solely for presumed superiority.
Polysaccharide, heme, or proprietary products Varies Often more expensive; no universal evidence that they are superior to standard ferrous salts.

Administration

  • Absorption is generally greatest away from food, but administration with food is reasonable if needed for tolerability.
  • Separate iron from calcium, antacids, tea, coffee, and interacting medications when practical.
  • Vitamin C may increase iron absorption, but the clinical magnitude of benefit is variable. [2]
  • Warn patients about dark stools, nausea, constipation, and abdominal discomfort.
Do not reflexively prescribe two or three daily doses. Frequent dosing may worsen gastrointestinal toxicity and increase hepcidin-mediated reduction in subsequent iron absorption. [1] [3]

5. When to switch to intravenous iron

Consider IV iron when oral iron is not tolerated, ferritin or hemoglobin does not improve after a reasonable trial, absorption is unlikely, ongoing loss exceeds oral replacement, or faster repletion is clinically important. [2]

  • Persistent intolerance despite dose or schedule adjustment
  • Confirmed adherence without an adequate response
  • Celiac disease or significant malabsorptive anatomy
  • Active inflammatory bowel disease in selected circumstances
  • Ongoing blood loss that exceeds oral replacement
  • Need for more rapid repletion
  • CKD-specific indication
  • Heart-failure-specific indication

AGA favors formulations capable of replacing the deficit in one or two infusions when clinically and operationally appropriate. [2]

IV formulation Common adult course in US practice Important considerations
Iron sucrose Commonly administered in divided doses, such as 200 mg on multiple occasions Familiar in CKD care but may require several visits.
Ferric gluconate Usually administered in divided doses Frequently used in dialysis settings; total course depends on indication and protocol.
Ferumoxytol Commonly 510 mg followed by a second 510-mg dose Follow current labeling and consider effects on subsequent MRI interpretation.
Ferric carboxymaltose Common US regimen: 750 mg followed by a second 750-mg dose Can provide high-dose replacement; clinically important hypophosphatemia may occur.
Ferric derisomaltose Often permits up to 1000 mg in one infusion May complete replacement in one visit depending on calculated need and current labeling.
Low-molecular-weight iron dextran May permit total-dose replacement under an institutional protocol Follow current product labeling and local test-dose or monitoring requirements.
Formulation limits, infusion time, indications, renal dosing pathways, payer requirements, and labeling can change. Verify the current package insert, pharmacy protocol, and institutional formulary before placing an order.

Acute symptoms during IV iron

  1. Pause or stop the infusion.
  2. Assess airway, breathing, circulation, vital signs, and oxygenation.
  3. Distinguish transient infusion symptoms from severe hypersensitivity or anaphylaxis.
  4. Treat severe reactions using standard institutional emergency and anaphylaxis protocols.
  5. Document the formulation, dose, symptom timing, interventions, and outcome.

Most acute IV iron reactions are not proven IgE-mediated anaphylaxis. Routine reflexive treatment of every reaction with sedating antihistamines can complicate assessment, particularly when hypotension, tachycardia, or somnolence is present. [3]

6. Monitor treatment response

Within days Reticulocytosis may begin if marrow response is intact.
2–4 weeks CBC should show a meaningful hemoglobin rise when treatment is effective and loss is controlled.
After Hb normalizes Continue oral therapy long enough to restore stores, commonly for about three additional months.
After IV iron Do not interpret iron studies immediately; serum iron and ferritin can be transiently elevated.

A rise of approximately 1 g/dL within 2–4 weeks is a useful practical indicator of response, though the trajectory varies with baseline severity, ongoing bleeding, inflammation, adherence, absorption, renal function, and mixed etiologies. [1] [3]

Continue oral iron after hemoglobin normalization to rebuild storage iron rather than stopping as soon as the CBC enters the reference range. [1]

Failure to respond

  • Incorrect diagnosis
  • Nonadherence or intolerance
  • Incorrect administration
  • Ongoing gastrointestinal or gynecologic blood loss
  • Malabsorption
  • Inflammatory iron restriction
  • Chronic kidney disease
  • Mixed vitamin B12, folate, or copper deficiency
  • Hemolysis or hemoglobinopathy
  • Bone-marrow disease

7. Chronic kidney disease

CKD not receiving hemodialysis

KDIGO 2026 suggests initiating iron in patients with anemia and CKD not receiving hemodialysis when either of the following is present: [4]

  • Ferritin <100 ng/mL and TSAT <40%
  • Ferritin 100–300 ng/mL and TSAT <25%

Select oral versus IV therapy based on severity, prior response, tolerance, patient preference, access, and the urgency of repletion.

