Family Medicine Board Review · Hematology · Source: AAFP 11/2025
Iron Deficiency Anemia: High-Yield Board Summary
Ferritin's role as an acute-phase reactant, the IDA/anemia-of-chronic-disease/thalassemia lab comparison, evaluation triggers for endoscopy, and the exact treatment timeline and thresholds.
Diagnosis
- Iron deficiency is the most common cause of microcytic anemia; other causes include thalassemia, sideroblastic anemia, and anemia of chronic disease
- Initial testing: CBC, iron studies, ferritin, and peripheral blood smear
- Reticulocyte count helps in diagnosis: low in IDA, high in hemolytic anemia
- Ferritin is the most accurate biomarker correlated with total iron stores — but it is an acute phase reactant, meaning it will rise (falsely reassuring) in the setting of infection or inflammation
Board trap: a "normal" or even elevated ferritin does NOT exclude iron deficiency in a patient with concurrent infection/inflammation — ferritin's acute-phase behavior can mask true iron deficiency. When inflammation is suspected, use additional markers (e.g., transferrin saturation) rather than ferritin alone.
Differential Diagnosis — Laboratory Comparison
| Iron Deficiency Anemia | Anemia of Chronic Disease | Thalassemia |
| MCV | Low/normal | Low/normal | Low/normal |
| RDW | High | Normal | Normal |
| Iron | Low | Low | Normal/high |
| TIBC | High | Low/normal | Normal |
| Ferritin | Low | Normal/high | Normal |
| Transferrin saturation | Low | Low/normal | Normal/high |
| Transferrin | High | Low/normal | Normal |
Exam pearl — the single best discriminator: RDW is high in IDA but normal in both anemia of chronic disease and thalassemia. When MCV is low across all three and you need one number to separate IDA from the others, go to RDW first.
Second discriminator: TIBC/transferrin is HIGH in IDA (the body upregulates transport capacity when iron stores are depleted) but low-to-normal in anemia of chronic disease — the opposite direction, reflecting inflammatory sequestration of iron rather than true depletion.
Etiologies & Risk Factors for Iron Deficiency
Decreased Intake
Eating disorders · Food insecurity · Fussy/picky eating · Vegetarian or vegan diet
Impaired Absorption
Bariatric surgery · Celiac disease · Chronic inflammation · Chronic PPI use ·
H. pylori infection · Inflammatory bowel disease · Malabsorption syndromes
Increased Loss (responsible for up to ~⅔–90%+ of cases in adult women)
Bleeding disorders · Antiplatelet/anticoagulant medications · Frequent blood donation · GI bleeding · Hemodialysis · Hemoptysis · Hematuria · Menorrhagia · Parasitic infections · Surgical blood loss
Increased Demand
Children/growth · Multiple or closely spaced pregnancies · Endurance athletes · Lactation · Pregnancy · Puberty
Socioeconomic/demographic risk factors: age <5 years, female sex, living in a lower-resource country, lower socioeconomic status.
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Screening & Prevention
1. Pregnancy
- Screen for IDA in the first trimester, and again between 24–29 weeks
- Low-dose (27 mg) iron supplementation for all pregnant women, starting in the first trimester
2. Pediatrics
- Screen at age 12 months
- Iron supplementation for exclusively breastfed infants starting at age 4 months, until iron-fortified foods are started
- Delayed cord clamping by 2 minutes decreases the risk of IDA in infancy at age 6 months
Board trap: the 27 mg low-dose iron supplementation is recommended for all pregnant women (universal), not just those already diagnosed with IDA — this is a prevention strategy, not just treatment.
Signs & Symptoms
Signs
Alopecia · Atrophic glossitis · Brittle nails · Cheilitis · Dry skin · Koilonychia · Pallor · Pica · Tachycardia
Symptoms
Attention-deficit/hyperactivity-type features in children · Chills · Dizziness · Dyspnea · Fatigue · Irritability in infants · Palpitations · Restless leg syndrome · Tinnitus
Exam pearl: koilonychia (spoon nails) and pica (craving non-food substances, e.g., ice/dirt) are classic, highly specific exam findings for iron deficiency — recognize them instantly on boards. Restless leg syndrome is also a specifically targeted symptom with its own ferritin treatment goal (see below).
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Evaluation
- The AGA recommends bidirectional endoscopy — including esophagogastroduodenoscopy (EGD) and colonoscopy — to evaluate asymptomatic men and postmenopausal women with IDA
- Patients need to be evaluated for H. pylori and celiac disease
- In younger patients with a plausible cause of IDA (e.g., heavy menstrual bleeding), it is reasonable to treat the bleeding, provide iron supplementation, and follow up to document clinical response — without immediately pursuing endoscopy
Board trap: bidirectional endoscopy is specifically triggered by asymptomatic men and postmenopausal women with IDA — this population has no obvious physiologic explanation (unlike menstruating women), making an occult GI source (including malignancy) a higher concern. A young woman with heavy menses and IDA does NOT automatically need endoscopy first.
Treatment
- Every-other-day dosing of oral iron can be more effective than daily dosing (improved fractional absorption)
- Patients on oral iron should avoid tea, coffee, and calcium-containing foods for 1 hour — these inhibit absorption
- Reticulocytosis begins 3–4 days after starting oral iron
- Hemoglobin should be measured 2–4 weeks after initiation to evaluate improvement — a rise of 1–2 g/dL (10–20 g/L) is considered an adequate response
- Patients adherent to oral therapy with a hemoglobin response <1 g/dL after 2–4 weeks should be transitioned to IV iron
- Experts recommend against IV iron in patients with active infections, given the biologic plausibility of iron's role in promoting bacterial growth
- Phosphorus level should be checked if a patient develops fatigue, bone pain, or muscular weakness after receiving IV iron — it may cause hypophosphatemia
Board trap: IV iron's specific complication to know is hypophosphatemia — presenting with new fatigue, bone pain, or muscle weakness after IV iron administration. This is a distinct, testable adverse effect separate from typical infusion reactions.
Timeline to memorize: reticulocytosis at 3–4 days → recheck Hgb at 2–4 weeks → adequate response = +1–2 g/dL → inadequate response (<1 g/dL rise despite adherence) = switch to IV iron.
Targeted Ferritin Goals
Restless Leg Syndrome
Target ferritin
>75
IDA-Related Alopecia
Target ferritin
>70
Exam pearl: these condition-specific ferritin targets (RLS >75, alopecia >70) are higher than the ferritin level needed simply to diagnose or resolve garden-variety IDA — treating to a "normal" ferritin alone may under-treat these specific symptom-driven indications.