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Figure 91-1 indicates pathways to a diagnosis of anemia.


Underlying causes for neonatal anemia.

Graphic Jump Location

Blood Loss


  1. Maternal factors

    1. Vaginal bleeding

    2. Abruptio placentae

    3. Placenta previa

  2. Hemorrhage From the Umbilical Cord

    1. Velamentous insertion

    2. Rupture during delivery

    3. Entanglement/nuchal cord

  3. Fetal-fetal transfusion (only in monozygotic multiples)

  4. Fetomaternal hemorrhage

    1. Occurs in 30%–50% of pregnancies although usually with clinically insignificant volumes

    2. Incidence increases with preeclampsia, cesarean section, delayed cord clamping

  5. Birth trauma: extraction, breech, instrumentation

    1. Intracranial hemorrhages (subdural, subarachnoid, or subependymal bleeding)

    2. Caput succedaneum (common)

    3. Cephalohematoma (largest-volume blood loss)

  6. Internal bleeding

    1. Defects in hemostasis

    2. Consumption of coagulation factors from disseminated intravascular coagulation (DIC), sepsis

    3. Congenital factor deficiency

    4. Deficiency of vitamin K-dependent factors (II, VII, IX, X) caused by failure to administer vitamin K after birth or use of antibiotics


Increased Red Blood Cell Destruction/Hemolytic Anemia


Increased red blood cell (RBC) destruction or hemolytic anemia is usually accompanied by reticulocytosis and hyperbilirubinemia.


  1. Extrinsic factors

    1. Immune

      1. Isoimmune hemolytic anemia (warm or cold)

      2. Alloimmune hemolytic disease of the newborn (ABO, Rh or minor blood group antigens)

      3. Drug reaction

    2. Nonimmune/infections

      1. Bacterial

      2. Congenital viral infections

  2. Intrinsic factors/congenital

    1. RBC structural defects

      1. Hereditary spherocytosis

      2. Hereditary elliptocytosis

      3. Hereditary pyropoikilocytosis

    2. RBC enzyme defects

      1. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency

      2. Pyruvate kinase deficiency

    3. Hemoglobinopathies

      1. Quantitative defects (eg, thalassemias α and β)

      2. Qualitative defects (eg, sickle cell syndromes [including hemoglobin SS, SC]), Unstable hemoglobins (>500 variants)

  3. Acquired factors

    1. Iatrogenic blood loss (eg, from surgery, repeated phlebotomy)

    2. Mechanical (eg, extracorporeal membrane oxygenation [ECMO], artificial heart valve)




  1. Acquired

    1. Iron deficiency anemia (supplement in neonates, especially preterm)

    2. Vitamin E deficiency (supplement in neonates receiving intravenous nutrition)

    3. Aplastic anemia (parvovirus B19)

    4. Anemia of prematurity: low reticulocyte count, inadequate response to erythropoietin

    5. Infections (eg, rubella, syphilis)

  2. Congenital

    1. Diamond-Blackfan anemia

    2. Fanconi anemia

    3. Congenital dyserythropoietic anemias

    4. Sideroblastic anemias

    5. Congenital leukemia (usually associated with other hematologic abnormalities)




The clinical workup for anemia in the neonate is shown in Figure 91-2.


Clinical workup for anemia in the neonate. CBC, complete blood cell count; HPLC, high-performance liquid chromatography; MCV, mean corpuscular volume; RBC, red blood cells; R/O, rule out.

Graphic Jump Location

Primary Workup


  1. Hemoglobin

  2. RBC indices

    1. Microcytic or hypochromic suggest fetomaternal or twin-twin hemorrhage or α-thalassemia

    2. Normocytic or normochromic suggest acute hemorrhage, systemic disease, intrinsic RBC defect, or hypoplastic anemia.

  3. Reticulocyte count

    1. Elevation suggests antecedent hemorrhage or hemolytic anemia.

    2. A low count is seen with hypoplastic anemia.

  4. Blood smear looking for

    1. Spherocytes (immune-mediated hemolysis or hereditary spherocytosis)

    2. Elliptocytes (hereditary elliptocytosis)

    3. Pyknocytes (G-6-PD)

    4. Schistocytes (consumption coagulopathy)

  5. Direct Coombs test: positive in isoimmune or autoimmune hemolysis


Secondary Workup



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