Overview of Rhesus D alloimmunization in pregnancy
- Kenneth J Moise Jr, MD
Kenneth J Moise Jr, MD
- Professor of Obstetrics, Gynecology and Reproductive Sciences
- Professor of Pediatric Surgery
- University of Texas School of Medicine at Houston
Rhesus (Rh)-D negative women who deliver an Rh(D) positive baby or who are otherwise exposed to Rh(D) positive red cells are at risk of developing anti-D antibodies. Rh(D) positive fetuses/neonates of these mothers are at risk of developing hemolytic disease of the fetus and newborn (HDFN), which can be associated with serious morbidity or mortality.
Implementation of programs for antenatal and postnatal anti-D immune globulin prophylaxis has led to a significant reduction in the frequency of Rh(D) alloimmunization and associated fetal/neonatal complications. However, Rh(D) alloimmunization with serious sequelae in offspring still occurs, particularly in low resource countries where anti-D immune globulin is not widely available . Where appropriate monitoring and intervention are available, HDFN can be treated successfully in most cases.
This topic provides an overview of Rh disease in pregnancy. Prevention and management of Rh disease, as well as management of pregnancies with alloimmunization to other red cell antigens, are reviewed in detail separately.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Bhutani VK, Zipursky A, Blencowe H, et al. Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels. Pediatr Res 2013; 74 Suppl 1:86.
- Sandler SG, Li W, Langeberg A, Landy HJ. New laboratory procedures and Rh blood type changes in a pregnant woman. Obstet Gynecol 2012; 119:426.
- Zipursky A, Paul VK. The global burden of Rh disease. Arch Dis Child Fetal Neonatal Ed 2011; 96:F84.
- Wagner FF, Gassner C, Müller TH, et al. Molecular basis of weak D phenotypes. Blood 1999; 93:385.
- Singleton BK, Green CA, Avent ND, et al. The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype. Blood 2000; 95:12.
- van der Schoot CE, Tax GH, Rijnders RJ, et al. Prenatal typing of Rh and Kell blood group system antigens: the edge of a watershed. Transfus Med Rev 2003; 17:31.
- Garratty G. Do we need to be more concerned about weak D antigens? Transfusion 2005; 45:1547.
- Sandler SG, Flegel WA, Westhoff CM, et al. It's time to phase in RHD genotyping for patients with a serologic weak D phenotype. College of American Pathologists Transfusion Medicine Resource Committee Work Group. Transfusion 2015; 55:680.
- Avent ND, Reid ME. The Rh blood group system: a review. Blood 2000; 95:375.
- Bergström H, Nilsson LA, Nilsson L, Ryttinger L. Demonstration of Rh antigens in a 38-day-old fetus. Am J Obstet Gynecol 1967; 99:130.
- Kumpel BM. On the immunologic basis of Rh immune globulin (anti-D) prophylaxis. Transfusion 2006; 46:1652.
- Bowman J, Harman C, Manning F, et al. Intravenous drug abuse causes Rh immunization. Vox Sang 1991; 61:96.
- Lappen JR, Stark S, Gibson KS, et al. Intravenous drug use is associated with alloimmunization in pregnancy. Am J Obstet Gynecol 2016; 215:344.e1.
- Markham KB, Scrape SR, Prasad M, et al. Hemolytic Disease of the Fetus and Newborn due to Intravenous Drug Use. AJP Rep 2016; 6:e129.
- Cid J, Lozano M, Fernández-Avilés F, et al. Anti-D alloimmunization after D-mismatched allogeneic hematopoietic stem cell transplantation in patients with hematologic diseases. Transfusion 2006; 46:169.
- Medearis AL, Hensleigh PA, Parks DR, Herzenberg LA. Detection of fetal erythrocytes in maternal blood post partum with the fluorescence-activated cell sorter. Am J Obstet Gynecol 1984; 148:290.
- Bowman JM, Pollock JM, Penston LE. Fetomaternal transplacental hemorrhage during pregnancy and after delivery. Vox Sang 1986; 51:117.
- Stroustrup A, Plafkin C, Savitz DA. Impact of physician awareness on diagnosis of fetomaternal hemorrhage. Neonatology 2014; 105:250.
- Kudva GC, Branson KD, Grossman BJ. RhD alloimmunization without apparent exposure to RhD antigen. Am J Hematol 2006; 81:218.
- Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J 1967; 97:1245.
- Pollack W, Ascari WQ, Kochesky RJ, et al. Studies on Rh prophylaxis. 1. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion 1971; 11:333.
- Kumpel BM. On the mechanism of tolerance to the Rh D antigen mediated by passive anti-D (Rh D prophylaxis). Immunol Lett 2002; 82:67.
- Boctor FN, Ali NM, Mohandas K, Uehlinger J. Absence of D- alloimmunization in AIDS patients receiving D-mismatched RBCs. Transfusion 2003; 43:173.
- Hadley AG. Laboratory assays for predicting the severity of haemolytic disease of the fetus and newborn. Transpl Immunol 2002; 10:191.
- Nicolaides KH, Thilaganathan B, Rodeck CH, Mibashan RS. Erythroblastosis and reticulocytosis in anemic fetuses. Am J Obstet Gynecol 1988; 159:1063.
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 75: Management of alloimmunization during pregnancy. Obstet Gynecol 2006; 108:457.
- Geaghan SM. Diagnostic laboratory technologies for the fetus and neonate with isoimmunization. Semin Perinatol 2011; 35:148.
- Finck R, Lui-Deguzman C, Teng SM, et al. Comparison of a gel microcolumn assay with the conventional tube test for red blood cell alloantibody titration. Transfusion 2013; 53:811.
- Cheng D, Hao Y. Comparative evaluation of the microcolumn gel card test and the conventional tube test for measurement of titres of immunoglobulin G antibodies to blood group A and blood group B. J Int Med Res 2011; 39:934.
- Novaretti MC, Jens E, Pagliarini T, et al. Comparison of conventional tube test with diamed gel microcolumn assay for anti-D titration. Clin Lab Haematol 2003; 25:311.
- Thakur MK, Marwaha N, Kumar P, et al. Comparison of gel test and conventional tube test for antibody detection and titration in D-negative pregnant women: study from a tertiary-care hospital in North India. Immunohematology 2010; 26:174.
- Contreras M, de Silva M, Teesdale P, Mollison PL. The effect of naturally occurring Rh antibodies on the survival of serologically incompatible red cells. Br J Haematol 1987; 65:475.
- Moise KJ Jr, Argoti PS. Management and prevention of red cell alloimmunization in pregnancy: a systematic review. Obstet Gynecol 2012; 120:1132.
- Moncharmont P, Juron Dupraz F, Vignal M, et al. Haemolytic disease of the newborn infant. Long term efficiency of the screening and the prevention of alloimmunization in the mother: thirty years of experience. Arch Gynecol Obstet 1991; 248:175.
- Moise KJ. Fetal anemia due to non-Rhesus-D red-cell alloimmunization. Semin Fetal Neonatal Med 2008; 13:207.
- THE RHESUS SYSTEM
- D, d, C, c, E, e, and G
- Prevalence of Rh(D)-negative blood type
- Rh(D) variants
- PATHOGENESIS AND CONSEQUENCES OF ALLOIMMUNIZATION
- False positive
- MANAGEMENT OF PREGNANCIES COMPLICATED BY ALLOIMMUNIZATION
- NEONATAL ISSUES
- ALLOIMMUNIZATION OTHER THAN RH(D)
- SUMMARY AND RECOMMENDATIONS