Rh Blood Group System Lecture PDF

The Rhesus (Rh) Blood Group system Lecture (D) The Rh(D) Antigen ● ● ● ● ● Rh is the most complex system, with over 45 antigens The complexity of the Rh blood group Ags is due to the highly polymorphic genes that encode them. Discovered in 1940 after work on Rhesus monkeys The 2nd most impor...

The Rhesus (Rh) Blood Group system Lecture (D) The Rh(D) Antigen ● ● ● ● ● Rh is the most complex system, with over 45 antigens The complexity of the Rh blood group Ags is due to the highly polymorphic genes that encode them. Discovered in 1940 after work on Rhesus monkeys The 2nd most important after ABO in the crossmatch test Only the most clinically significant Ags will be discussed Rh Genetics ● The genes that control the system are autosomal codominant located on the short arm of chromosome 1. Rh Antigen Frequency ● ● ● ● ● ● ● D antigen – 85% d antigen – 15% C antigen – 70% c antigen – 80% E antigen – 30% e antigen – 98% Rh Positive Rh Negative The presence or absence of D Ag determines if the person is Rh+ or Rh- Nomenclature of the RH system 4 Different nomenclatures: 1- Fisher-Race 2- Weiner 3- Rosenfield Nomenclature 4- ISBT (1) Fisher-Race Theory ● ● ● ● Rh inheritance is controlled by 3 closely linked loci on each chromosome of a homologous pair Each locus has its own set of alleles which are: Dd , Cc , and Ee . The D gene is dominant to the d gene, but Cc and Ee are co-dominant. The 3 loci are so closely linked that crossing over does NOT occur, and the 3 genes on one chromosome are always inherited together. Fisher-Race D D d C c E Produces D antigen d 3 closely linked genes C c E e “d” antigen not produced e Produces C/c antigen Produces E/e antigen Fisher-Race ● ● ● There are 8 gene complexes at the Rh locus Fisher-Race uses DCE as the order Others alphabetize the genes as CDE DCe dCe DcE dCE Dce dcE DCE dce Fisher-Race Nomenclature Gene Combination Dce DCe DcE DCE dce dCe dcE dCE Antigens D, c, e D, C, e D, c, E D, C, E c,e C,e c,E C,E Fisher-Race Example: ● ● DCe/DCe individual is homozygous for D, C, and e genes DCe/dcE individual is heterozygous for D, C, e, d, c, and E genes Fisher-Race: Genetics/Terminology ● • • • ● Rh phenotype is designated by the presence or absence of Rh antigens: D, C, c, E, e little d: Indicates the ABSENCE of the D antigen and nothing more. There is NO little d antigen or allele. Many blood bankers today are leaving the ‘d’ out the the nomenclature entirely. Rh genes are codominant. In the Fish-Race theory the D gene codes for the D antigen. The C gene codes for the C antigen, etc. (2) Wiener Theory ● ● ● ● ● • • Good for describing phenotype There is one Rh locus at which occurs one Rh gene, but this gene has multiple alleles. For example, one gene R1 produces one agglutinogen (antigen) Rh1 which is composed of three "factors" The three factors are analogous to C, D, and e respectively The main difference between the Fisher-Race and Wiener theories is that the: Fisher-Race theory has three closely linked loci, the Wiener theory has only one gene locus at which multiple alleles occur. Wiener Theory Produces D antigen on RBC r” R0 R” R’ Produces C antigen on RBC r’ Single gene at Rh locus Wiener ● • • Wiener further theorized that 8 major genes led to different combinations of antigens (D, C, E, c, e): R0, R1, R2, Rz r, r′, r″, ry Weiner Nomenclature Nomenclature expressed by the use of a single letter. R D present r D absent Prime ′ or 1 C Double ″ or 2 E Conversion of Wiener to FisherRace ● ● ● ● ● ● R in Wiener = D in Fisher-Race r is absence of D (d) 0 or no symbol implies c and e 1 or ′ implies C and e 2 or ″ implies c and E z or y implies C and E Fisher-Race and Wiener Nomenclature Fisher-Race Dce DCe DcE DCE dce dCe dcE dCE Antigens D, c, e D, C, e D, c, E D, C, E c,e C,e c,E C,E (Weiner Gene) R0 R1 R2 Rz r r′ r″ ry Converting Wiener into FisherRace or vice versa R D r no D 1 and ′ C 2 and ″ E Written in shorthand Example: DcE R2 r″ dcE (3) Rosenfield Nomenclature ● ● ● ● ● ● ● ● Each antigen assigned a number Rh 1 = D Rh 2 = C Rh 3 = E Rh 4 = c Rh 5 = e In writing the phenotype, the prefix “Rh” is followed by colon, then number (if negative, number is preceded by -) e.g. D+, C+, E-, c+, e+ is written as Rh:1,2,-3,4,5 (4) ISBT Significance ● ● ● ● ● ● After ABO, the Rh system is the second most important system. This is because: The D antigen is extremely immunogenic. It causes the production of anti-D in 50 - 70% of Rh(D) negative people who are exposed to the D antigen. Moreover, anti-D is the most common cause of severe HDN and can cause in Utero death. Because of this, in blood transfusion, the patient and donor are matched for Rh(D) type as well as ABO groups. The C and E Ags are not as immunogenic as D, routine typing for these Ags is not performed Weak D Phenotype ● • • ● Most D positive rbc’s react macroscopically with Reagent anti-D at immediate spin These patients are referred to as Rh positive Reacting from 1+ to 3+ or greater HOWEVER, some D-positive rbc’s DO NOT react (do NOT agglutinate) at Immediate Spin using Reagent Anti-D. These require further testing (37oC and/or AHG) to determine the D status of the patient. Variants of D • • Weak expression of the Rh system on the RBC, (Du) Du red cells can be classified into three categories according to the mechanism that account for the Weak D antigen Categories of Du red cells 1- Acquired Du (Position Effect) 2- Du Variant (Partial D) 3- Hereditary Du (Genetically Transmissible) Rh antibodies ● • • • Result from the exposure to Rh antigens IgG form Bind at 37°C Form agglutination in IAT phase Rh Abs Clinically Abs class Significant IgG Yes Thermal HDNB range Yes 4 - 37 Transfusion Reactions Extravascul Intravascul ar ar Yes No Clinical Significance of Rh antibodies • • • Related to Hemolytic transfusion reactions Re-exposure to antigen cause rapid secondary response Always check patients history for previous transfusion or pregnancy to avoid re-exposure. Immunogenicity Hemolytic disease of the Newborn (HDN) ● Usually related to D antigen exposure and the formation of anti-D ● Usually results from D negative female and D positive male producing and offspring. • ● The baby will probably be D positive. 1st pregnancy not effected, the 2nd pregnancy and on will be effected-results in still birth, severe jaundice, anemia related to HDN. ● To prevent this occurrence the female is administered RHIG. Rh factor ● ● Rh factor can cause complications in some pregnancies. Mother is exposed to Rh antigens at the birth of her Rh+ baby. First pregnancy Placenta Rh+ antigens ● ● Mother makes anti-Rh+ antibodies. During the mother’s next pregnancy, Rh antibodies can cross the placenta and endanger the fetus. Anti-Rh+ antibodies Possible subsequent pregnancies