Iron Deficiency Anemia
Clinical Snapshot
Iron deficiency anemia (IDA) is the endpoint of a continuum that begins with depleted iron stores and progresses to impaired hemoglobin synthesis once storage iron is exhausted; it is the most common nutritional cause of anemia worldwide. It is defined by a hemoglobin below the WHO threshold — under 130 g/L in men, under 120 g/L in nonpregnant women[1] — together with biochemical evidence of iron deficiency, most reliably a low serum ferritin. Because iron deficiency in an adult is a sign of an underlying cause — most often blood loss — rather than a stand-alone diagnosis, correcting the anemia with iron replacement is only half the task: identifying and, where possible, treating the source of iron loss is the other half, and is a genuine patient-safety issue in men and postmenopausal women, where an undiagnosed gastrointestinal malignancy is a real possibility.[2]
Recognize the Condition
General anemia symptoms
Fatigue, exertional dyspnea, pallor, tachycardia, headache, and reduced exercise tolerance — common to any anemia and often the presenting complaint.
Findings more specific to iron deficiency
- Koilonychia — spoon-shaped, concave nails.
- Glossitis and angular cheilitis (cracking at the corners of the mouth).
- Pica, including pagophagia (craving and chewing ice) — a classic and reasonably specific symptom worth asking about directly, since patients rarely volunteer it unprompted.
- An association with restless legs syndrome — iron repletion is indicated in restless legs syndrome once ferritin is low, even before frank anemia develops.
Risk Factors
- Menstrual blood loss, particularly heavy menstrual bleeding.
- Pregnancy — expansion of maternal red cell mass and fetal/placental iron demand.
- Gastrointestinal blood loss: peptic ulcer disease, colorectal or gastric malignancy, angiodysplasia, hemorrhoids, chronic NSAID or antiplatelet/anticoagulant use.
- Regular blood donation.
- Reduced dietary iron intake, including vegetarian/vegan diets without adequate planning (nonheme iron has lower bioavailability than heme iron).
- Malabsorption: celiac disease, autoimmune atrophic gastritis, inflammatory bowel disease, prior bariatric/gastric bypass surgery, H. pylori infection.
- Chronic hemolysis.
- Rapid growth demands in infancy and adolescence.
Red Flags & Refer
Escalate or refer for any of the following:
- Adult man or postmenopausal woman with newly diagnosed iron deficiency and no obvious cause (no known menstrual loss, pregnancy, or dietary explanation) — refer for bidirectional GI endoscopy to exclude a GI malignancy or other significant bleeding source; this applies even if the patient is otherwise well and has no GI symptoms.[3]
- Active GI bleeding signs — melena, hematochezia, or hematemesis — warrant urgent GI referral, not a trial of oral iron first.
- Severe or rapidly progressive anemia with hemodynamic instability, chest pain, or severe dyspnea — same-day assessment and consideration of transfusion.
- Iron deficiency anemia in a child — refer for pediatric evaluation of dietary intake and, where indicated, occult blood loss or malabsorption.
- No response, or an inadequate response, to a genuinely adequate oral iron trial once adherence and ongoing losses have been excluded — refer rather than repeating the same oral regimen indefinitely.
Assessment & Diagnosis
Differentiating iron deficiency anemia from anemia of chronic disease
| Parameter | Iron deficiency anemia | Anemia of chronic disease | Both together (IDA + ACD) |
|---|---|---|---|
| C-reactive protein | Normal | High | High |
| Hemoglobin | Low | Low | Low |
| Ferritin | Low | Normal-high | Normal-high |
| Transferrin saturation | Low | Low-normal | Low-normal |
| Transferrin (TIBC) | High | Low-normal | Low |
| Mean corpuscular volume | Low | Low-normal | Low |
Ferritin is an acute-phase reactant — its level rises with inflammation, infection, or tissue injury independent of iron stores, so a normal or high ferritin does not exclude iron deficiency once significant inflammation is present. In a patient with active inflammation, a ferritin under 100 mcg/L (rather than the usual under 30 mcg/L cutoff) should raise concern for coexisting iron deficiency; laboratory-specific reference ranges vary and should be interpreted in context.
History
- Ask specifically about menstrual bleeding, blood donation history, GI symptoms (dyspepsia, change in bowel habit, weight loss), jaundice, diet, alcohol intake, family history of anemia or GI cancer, and comorbid conditions (chronic kidney disease, liver disease).
- Review the medication list for drugs that cause or worsen GI blood loss (NSAIDs, anticoagulants, antiplatelets) or impair iron absorption (proton pump inhibitors, H2-receptor antagonists).
