Description

• 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

Epidemiology

Incidence
Predominant age and sex: Affects fetuses/neonates of isoimmunized child-bearing females

Risk Factors

• Of white population, 15% and smaller fractions of other races are Rh-negative and susceptible to sensitization (1).
• Any Rh-positive pregnancy in an Rh-negative woman can result in sensitization.
• 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 (2).
• Use of Rho(D) immunoglobulin prophylaxis has reduced incidence of isoimmunization to <1% of susceptible pregnancies.

• Complex autosomal inheritance of polypeptide Rh antigens; 3 genetic loci with closely related genes carry an assortment of alleles: Dd, Cc, and Ee (3).
• Individuals who express the D antigen (also called Rho or Rho[D]) or its weak D (D^u) variant are considered Rh-positive. Individuals lacking the D antigen are Rh-negative. (There is no antigen identified with the d allele.)
• Another variant D antigen, DEL, has been identified in some individuals (predominantly Asians) who are classified as Rh-negative by the usual assays. While testing Rh-negative, these individuals are not likely to be sensitized by exposure to Rh-D antigens through pregnancy or transfusion (4).
• Antibodies may be produced to C, c, D, E, or e in individuals lacking the specific antigen; only D is strongly immunogenic (5).
• Isoimmunization to Rh antigens in susceptible individuals is acquired, not inherited.

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
• 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).

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.

Etiology

• Transfusion of Rh-positive blood to Rh-negative recipient
• Maternal exposure to fetal Rh antigens, either antepartum or intrapartum
• Most commonly seen in the Rh-positive fetus or infant of an Rh-negative mother

Commonly Associated Conditions

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