Background
There is controversy on critical cut-off values of laboratory testing to select pregnancies
at increased risk for anti-Kell-mediated hemolytic disease of the fetus and newborn.
Without early detection and treatment, anti-Kell-mediated hemolytic disease of the
fetus and newborn may result in progressive fetal anemia, fetal hydrops, asphyxia,
and perinatal death.
Objective
We aimed to determine the value of repeated anti-Kell titer determination and biological
activity measurement using the antibody-dependent cellular cytotoxicity test determination
in the management of pregnancies at risk for anti-Kell-mediated hemolytic disease
of the fetus and newborn.
Study Design
This was a retrospective cohort study of pregnancies with anti-Kell and a Kell-positive
fetus, identified from January 1999 through April 2015. Laboratory test results and
clinical outcome were collected from the Dutch nationwide screening program and the
national reference center for fetal therapy in The Netherlands, the Leiden University
Medical Center. Diagnostic accuracy was measured (receiver operating characteristic
curves, sensitivity, specificity, positive and negative predictive values) for anti-Kell
titers and antibody-dependent cellular cytotoxicity test. The relationship between
the titer and antibody-dependent cellular cytotoxicity measurements and the 2 foregoing
measurements were computed with a Pearson product-moment correlation coefficient.
Results
In a 16-year unselected cohort, representing screening results of 3.2 million pregnancies
resulting in live births in The Netherlands, we identified 1026 Kell-immunized pregnancies.
In all, 93 pregnant women had anti-Kell and a Kell-positive child, without other red
cell alloantibodies. In all, 49 children (53%) needed intrauterine or postnatal transfusion
therapy. The first anti-Kell titer showed already a high diagnostic accuracy with
an area under the curve of 91%. The optimal cut-off point for the titer was 4 (sensitivity
100%; 95% confidence interval, 91–100), specificity 27% (95% confidence interval,
15–43), and positive predictive value 60% (49–71%). The antibody-dependent cellular
cytotoxicity test was not informative to select high-risk pregnancies. Linear regression
showed no significant change during pregnancy, when antibody titer and antibody-dependent
cellular cytotoxicity test results were compared with every 2 foregoing measurements
(P < .0001).
Conclusion
Early determination of the anti-Kell titer is sufficient to select pregnancies at
increased risk for hemolytic disease of the fetus and newborn with need for transfusion
therapy. If the Kell status of the fetus is known to be positive, a titer of ≥4 can
be used to target intensive clinical monitoring.
Key words
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References
- Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in The Netherlands.Transfusion. 2008; 48: 941-952
- Hemolytic disease of the fetus and newborn.Vox Sang. 2015; 109: 99-113
- Erythropoietic suppression in fetal anemia because of Kell alloimmunization.Am J Obstet Gynecol. 1994; 171: 247-252
- Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia.Am J Obstet Gynecol. 1996; 174: 547-551
- Causes of fetal anemia in hemolytic disease due to anti-K.Transfusion. 2003; 43: 115-116
- Implementation of routine screening for Kell antibodies: does it improve perinatal survival?.Transfusion. 2008; 48: 953-957
- Blood group antibodies in hemolytic disease of the fetus and newborn.in: Hadley A. Soothill P. Alloimmune disorders of pregnancy. Anemia, thrombocytopenia and neutropenia in the fetus and newborn. Cambridge University Press, Cambridge (United Kingdom)2002
- Fetal anemia due to non-Rhesus-D red-cell alloimmunization.Semin Fetal Neonatal Med. 2008; 13: 207-214
- Management of rhesus alloimmunization in pregnancy.Obstet Gynecol. 2008; 112: 164-176
- Prevention of rhesus hemolytic disease of the fetus and newborn.Lancet. 2009; 373: 1082
- Hemolytic disease of the fetus and the newborn.in: Klein H.G. Anstee D.J. Mollison's blood transfusion in clinical medicine. John Wiley & Sons Ltd., Oxford, UK2012: 499-548
- Bilirubin-induced neurologic damage–mechanisms and management approaches.N Engl J Med. 2013; 369: 2021-2030
- Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels.Pediatr Res. 2013; 74: 86-100
- Treatment of fetal anemia due to red-cell alloimmunization with intrauterine transfusions in The Netherlands, 1988-1999.Acta Obstet Gynecol Scand. 2004; 83: 731-737
- Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study.Am J Obstet Gynecol. 2012; 206: 141-148
- Exchange transfusions and top-up transfusions in neonates with Kell hemolytic disease compared to Rh D hemolytic disease.Vox Sang. 2011; 100: 312-316
NVOG Dutch Association Obstetrics and Gynecology. Red blood cell immunization and pregnancy. Version 2.1. 2009. Available at: https://www.nvog.nl/wp-content/uploads/2018/03/Erytrocytenimmunisatie-en-zwangerschap_.pdf. Accessed August 31, 2018.
