Microcytic hypochromic anemia from depleted iron stores — most common anemia worldwide.
Also known as: IDA, iron deficiency, microcytic anemia, hypochromic anemia
Overview
Anemia resulting from insufficient body iron to sustain normal erythropoiesis. Defined by reduced hemoglobin with low ferritin (<30 ng/mL in most adults, <15 ng/mL highly specific) and reduced transferrin saturation (<20%).
Epidemiology
Most common cause of anemia globally and in the United States. Highest prevalence in menstruating women, pregnant patients, infants/toddlers, and adults with chronic blood loss. In men and postmenopausal women, GI blood loss must be excluded.
Try two board-style Iron Deficiency Anemia questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1HematologyMedium
A 65-year-old man presents with fatigue and exertional dyspnea. Labs show Hgb 8.4 g/dL, MCV 72 fL, ferritin 8 ng/mL, and elevated total iron-binding capacity. He reports no overt bleeding and takes no NSAIDs. Which of the following is the most important underlying cause to exclude?
ADietary iron deficiency
BMalabsorption from celiac disease
CBleeding colonic angiodysplasia
DBleeding peptic ulcer disease
EOccult gastrointestinal malignancy
Reveal answer & full explanation
Correct answer: E — Occult gastrointestinal malignancy
ADietary iron deficiency
BMalabsorption from celiac disease
CBleeding colonic angiodysplasia
DBleeding peptic ulcer disease
EOccult gastrointestinal malignancy✓
Why Occult gastrointestinal malignancy is correct
Iron deficiency anemia (low MCV, low ferritin, high TIBC) demands a cause-directed workup.
In men and postmenopausal women, occult gastrointestinal blood loss must be investigated with endoscopy/colonoscopy, and GI malignancy is the most important cause to exclude.
Low ferritin is the most sensitive indicator of iron deficiency, and a high TIBC supports the diagnosis.
Why the others are wrong
Dietary iron deficiency — Dietary deficiency is uncommon in adults eating a Western diet.
Bleeding peptic ulcer disease — H. pylori or idiopathic ulcers can cause occult upper GI blood loss and are evaluated on the same endoscopic workup, but in a 65-year-old man without NSAID use the cause that must not be missed is colorectal or gastric cancer, so malignancy is the most important to exclude.
Malabsorption from celiac disease — Can cause iron deficiency and should be considered, but is far less likely than occult GI malignancy in an older man and would usually have other malabsorptive features.
Bleeding colonic angiodysplasia — vascular ectasias are a common source of occult GI blood loss in older adults and are seen on the same endoscopic evaluation, but they are benign and should be accepted as the cause only after malignancy has been excluded, because colorectal or gastric cancer is the must-not-miss lesion in a 65-year-old man.
Question 2HematologyMedium
A 65-year-old man with no prior GI workup is found to have iron deficiency anemia on routine labs (Hgb 10.2 g/dL, MCV 72 fL, ferritin 8 ng/mL). He is asymptomatic and reports no overt bleeding. Which of the following is the most important cause to exclude?
