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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.
- ~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).
- 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
- 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
- See “Erythroblastosis Fetalis” topic.