Rh blood group

Learning Outcomes

  • Utilize the Rh blood group system as a primary example of protein-based blood grouping (BG) to review:

    • Inheritance (genetics/terminology)

    • Basic biochemistry (antigens and phenotyping)

    • Clinical significance (Antibodies and HDFN)

History of the Rh Blood Type

  • 1939: Levine and Stetson identified severe hemolytic reactions in a mother during transfusion due to lack of a new antigen inherited from the fetus.

    • Maternal antibodies reacted with the transfused husband's compatible blood.

  • 1940: Landsteiner and Wiener discovered the Rh antigen (D) after immunizing rabbits with rhesus monkey blood, finding human antibodies agglutinated RBCs.

  • Distinction was later made that human-derived antibodies and animal antibodies targeted different systems leading to the Rh designation.

  • Discovery of five major Rh antigens: D, C, E, c, and e indicating complex, multi-allelic systems.

  • Clarified two medical mysteries:

    1. Hemolytic transfusion reactions in patients receiving ABO identical blood.

    2. Erythroblastosis fetalis in newborns.

Rh Locus

  • RHD gene: D antigen - Highly immunogenic.

    • D+ individuals: Inherit 2 Rh genes (RHD + 1 RHCE allele from each parent).

    • D– individuals: Only possess RHCE genes as RHD is deleted.

  • Major Rh antigens include: D, C, c, E, and e.

  • Rh genes inherited as a haplotype; RHCE genes can produce antigens (ce, Ce, cE, or CE).

  • Antithetical Ags controlled by various RHCE genes (C/c and E/e).

Rh Inheritance

  • Inheritance involves two genes (RHD and RHCE), similar (94% identical) but oriented oppositely.

  • Gene combinations can produce 8 haplotypes based on presence/absence of RHD gene.

  • Notation explained:

    • d: RHD deletion (inactive)

    • R: Presence of RHD and D antigen

    • r: Absence of RHD antigen.

Haplotype Notation

  • Haplotype combinations include:

    • DCe, dce, DcE, dce

    • Each designation denotes specific alleles present.

    • R used for presence of D antigen, while subscripts denote other antigens.

Rh Antigens

  • Expressed as a protein complex in RBC membrane.

  • Complex thought to be a tetramer:

    • RhD (D antigen)

    • RhCE (C/c and E/e antigens)

  • In D– individuals, only the RhCE complex is present.

  • Rh-associated glycoprotein (RhAG) directs Rh antigens to the RBC membrane.

Clinical Significance of the Rh System

  • Rh antibodies: Usually IgG types formed post-exposure to foreign RBCs via transfusion or pregnancy.

  • Major clinical significances:

    1. Transfusion: Rh antibodies can lead to severe transfusion reactions; D– individuals must avoid transfusion of D+ blood.

    2. HDFN: Rh antibodies (especially anti-D) can cause hemolytic disease in newborns through fetomaternal hemorrhage (FMH).

Mechanism of HDFN

  • FMH: Occurs during pregnancy/delivery and exposes D– mother to D+ fetal blood.

  • Results in maternal production of anti-D antibodies, creating risks in subsequent D+ pregnancies, potentially causing increased severity of HDFN.

Symptoms & Consequences

  • Symptoms of severe anemia: Increased fetal RBC destruction leads to elevated unconjugated bilirubin in newborns, which can cause neurological damage (kernicterus) and cardiovascular failure.

  • Maternal liver may struggle to manage bilirubin.

Summary of RhD Importance

  • Transfusion of D+ blood into D– individuals can result in:

    • Production of anti-D antibodies leading to hemolytic transfusion reactions.

  • Patients must be carefully typed to avoid this.

  • The presence of distinct antibody types (IgG vs. IgM) plays a crucial role in both transfusion practices and understanding of HDFN pathology.