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

2. Definitions Anemia: Central venous hemoglobin 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  -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