Original Research
Anemic Disease of the Newborn With Little Increase in Hemolysis and Erythropoiesis Due to Maternal Anti-Jra: A Case Study and Review of the Literature

https://doi.org/10.1016/j.tmrv.2019.03.002Get rights and content

Highlights

  • Of 39 reported newborns born to mothers with anti-Jra, only 10 developed anemia and many did not need interventions.

  • Maternal anti-Jra titer or IgG3 subclass, and newborn's direct antiglobulin test did not correlate with the morbidity of the neonates.

  • Hematopoiesis of the affected neonates did not increase effectively.

  • Anti-Jra may suppress fetal erythropoiesis via mechanism different from the established HDFN.

Abstract

The severity of the hemolytic disease of the fetus and newborn (HDFN) due to Jra mismatch ranges from no symptoms to severe anemia that requires intrauterine and exchange transfusions. We encountered a newborn, born to a healthy mother having anti-Jra at 38 weeks of pregnancy, who had moderate anemia, a positive direct antiglobulin test (DAT) result, no increased erythropoiesis, and no jaundice at birth. Flow cytometry revealed that the Jra antigen of red cells in the infant was nearly negative at birth, biphasic at 5 weeks, and lowly expressed at 7 months of life. We searched online for previous case reports on HDFN due to Jra incompatibility. Among 63 reported cases, excluding 25 cases, 38 were included with the present case for analysis. Of 39 newborns, 10 developed clear anemia (hemoglobin <10.0 g/dL), and 1 died, 5 developed hydrops fetalis, 4 needed intrauterine transfusion and/or exchange transfusion, and 3 received red cell transfusion after birth; overlaps were included. Among 29 neonates with no anemia, 8 needed interventions including phototherapy and γ-globulin infusion, and the remaining 21 received conservative supports only. The maternal anti-Jra titer, ranging between 4 and 2048, did not correlate with the severity of anemia, levels of bilirubin, or any interventions required. The DAT of red cells was positive in 29 of 36 fetuses/newborns tested, whereas it was often negative among anemic neonates (4 of 9) (P < .05). Hematopoiesis did not increase effectively, as indicated by reticulocyte ratios between 1.7% and 22.3%, even with the increase in reticulocytes in anemic neonates compared with nonanemic neonates (P < .05). Total bilirubin levels ranged broadly between 0.2 and 14.3 mg/dL but were generally low. The maternal anti-Jra titer and IgG3 subclass did not correlate with the morbidity of the newborns. Being identical/compatible between mothers and their infants may possibly enhance infants' morbidity, as a weak tendency was observed (P = .053). Maternal anti-Jra may suppress erythropoiesis in fetuses via a mechanism different from the established HDFN, such as anti-D, as evidenced by the lower reticulocyte count and small increase in bilirubin in neonates. As the anti-Jra titer, IgG subclass, and DAT were not correlated with the severity, the mechanism of anti-Jra–induced HDFN remains to be elucidated.

Section snippets

Case Report

Anti-Jra was identified in an untransfused 33-year-old Japanese woman, gravida 2, para 0, who presented at 10 weeks of pregnancy following in vitro fertilization embryo transfer. The maternal anti-Jra titer persisted at 64 by the indirect antiglobulin test (IAT) at 18 and 27 weeks but rose slightly to 128 at 13 days and 10 months after delivery. A 3415-g male infant, blood type A D+, was delivered at 38 weeks and 4 days of gestation. Laboratory results included complete blood count (hemoglobin

Serology

At the initial hospital, ABO and D blood typing, and antibody screening were performed using the beads column method (Ortho BioVue System ABO-Rh/Reverse Grouping Cassette and Poly/Neutral Cassette, Ortho Clinical Diagnostics, Tokyo Japan). A 6-cell reagent (Ortho BioVue Screen J, Ortho) was used for antibody screening. Subsequent antibody identification was carried out by the LISS-IAT and ficin-enzyme test using an 11-cell panel (Resolve Panel C, Ortho) per the manufacturer's instructions.

Time Course of Anti-Jra and Jra Expression in the Infant and Family Study

Routine antibody identification confirmed anti-Jra with a titer of 64 at 18 and 27 weeks of gestation in the maternal plasma with no coexistence of autologous or allogeneic antibody (Fig 1). Anti-Jra was detected with a titer of 4 in the plasma of the infant at 3 days of life, and the DAT was positive (1+). However, both IAT and DAT were negative by day 13 of life. The Jra antigen status of the infant's red cells was inconclusive when cells were untreated but was confirmed to be positive after

Discussion

Although anti-Jra is not commonly thought to cause severe transfusion reactions or HDFN, this antibody can cause fatal hemolytic reaction [43] and intrauterine fetal death [6], [7], [8], [9], albeit rare. As anti-Jra has been reported predominantly among Japanese, we searched case reports written in Japanese and/or English.

Among 400 000 screened blood donors at the Japan Red Cross Saitama Processing Center (donors mainly within 300 km north of Tokyo) in Japan, 238 (0.06%) were Jr. (a−), with no

Disclosure

Authors declare they have nothing to disclose.

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