In the absence of a positive Coombs test and blood group differences between the mother and fetus, other causes of non-immune hemolysis must be considered. RBC enzyme assays, hemoglobin electrophoresis, or RBC membrane tests (osmotic fragility, spectrin assay) should be performed. Internal hemorrhage also may be associated with anemia, reticulocytosis, and jaundice when the hemorrhage reabsorbs; ultrasound evaluation of the brain, liver, spleen, or adrenal gland may be indicated when nonimmune hemolysis is suspected. Shock is more typical in patients with internal hemorrhage, whereas in hemolytic diseases, heart failure may be seen with severe anemia. Evaluation of a possible fetal-maternal hemorrhage should include the Kleihauer-Betke test.
The treatment of symptomatic neonatal anemia is transfusion of cross-matched packed RBCs. If immune hemolysis is present,the cells to be transfused must be cross-matched against maternal and neonatal plasma. Acute volume loss may necessitateresuscitation with nonblood products, such as saline if bloodis not available; packed RBCs can be given subsequently. Tocorrect anemia and any remaining blood volume deficit, 10 to15 mL/kg of packed RBCs should be sufficient. Cytomegalovirus-seronegative blood should be given to cytomegalovirusseronegative infants, and all blood products should be irradiatedto reduce the risk of graft-versus-host disease; blood should bescreened for HIV, hepatitis B and C, and syphilis. Recombinanterythropoietin may improve the hematocrit in infants with ahyporegenerative anemia after in utero transfusion.
Hemolytic disease of the newborn is a common cause of neonatal jaundice. Nonetheless, because of the immaturity of the pathways of bilirubin metabolism, many newborn infants without evidence of hemolysis become jaundiced.
Bilirubin is produced by the catabolism of hemoglobin in the reticuloendothelial system. The tetrapyrrole ring of heme is cleaved by heme oxygenase to form equivalent quantities of biliverdin and carbon monoxide. Because no other biologic source of carbon monoxide exists, the excretion of this gas is stoichiometrically identical to the production of bilirubin. Biliverdin is converted to bilirubin by biliverdin reductase. One gram of hemoglobin produces 35 mg of bilirubin. Sources of bilirubin other than circulating hemoglobin represent 20% of bilirubin production; these sources include inefficient (shunt) hemoglobin production and lysis of precursor cells in bone marrow. Compared with adults, newborns have a twofold to threefold greater rate of bilirubin production (6 to 10 mg/kg/24 hr versus 3 mg/kg/24 hr). This increased production is caused, in part, by an increased RBC mass (higher hematocrit) and a shortened erythrocyte life span of 70 to 90 dayscompared with the 120-day erythrocyte life span in adults.