A full term female baby, with a birth weight of 2.24 kg presented with yellowish discoloration of eyes and skin at 18 hours of life. Antenatally, there was no evidence of fetal anemia or hydrops fetalis. On examination, baby had icterus till palms and soles but mental status, cry and muscle tone were normal. Baby was started on intensive phototherapy. Blood group was O positive in both the mother and the baby. Laboratory investigations showed total serum bilirubin (TSB) of 24 mg/dL with direct bilirubin (DB) of 2.72 mg/dL, reticulocyte count of 24%, direct Coomb test (DCT) of 3+, and hemoglobin of 8.2 g/dL. Peripheral smear was suggestive of hemolysis with macrocytes, microcytes, spherocytes and polychromasia with nucleated RBC.

In view of strongly positive DCT and no Rh negative or ABO setting and minor blood group incompatibility was done. The results of antibody testing for screening tests revealed the presence of multiple alloantibodies (anti-Rh17) in maternal serum. The Rh-kell antigenic phenotyping of the family members were as follows: Mother (blood group O, D+, C-, c-, E-, e-, K- (i.e D–), index case (blood group O, D+, C+ c-, E-, e+, K-), father (D+, C+ c-, E-, e+, K-) and sibling (D+, C+, c-, E+, e-, K+).

Baby was treated with intensive phototherapy and 1 g/kg of intravenous immunoglobulin (IVIG). Due to this rare variety of blood group, cross matching was not compatible with the available blood in various blood banks despite extensive search. By 30 hours of age, serum bilirubin reduced to 13 mg/dL and was out of exchange transfusion zone. Baby had rebound hyperbilirubinemia, probably due to mild hemolysis by persisting antibodies, and required intensive phototherapy on day 15 of life, and was discharged on day 19 of life. At discharge, parents were advised for regular follow-up for jaundice and anemia, and also counselled regarding the need of anti-Rh 17 antibody titers in next pregnancy, and periodic monitoring for fetal anemia and possible need of intrauterine transfusion.

The Rh blood group system is inherited as group of Rh D and Rh CE genes located on chromosome 1 [1,2]. Based on the expression of the major D antigen on their RBCs, typing as Rh positive or negative is done. RBCs also express C or c, E or e antigens. Rh deletion of C/c and E/e loci can rarely occur leading to D– blood group phenotype [4].

The mother’s RBC Rh-kell phenotyping was (D–). Individuals with D– phenotype produce multiple Rh alloantibodies known as anti-Rh17 or Anti-Hro antibodies against C,c,E,e antigens if there is a history of sensitization such as childbirth (fetomaternal hemorrhage) or transfusion with red blood cells that express C/c or E/e antigens [3]. Anti-Rh 17 antibody is an antibody against Hro (Rh17) antigen and is produced in persons lacking any Rh group antigens except D antigen [4].

The Rh-kell phenotype of the index case suggested that the possible antibodies leading to hemolysis were anti-C and anti-e. The management of anti Rh-17 isoimmunization is similar to the management of Rh D isoimmunization including antenatal monitoring, intrauterine transfusion, use of IVIG and exchange transfusion, with a specification that blood used for fetal or neonatal transfusion should be Rh17 antigen negative blood [3]. However, it may be extremely difficult to get compatible or antigen negative red cells for transfusion. A recent review of case reports showed that most of the cases were managed by exchange transfusion, with or without intra uterine transfusion, with very few cases managed by phototherapy alone [5]. They also recommend the first choice of blood that needs to be used in these neonates is washed and irradiated mothers’ RBCs. If this is not available, then blood of relatives of pregnant woman, usually siblings, can be used. Other options include storage of woman’s blood by freezing the RBCs before pregnancy or use of blood from blood banks where this blood is stored.

This case highlights the importance of considering isoimmunization due to other Rh antigens as an important cause of hemolytic disease of newborn.

1. Mina SS, Bhardwaj R, Gupta S. Hemolytic disease of newborn: Can think beyond Rh (D) and ABO incompatibilities. J Clin Neonat. 2017;6:37-39.

2. Landsteiner K, Wiener A. An agglutinable factor in human blood recognized by immune sera for rhesus blood. Proc Soc Exp Bio Med. 1940;43:223-223.

3. Choobdar AF, Milani H, Behrouzi K, et al. Anti-Rh17 allo immunization: A rare case of severe hemolytic disease of the newborn and review of the literature. J Pediatr Rev. 2020;8:29-34.

4. Mario. E, Oyen RR, Morsh WL. Summary of the clinical significance of blood group alloantibodies. Sem Hematol. 2000;37:197-216.

5. Dajak S, Ipavec N, Cuk M, et al. The outcome of hemolytic disease of the fetus and newborn caused by anti-rh17 antibody: Analysis of three cases and review of the literature. Transfus Med Hemother. 2020;47:264-71.