Anemia & Deficiency Disorders: Iron, Folate, B12

Hematological assessment · Approach to anemia · Microcytic vs macrocytic · Iron deficiency · Folate deficiency · Vitamin B12 deficiency · Other megaloblastic anemias
🩸 Key concepts: CBC, reticulocytes, RDW, iron studies (ferritin, TIBC), peripheral smear, B12/folate levels, Schilling test, causes of macrocytosis, treatment and prevention of nutritional deficiencies.

📖 Hematological assessment & deficiency anemias

🩸 Hematological assessment
Full blood count: Hb, MCV (micro <80, macro >100), MCH, RDW. Reticulocytes (bone marrow response). Peripheral smear (target cells, spherocytes, hypersegmented neutrophils). Iron studies, B12/folate.
🔍 Approach to anemia
Step 1: Is it microcytic (low MCV) or macrocytic (high MCV)? Step 2: Reticulocyte count (low → production, high → loss/hemolysis). Step 3: Iron, ferritin, TIBC, hemoglobin electrophoresis, B12/folate.
⚙️ Iron deficiency anemia
Most common worldwide. Causes: inadequate intake (cow's milk excess, poor weaning), blood loss (Meckel's, menorrhagia), malabsorption. Low ferritin, high TIBC, low serum iron. Pica, koilonychia.
🍃 Folate & B12 deficiency
Macrocytic megaloblastic anemia. Folate: dietary (poor vegetables), increased demand (hemolysis), anticonvulsants. B12: pernicious anemia (autoimmune), nutritional (vegans), malabsorption (ileal resection, Crohn's). Neurologic signs in B12.
🧬 Other megaloblastic anemias
Orotic aciduria, Lesch-Nyhan, thiamine-responsive megaloblastic anemia (TRMA), copper deficiency, drugs (methotrexate, azathioprine).
⚠️ Key red flags: Pica (iron deficiency), neurologic symptoms (B12 deficiency - subacute combined degeneration), glossitis (B12/folate), family history (hereditary megaloblastic anemias).

🩺 Diagnostic approach to anemia in childhood

1
History – Age, diet (cow's milk intake, weaning), bleeding (melena, menorrhagia), pica, family history (thalassemia), drug exposure, neurologic symptoms (B12).
2
Physical exam – Pallor, jaundice (hemolysis), glossitis (B12/folate), koilonychia (iron deficiency), splenomegaly (hemolysis, thalassemia), neurologic (position/vibration loss in B12).
3
Key labs – CBC, MCV, RDW, reticulocyte count. Iron panel (ferritin, serum iron, TIBC). B12, folate, MMA (methylmalonic acid) if B12 deficiency suspected.
4
Interpreting microcytosis (low MCV) – Iron deficiency: low ferritin, high TIBC. Thalassemia trait: normal/elevated ferritin, normal TIBC, elevated HbA2 (beta) or normal electrophoresis (alpha).
5
Interpreting macrocytosis (high MCV) – B12/folate deficiency: hypersegmented neutrophils, low B12/folate. Reticulocytosis (hemorrhage/hemolysis) also elevates MCV. Liver disease, hypothyroidism.
📌 Clinical pearl: A low MCV with elevated RDW suggests iron deficiency; low MCV with normal RDW suggests thalassemia trait. B12 deficiency causes neurologic symptoms (subacute combined degeneration) even without anemia.

📋 Stepwise management of deficiency anemias

1
Iron deficiency anemia – Oral ferrous sulfate (3-6 mg elemental iron/kg/day). Counsel diet (reduce cow's milk, increase iron-rich foods). Vitamin C enhances absorption. Recheck Hb at 4 weeks, continue 3 months after correction.
2
Refractory iron deficiency – Evaluate for ongoing blood loss (celiac disease, Meckel's, inflammatory bowel disease). Consider parenteral iron (ferric carboxymaltose) if oral intolerance or severe malabsorption.
3
Folate deficiency – Oral folic acid 1-5 mg/day. Treat underlying cause (dietary, hemolysis, anticonvulsants). Prophylaxis in chronic hemolytic anemias.
4
Vitamin B12 deficiency – Intramuscular hydroxocobalamin (1000 µg every 2-3 days for 2 weeks, then monthly). Neurologic symptoms require high-dose IM. If nutritional (vegan), oral B12 may suffice.
5
Megaloblastic anemia from other causes (e.g., orotic aciduria) – Uridine replacement, treat specific inborn error. Discontinue offending drugs (methotrexate).
🚨 Emergency red flags in B12 deficiency: Severe neurologic impairment (gait, paresthesia) requires prompt parenteral B12 to prevent irreversible damage. Do not give folate alone (may mask B12 deficiency).

🧠 Clinical reflex prompts: deficiency anemias & hematological assessment

🩸 12-month-old exclusively fed cow's milk, pale, Hb 7.5, MCV 62, ferritin 3. Diagnosis?
Iron deficiency anemia due to excessive cow's milk. Treat with iron supplements, reduce milk intake.
🧪 Child with microcytic anemia, normal ferritin, and elevated HbA2 (5.5%). Diagnosis?
Beta-thalassemia trait. No iron therapy needed; genetic counseling.
📊 Which laboratory finding is earliest indicator of iron deficiency?
Low serum ferritin (reflects iron stores). Then low serum iron, high TIBC, low transferrin saturation.
🍃 Teenage vegan with fatigue, macrocytic anemia, and neurologic symptoms. Most likely deficiency?
Vitamin B12 deficiency. Check B12 level, treat with IM hydroxocobalamin.
🩸 Hypersegmented neutrophils (≥5 lobes) on smear suggest?
Megaloblastic anemia (B12 or folate deficiency). Also seen in rare congenital disorders.
🧬 Pica (eating dirt, ice) is characteristic of which deficiency?
Iron deficiency. Resolves with iron therapy.
🩺 Child with macrocytic anemia, glossitis, and positive anti-parietal cell antibodies. Diagnosis?
Pernicious anemia (autoimmune B12 deficiency). Treat with lifelong IM B12.
🧪 What is the role of methylmalonic acid (MMA) in B12 deficiency workup?
Elevated MMA is more sensitive than B12 for tissue deficiency. Normal MMA excludes B12 deficiency.
📚 Most common cause of folate deficiency in children?
Inadequate dietary intake (green vegetables, fruits). Increased demand in hemolytic anemia also common.
🧬 Which drug commonly causes megaloblastic anemia by inhibiting dihydrofolate reductase?
Methotrexate (also trimethoprim, pyrimethamine). Treat with folinic acid (leucovorin).