Lecture 6_ Chapter_006 (1)

Chapter 6: Rh Blood Group System

Overview

  • The Rh blood group system is a significant blood group system focused on the D antigen.

  • Understanding the Rh system is crucial for blood transfusions and preventing Hemolytic Disease of the Newborn (HDN).

Objectives of the Lecture

  • Recognize differences between ABO/Rh systems concerning immunoglobulin class, optimal temperature, and HDN.

  • Discuss five major alleles of the Rh system and inheritance theories.

  • Define classifications for weakened expressions of D antigen and their significance.

  • Understand implications for weak D antigen positive donors and recipients.

  • Compare theories of Rh null inheritance and their effects.

  • Identify actions of major types of Rh antisera and controls.

  • Interpret D and weak D results and corrective actions for false results.

Significance of D Antigen

  • The D antigen is highly immunogenic and is the most significant antigen after ABO.

  • Minimal exposure to the D antigen can prompt antibody production.

History of Rh System

  • In 1940, Levine and Stetson linked the Rh system with HDN.

  • Landsteiner and Wiener identified anti-Rh antibodies that agglutinate 85% of human RBCs.

Immunoglobulin Class Comparison

ABO Antibodies

  • Class: IgM

  • Nature: Naturally occurring; exposed through environmental antigens.

  • Optimal Temperature: Room temperature (20-25°C).

Rh Antibodies

  • Class: IgG

  • Nature: Produced through immunization during pregnancy or transfusions.

  • Optimal Temperature: 37°C.

Antigens of Rh System

  • D Positive/D Negative: Presence/absence of D antigen on RBCs.

  • Identifies C, c, E, and e antigens based on Fisher's naming convention.

  • Major alleles include C/c and E/e with recognized variations.

Genetics and Biochemistry of Rh Antigens

  • Involves genes closely linked on chromosome one:

    • RHD Gene: Determines D antigen expression.

    • RHCE Gene: Controls C, c, E, and e antigens.

    • RHAG Gene: Contributes to expression on chromosome 6.

  • Alleles show codominant inheritance.

Theories of Inheritance: Wiener vs. Fisher-Race

  • Fisher-Race Theory: Controlled by three sets of linked genes; phenotype based on D, C, E, c, e antigens.

  • Wiener Theory: A single gene at Rh locus produces a series of factors/antigens.

Rosenfield Terminology

  • Simplifies data entry, indicating antigens by number:

    • Rh1: D,

    • Rh2: C,

    • Rh3: E,

    • Rh4: c,

    • Rh5: e.

  • Example: D+, C+, E–, c+, e+ is denoted as Rh:1,2,-3,4,5.

Genotype vs. Phenotype

  • Genotype: Actual genetic makeup regarding Rh antigens.

  • Phenotype: Observable characteristics (e.g., blood type).

  • Variation in genotype frequency exists among ethnic groups.

Weak Expression of D

  • Not all D positive cells agglutinate reliably with anti-D.

  • Weak D testing involves incubation with anti-D at 37°C and follow-up AHG.

  • Positive result indicates weak D positive; negative indicates D negative.

Significance of Weak D

  • Recognizes weak D cells' potential to induce immune responses in transfusions.

  • Standard practice dictates transfusing D negative blood.

  • Weak D mothers do not receive RhIG.

Rh Null Phenotypes

  • Rh null red cells show no antigen sites, affecting red cell membrane structure.

  • Associated with stomatocytosis, hemolytic anemia, and decreased RBC survival.

Testing for Weak D Antigens

  • Uses indirect antiglobulin test (IAT) and monoclonal reagents.

  • Controls must validate weak D tests to avoid false positives.

False Positive and False Negative Results

  • False Positive Causes: Positive DAT, autoantibodies, rouleaux, reagent contamination.

  • False Negative Causes: Reagent issues, neutralization, improper testing procedure.

Rh Antibodies

  • Develop through immunization from transfusions/pregnancy.

  • Characteristics: IgG (low IgM), primarily detectable at 37°C.

  • Immunogenicity order: D > c > E > C > e.

Rarer Rh Alleles

  • Cw: observed in only 2% of whites.

  • V and VS antigens linked to f antigen on c/e haplotypes present in American blacks.

Additional Resources

  • Media Lab: Overview Of Major Antigens of the Rh Blood Group System.

  • Course: Clear as Glass Blood Banking: RhD Type Determination.