Laboratory evaluation
- CBC — hemoglobin below the WHO threshold; MCV under 80 fL (microcytic) is typical, though early or mild IDA can present with a normal MCV.
- Peripheral blood smear — microcytic, hypochromic red cells; useful to identify coexisting causes (e.g., features of hemolysis).
- Serum ferritin is the single most useful test. A ferritin under 30 mcg/L is diagnostic of iron deficiency in most adults (population-level screening studies support a threshold as low as under 15 mcg/L in a healthy population without anemia[4]); in the presence of active inflammation, a threshold under 100 mcg/L is more appropriate, since ferritin is an acute-phase reactant that rises independent of iron stores.
A genuinely important, somewhat counterintuitive point: a separate, higher ferritin threshold — under 45 mcg/L — has been specifically validated for diagnosing iron deficiency in patients who already have anemia, with substantially better sensitivity (85%) than the classic under-15-mcg/L population-screening cutoff (59% sensitivity) at an acceptable trade-off in specificity (92%). Do not apply the lower population-screening threshold when evaluating a patient who already has anemia — it will miss a meaningful proportion of true iron deficiency.[3] - Transferrin saturation under 20% supports iron deficiency; over 50% suggests iron overload instead.
- Total iron-binding capacity (TIBC) is typically elevated in isolated iron deficiency (reflecting elevated transferrin), unlike anemia of chronic disease, where it is low-normal.
Investigating the underlying cause
In asymptomatic postmenopausal women and men with IDA, pursue bidirectional (upper and lower) GI endoscopy over no endoscopy. In asymptomatic premenopausal women with IDA, bidirectional endoscopy is a reasonable option over iron replacement alone, individualized to risk factors and symptoms — a clear menstrual or dietary explanation lowers but does not eliminate the value of considering GI evaluation if response to iron is inadequate. If bidirectional endoscopy does not identify a cause, noninvasive H. pylori testing (with treatment if positive) and celiac serology are reasonable next steps before further invasive testing.[3]
Treatment Targets
- Restore hemoglobin to normal.
- Fully replete iron stores, not merely normalize hemoglobin — stopping iron the moment hemoglobin normalizes leaves stores depleted and anemia prone to recur.
- Resolve symptoms and improve quality of life.
- Identify and, where possible, treat the underlying cause of iron loss.
Choose Initial Treatment
1st line, essentially all patients a simple oral ferrous salt (ferrous sulfate, ferrous fumarate, or ferrous gluconate) — no oral iron salt has been shown to be more effective than another at an equivalent elemental iron dose, so selection is driven by tolerability and elemental iron content per tablet.
Alternate-day, single-dose iron is a genuinely important, current, and somewhat counterintuitive point: giving the same total weekly elemental iron dose on alternate days, as a single dose, rather than split into daily divided doses, produces higher fractional iron absorption than consecutive-day dosing (iron ingestion transiently raises hepcidin, which suppresses absorption from the next dose for roughly 24 hours) and is associated with fewer GI side effects, with hemoglobin-response outcomes that are at least as good as daily dosing. Alternate-day, single-morning dosing is a reasonable default starting approach for most patients, not just a fallback for those who cannot tolerate daily dosing.[5][6]
Use ferric maltol when ferrous salts are not tolerated, or specifically in inflammatory bowel disease, where its formulation may improve tolerability — but avoid initiating during an active IBD flare.
Escalate to IV iron when oral iron is not tolerated despite dose/formulation adjustment, when documented malabsorption is present, when ongoing losses exceed the capacity of the GI tract to absorb oral iron, or when a large iron deficit needs correcting quickly (e.g., before surgery, or in significant symptomatic anemia). Newer high-dose formulations (ferric carboxymaltose, ferric derisomaltose) can deliver a full replacement dose in 1-2 infusions rather than the many visits older parenteral products required.
Investigate the underlying cause in parallel with treatment, never instead of it — in an adult man or postmenopausal woman without an obvious explanation, do not treat the anemia and consider the case closed; arrange GI evaluation regardless of the hemoglobin response to iron.[2]
Non-Pharmacologic Treatment
- Dietary iron, particularly heme iron from liver, lean red meat, and seafood (oysters, clams, tuna, salmon, sardines, shrimp), contributes to treatment but is generally too slow and too limited in quantity to be sufficient as sole therapy for confirmed IDA.
