Pocket Pediatrics: The Massachusetts General Hospital for Children Handbook of Pediatrics (Pocket Notebook Series), 2 Ed.

ANEMIA

Definition (Am Fam Physician 2010;81:12)

• RBC volume as a fraction of whole blood (hematocrit) or hemoglobin concentration <5th percentile for age (e.g., <11 g/dL for age 2–35 mo)

• Hematologic parameters vary w/ age (interpret using age-specific indices)

• “Physiologic anemia of infancy”: Incr tissue oxygen level at birth depresses production of erythropoietin (reaches nadir at 1 mo); RBC production is lowest during 2nd wk and reaches max at 3 mo. Hgb nadir occurs at 6–9 wk of age

• Microcytic anemia is the most common category of anemia in children

Clinical Manifestations

• Can be asymptomatic or p/w fatigue, irritability, dyspnea, heart failure, growth delay

• Pica, pagophagia (craving and eating ice; common with iron deficiency)

• Signs or symptoms of blood loss: Hematochezia, melena, heavy menses

• Signs or symptoms of hemolysis: Jaundice, scleral icterus, change in urine color

• History: Diet Hx (nutritional iron def is the primary cause of microcytic anemia in children), medications (including herbal), birth, growth/development, menstrual hx

• FHx: Eval hemoglobinopathy in African-Americans, Mediterranean region/Southeast Asia

• Exam: Pallor when examining conjunctivae, tongue, palm, nail beds (correlates well with severe dz; 94% sens for Hgb <5/dL); tachycardia or flow murmur; splenomegaly

Diagnostic Studies

• CBC, MCV, MCHC, RDW, retic, hemolysis labs (Coombs, bili, haptoglobin, LDH), smear

• Absolute reticulocyte count = retic% × RBC count/L; Reticulocyte index (to correct for low Hct) = retic% × (patient Hct/Normal Hct) × (1/retic maturation factor) nml 1–2% (<1: Decr pdtn >2: Incr loss)

• Hemoglobin and mean corpuscular volume by age (J Pediatr 1979;94:26)

• Exam: 6 mo MCV nml range 71–94 fL, 18 yo MCV nml range 78–98 fL

• Hgb does not detect early/mild anemia as RBC life span reflects marrow iron content up to 120 d prior; retic Hgb count more accurate due to 1–2 d life span

Microcytic Anemia (Pediatr Rev 2007;28:5; N Engl J Med 1999;341:1986)

• Mentzer index (MCV/RBC): >13 consistent w/ iron def; <13 with β-thal trait

• Iron studies

• Iron deficiency: Decr Iron, incr TIBC, decr ferritin

• Chronic disease: Decr Iron, decr TIBC, incr ferritin

• Thalassemia/lead: Incr nml Iron, decr TIBC, incr ferritin

• Iron deficiency anemia: Most common form of microcytic anemia (Pediatrics 2010; 126:e874). Risk factors: Low SES, premature, low birth wt, lead exposure, exclusive breast-feed over 4 mo without supp, weaning to iron-poor foods, feeding problems

• Requirements: Birth—6 mo 0.27 mg/d; 6–12 mo 11 mg/d; age 1–3yo 7mg/d

• Preterm infants may miss 3rd tri accretion of iron stores; may need 2–4 mg/kg PO daily

• Term infants taking breast milk >50% daily feeds: 1 mg/kg/d oral Fe starting at 4 mo

• Universal screening at 12 mo: Check risk factors and serum Hgb. If + anemia, measure ferritin and CRP levels or retic Hgb conc; OR empirical trial of iron supps (retest Hgb after 1 mo; should incr by 1 g/dL)

• Rx: 6 mg/kg elemental Fe × 6 wk in 2–3 doses, IV Fe in severe def; RBC xfusion

• Vit C increases iron absorption. Tea, phytates (e.g., corn) decr iron absorption (see

AAP statement Pediatrics 2010 for advised foods)

• Typically improvement in retic count in 2–3 d, MCV and Hgb in 1–4 wk

• Anemia of chronic disease: Can be microcytic or normocytic. (N Engl J Med 2005;352:1011); hepcidin (incr w/ inflam) blocks Fe release

• Treat underlying disorder (i.e., epo for renal disease)

Normocytic Anemia (Pediatr Rev 1988;10:77)

• Low retic: Diamond–Blackfan, trans-erythroblastopenia of childhood, aplastic crisis (see

later section on Pure RBC Aplasia)

• High retic: Hemolytic anemias

• Intrinsic: Inh abnl Hgb (for sickle cell & thalassemia see below, unstable Hgb mutations e.g., congenital Heinz body anemia, Hgb Hasharon); abnl RBC membrane (e.g., spherocytosis, elliptocytosis), abnl RBC enzymes (e.g., pyruvate kinase or G6PD deficiency)

• Extrinsic: Autoimmune hemolytic anemia (warm-reactive or cold agglutinin), liver disease, hypersplenism, oxidant agents, microangiopathies, paroxysmal cold hemoglobinuria, paroxysmal nocturnl hemoglobinuria

• Hereditary spherocytosis: ∼75% autosomal dominant, deficient, or abnl membrane structural protein (usually spectrin); splenomegaly, jaundice, chronic anemia; dx: smear, FHx, osmotic fragility

• G6PD deficiency: X-linked, lack of G6PD allows oxidant metabolites of drugs to denature Hgb, acute hemolysis occurs with exposure to sulfa, antimalarials, naphthoquinones, or fava; hemoglobinemia and hemoglobinuria within 24–48 hr of ingestion, self-resolution in 3–4 d

• AIHA: Ab against intrinsic membrane Ag, positive DAT (Coombs); pallor, jaundice,

hemoglobinuria, splenomegaly; may be a/w resp infxn or chronic dz, e.g., SLE or lymphoma

Macrocytic Anemia (Ped Rev 1988;10:77; N Engl J Med 1999;341:1986)

• Vit B12 deficiency: Rare in kids, 2/2 pernicious anemia and ileal disease (Crohns)

• Assoc w/ pancytopenia w/ macrocytosis, hyperseg PMNs

• Exam: Glossitis and decreased vibration and position senses

• Neuro manifestations → can be irreversible if untreated

• Rx: Oral or parenteral Vitamin B12 supplementation

• Folate deficiency: Rare 2/2 incr in folate supplementation for pregnancy

• Found in malabsorption syndromes, EtOH use, chronic hemolysis, drugs (MTX)

• R/o Vit B12 def (folate supps fix RBC parameters; B12 def can be missed)



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