About This Page
This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Iron deficiency anemia is the most common anemia worldwide and becomes microcytic once advanced
- Low ferritin is the most specific test, but inflammation can falsely elevate ferritin
- In adult men and postmenopausal women, iron deficiency anemia is gastrointestinal blood loss until proven otherwise
- First-line therapy is oral iron; IV iron is used for intolerance, malabsorption, CKD, inflammatory bowel disease, or urgent repletion
- Step 2 CK pearl: do not attribute new iron deficiency anemia in an older man to diet alone — evaluate for colon cancer
Overview
Iron deficiency anemia develops when iron loss or demand exceeds intake and absorption. Iron depletion first lowers ferritin, then reduces transferrin saturation, and eventually produces microcytosis, hypochromia, and impaired oxygen delivery. In menstruating patients, heavy menstrual bleeding and pregnancy are common causes. In adult men and postmenopausal women, occult gastrointestinal bleeding from colorectal cancer, peptic ulcer disease, angiodysplasia, or inflammatory bowel disease must be considered.
Epidemiology
Iron deficiency is common in children, menstruating adolescents and adults, pregnancy, and patients with chronic blood loss or malabsorption. In the United States, risk is increased by heavy menstrual bleeding, pregnancy, bariatric surgery, celiac disease, inflammatory bowel disease, frequent blood donation, low dietary iron intake, and chronic NSAID use.
Clinical Features
Symptoms
Fatigue, weakness, exertional dyspnea, and reduced exercise tolerance
Pica, especially pagophagia (ice craving)
Restless legs, headaches, dizziness, or poor concentration
Heavy menstrual bleeding or symptoms of occult gastrointestinal blood loss
Chest pain, syncope, or heart failure symptoms in severe anemia
Signs
Pallor, tachycardia, flow murmur
Koilonychia, brittle nails, angular cheilitis, glossitis
Conjunctival pallor
Melena, hematochezia, abdominal mass, or weight loss suggesting gastrointestinal malignancy
Orthostatic hypotension if active bleeding
Investigations
First-line
CBC with indices and RDWLow hemoglobin with low MCV; RDW is often elevated early
FerritinBest single test for iron stores. Low ferritin confirms iron deficiency; normal/high ferritin may not exclude deficiency in inflammation
Iron studiesLow serum iron, high TIBC, low transferrin saturation
Second-line
Reticulocyte countUsually low before treatment; rises 5-10 days after effective iron therapy
Peripheral smearMicrocytic hypochromic RBCs, anisopoikilocytosis, pencil cells
Stool and pregnancy testing when appropriateUseful adjuncts but do not replace endoscopic evaluation when indicated
Specialist
Bidirectional endoscopyRecommended in adult men and postmenopausal women with iron deficiency anemia
Celiac serologyConsider in malabsorption, refractory anemia, or compatible symptoms
1
Confirm and identify the cause
- Confirm iron deficiency with ferritin and iron studies
- Assess menstrual, pregnancy, dietary, medication, blood donation, bariatric surgery, and gastrointestinal history
- Adult men or postmenopausal women: investigate for gastrointestinal blood loss, especially colorectal cancer
- Do not delay urgent evaluation with weight loss, melena, abdominal pain, or change in bowel habit
2
Iron replacement
- Oral ferrous sulfate, gluconate, or fumarate; alternate-day dosing may improve absorption and tolerability
- Continue for about 3 months after hemoglobin normalizes to replenish stores
- Expected response: reticulocytosis within 1 week and hemoglobin rise about 1 g/dL every 2-3 weeks
3
When to use IV iron
- Intolerance or nonresponse to oral iron
- Malabsorption, active inflammatory bowel disease, CKD on dialysis, post-bariatric surgery, or need for rapid repletion
4
Transfusion
- Packed RBC transfusion for hemodynamic instability, active major bleeding, severe symptomatic anemia, or Hb generally <7 g/dL in stable hospitalized adults
Complications
- Cardiac strain: Tachycardia, angina, high-output failure in severe chronic anemia
- Pregnancy complications: Preterm delivery, low birth weight, maternal fatigue
- Missed malignancy: Colorectal cancer may present only as iron deficiency anemia
USMLE Step 2 CK Exam Tips
- 1Microcytic anemia + low ferritin = iron deficiency anemia
- 2Microcytic anemia + high RDW + pica = iron deficiency, not thalassemia trait
- 3Older man with new iron deficiency anemia: next best step is colonoscopy plus upper endoscopy
- 4Ferritin is an acute phase reactant; inflammation can mask iron deficiency
- 5Oral iron failure: check adherence, ongoing bleeding, celiac disease, H. pylori, or inflammatory bowel disease
- 6Reticulocyte count should rise within about 1 week after effective iron therapy
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