AUndiagnosed celiac disease
BAutoimmune atrophic gastritis
CBleeding peptic ulcer disease
DOccult colorectal malignancy
EInadequate dietary iron intake
Reveal answer & full explanation
Correct answer: D — Occult colorectal malignancy
AUndiagnosed celiac disease
BAutoimmune atrophic gastritis
CBleeding peptic ulcer disease
DOccult colorectal malignancy✓
EInadequate dietary iron intake
Why Occult colorectal malignancy is correct
Iron deficiency in men and postmenopausal women: GI blood loss is assumed until proven otherwise
Colorectal cancer is the most important cause to exclude
Bidirectional endoscopy (colonoscopy plus upper endoscopy, typically in the same session) is indicated because dual pathology occurs
Upper endoscopy evaluates for H. pylori-positive peptic ulcer disease (PUD), gastric cancer, or celiac disease
Why the others are wrong
Bleeding peptic ulcer disease — a genuine source of occult upper GI blood loss and part of the bidirectional endoscopic workup, but a missed colorectal cancer carries far greater consequences, so malignancy remains the priority to exclude in a 65-year-old man
Autoimmune atrophic gastritis — achlorhydria impairs iron absorption, making it a recognized cause of iron deficiency in older adults that often precedes the B12 deficiency of pernicious anemia, but it is diagnosed on gastric biopsies at upper endoscopy and carries none of the consequences of a missed cancer, so colorectal malignancy remains the priority to exclude
Inadequate dietary iron intake — uncommon as the sole cause in an adult man and accepted only after GI blood loss has been excluded
Undiagnosed celiac disease — celiac disease is a recognized cause of iron deficiency from duodenal malabsorption and is part of the evaluation (serology or duodenal biopsies at upper endoscopy), but it is far less likely than colorectal cancer in a 65-year-old man and less consequential if missed, so malignancy remains the priority to exclude
Additional high-yield points
In premenopausal women, menorrhagia is the most common cause of iron deficiency
Management requires both treating the iron deficiency AND identifying the source
That's 2. Get 7,700+ more.
Unlock the full FirstPassPA bank: 7,700+ board-style questions, flashcards, and an AI tutor that explains every answer. Your 7-day free trial includes everything, and there's no credit card required.
You've read your 2 free diagnosis previews. Create your free account to unlock the full Iron Deficiency Anemia outline — plus all 514 diagnoses, 7,700+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Malabsorption: celiac disease, atrophic gastritis, H. pylori, post-gastric bypass, PPI use
Inadequate intake: strict vegetarian/vegan diet, whole cow's milk before age 1 or excessive intake in toddlers (>24 oz/day), which displaces iron-rich foods and can cause occult GI blood loss
Iron is required for heme synthesis. When demand exceeds supply (loss > absorption), storage iron (ferritin) is mobilized first, then transport iron (transferrin saturation falls), and finally functional iron in erythrocytes. Erythropoiesis becomes iron-restricted, producing small (microcytic), pale (hypochromic) red cells with reduced hemoglobin content.
Clinical presentation
Symptoms
Fatigue, dyspnea on exertion, exercise intolerance, lightheadedness
Headache, poor concentration, irritability
Pica (craving ice/pagophagia, clay, starch) — relatively specific for iron deficiency
Restless legs syndrome
Hair loss, brittle nails
Signs / physical exam
Pallor of conjunctiva, palms, nail beds
Tachycardia, systolic flow murmur
Koilonychia (spoon nails) — advanced/chronic
Angular cheilitis, atrophic glossitis (smooth red tongue)
Plummer-Vinson syndrome: dysphagia + esophageal web + IDA (rare, premalignant)
Classic findings
Pica with ice craving plus microcytic anemia and low ferritin is highly suggestive of iron deficiency.
Differential diagnosis
Anemia of chronic disease (ACD) — Ferritin normal or elevated (acute phase reactant), low TIBC, low transferrin saturation; iron sequestered by hepcidin
Thalassemia trait — Microcytosis disproportionate to mild anemia, normal RDW, Mentzer index <13 (MCV/RBC); hemoglobin electrophoresis abnormal in beta-thal
Sideroblastic anemia — Microcytic or dimorphic; ringed sideroblasts on marrow iron stain; elevated ferritin and iron
Lead poisoning — Basophilic stippling, occupational/environmental exposure, elevated blood lead level
Combined deficiency (B12/folate + iron) — Normocytic MCV with wide RDW; both micro- and macrocytic populations on smear
Diagnostic workup
Diagnostic criteria
Anemia (low Hb for age and sex) plus ferritin <30 ng/mL indicates iron deficiency (<15 ng/mL is highly specific). With inflammation or CKD, which raise ferritin, a ferritin <100 ng/mL with transferrin saturation <20% still supports iron deficiency. Low transferrin saturation alone does not separate IDA from anemia of chronic disease. MCV may be normal early; microcytosis (MCV <80 fL) develops as deficiency progresses.
