• Definition: Hb, HCT, and/or RBC count <2 SD below age-specific norms
  
• Mechanism: Hemorrhage, hemolysis, ineffective hematopoiesis

Diagnosis

• History and physical exam: Determine if acute or chronic bleeding, detailed diet history (milk intake, iron supplementation [breastfed neonates], folate, vitamin B12), infection, drugs, chemicals (lead ingestion), FHx (G6PD, thalassemia, splenomegaly, autoimmune d/o, bleeding d/o, jaundice), other chronic medical conditions. Check vitals (HR, BP, RR) and plot growth parameters. Perform a CV exam (systolic ejection murmur, gallop, cardiomegaly). Check for hepatomegaly and splenomegaly and signs of hypothyroidism.
  
• Initial lab workup: Primary: CBC, reticulocyte, peripheral smear; Secondary (if hemolysis suspected): Bilirubin, LDH, haptoglobin, UA (urobilinogen).

Classification

Microcytic, Hypochromic Anemia

Iron-Deficiency Anemia

• Presentation: Usually asymptomatic (screen at 6 and 12 mo or found incidentally on CBC); may show pallor and fatigue; ↑ HR. Usually caused by increased cow’s milk intake → which can lead to developmental delay in severe cases.
  
  
  
  • Pathogenesis: Nutritional (child with ↑ milk intake with poor iron content, malabsorption). In adolescents, rapid growth and poor dietary intake or blood loss.
  
  
• Diagnosis: Usually made by history alone with trial of iron supplement, suggested by microcytic anemia on RBC indices, iron studies (see table above).
  
• Treatment: Limit cow’s milk intake to 16 oz/d. Start elemental iron (3–4 mg/kg/day) with a small amount of orange juice; treat until Hb is normal and then continue for 1 mo to replete stores.

Thalassemia:

Macrocytic Anemia

Folate Deficiency

• Presentation: Rare in developed countries secondary to fortified grains and juices; Beefy, red, tongue, oral lesions, angular stomatitis, nausea/vomiting, abdominal pain, diarrhea.
  
• Pathogenesis: Dietary deficiency (infants drinking goat’s milk) or malabsorption, ↑ increased requirement because of high cell turnover or abnormal metabolism (patients taking phenytoin, phenobarbital, methotrexate or trimethoprim-sulfamethoxazole).
  
• Diagnosis: ↓ Folate level (<2 ng/mL is diagnostic; 2–4 ng/mL is equivocal; >4 ng/mL is not deficient). Also check serum cobalamin level.
  
• Treatment: Daily folate until anemia and megaloblastosis are resolved.

Vitamin B12 Deficiency

• Presentation: Diarrhea and weight loss, neurologic symptoms (ataxia and paresthesias).
  
• Pathogenesis: Dietary (child of a breastfeeding mother who is strict vegetarian), children with previous small bowel surgery (eg, NEC, intestinal atresia), ↓ absorption in terminal ileum because of ↓ intrinsic factor (pernicious anemia (pregnancy, lactation, malignancy); very rare in children).
  
• Diagnosis: ↓ Vitamin B12 level; WBC and platelets are often low to low-normal.
  
• Treatment: Vitamin B12 IM or deep SubQ loading dose; then monthly maintenance.

Normocytic, Normochromic Anemia

Red Cell Aplasia

• Transient Erythroblastopenia of Childhood (TEC)
  
  
  
  • Presentation: Later in infancy (usually between age 18–26 mo [range 6 mo–10 yr])
    
  • Pathogenesis: Unknown but likely results from prolonged viral bone marrow suppression
    
  • Diagnosis: Dx of exclusion; low reticulocytes, normal hemoglobin F
    
  • Treatment: Blood transfusion only in cases of hemodynamic compromise; most cases resolve in 2-4 wk.

Hemolytic Anemia

• Autoimmune hemolytic anemias
  
  
  
  • Presentation: Often severe anemia found in the context of another underlying disorder
    
  • Pathogenesis: Varied causes including infection, drugs, lymphoid neoplasm, SLE. Either intravascular coating of RBC by IgM Ab followed by destruction via complement activation, OR extravascular destruction (eg, by macrophages in spleen/liver) of IgG Ab coated RBCs.
    
  • Diagnosis: Positive direct Coombs test result; spherocytes on peripheral smear ↑ bilirubin, LDH
    
  • Treatment: Depends on the underlying cause: supportive care, transfusion, corticosteroids, splenectomy, immunosuppression

Membrane Defects

• Hereditary spherocytosis
  
  
  
  • Presentation: May present as neonatal jaundice; jaundice or dark urine during metabolic or immunologic stress; splenomegaly
    
  • Pathogenesis: AD transmission; defect in spectrin protein
    
  • Diagnosis: Spherocytes on peripheral smear
    
  • Treatment: Folic acid supplementation, RBC transfusion, splenectomy (definitive tx; consider in severe dz)

Intracellular Defects

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  
• Sickle cell disorders

Sickle Cell Disease

• Description: AR inheritance; 8% of African Americans have sickle cell trait (heterozygous); variations cause different severity (SS severity > Sβ0 thalassemia > SC > Sβ+ thalassemia)
  
• Diagnosis: Often identified on NBS or with positive FHx; send hemoglobin electrophoresis.
  
• Presentation: Symptoms occur > 6 mo age; persistence of fetal Hb (>30%) have mild or no.
  
• Secondary manifestations: Gallstones, renal disease, pulmonary hypertension, avascular necrosis, infection, retinopathy (autosplenectomy, 90% by age 6 yr).
  
• Treatment: Prophylactic penicillin VK (start by age 3 mo), folic acid (start by age 1 yr); chronic therapies → simple or partial exchange transfusions of PRBC (goal HbS fraction <30% and goal Hb to no higher than 10 g/dL)), hydroxyurea; stem cell transplant may be an option for patients with a matched sibling.