- Management of alloimmunization during pregnancy. Practice bulletin no. 75.Obstet Gynecol. 2006; 108: 457-464
- Doppler ultrasonography versus amniocentesis to predict fetal anemia.N Engl J Med. 2006; 355: 156-164
- Management of red cell alloimmunization in pregnancy: the non-invasive monitoring of the disease.Prenat Diagn. 2010; 30: 668-673
- Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses.N Engl J Med. 2000; 342: 9-14
- Rhesus hemolytic disease of the newborn: postnatal management, associated morbidity and long-term outcome.Semin Fetal Neonatal Med. 2008; 13: 265-271
- Noninvasive fetal blood group genotyping of rhesus D, c, E and of K in alloimmunized pregnant women: evaluation of a 7-year clinical experience.BJOG. 2011; 118: 1340-1348
- ADCC and other cellular bioassays for predicting the clinical significance of red cell alloantibodies.Baillieres Clin Haematol. 1990; 3: 321-337
- ADCC (K-cell) lysis of human erythrocytes sensitized with rhesus alloantibodies. III. Comparison of IgG anti-D agglutinating and lytic (ADCC) activity and the role of IgG subclasses.Br J Haematol. 1980; 46: 447-453
- Laboratory assays for predicting the severity of hemolytic disease of the fetus and newborn.Transpl Immunol. 2002; 10: 191-198
- Management of pregnancies complicated by anti-Kell isoimmunization.Obstet Gynecol. 1999; 93: 667-673
- Anti-Kell in pregnancy.BJOG. 1991; 98: 162-165
- Obstetric history and antibody titer in estimating severity of Kell alloimmunization in pregnancy.Obstet Gynecol. 2007; 109: 1093-1098
- Non-anti-D antibodies in red-cell alloimmunization.Eur J Obstet Gynecol Reprod Biol. 2000; 92: 75-81
de Haas M, Koelewijn JM, Bilgin K, Vrijkotte TGM, van der Schoot CE, Bonsel GJ. Diagnostic performance of laboratory monitoring to predict severe hemolytic disease of the fetus and newborn in non-RhD-alloimmunized pregnancies. Detection and prevention of pregnancy immunization, the OPZI-study, Academic Thesis 2009;4:73-85.
- Intrauterine transfusion.Ann Obstet Ginecol Med Perinat. 1971; 92: 539-542
Downes KAS, IA. Pretransfusion testing. In: Fung MG, BJ, Hillyer CD, Westhoff CM, eds. Technical manual, 18th ed. Bethesda (MD): AABB.
- Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of hemolytic disease of the fetus and newborn.Br J Haematol. 2017; 176: 651-660
- Correlation of serological, quantitative and cell-mediated functional assays of maternal alloantibodies with the severity of hemolytic disease of the newborn.Br J Haematol. 1991; 77: 221-228
- Monocyte monolayer assay: an efficient noninvasive technique for predicting the severity of hemolytic disease of the newborn.Am J Clin Pathol. 1989; 92: 89-92
- Prenatal typing of Rh and Kell blood group system antigens: the edge of a watershed.Transfus Med Rev. 2003; 17: 31-44
- Fetal genotyping for the K (Kell) and Rh C, c, and E blood groups on cell-free fetal DNA in maternal plasma.Transfusion. 2007; 47: 2126-2133
Article Info
Publication History
Published online: July 28, 2018
Accepted:
July 24,
2018
Received in revised form:
June 21,
2018
Received:
May 1,
2018
Footnotes
This research was supported by a grant from Sanquin Blood Supply ( Product and Process Development 14–15 ). The design, conduct, or publication of the study was not influenced by this financial support.
The authors report no conflict of interest.
Cite this article as: Slootweg YM, Lindenburg IT, Koelewijn JM, et al. Predicting anti-Kell-mediated hemolytic disease of the fetus and newborn: diagnostic accuracy of laboratory management. Am J Obstet Gynecol 2018;219:393.e1-8.
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