15.1 Pediatric Anemias (Iron Deficiency, Thalassemia)

Approaching Microcytic Anemia in Children

Anemia is defined as a hemoglobin (Hb) concentration more than 2 standard deviations below the age- and sex-adjusted mean. In pediatrics, the first and most powerful step in working up any anemia is classifying it by mean corpuscular volume (MCV): microcytic (low MCV), normocytic, or macrocytic (high MCV). On the Arab Board written paper, the overwhelming majority of anemia vignettes are microcytic, and the exam is testing whether you can separate the two dominant causes -- iron deficiency anemia (IDA) and thalassemia trait -- using cheap, first-line laboratory clues rather than jumping straight to hemoglobin electrophoresis.

The classic microcytic differential (mnemonic TAILS) is: Thalassemia, Anemia of chronic disease, Iron deficiency, Lead poisoning, Sideroblastic anemia. Of these, iron deficiency and thalassemia trait dominate exam questions because they look nearly identical on a basic complete blood count (CBC) but are managed completely differently -- one needs iron supplementation, the other needs genetic counseling and must NOT be given empiric iron.

Iron Deficiency Anemia: The Hematologic Workup

The nutritional and dietary drivers of iron deficiency (excessive cow's milk intake before 12 months, prolonged exclusive breastfeeding without iron-fortified weaning foods, prematurity) are covered in the Nutrition chapter. Here, focus on the laboratory staging and diagnostic workup, which the exam tests heavily.

Iron deficiency progresses through three sequential stages: (1) iron store depletion -- ferritin falls first, with no anemia yet; (2) iron-deficient erythropoiesis -- transferrin saturation falls and total iron-binding capacity (TIBC) rises, but Hb is still normal; (3) iron deficiency anemia -- Hb falls, MCV falls, and RDW rises as the marrow produces progressively smaller, more variably sized red cells.

Exam trap: Ferritin is an acute-phase reactant. In a child with concurrent infection or inflammation, a "normal" ferritin does not exclude iron deficiency -- the exam may give you a borderline ferritin with a high CRP to test whether you recognize this confounder.

Management of Iron Deficiency Anemia

Once iron deficiency is confirmed, first-line treatment is oral elemental iron (typically ferrous sulfate, roughly 3-6 mg/kg/day of elemental iron divided once or twice daily), ideally given with vitamin C and away from milk or tea, which inhibit absorption. A reticulocyte rise by day 5-10 and hemoglobin rise of about 1 g/dL over 4 weeks confirm response. Continue iron for 2-3 months after hemoglobin normalizes to replete stores. Dietary counseling (limiting cow's milk, iron-rich complementary foods) is covered in the Nutrition chapter, but the exam also tests that you do not give empiric iron to a child whose microcytosis pattern (normal ferritin, normal RDW, low Mentzer index) points to thalassemia trait -- iron will not correct thalassemia and delays appropriate counseling.

Thalassemia: The Genetic Mimicker

Thalassemia is an inherited defect in globin chain synthesis. Unlike iron deficiency, red cell number is preserved or even elevated because the marrow compensates by producing more (smaller) cells -- this is the physiologic basis for the key discriminators below.

Mentzer index = MCV ÷ RBC count.

• >13 → suggests iron deficiency (few, larger-than-expected cells for the low MCV)
• <13 → suggests thalassemia trait (many small cells; RBC count disproportionately preserved/high)

Worked example: a 4-year-old girl has Hb 10.2 g/dL, MCV 62 fL, RBC count 5.8 x 10^12/L, RDW 13.2% (normal), ferritin 45 ng/mL (normal). Mentzer index = 62/5.8 = 10.7 (<13). Normal RDW and normal ferritin argue against iron deficiency. This pattern -- normal RDW, normal ferritin, low Mentzer index -- is the classic thalassemia trait vignette.

Alpha-thalassemia results from deletion of 1-4 of the four alpha-globin genes:

Beta-thalassemia results from reduced (beta+) or absent (beta0) beta-globin synthesis:

Exam trap: Alpha-thalassemia trait (2-gene deletion) usually has a normal hemoglobin electrophoresis because there is no compensatory HbA2 or HbF rise -- the diagnosis is one of exclusion (normal ferritin, low Mentzer index, but normal electrophoresis) or confirmed by DNA-based genetic testing. If a vignette gives you microcytosis with a normal electrophoresis and normal iron studies, think alpha-thalassemia trait, not "no diagnosis."

Beta-Thalassemia Major: The Clinical Picture

Infants with beta-thalassemia major are normal at birth (protected by HbF) and present at 6-12 months as HbF physiologically declines and HbA fails to compensate. Expect: severe pallor, failure to thrive, hepatosplenomegaly (extramedullary hematopoiesis), and -- if undertreated -- the classic "chipmunk facies" (frontal bossing, maxillary hypertrophy) from marrow expansion, and skull X-ray showing a "hair-on-end" appearance. Management is chronic transfusion to keep Hb above ~9-10.5 g/dL to suppress marrow expansion, combined with iron chelation therapy (deferoxamine, deferasirox, or deferiprone) to prevent transfusional iron overload -- cardiac siderosis is the leading cause of death if chelation is inadequate. Curative therapy is hematopoietic stem cell transplant.

Putting It Together for the Exam

When a vignette presents microcytic anemia, work through this order: (1) Is RDW high or normal? (2) What is the Mentzer index? (3) Is ferritin low, normal, or high (and is there concurrent inflammation)? (4) Does the child have a positive family history of anemia or a Mediterranean/Southeast Asian/South Asian/Arab ancestry pattern consistent with thalassemia carrier frequency? Only after these clues point you toward thalassemia should you reach for hemoglobin electrophoresis to confirm.