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RH Incompatibility

RH Incompatibility is a topic covered in the 5-Minute Clinical Consult.

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  • Antibody-mediated destruction of red blood cells (RBCs) that bear Rh surface antigens in individuals who lack the antigens and have become isoimmunized (sensitized) to them
  • System(s) affected: hematologic/lymphatic/immunologic
  • Synonym(s): Rh isoimmunization; Rh alloimmunization; Rh sensitization


Predominantly affects fetuses/neonates of isoimmunized, childbearing females; varies by race and ethnicity

Etiology and Pathophysiology

  • Circulating antibodies to Rh antigens (transplacentally transferred antibodies in the case of a fetus/newborn) attach to Rh antigens on RBCs
  • Immune-mediated destruction of RBCs leads to hemolysis, anemia, and increased bilirubin production.
  • Transplacental fetomaternal hemorrhage (most common etiology) during pregnancy or at delivery
  • Transfusion of Rh-positive blood to Rh-negative recipient; exposure to needles contaminated with Rh-positive blood
  • Most commonly seen in the Rh-positive fetus of an Rh-negative mother

  • Complex autosomal inheritance of polypeptide Rh antigens; three genetic loci with closely related genes carry an assortment of alleles: Dd, Cc, and Ee.
  • Individuals who express the D antigen (also called Rho or Rho[D]) are considered Rh-positive. Individuals lacking the D antigen are Rh-negative.
  • Variant D alleles (weak D and partial D) are heterogeneous, altered forms of the D antigen. Some D variants are at risk of formation of anti-D antibodies, whereas others are not. With current blood typing procedures, certain D variants likely to produce alloimmunization are typed as D-negative, although this does not include all genetic subtypes at risk of isoimmunization.
  • Another variant D antigen, DEL, has been identified in some individuals (predominantly Asians). Those with partial DEL expression are at risk for alloimmunization and should be considered clinically Rh-negative. Women with complete DEL are not likely to be sensitized by exposure to Rh-D antigens through pregnancy or transfusion and should be considered clinically Rh-positive and do not need RhD prophylaxis.
  • Antibodies may be produced to C, c, D, E, or e in individuals lacking the specific antigen; only D is strongly immunogenic.
  • Isoimmunization to Rh antigens in susceptible individuals is acquired, not inherited.

Risk Factors

  • ~15% of the white population and smaller fractions of other races are Rh-negative and susceptible to sensitization.
  • Any Rh-positive pregnancy in an Rh-negative woman can result in sensitization.
  • Weak D and partial D women are a heterogeneous group. Although previously reported to be Rh-positive and treated as such, alloimmunization has been reported and can result in HDFN or fatal hydrops fetalis.
  • Native risk of isoimmunization after Rh-positive pregnancy had been estimated at ≤15% but seems to be decreasing.
  • The risk of isoimmunization antepartum is only 1–2%.
  • The risk of isoimmunization is 1–2% after spontaneous abortion and 4–5% after induced abortion.
  • Use of Rho(D) immunoglobulin prophylaxis has reduced incidence of isoimmunization to <1% of susceptible pregnancies (1).

General Prevention

  • Blood typing (ABO and Rh) on all pregnant women and prior to blood transfusions
  • Antibody screening early in pregnancy
  • Rh immunoglobulin prevents only sensitization to the D antigen.
  • For prophylaxis, Rho(D) immunoglobulin (RhIG, RhoGAM, HyperRHO, Rhophylac) given to unsensitized, Rh-negative women after the following:
    • Spontaneous abortion
    • Induced abortion
    • Ectopic pregnancy
    • Antepartum hemorrhage
    • Trauma to abdomen
    • Amniocentesis
    • Chorionic villus sampling
    • Within 72 hours of delivery of an Rh-positive infant
    • Given routinely at 28 weeks’ gestation
  • Prophylaxis is to prevent sensitization affecting a subsequent pregnancy and has little effect on the current pregnancy.
  • Dose for prophylaxis
    • 50-μg dose for events up to 12 weeks’ gestation
    • 300-μg dose for events after 12 weeks’ gestation
    • Higher doses may be required in the event of a large fetal–maternal hemorrhage (>30 mL of whole blood).

Commonly Associated Conditions

  • Hemolytic disease of newborn
  • Hydrops fetalis
  • Neonatal jaundice
  • Kernicterus
  • See “Erythroblastosis Fetalis” topic.

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Stephens, Mark B., et al., editors. "RH Incompatibility." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116530/all/RH_Incompatibility.
RH Incompatibility. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116530/all/RH_Incompatibility. Accessed April 19, 2019.
RH Incompatibility. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116530/all/RH_Incompatibility
RH Incompatibility [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 19]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116530/all/RH_Incompatibility.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - RH Incompatibility ID - 116530 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116530/all/RH_Incompatibility PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -