Severe hemolytic disease of the fetus due to anti‐Jkb

Although anti-Jkb is a well-recognized cause of severe acute or delayed hemolytic transfusion reactions, anti-Jkb is rarely associated with severe hemolytic disease of the fetus or newborn (HDFN).1-4 The reason why anti-Jkb rarely causes HDFN, even when present in a relatively high titer, is unclear.5 We would like to share with readers of TRANSFUSION our experience concerning a fatal case of HDFN due to anti-Jkb. A 39-year-old Spanish woman, gravida 4/para 3, was referred in the 25th week of pregnancy after routine ultrasonography showed fetal ascites. She had no significant medical conditions, was not taking medication, and had never received a blood transfusion. Three prior pregnancies were uneventful. An amniocentesis performed at 16 weeks of gestation yielded a normal karyotype. Routine ultrasonography performed at the 20th week of pregnancy showed no detectable abnormalities. Because the patient's blood group phenotype was D+, a routine antibody screen was not performed, in accordance with policies of physicians managing her pregnancy at that time. The ultrasound examination performed at 25 weeks of gestation showed marked fetal ascites, pericardial effusion, hepatomegaly, cardiomegaly, subcutaneous edema, and thickened placenta, compatible with hydrops fetalis. At that time, fetal growth was appropriate for the gestational age. The estimated fetal body weight was 893 g. The middle cerebral artery Doppler peak systolic velocity was 51.16 cm per second (1.55 MoM), suggesting severe fetal anemia. Her red blood cell (RBC) phenotype was group O, D+C+c+E–e+, K–, Jk(b–). An antibody screen and identification revealed anti-K and anti Jkb, both with anti-human globulin titers of 64 (Makropanel 16, Amsterdam, Netherlands; Panocell 10, Immucor Gamma, Norcross, GA; DiaMed, Morat, Switzerland). The IgG subclasses of anti-Jkb were IgG1 and IgG3, performed with murine monoclonal antibodies (PeliClass human IgG subclass kit, Sanquin Reagents, Amsterdam, the Netherlands). The result of the monocyte monolayer assay (MMA) with maternal serum and Jk(b+), K– RBCs was 20 percent (control value, 7.2%), by the method of Nance and colleagues.6 The father's RBC phenotype was group O, D+, K+k+, Jk(a–b+). One week later, a percutaneous umbilical blood sample revealed severe anemia (hematocrit [Hct], 5.9 percent; hemoglobin, 2.1 g/dL). The fetal RBC phenotype was group O, D+, K–k+, Jk(b+). The K– phenotype was confirmed by polymerase chain reaction.7 The Jk(b+) typing result was confirmed by two different monoclonal antibodies (InmuneClone, Immucor Gamma; and DiaClon, DiaMed AG, Cressier, Switzerland). Anti-K and anti-Jkb were identified in the fetus' serum sample. The direct antiglobulin test on fetal RBCs was strongly positive (3+), but only anti-Jkb was present in the eluate. The fetus was transfused via the umbilical vein with 40 mL of irradiated group O, D–, Jk(a+b–), K–k+ RBCs (Hct, 60%). Despite the transfusion, fetal intrauterine death occurred 2 days later. An autopsy confirmed hydrops fetalis with ascites and pleural effusion. An immunohistochemical study of the liver demonstrated the presence of hematopoietic tissue. Most of the few case reports of anti-Jkb–related HDFN describe a clinically mild course. We found only two case reports of neonatal death without intrauterine hydrops.1,4 In our case, fetal death occurred despite an intrauterine transfusion of matched RBCs. We encourage additional case reports describing IgG subclass and MMA test results to better define the biologic characteristics that determine high risk in pregnancies involving these uncommonly observed antibodies. This case confirms the importance of routine blood group antibody screening and quantification of alloantibodies, even in D+ women, during the first and third trimesters of pregnancy.