Hemolytic disease of the newborn (HDN) is a state in which a maternal antibody passes through the placenta and destruction of red blood cells (RBC) of fetus or newborn . Maternal antibodies are produced by homologous immune responses that are exposed through events such as transfusion or fetomaternal hemorrhage . Hemolysis results in anemia, hyperbilirubinemia, thrombocytopenia, and leukopenia .
The most common cause of HDN is anti-RhD . How-ever, with the use of immunoglobulins against RhD (RhoGAM) in 1965, its frequency is greatly reduced . After introduction of RhD immunoprophylaxis, other antibodies to minor type of RBC antigens such as Kell, Duffy, and Kidd are considered to be the cause of hemolytic diseases [1,2].
In 1951, Kidd blood group, anti-Jka, was described by Allen et al. and 2 years later, Plaut et al. discovered anti-Jkb [3-5]. Anti-Jkb may cause severe hemolytic reaction in transfusion, but HDN by anti-Jkb usually had favorable prognosis .
The authors experienced a case of a newborn which was given an exchange transfusion due to hemolytic disease caused by anti-Jkb.
A male patient was admitted for jaundice at the fourth day of born. He was delivered from a 33-year-old woman with gravida 2, para 1 at 38-weeks and 4-days gestation. The first baby had jaundice but did not need to treat. His mother had anti-Jkb confirmed by serum antibody screen-ing test at the second trimester of pregnancy. Any antibody was not found during the first pregnancy and the first trimester of second pregnancy. There were no history of transfusion and medication.
He had been fed formula milk and 60 to 70 mL every three hours. His icteric skin color was detected at the fourth day of birth, and he visited local hospital and checked total bilirubin level which was 23.1 mg/dL (Reference range: <18 mg/dL). He didn’t have splenomegaly and hepatomegaly. The laboratory data were shown as following at our hospital. The levels of hemoglobin, hematocrit and reticulocyte count were 13.0 g/dL, 39.0%, and 2.19%, respectively. Result of peripheral blood smear was normocytic normochromic RBCs, and WBC and platelet count were in within the normal limit. The result of direct antiglobulin test was IgG positive (2+), and indirect antiglobulin test negative. The results of aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, and direct bilirubin levels were 39 U/L, 16 U/L, 25.02 mg/dL, and 1.68 mg/dL, respectively. His blood type was A, RhD positive, and mother’s blood type was A, RhD positive, too. Irregular antibody was detected in his serum, but we could not identify a specific anti-body. It was only assumed that the irregular antibody was Jkb antibody because it was found in the mother’s blood (Table 1).
Although we immediately started intensive phototherapy and fluid therapy, the level of total bilirubin was elevated up to 30.2 mg/dL. We decided to do exchange transfusion for resolving hyperbilirubinemia avoiding kernicterus. Exchange transfusion was done successfully without complications. After exchange transfusion, total bilirubin level was decreased to 8.79 mg/dL. Blood tests were conducted on the next day and showed moderate anemia (hemoglobin 8.1 g/dL) and hyperbilirubinemia (total bilirubin 13.01 mg/dL). Irradiated and filtered RBC transfusion (10 mL/kg, over 3 hours) was carried out. He was subsequently discharged from the hospital after confirmed without further hemolytic reaction and hyperbilirubinemia (total bilirubin 6.0 mg/dL) on the 8th day of hospitalization. Auditory brainstem response was normal and brain MRI findings are a cystic change of germinal matrix hemorrhage grade I, which is thought to be rarely related with jaundice and exchange transfusion.
After discharge, IgG titer in direct antiglobulin test was monitored at outpatient department, which was decreased gradually and became negative for one month of age.
The International Society of Blood Transmission (ISBT) introduces a total of 36 blood group systems and 322 antigens . Among them, Kidd blood group is the ninth . The Kidd Blood group consists of three antigen, Jka, Jkb, and Jk3, with four phenotypes, Jk(a+b+), Jk(a-b+), Jk(a+b−), and Jk(a−b−) . Antigens are located on the RBC’s urea transporter, UT-B glycoprotein . Kidd glycoprotein as a urea transporter has no significant clinical significance, but only two cases have been reported that showed mild urine-concentrating defects in the Jk (a−b−) phenotype . However, if an antibody is developed due to the sensitization of Kidd antigen, it is known that severe hemolytic transfusion reaction can occur . Therefore, an antigen-negative RBC must be used for transfusions. However, even if antibodies are formed, it is difficult to detect because the antibody’s level decreases rapidly, so sensitive methods such as enzyme indirect antiglobulin tests may be required .
Most of the pathways exposed to Kidd antigen are transfusions and are known to cause immediate and delayed hemolytic transmission reactions during transfusions . However, since the antibody is IgG, it can cross through the placenta and cause hemolysis, but it is known that it is rarely sensitized .
In this case, any antibodies were not identified during the first pregnancy and until the first trimester of the second pregnancy, but anti-Jkb was identified in the second trimester of that. The mother had no history of transfusion, and the path of antigen exposure from outside was unclear. Supposedly, the first baby had Jkb antigen positive RBC, and during pregnancy or delivery, the mother was sensitized by the first baby’s RBC to produce anti-Jkb. Antibody that formed during the first pregnancy was transmitted to the patient through the placenta, causing hemolysis. The irregular antibody identified in the serum of the patient is likely to be anti-Jkb delivered from the mother, but it did not be confirmed by laboratory test because of the characteristics of Kidd antibody which level is quickly reduced and difficult to detect . It is assumed that jaundice in the first baby was also a weak antibody reaction. We also think that the analysis of the first baby’s RBC surface antigens is necessary to support the above. However mother didn’t want to take blood sample to detect the first baby’s phenotype. We just performed antigen tests attached to RBCs with the patient’s blood, and Jkb antigen was confirmed to be positive. Therefore, we were able to determine that the mother’s Jkb antibody was the cause of hemolysis in the patient (Table 1).
So far, only 13 cases of hemolysis have been reported in newborns by anti-Jkb . Most of them improved with phototherapy or without treatment, but there were rare fatal cases (Table 2) [7-19]. In this case, there was no indication that the prepartum examination would suggest the hemolysis of the fetus, such as hydrops fetalis, fortunately. In addition, symptoms such as jaundice and anemia were not shown immediately after birth. But jaundice occurred from the fourth day of birth, and the exchange transfusion was carried out because it did not improve due to phototherapy. The past history of the mother’s exposure to Kidd antigen was not clear, but it was discovered incidentally on antibody screening test during second trimester of pregnancy. However jaundice and anemia symptoms were not prominent after birth, he was discharged without any special management on the 3rd day of birth. In order to prediction and early treatment of HDN, we recommend that a screening test of unexpected antibody for mother should be conducted thorough prepartum examination even if the mother does not have a special past history, especially the first baby had past medical history of neonatal jaundice. It is also necessary to clarify the etiology of neonatal jaundice excluding physiologic jaundice.
The authors have no conflict of interest to declare.