Neonatal Anemia

1. Neonatal Anemia Kirsten E. Crowley, MD June 2005

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. Hypoplastic anemia • Congenital • Diamond-Blackfan syndrome, congenital leukemia, sideroblastic anemia • Acquired • Infection: Rubella and syphilis are the most common • Aplastic crisis, aplastic anemia

11. Clinical presentation • Determine the following factors • Age at presentation • Associated clinical features • Hemodynamic status of the infant • Presence or absence of comensatory reticulocytosis

12. 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

13. 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

14. 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

15. Presentation of hypoplastic anemia • Uncommon • Presents after 48 hours of age • Absence of jaundice • Reticulocytopenia

16. 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

17. Diagnosis • Initial studies • Hemoglobin • RBC indices • Microcytic or hypochromic suggest fetomaternal or twin-twin hemorrhage, or a-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

18. 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

19. 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

20. 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%

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

22. 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