Neonatal Anemia

Kirsten E. Crowley, MDJune 2005

Definitions• Anemia: Central venous hemoglobin < 13

g/dL or capillary hemoglobin < 14.5 g/dL in infant > 34 weeks and 0-28 days old

• Average value for central venous hemoglobin at birth for > 34 weeks GA is 17 g/dL

• Reticulocyte count in cord blood 3-7%• Average mean corpuscular volume 107 fL

Physiologic anemia of infancy

• In healthy term infants, hemoglobin levels begin to decline around the third week of life

• Reach a nadir of 11 g/dL at 8-12 weeks

Differences in premature infants• At birth they have slightly lower

hemoglobin levels, and higher MCV and retic counts

• The nadir is lower and is reached sooner– Average nadir is 7-9 g/dL and is reached at 4-8

weeks of age– Related to a combination of decreased RBC

mass at birth, increased iatrogenic losses from lab draws, shorter RBC life span, inadequate erythropoietin production, and rapid body growth

Pathophysiology

• Anemia in the newborn results from three processes– Loss of RBCs: hemorrhagic anemia

• Most common cause

– Increased destruction: hemolytic anemia

– Underproduction of RBCs: hypoplastic anemia

Hemorrhagic anemia• Antepartum period (1/1000 live births)

– Loss of placental integrity• Abruption, previa, traumatic amniocentesis

– Anomalies of the umbilical cord or placental vessels

• Velamentous insertion of the cord in twins, communicating vessels, cord hematoma, entanglement of the cord

– Twin-twin transfusion syndrome• Only in monozygotic multiple births• 13-33% of twin pregnancies have TTTS• Difference in hemoglobin usually > 5 g/dL• Congestive heart disease common in anemic twin and

hyperviscosity common in plethoric twin

Hemorrhagic anemia• Intrapartum period

– Fetomaternal hemorrhage (30-50% of pregnancies)

• Increased risk with preeclampsia-eclampsia, need for instrumentation, and c-section

– C-section: anemia increased in emergency c-section

– Traumatic rupture of the cord– Failure of placental transfusion due to cord

occlusion (nuchal or prolapsed cord)– Obstetric trauma causing occult visceral or

intracranial hemorrhage

Hemorrhagic anemia• Neonatal period

– Enclosed hemorrhage: suggests obstetric trauma or severe perinatal distress

• Caput succedaneum, cephalhematoma, intracranial hemorrhage, visceral hemorrhage

– Defects in hemostasis• Congenital coagulation factor deficiency• Consumption coagulopathy: DIC, sepsis• Vitamin K dependent factor deficiency

– Failure to give vit K causes bleeding at 3-4 days of age• Thrombocytopenia: immune, or congenital with

absent radii

– Iatrogenic blood loss due to blood draws

Hemolytic anemia• Immune hemolysis: Rh incompatibility or

autoimmune hemolysis• Nonimmune: sepsis, TORCH infection• Congenital erythrocyte defect

– G6PD, thalassemia, unstable hemoglobins, membrane defects (hereditary spherocytosis, elliptocytosis)

• Systemic diseases: galactosemia, osteopetrosis

• Nutritional deficiency: vitamin E presents later

Hypoplastic anemia

• Congenital – Diamond-Blackfan syndrome,

congenital leukemia, sideroblastic anemia

• Acquired– Infection: Rubella and syphilis are the

most common– Aplastic crisis, aplastic anemia

Clinical presentation

• Determine the following factors– Age at presentation– Associated clinical features– Hemodynamic status of the infant– Presence or absence of comensatory

reticulocytosis

Presentation of hemorrhagic anemia• Acute hemorrhagic anemia

– Pallor without jaundice or cyanosis and unrelieved by oxygen

– Tachypnea or gasping respirations– Decreased perfusion progressing to

hypovolemic shock• Decreased central venous pressure

– Normocytic or normochromic RBC indices– Reticulocytosis within 2-3 days of event

Presentation of hemorrhagic anemia

• Chronic– Pallor without jaundice or cyanosis and

unrelieved by oxygen– Minimal signs of respiratory distress– Central venous pressure normal– Microcytic or hypochromic RBC indices– Compensatory reticulocytosis– Enlarge liver d/t extramedullary

erythropoiesis– Hydrops fetalis or stillbirth may occur

Presentation of hemolytic anemia

• Jaundice is usually the first symptom• Compensatory reticulocytosis• Pallor presents after 48 hours of age• Unconjugated hyperbilirubinemia of >

10-12 mg/dL• Tachypnea and hepatosplenomegaly

may be present

Presentation of hypoplastic anemia

• Uncommon• Presents after 48 hours of age• Absence of jaundice• Reticulocytopenia

Presentation of other forms• Twin-twin transfusion

– Growth failure in the anemic twin, often > 20%

• Occult internal hemorrhage– Intracranial: bulging anterior fontanelle and

neurologic signs (altered mental status, apnea, seizures)

– Visceral hemorrhage: most often liver is damaged and leads to abdominal mass

– Pulmonary hemorrhage: radiographic opacification of a hemithorax with bloody tracheal secretions

Diagnosis• Initial studies

– Hemoglobin– RBC indices

• Microcytic or hypochromic suggest fetomaternal or twin-twin hemorrhage, or -thalassemia

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

– Reticulocyte count• elevation suggests antecedent hemorrhage or

hemolytic anemia while low count is seen with hypoplastic anemia

Diagnosis

• Initial studies continued– Blood smear looking for

• spherocytes (ABO incompatibility or hereditary spherocytosis)

• elliptocytes (hereditary elliptocytosis)• pyknocytes (G6PD)• schistocytes (consumption coagulopathy)

– Direct Coombs test: positive in isoimmune or autoimmune hemolysis

Other diagnostic studies• Blood type and Rh in isoimmune hemolysis• Kleihauer-Betke test on maternal blood looking

for fetomaternal hemorrhage• CXR for pulmonary hemorrhage• Bone marrow aspiration for congenital

hypoplastic or aplastic anemia• TORCH: bone films, IgM levels, serologies,

urine for CMV• DIC panel, platelets looking for consumption• Occult hemorrhage: placental exam, cranial or

abdominal ultrasound• Intrinsic RBC defects: enzyme studies, globin

chain ratios, membrane studies

Management• Simple replacement transfusion

– Indications: • acute hemorrhage

– Use 10-15 ml/kg O, RH- packed RBCs or blood cross-matched to mom and adjust hct to 50%

– Give via low UVC or central UVC if time permits– Draw diagnostic studies before transfusion

• ongoing deficit replacement• maintenance of effective oxygen-carrying capacity

– Hct < 35% in severe cardiopulmonary disease– Hct < 30% in mild-moderate cardiopulmonary

disease, apnea, symptomatic anemia, need for surgery

– Hct < 21%

Management

• Exchange transfusion– Indications

• Chronic hemolytic anemia or hemorrhagic anemia with increased central venous pressure

• Severe isoimmune hemolytic anemia• Consumption coagulopathy

• Nutritional replacement: iron, folate, vitamin E

Prophylactic management• Erythropoietin

– Increased erythropoiesis without significant side effects

– Decreases need for late transfusions– Will not compensate for anemia due to

labs• Need to have restrictive policy for blood

sampling and micromethods in the lab

• Nutritional supplementation: iron, folate, vitamin E