Intrauterine Transfusion Navigates Severe Fetal Anemia due to Anti-Jkb

Introduction The Kidd (JK) blood group system comprises the Jka, Jkb and Jk3 antigens. The Kidd antigens commonly cause typical acute hemolytic transfusion reactions but also cause delayed hemolytic transfusion reactions due to the strong anamnestic response. Jkb antibodies can result in hemolytic disease of the newborn (HDN) but rarely lead to severe fetal anemia.1 We report a successful case of severe early intrauterine anemia (23 g/L, 22 weeks gestation) caused by Jkb antibodies with a good pregnancy outcome after three intrauterine transfusions (IUTs). Clinical observation A 21-year-old parous female (gravida 2, para 1) without a history of blood derivative transfusion presented to Shenzhen Maternity and Child Healthcare Hospital for clinical treatment because of fetal hydrops at 22+2 weeks gestation. Her first daughter was 3 years old and was born at term with no complications. Ultrasound revealed that the middle cerebral artery-peak systolic velocity (MCA-PSV) was 55.51 cm/s (1.97 MoM), and the manifestations of fetal hydrops included subcutaneous edema, hydropericardium and seroperitoneum. Based on the smoothly executed percutaneous umbilical blood sampling, the fetal blood type was A RhD (+) (the same as that in the gravida), the hemoglobin (Hb) level was 16 g/L, and the hematocrit (HCT) level was 5.3%. Hemoglobin electrophoresis revealed no Bart’s peaks, which ruled out alpha thalassemia. The test result to identify irregular antibodies in the maternal serum was negative. There were no abnormalities in the fetal chromosome karyotype, chromosome microarray, pathogen in utero (including human parvovirus B19), or thalassemia genes. This study was approved by the Shenzhen Maternity and Childcare Hospital Medicine Ethics Committee (No. 2018-280). The research was conducted ethically, with all study procedures performed according to the requirements of the World Medical Association’s Declaration of Helsinki. Written informed consent was obtained from the patient for study participation and data publication. Treatment and prognosis IUTs with A RhD (+) de-white suspension of irradiated red blood cells (RBCs) were successively conducted at 22+6 weeks of gestation, 23+3 weeks of gestation, and 26+2 weeks of gestation (Table 1). Regular fetal monitoring was performed by incorporating MCA-PSV weekly until 32 weeks of gestation. Fetal hydrops disappeared completely at 28 weeks of gestation. The mother underwent lower segment cesarean section due to malpresentation at 37+6 weeks of gestation and gave birth to a male infant weighing 3510 g with APGAR scores of 8-10-10. The neonate was admitted to the neonatal intensive care unit. His Hb level was 113 g/L, and his HCT was 37% at birth. He was treated with phototherapy for hemolytic icterus and was discharged 10 days later without a blood transfusion after birth. The neonate’s direct antiglobulin test (DAT) result was strongly positive, and anti-Jkb was detected in the eluate. Anti-Jkb was also detected in the maternal serum, which was negative before intrauterine transfusion (IUT). The genotype of the mother was Jka+/Jkb–, and the genotype of the infant and the eldest daughter was Jka+/Jkb+. The cause of severe fetal anemia was defined as maternal Kidd blood group alloimmunization of Jkb antibodies. The infant is now 18 months old and continues to reach development milestones appropriately. Table 1 - Changes in routine fetal blood test and fetal MCA-PSV results after IUT. No. Gestational age (weeks) HCT level of the donor (%) Transfusion volume (mL) Fetal HCT before IUT (%) MCA-PSV before IUT (MoM) Fetal Hb level before IUT (g/L) Fetal HCT after IUT (%) MCA-PSV after IUT (MoM) Fetal Hb level after IUT (g/L) 1 22+6 55.2 20 7.3 1.97 23 14.1 1.79 48 2 23+3 84.2 31 13.1 1.79 43 19.3 1.11 61 3 26+2 77.9 55 15.4 1.48 52 35.3 0.96 120 Hb: Hemoglobin; HCT: Hematocrit; IUT: Intrauterine transfusion; MCA-PSV: Middle cerebral artery-peak systolic velocity. Discussion Studies on the antenatal management of Kidd alloimmunization are scarce.1 Velasco Rodríguez et al. reported a positive anti-Jkb test at the 13 superscript gestational week with an uneventful pregnancy.2 Among 13 published cases of anti-Jkb-related HDN, 10 were mild, and only 4 required phototherapy. In one case, similar to ours, fetal hydrops and severe anemia (HCT 5.9%; Hb 21 g/L) were observed at 25 weeks, but the outcome was intrauterine death after IUT. In contrast, no exchange transfusion was needed for the newborn in our study.2 Kidd antibodies, like immunoglobulin G, cross the placenta. Approximately 52% disappear within a month post-antigenic exposure.3 Reexposure triggers a strong anamnestic response, leading to severe hemolytic transfusion reactions.3 In our case, anti-Jkb was detected post-delivery but not at the time of anemia diagnosis, suggesting immunization during the first pregnancy by the eldest daughter’s Jkb+ antigen. During the second pregnancy, reexposure via the placenta led to rapid IgG anti-Jkb production, causing fetal anemia and hydrops fetalis. Notably, anti-Jkb levels decreased post-partum but rose during delivery, allowing for monitoring. Maternal alloimmunization is the most common cause of fetal anemia.4 Fetal anemia is classified by Hb deviation from gestational age means or HCT < 30% (preferred for diagnosis). Suspect fetal anemia in cases of hydrops, isolated effusions, placental thickening, hepatomegaly, or reduced/absent movements. Hydrops typically develop when Hb < 70 g/L or absolute Hb < 50 g/L.5 MCA-PSV is a noninvasive assessment for fetal anemia.6 Our case aligned with these descriptions. Recent refinements in IUT and early detection have improved survival rates to 82.4%.7 Key considerations during IUT include cord insertion site (hepatic vein or placental cord safest), fetal paralysis (atracurium, vecuronium, or rocuronium), and transfusion volume (target HCT 40%–50%).8,9,10 Higher donor HCT minimizes blood volume and the risk of fetal heart failure and intrauterine death.10 Conclusion We report the successful management of a fetus with 22-week gestation hydrops and severe anemia due to Kidd alloimmunization. Despite prenatal etiology remaining unidentified, a multidisciplinary approach avoided intrauterine delivery. Comprehensive prenatal exclusion and post-delivery DAT confirmed the diagnosis of fetal anemia from blood incompatibility. Funding Supported by Sanming Project of Medicine in Shenzhen (No. SZSM202311010). Conflicts of Interest None. Data Availability All data generated or analyzed during this study are included in this published article.