Neonatal Anemia

Neonatal Anemia

• Kirsten E. Crowley, MD

• June 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