- Nonheme iron (beans, lentils, tofu, spinach, fortified cereals) has lower bioavailability; pairing plant-based iron sources with vitamin C-rich foods is a reasonable general dietary recommendation, particularly for vegetarian/vegan patients, though vitamin C supplementation taken alongside a standard oral iron supplement has not shown a clear absorption benefit in trials.[6]
- Avoid taking iron with tea or coffee — polyphenols and phytates in these beverages inhibit nonheme iron absorption.
- Treat the identified underlying cause (e.g., celiac disease, H. pylori, menorrhagia) whenever one is found — iron replacement alone will not prevent recurrence if the cause persists untreated.
Special Populations
Pregnancy
Iron requirements rise substantially in pregnancy from expansion of maternal red cell mass and fetal/placental growth. Treat iron deficiency in pregnancy the same way as in nonpregnant adults — oral iron salts are the mainstay and are not associated with teratogenic effects. Patients with significant nausea can lower the dose, take iron with meals, or use intermittent (once, twice, or three times weekly, on nonconsecutive days) dosing, which limited data suggest is as effective as daily dosing and better tolerated. IV iron is reserved for pregnant patients with malabsorption, true oral intolerance, or blood loss exceeding oral absorptive capacity causing severe anemia — avoid IV iron in the first trimester and confirm current product-specific pregnancy guidance before use; postpartum anemia responds faster to IV than oral iron when a rapid correction is clinically important.[6]
Breastfeeding
Iron passes into breast milk, but the amount is not significantly influenced by maternal iron status or supplementation — both oral and IV iron are compatible with breastfeeding.
Pediatrics
Dose by elemental iron and body weight. Low-dose ferrous sulfate has shown a greater hemoglobin response than polysaccharide-iron complex in at least one pediatric trial — this is a relevant consideration when choosing a product for a child.
Older adults
Older patients are more prone to GI intolerance; daily elemental iron doses as low as 15-50 mg are effective and often better tolerated, and alternate-day dosing is a reasonable default in this population as well.
Monitoring & Follow-Up
Expect a reticulocyte response within 1 week of starting effective iron therapy, with hemoglobin rising by roughly 10 g/L every 7-10 days thereafter. Recheck hemoglobin and reticulocytes at 2-4 weeks to confirm response, and recheck ferritin once hemoglobin normalizes to confirm stores have actually been replenished, not just the hemoglobin value corrected. Continue iron for approximately 3 months after the target hemoglobin is reached to fully replete stores if the underlying cause has been identified and addressed. If no clear cause is identified or the cause cannot be definitively treated, educate the patient on recurrence symptoms and arrange periodic screening.
Common Errors to Avoid
- Treating iron deficiency in an adult man or postmenopausal woman without arranging GI evaluation — this is a missed-cancer patient-safety issue, not just a suboptimal workup.
- Using an enteric-coated or delayed-release oral iron product — these are poorly absorbed because they release iron beyond the primary duodenal/proximal-jejunal absorption site.
- Stopping iron the moment hemoglobin normalizes, without continuing long enough to replete stores.
- Assuming routine vitamin C co-administration meaningfully improves absorption from a standard oral iron supplement — trial evidence does not support this for supplement-based iron.
- Missing a clinically significant drug interaction — proton pump inhibitors, antacids, calcium, levodopa, methyldopa, penicillamine, quinolones, and tetracyclines all reduce iron absorption or have their own absorption reduced by iron.
- Assuming a normal or high ferritin excludes iron deficiency in a patient with active inflammation — reassess using the inflammation-adjusted threshold.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.
