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DIFFERENTIAL DIAGNOSIS OF ANEMIA

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

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FIGURE 91-1

Underlying causes for neonatal anemia.

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Blood Loss

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  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

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Increased Red Blood Cell Destruction/Hemolytic Anemia

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

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  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)

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Hypoproduction

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  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)

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WORKUP

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

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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
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Primary Workup

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  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

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Secondary Workup

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