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Approach to Anemia in Pediatrics

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1. Screening

• Prematurity or low birth weight
• Lead exposure
• Exclusive breastfeeding without iron supplementation beyond 4 months
• Diet lacking iron-fortified cereals or iron-rich foods
• Feeding problems, poor growth, or inadequate nutrition

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2. Definition

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3. Framework: Approach by MCV + Reticulocyte Index

Step 1 - Calculate the Reticulocyte Index

Reticulocyte Index = % reticulocytes × patient Hct / normal Hct

• >2 = adequate RBC production (hemolytic or blood loss)
• <2 = hypoproliferative anemia (bone marrow failure, nutritional deficiency, chronic disease)

Step 2 - Classify by MCV

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4. Diagnostic Flowcharts

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5. Key Indices and Calculations

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6. Causes by Category

Non-Hemolytic Anemia

• Iron deficiency anemia (IDA) - Most common. Causes: poor intake, GI bleed, menstrual losses, malabsorption (celiac, H. pylori, IBD). Ferritin falls first. Low MCHC, elevated transferrin receptor. Usually normocytic; microcytic if severe/prolonged.
• B12 deficiency - Macrocytic; elevated MMA + homocysteine
• Folate deficiency - Macrocytic; elevated homocysteine, normal MMA

• Secondary to prolonged/frequent infections, autoimmune conditions (SLE, JIA, IBD), vasculitis
• Labs: low Fe, low TIBC, low transferrin; HIGH ferritin, CRP, ESR

• Lead poisoning - Interferes with iron absorption and inhibits heme synthesis; look for basophilic stippling on PBS

• Primary red cell aplasia (autoimmune, autoantibody-mediated)
• Secondary red cell aplasia (parvovirus B19, EBV, CMV, HHV-6, HIV, hepatitis, medications)
• Aplastic anemia (parvovirus, EBV, benzene, alkylating agents, chloramphenicol; hypocellular BM + peripheral cytopenia)

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Hemolytic Anemia

• Autoimmune hemolytic anemia
• Transfusion reaction
• Medications

• Membranopathy - hereditary spherocytosis, elliptocytosis
• Enzyme deficiency - G6PD, pyruvate kinase (PK) deficiency
• MAHA - HUS, TTP
• Hemoglobinopathy - sickle cell disease

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7. Peripheral Blood Smear (PBS) Findings

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8. Management

Iron Deficiency Anemia

• Oral iron (ferrous sulfate): First-line. Empirically treat microcytic anemia with poor dietary iron history.
  • Expect reticulocyte rise within 1 week
  • Hb increase of 1 g/dL in 4 weeks (if Hb <9 g/dL, response expected in 2 weeks)
  • In anemia of chronic disease, only use iron if ferritin <100 ng/mL with evidence of absolute iron deficiency
• IV iron (low-molecular-weight iron dextran or iron sucrose): For malabsorption (PPI use, short bowel syndrome), oral iron intolerance, poor response, or hemodialysis patients on EPO

Sickle Cell Anemia

• Diagnosis often made on newborn screen (Hb electrophoresis)
• Most severe subtypes: HbSS and HbSβ⁰
• Collect baseline labs: CBC, reticulocyte count, Hb electrophoresis (% HbF), renal/liver function, UA, fractionated bilirubin
• RBC exchange transfusion indications: stroke, acute chest syndrome (ACS), multi-organ failure, intrahepatic cholestasis, refractory priapism, prior stroke, or transcranial Doppler >200 cm/sec
  • Use HbS-negative cells; keep Hct <30% to avoid hyperviscosity

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Summary Algorithm

Pediatric Anemia
└── MCV (age-adjusted)
    ├── LOW (microcytic)
    │   └── Fe, TIBC, Ferritin
    │       ├── Low Fe + Low TIBC + High Ferritin → Anemia of Chronic Disease
    │       ├── Low Fe + High TIBC + Low Ferritin → Iron Deficiency Anemia
    │       └── Normal Fe + Normal Ferritin → Hb Electrophoresis → Thalassemia
    │
    ├── NORMAL (normocytic)
    │   └── Reticulocyte Index
    │       ├── High (>2.5) = Hemolytic → Coombs test
    │       │   ├── DAT+ → Autoimmune / Transfusion Rx / Drugs
    │       │   └── DAT- → PBS → Membranopathy / Enzyme deficiency / MAHA / Hemoglobinopathy
    │       └── Low (<2.5) = Hypoproliferative
    │           ├── Acute blood loss (GI bleed, hemorrhage)
    │           ├── Bone marrow failure (aplasia, leukemia, granulomatous disease)
    │           ├── Lead poisoning (elevated lead + basophilic stippling on PBS)
    │           ├── Low EPO → CKD or Systemic inflammation
    │           └── Endocrine (hypothyroidism, Addison disease, panhypopituitarism)
    │
    └── HIGH (macrocytic)
        └── B12, Folate, MMA/Homocysteine
            ├── Low B12 + High MMA + High homocysteine → B12 deficiency
            ├── Normal B12 + High homocysteine + Low folate → Folate deficiency
            ├── Normal → Review meds (AEDs, zidovudine, methotrexate) / hypothyroidism / asplenia

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