| Neonatal7 |
| Blood loss | Hemorrhage (placental abruption, subgaleal, traumatic); maternal-fetal and twin-twin transfusion | Tachypnea, pallor, and mental status change (irritability, poor feeding); > 20 percent loss of blood volume results in shock and cardiopulmonary collapse | Anemia with normal indices; reticulocyte count is initially normal, then increases; positive Kleihauer-Betke test in maternal-fetal hemorrhage |
| Accounts for 5 to 10 percent of all cases of severe neonatal anemia |
| Isoimmunization | ABO incompatibility, Rh incompatibility | Jaundice and mild anemia; infants with severe isoimmunization (e.g., untreated Rh incompatibility) may present with hydrops fetalis | Positive Coombs test; elevated bilirubin level; normocytic anemia with elevated reticulocyte count |
| Rh incompatibility occurs in 10.6 per 10,000 live births; 50 percent of these infants develop anemia |
| Congenital hemolytic anemia | Spherocytosis, G6PD deficiency | Hyperbilirubinemia and moderate jaundice | Low enzyme activity; with hemolysis, smear may show poikilocytosis, reticulocytosis, Heinz bodies, and bite cells (in G6PD deficiency) or spur cells (in pyruvate kinase deficiency) |
| Congenital infection | Parvovirus B19, human immunodeficiency virus, syphilis, rubella, sepsis | Pallor, irritability, and other findings associated with infection (e.g., deafness) | Normocytic anemia with low reticulocyte count |
| Diamond-Blackfan syndrome | Congenital pure red cell aplasia resulting from increased apoptosis in erythroid precursors | Neonatal pallor progressing to symptomatic anemia; average age of diagnosis is 3 months; about 30 percent have other abnormalities | Macrocytic anemia with low reticulocyte count |
| Affects 7 per 1 million live births |
| Fanconi anemia | Increased susceptibility of progenitor cells in bone marrow leads to increased apoptosis, progressing to pancytopenia | Average age of diagnosis is 8 years, but associated congenital abnormalities may facilitate early diagnosis (e.g., café-au-lait spots; microsomy; low birth weight; thumb, renal, skeletal, and eye abnormalities) | Microcytic anemia and reticulocytopenia, thrombocytopenia, or leukopenia; DNA sequencing can detect genetic mutations for Fanconi anemia complementation groups |
| Infancy to toddlerhood2 |
| Iron deficiency | Inadequate dietary intake, chronic occult blood loss (excessive cow's milk consumption, inflammatory bowel disease, Meckel diverticulum, parasites) | Usually asymptomatic; severe cases can present with fatigue, pallor, or dyspnea; rarely occurs before 6 months of age; highest risk is at 6 to 36 months of age | Microcytic anemia with elevated RBC distribution width; peripheral smear shows hypochromic microcytes and may show target cells; iron and ferritin levels and iron saturation are low; transferrin level is elevated |
| Prevalence is 8 to 15 percent |
| Concurrent infection | Bacterial or viral infection leading to cytokine-mediated decrease in iron utilization and RBC production | Presenting symptoms usually result from infectious process | Normocytic or mildly microcytic, low/normal serum iron level with low transferrin level; ferritin level may be elevated because it is an acute phase reactant |
| Blood loss | Trauma, gastrointestinal bleeding | Tachypnea, tachycardia, pallor, hypotension | Hgb levels may initially be normal, followed by anemia with normal indices |
| Disorder of Hgb structure or synthesis | Thalassemia, sickle cell disease | Anemia in thalassemia may range from mild and asymptomatic to severe, depending on number of heme chains affected; sickle cell disease presents with hemolysis, pain crises, dactylitis, and aplastic crisis; symptoms are rarely present at birth but typically develop in the first year | Microcytic anemia, low RBC distribution width, and low Mentzer index in thalassemia; Hgb electrophoresis may show Hgb F; smear with basophilic stippling; hemolysis, reticulocytosis, and Hgb S on electrophoresis in sickle cell disease |
| RBC enzyme defects | G6PD deficiency, pyruvate kinase deficiency | Neonatal hyperbilirubinemia and hemolytic anemia when exposed to oxidative stress | Low enzyme activity; with hemolysis smear may show poikilocytosis, reticulocytosis, Heinz bodies, and bite cells (in G6PD deficiency) or spur cells (in pyruvate kinase deficiency) |
| 10 percent of the black population has G6PD deficiency |
| RBC membrane defects | Spherocytosis, elliptocytosis | Hyperbilirubinemia, splenomegaly, gall bladder disease, and aplastic crisis; autosomal dominant, so family history is positive in about 75 percent of patients | Macrocytosis, reticulocytosis, elevated bilirubin and lactate dehydrogenase levels; spherocytes or elliptocytes on smear; osmotic fragility test is commonly done but not specific |
| Acquired hemolytic anemias | Antibody-mediated hemolysis, drug-induced hemolysis, hemolytic uremic syndrome, disseminated intravascular coagulation | Jaundice, fatigue, dyspnea | Positive Coombs test and spherocytes visible on smear in antibody-mediated hemolysis; schistocytes visible on smear in hemolytic uremic syndrome or disseminated intravascular coagulation |
| Transient erythro-blastopenia of childhood | Transient immune reaction against erythroid progenitor cells | Anemia after toxin ingestion or viral illness, usually in children 6 months to 3 years of age | Normocytic anemia, initially with reticulocyte count of 0; anemia resolves within 2 months |
| Leukemia, myelofibrosis | Usually spontaneous, but rates are increased in patients with prior radiation exposure or chemotherapy | Anemia causes pallor, fatigue, and dyspnea; patients with leukemia may present with petechiae, low-grade fever, nonspecific bone pain, gum swelling, or rash | Normocytic anemia with decreased reticulocyte count; leukopenia, leukocytosis, or thrombocytopenia; peripheral smear shows blast cells |
| Lead poisoning | Risk factors include young age, living in a home built before 1970 or in areas where soil is contaminated, and pica (as in iron deficiency) | In addition to anemia, patients may present with abdominal pain, altered mental status, renal disease, and hypertension | Microcytic anemia may be concurrent with iron deficiency; peripheral smear may show basophilic stippling; hemolysis may be present |
| Late childhood and adolescence2 |
| Iron deficiency | Second peak in iron deficiency occurs in adolescence because of growth spurt, menstruation, and poor dietary iron intake | Pallor, fatigue, dyspnea | Same as for infants and toddlers, above |
| Chronic disease | Renal disease, liver disease, hypothyroidism, other chronic illnesses | Usually mild and asymptomatic | Normocytic or mildly microcytic, low/normal serum iron level with low transferrin level; ferritin level may be elevated because it is an acute phase reactant |
| Blood loss | Same as for infants and toddlers, above |
| Menstruation in adolescent girls |
| Disorders of Hgb synthesis or RBC membrane defects | Same as for infants and toddlers, above |
| Acquired hemolytic anemias | Same as for infants and toddlers, above |
| Leukemia and other bone marrow disorders | Same as for infants and toddlers, above |