CKD G5 receiving hemodialysis

KDIGO suggests initiating iron when ferritin ≤500 ng/mL and TSAT ≤30%. IV iron is generally favored for patients receiving hemodialysis. [4]

When to withhold routine iron

KDIGO considers it reasonable to withhold routine iron when ferritin is greater than 700 ng/mL or TSAT is at least 40%, and to pause iron during active systemic infection while reassessing the clinical context. [4]

These are treatment thresholds—not stand-alone definitions of iron overload. Consider inflammation, bleeding, ESA exposure, prior iron, transfusion history, and treatment response.

8. Heart failure

Heart-failure trials commonly define iron deficiency as:

  • Ferritin <100 ng/mL, or
  • Ferritin 100–299 ng/mL with TSAT <20%

In selected patients with symptomatic HFrEF and iron deficiency, IV iron is reasonable to improve functional status and quality of life. Evidence has been most consistent for symptoms, exercise capacity, and quality of life, with some support for reducing heart-failure hospitalization; mortality benefit has not been consistently demonstrated. [5]

TSAT below 20% may identify iron-restricted patients more reliably than ferritin alone. A ferritin below 100 ng/mL with TSAT above 20% may not represent the same treatment-responsive phenotype.

Oral iron has not demonstrated equivalent clinical benefit in HFrEF and should not be assumed to substitute for disease-specific IV iron therapy.

9. Knowledge check

Question 1

A patient with anemia has ferritin 18 ng/mL and TSAT 11%. Which interpretation is most appropriate?

Question 2

Which laboratory pattern most strongly favors anemia of inflammation over uncomplicated iron deficiency?

Question 3

Which oral iron strategy best reflects current AGA best-practice advice?

Question 4

A patient with anemia and nondialysis CKD has ferritin 180 ng/mL and TSAT 18%. Which statement is most accurate?

Question 5

A patient has taken oral iron as prescribed for four weeks without improvement in hemoglobin or ferritin. Which next step is most appropriate?

10. Resident summary

  1. Diagnose iron deficiency using ferritin and TSAT in clinical context—not serum iron alone.
  2. Ferritin below 30 ng/mL strongly supports depleted stores; ferritin below 45 ng/mL is the AGA cutoff in an adult with anemia.
  3. TSAT below 20% is particularly useful when inflammation may make ferritin difficult to interpret.
  4. Identify the source of loss or impaired absorption.
  5. Start standard oral iron once daily or every other day for many stable patients.
  6. Check for a meaningful hematologic response within roughly 2–4 weeks when confirmation is clinically important.
  7. Use IV iron when oral therapy is not tolerated, ineffective, unlikely to be absorbed, too slow, or supported by disease-specific guidance.
  8. Apply CKD and heart-failure thresholds only within those clinical contexts.

References

  1. Iolascon A, et al. Recommendations for diagnosis, treatment, and prevention of iron deficiency and iron deficiency anemia. HemaSphere. 2024. Free full text
  2. Ko CW, et al. AGA Clinical Practice Update on Management of Iron Deficiency Anemia: Expert Review. Clinical Gastroenterology and Hepatology. 2024. Full text AGA summary
  3. Ning S, Zeller MP. Management of iron deficiency. ASH Education Program. 2019. Article
  4. Kidney Disease: Improving Global Outcomes. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. 2026. Guideline suite
  5. Heidenreich PA, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. Guideline page

Educational disclaimer

This page is intended for clinician education and does not replace institutional protocols, specialist consultation, product labeling, pharmacy review, prescribing information, or individualized clinical judgment. Drug formulations, dosing limits, and recommendations may change. Verify current primary guidance before clinical use.