Oral iron salts
No salt has been shown to be more effective than another at an equivalent elemental iron dose. Avoid enteric-coated preparations for all agents in this class. Absorption is decreased by food and by antacids, calcium carbonate, cholestyramine, levodopa, methyldopa, penicillamine, quinolones, sodium bicarbonate, and tetracyclines — separate administration by about 2 hours.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ferrous sulfate | Adults, daily divided dosing: 105-200 mg elemental iron/day in up to 3 divided doses Adults, alternate-day dosing (reasonable default): 1 single dose (60-120 mg elemental iron) every other day Older adults: 15-50 mg elemental iron/day is often sufficient and better tolerated | Nausea, dyspepsia, constipation/diarrhea, dark stools | See class note above; also reduced by PPIs/H2-blockers | 60 mg elemental iron/tablet. |
| Ferrous fumarate | Adults, daily divided dosing: 105-200 mg elemental iron/day in up to 3 divided doses Adults, alternate-day dosing (reasonable default): 1 single dose (100 mg elemental iron) every other day | Nausea, dyspepsia, constipation/diarrhea, dark stools | See class note above; also reduced by PPIs/H2-blockers | 100 mg elemental iron/tablet — highest elemental content of the common salts. |
| Ferrous gluconate | Adults, daily divided dosing: 105-200 mg elemental iron/day in up to 3 divided doses Adults, alternate-day dosing (reasonable default): 1 single dose (35-70 mg elemental iron) every other day | Nausea, dyspepsia, constipation/diarrhea, dark stools | See class note above; also reduced by PPIs/H2-blockers | 35 mg elemental iron/tablet — lowest elemental content of the common salts. |
| Polysaccharide-iron complex | Adults: 105-200 mg elemental iron/day | Nausea, dyspepsia, constipation/diarrhea, dark stools | See class note above | 150 mg elemental iron/capsule. May be better tolerated than ferrous salts, though evidence is inconsistent; a pediatric trial found low-dose ferrous sulfate produced a greater hemoglobin increase. |
| Heme iron polypeptide | Preventative dose: 1 tablet PO TID | GI upset, generally milder than ferrous salts | Fewer absorption interactions than nonheme iron salts | 11 mg elemental iron/tablet, derived from bovine hemoglobin — a consideration for patients avoiding animal-derived products. Evidence for treating (rather than preventing) established IDA is limited. |
Ferric maltol (non-salt oral iron)
A ferric-trimaltol complex formulated to enhance small-intestinal absorption; often better tolerated than ferrous salts and a useful option in inflammatory bowel disease. Avoid initiating during an active IBD flare.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ferric maltol | Adults: 30 mg elemental iron PO BID on an empty stomach | Flatulence, diarrhea, constipation, abdominal pain | Same absorption-reducing interactions as ferrous salts | Reassess hemoglobin/ferritin after 12 weeks. |
Parenteral (IV) iron
Reserved for oral intolerance/failure, malabsorption, ongoing losses exceeding oral absorptive capacity, or when rapid repletion is clinically needed. Newer high-dose products deliver a full replacement dose in 1-2 visits. Rare but serious hypersensitivity reactions, including anaphylaxis, can occur — administer where resuscitation equipment and trained personnel are immediately available.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ferric carboxymaltose | Adults: Weight- and hemoglobin-based total dose, given as 1-2 IV infusions or bolus injections | Rare anaphylaxis; infusion reactions, hypotension, headache, hypophosphatemia | May reduce absorption of concurrent oral iron — do not combine | 0.9% NaCl is the preferred infusion solution; consult current prescribing information for dose calculation. |
| Ferric derisomaltose | Adults over 50 kg: 1000 mg as a single IV infusion Adults under 50 kg: 20 mg/kg actual body weight as a single IV infusion | Rare anaphylaxis; infusion reactions, headache, transient hypophosphatemia | May reduce absorption of concurrent oral iron — do not combine | Can deliver a full replacement dose in a single visit. |
| Iron sucrose | Chronic dialysis: 100 mg IV 1-3 times weekly until replete, then adjust to maintain iron availability | Rare anaphylaxis; infusion reactions, hypotension with rapid infusion | May reduce absorption of concurrent oral iron — do not combine | Requires multiple visits rather than a single/two-dose course; commonly used in chronic kidney disease/dialysis. |
| Sodium ferric gluconate complex | Chronic dialysis: 125 mg IV 1-3 times weekly for up to 8 doses, then adjust as needed | Rare anaphylaxis; fever, chills, headache, myalgia, arthralgia, urticaria, dizziness, hypotension with rapid injection | May reduce absorption of concurrent oral iron — do not combine | Test doses are no longer recommended by the manufacturer; delayed-onset reactions can occur. |
Evidence note: Drug inventory, dosing, adverse effects, and comments reflect current Canadian practice, cross-checked against the 2021 BSG and 2020 AGA guidelines and the 2025 international iron deficiency consensus.[2][6]
References
- Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity — World Health Organization. WHO/NMH/NHD/MNM/11.1, 2011
- British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults — Gut, British Society of Gastroenterology (Snook J, Bhala N, Beales ILP, et al.). Gut 2021;70(11):2030-2051
- AGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia — Gastroenterology, American Gastroenterological Association (Ko CW, Siddique SM, Patel A, et al.). Gastroenterology 2020;159(3):1085-1094
- WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations — World Health Organization. WHO, 2020
- Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women — The Lancet Haematology (Stoffel NU, Cercamondi CI, Brittenham G, et al.). Lancet Haematol 2017;4(11):e524-e533
- Management of iron deficiency in children, adults, and pregnant individuals: evidence-based and expert consensus recommendations — The Lancet Haematology (Iron Consortium, Oregon Health & Science University). Lancet Haematol 2025;12(5):e376-e388
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.