Raniah Al Amri, MD and Alesia Kaplan, MD
A 20-30 year old female, gravida 2, para 1 who presented for follow up of an established pregnancy. The patient denied any symptoms, and has no history of prior blood transfusion or other significant medical history. She has one healthy child from the same marriage. The husband is healthy. Upon current pregnancy workups, including routine blood type and screen, the mother's blood group was found to be AB Rh positive with a positive antibody screen. Anti-Jka antibodies were identified with antihuman globulin (AHG) phase titers of 1:8. The mother was phenotyped and she is Jka negative. The father of the baby (FOB) was phenotyped and he is homozygous for Jka (Jka+Jkb-). The predicted phenotype of the baby is Jka+Jkb+.
The patient was followed by maternal-fetal medicine (MFM) with monthly anti-Jka titers and at 20 weeks of gestation, her Jka titer was 1:64. This result indicated a significant increase from the previous 1:8 titer.
The Kidd protein (Jk antigen) is one of the blood group systems, located on chromosome 18 (18q11-q12). It is a trans-membrane multi-pass protein that transports urea across red blood cells (RBCs) membrane, help maintain osmotic stability and normal erythrocyte shape.
Kidd glycoprotein has three antigens, that are exclusively expressed on RBCs and kidneys, Jk1(a), Jk2(b) and Jk3; with three common Kidd phenotypes JK(a+b-), JK(a-b+), JK(a+b+), and a fourth null Jk (a-b-) phenotype that is exceedingly rare. The glycoprotein carrying the kidd antigens is made of 389- amino acid protein. Jka and Jkb antigens differ by a single nucleotide polymorphism resulting in aspartate and asparagine amino acids, respectively at the 280 amino acid position (Figure 1) (1).
Kidd antigen expression have been studied and reported in different ethnic groups without significant differences detected in phenotypic frequencies between White and Asian population, however Black population tend to express higher frequencies of Jka with a reciprocal lower frequencies of Jkb compared to other ethnic groups (Table 1) (1). Overall, given the common prevalence of Jk antigens in different ethnic groups, blood supply for Jka or Jkb negative blood is considered generally accessible, and this is in contrast to the difficulties in blood supply of the rare null Jk phenotype (a-b-).
Antibodies against any of the Kidd antigens are known to cause severe hemolytic transfusion reaction, especially delayed hemolytic reactions (DHTRs) and occasionally hemolytic disease of the fetus and newborn (HDFN).
Hemolytic disease of the fetus and newborn is a condition characterized by destruction of the fetus red blood cells via transplacental transmission of maternal alloantibodies. Majority of cases are due to ABO incompatibility or anti-D antibodies. However, kidd system antibodies are usually of IgG type, thus have the ability to cross the placenta and destroy the fetal red blood cells causing mild to severe HDFN as well. They can disappear or become undetectable (~50%) in between pregnancies or transfusions, however their strong amnestic response can lead to severe HDFN or persistent anemia in the infant (2)
Up to date, there are few reported cases in the literature on HDFN associated anti-Jka and most of these cases are mild, managed supportively with close observation or phototherapy and rarely requiring exchange transfusion (Figure 2) (2)
The mother is Jka - and the father is homozygous for Jka+. The mother had a previous pregnancy with the same FOB and most likely was immunized at that point. In the past the standard assessment of fetal anemia was by quantification of the amniotic fluid bilirubin levels through amniocentesis which carries a risk of spontaneous miscarriage and amniotic fluid leakage (3). At present, middle cerebral artery dopplers (MCA) peak systolic velocity (PSV) has emerged as the best tool for non-invasive determination of the fetal anemia with a 100% sensitivity of an increase in MCA-PSV (above 1.5 multiples of the median [MoMs]) for the prediction of moderate or severe anemia with potential early delivery in elevated middle cerebral artery (MCA) flow velocities (4)
In accordance, our patient was offered a regular weekly/biweekly MCA-PSV measurement with a possibility of percutaneous umbilical blood sampling (PUBS) and intrauterine transfusion if persistent fetal anemia was confirmed by a peak systolic flow is >1.5 MoM.
We recommend ABO/Rh typing and DAT for the baby after birth, antibody screen of a sample from the mother or baby, close monitoring of the Hgb and bilirubin levels. If transfusion or whole blood exchange is required, Jka negative RBC units should be provided. Consequently, if the mother needs any RBC transfusions in the future, Jka negative crossmatch compatible RBCs will be provided.