Iron studies — low ferritin (<30 ng/mL diagnostic in most adults; <100 ng/mL may indicate deficiency in inflammation/CKD), low serum iron, elevated TIBC, transferrin saturation <20%
Reticulocyte count — inappropriately low for degree of anemia
Soluble transferrin receptor — elevated in IDA, normal in ACD (useful when ferritin uninterpretable)
Celiac serology (tissue transglutaminase IgA) and noninvasive H. pylori testing (treat if positive) in unexplained IDA (AGA 2020); fecal occult blood testing is not recommended — a negative result does not exclude a GI source, so endoscopy is still needed
Imaging
Upper and lower endoscopy in men and postmenopausal women with IDA, and in premenopausal women not responding to iron
Capsule endoscopy if EGD/colonoscopy nondiagnostic and bleeding persists
Diagnostic algorithm
Parameter
Iron Deficiency
Anemia of Chronic Disease
Thalassemia Trait
MCV
Low
Normal or low
Low (disproportionate)
RDW
High
Normal
Normal
Ferritin
Low (<30)
Normal or high
Normal or high
Serum iron
Low
Low
Normal or high
TIBC
High
Low
Normal
Transferrin saturation
Low (<20%)
Low
Normal or high
sTfR
High
Normal
Normal or high
Iron studies pattern across the common microcytic anemias.
Treatment
First-line
Identify and correct the underlying cause (most important step)
Oral iron — ferrous sulfate 325 mg (65 mg elemental), ferrous gluconate, ferrous fumarate; one tablet every other day improves absorption and tolerability versus daily dosing
Take on empty stomach with vitamin C (orange juice) to enhance absorption; avoid concurrent calcium, antacids, PPIs, coffee, tea
Continue iron 3-6 months after hemoglobin normalizes to replete stores
Second-line / adjunct
IV iron — ferric carboxymaltose, iron sucrose, ferumoxytol, low-molecular-weight iron dextran; indicated for intolerance to oral iron, malabsorption (celiac, IBD, post-bypass), CKD on dialysis, ongoing blood loss exceeding oral absorption, or need for rapid replenishment (late pregnancy, or IDA before major surgery planned within a few weeks)
Transfusion reserved for hemodynamic instability, severe symptomatic anemia, or active hemorrhage
Complications
High-output heart failure (severe chronic anemia)
Impaired neurocognitive development in infants and young children
Worsened outcomes in HF, CKD, and post-operative recovery
Plummer-Vinson syndrome with risk of esophageal squamous cell carcinoma
PANCE pearls
Reticulocytosis should be visible within 7-10 days of starting oral iron; hemoglobin rises ~1 g/dL every 2-3 weeks.
Failure to respond to oral iron suggests ongoing loss, malabsorption, noncompliance, or wrong diagnosis (think thalassemia, ACD).
IV iron does NOT require a test dose for newer formulations (ferric carboxymaltose, ferumoxytol); anaphylaxis risk is much lower than with older high-molecular-weight iron dextran.
Ferritin is an acute phase reactant — can be falsely normal in inflammation, infection, malignancy, CKD. Use transferrin saturation and soluble transferrin receptor in these settings.
Every-other-day dosing minimizes hepcidin-driven absorption blockade and improves total iron uptake compared to daily dosing.
References
BSG 2021 — Snook J, Bhala N, Beales ILP, et al. British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Gut 2021;70(11):2030-2051.
AGA 2020 — AGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia (Ko et al., Gastroenterology 2020)
WHO 2024 — World Health Organization. Guideline on haemoglobin cutoffs to define anaemia in individuals and populations. Geneva: WHO; 2024.
Stoffel et al. — Iron absorption from oral iron supplements given on consecutive versus alternate days (Lancet Haematology 2017)
Practice Hematology questions on FirstPassPA
Turn this outline into retention. 7,700+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.