HEMOLYTIC DISEASE OF NEWBORNS

History: Women at risk for alloimmunization should undergo an indirect Coombs test and titers at their first prenatal visit. If positive, obtain a paternal blood type and genotype. Obtain serial maternal titers if the father is homozygous. If the father is heterozygous, determine fetal blood type by using polymerase chain reaction testing of fetal cells in amniotic fluid or maternal circulation or by performing cordocentesis. Indicators for severe HDN are previous children with hemolytic disease, rising maternal antibody titers, rising amniotic fluid bilirubin concentration, and ultrasonographic evidence of fetal hydrops (eg, ascites, edema, pleural and pericardial effusions, worsening biophysical profile, decreasing hemoglobin [Hb]).

The major advance in predicting the severity of hemolytic disease was the delta-OD 450 reported by Liley in 1961. The serial values of deviation from baseline at 450 nm and the wavelength at which bilirubin absorbs light are plotted on a Liley curve against the gestational weeks. The values above 65% on zone 2 are indication of direct fetal monitoring by cordocentesis, and hematocrit (Hct) below 30% or a single value in zone 3 is an indication for intrauterine transfusion. The modified Liley curve is used to correct for gestation less than 24 weeks because bilirubin levels normally peak at 23-25 weeks' gestation for unaffected fetuses.

Physical: The infant born to an alloimmunized mother shows clinical signs based on severity of the disease. The typical diagnostic findings are jaundice, pallor, hepatosplenomegaly, and hydrops fetalis in severe cases. The jaundice typically manifests at birth or in the first 24 hours after birth with rapidly rising unconjugated bilirubin level. Occasionally, conjugated hyperbilirubinemia is present because of placental or hepatic dysfunction in those infants with severe hemolytic disease. Anemia is most often due to destruction of antibody-coated RBCs by the reticuloendothelial system, and in some infants, anemia is due to intravascular destruction. The suppression of erythropoiesis by intravascular transfusion of adult Hb to an anemic fetus can also cause anemia. Hepatosplenomegaly results from extramedullary hematopoiesis and leads to portal hypertension, contributing to ascites. Anemia is not the only cause of hydrops. Excessive hepatic extramedullary hematopoiesis causes portal and umbilical venous obstruction and diminished placental perfusion because of edema. Increased placental weight and edema of chorionic villi interfere with placental transport. Hydrops fetalis results from fetal hypoxia, anemia, congestive cardiac failure, and hypoproteinemia secondary to hepatic dysfunction. Commonly, hydrops is not observed until Hb drops below approximately 4 g/dL (Hct <15%). Clinically significant jaundice occurs in up to 20% of ABO-incompatible infants.

Causes: In the absence of a positive direct Coombs test result, other causes of pathologic jaundice should be considered, including intrauterine congenital infections; erythrocyte membrane defects; RBC enzyme deficiencies; and nonhemolytic causes, such as enclosed hemorrhages, hypothyroidism, gastrointestinal obstruction, and metabolic diseases. Similarly, hydrops can occur from nonimmune hematologic disorders causing anemia, cardiac failure from dysrhythmia, congenital heart defects, and infections (eg, syphilis, cytomegalovirus [CMV], Parvovirus).
• Common causes for HDN
o Rh system antibodies
o ABO system antibodies

• Uncommon causes - Kell system antibodies

• Rare causes
o Duffy system antibodies
o MNS and s system antibodies
• No occurrence in HDN : Lewis system antibodies and P system antibodies