Mohammed Laqqan The Rhesus (Rh) Blood Group system.
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Transcript of Mohammed Laqqan The Rhesus (Rh) Blood Group system.
Mohammed Laqqan
The Rhesus (Rh) Blood Group systemThe Rhesus (Rh) Blood Group system
Mohammed Laqqan
The Rh(D) AntigenThe 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.
Mohammed Laqqan
Rh GeneticsRh Genetics
The genes that control the system are autosomal codominant located on the short arm of chromosome 1.
Mohammed Laqqan
Rh blood group antigens are proteinsRh blood group antigens are proteins
The antigens of the Rh blood group are proteins. The RhD gene encodes the D antigen, which is a large
protein on the red blood cell membrane, & the most important.
RHD gene RHCE gene
Chromosome 1
Proteins
Mohammed Laqqan
Rh Antigen Frequency
D antigen – 85% d antigen – 15% C antigen – 70% c antigen – 80% E antigen – 30% e antigen – 98%
The presence or absence of D Ag determines if the person is Rh+ or Rh-
Rh PositiveRh Positive
Rh NegativeRh Negative
Mohammed Laqqan
3 Different nomenclatures:1- Fisher-Race2- Weiner3- Rosenfield Nomenclature
Nomenclature of the RH systemNomenclature of the RH system
Mohammed Laqqan
Fisher-Race TheoryFisher-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 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.
Mohammed Laqqan
Fisher-RaceFisher-Race
Dd
Cc
Ee
3 close
ly linke
d genes
“d” antigen not produced
Produces D antigen
Produces C/c antigen
Produces E/e antigen
Dd
Cc
Ee
Mohammed Laqqan
Fisher-RaceFisher-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
Mohammed Laqqan
Fisher-Race NomenclatureFisher-Race Nomenclature
Gene Combination Antigens
Dce D, c, e
DCe D, C, e
DcE D, c, E
DCE D, C, E
dce c,e
dCe C,e
dcE c,E
dCE C,E
Mohammed Laqqan
Fisher-Race ExampleFisher-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
Mohammed Laqqan
Fisher-Race: Genetics/TerminologyFisher-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.
– Phenotype example: R1 phenotype is D, C, e
Rh genes are codominant.
Mohammed Laqqan
In the Fish-Race theory the D gene codes for the D antigen. The C gene codes for the C antigen, etc.
Mohammed Laqqan
Wiener TheoryWiener 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.
Mohammed Laqqan
Wiener TheoryWiener Theory
Single gene at Rh locus
R’
r’
R0
r”
R”
Produces D antigen on RBC
Produces C antigen on RBC
Mohammed Laqqan
WienerWiener
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
Mohammed Laqqan
22 - -Weiner NomenclatureWeiner Nomenclature
Nomenclature expressed by the use of a single letter.
R D present
r D absent
Prime ′ or 1 C
Double ″ or 2 E
Mohammed Laqqan
Conversion of Wiener to Fisher-RaceConversion of Wiener to Fisher-Race
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
Mohammed Laqqan
Fisher-Race and Wiener NomenclatureFisher-Race and Wiener Nomenclature
Fisher-Race Antigens (Weiner Gene)
Dce D, c, e R0
DCe D, C, e R1
DcE D, c, E R2
DCE D, C, E Rz
dce c,e r
dCe C,e r′
dcE c,E r″
dCE C,E ry
Mohammed Laqqan
Converting Wiener into Fisher-Race or vice versaConverting Wiener into Fisher-Race or vice versa
R D
r no D
1 and ′ C
2 and ″ E
Example: DcE R2
r″ dcE
Written in shorthand
Mohammed Laqqan
Rosenfield NomenclatureRosenfield 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
Mohammed Laqqan
SignificanceSignificance
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
Mohammed Laqqan
Rh DeletedRh Deleted
Red cells that express no Ags at the C & E loci ( D )
Number of D Ags greatly increase Anti-D IgG Abs can agglutinate these cells
Mohammed Laqqan
RH null: individual that appears to have no Rh antigens ( , , ) RBC has fragile membrane- short lived Must use autologous blood products
– No D, C, c, E, e antigens present on the RBC membrane Demonstrate mild hemolytic anemia (Rh antigens are integral part of
RBC membrane and absence results in loss of membrane integrity)– Stomatocytosis.
When transfusion is necessary ONLY Rh Null blood can be used to transfuse.
Rh nullRh null
Mohammed Laqqan
Rh antibodiesRh antibodies
Result from the exposure to Rh antigens
• IgG form• Bind at 37°C• Form agglutination in IAT
phase
Rh AbsClinically
Significant
Yes
Abs class
IgG
Thermal range
4 - 37
HDNB
Yes
Transfusion Reactions
Extravascular Intravascular
Yes No
Mohammed Laqqan
• 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.
Clinical Significance of Rh antibodiesClinical Significance of Rh antibodies
Mohammed Laqqan
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 RH-IG.
Hemolytic disease of the Newborn (HDN)Hemolytic disease of the Newborn (HDN)
Mohammed Laqqan
Rh factor can cause complications in some pregnancies.
Mother is exposed to Rh antigens at the birth of her Rh+ baby.
First pregnancy
PlacentaRh+ antigens
Rh factorRh factor
Mohammed Laqqan
Anti-Rh+ antibodies
Possible subsequent pregnancies
Mother makes anti-Rh+ antibodies.
During the mother’s next pregnancy, Rh antibodies can cross the placenta and endanger the fetus.
Mohammed Laqqan
Weak D PhenotypeWeak 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.
Mohammed Laqqan
• 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
Variants of DVariants of D
Mohammed Laqqan
Categories of DCategories of Duu red cells red cells
1- Acquired Du (Position Effect)
2- Du Variant (Partial D)
3- Hereditary Du (Genetically Transmissible)
Mohammed Laqqan
11 - -Acquired DAcquired Du u (Position Effect)(Position Effect)
C allele in trans position to D allele– Example: Dce/dCe, DcE/dCE
In both of these cases the C allele is in the trans position in relation to the D allele.
D antigen is normal, C antigen appears to be crowding the D antigen. (Steric hindrance)
Does NOT happen when C is in cis position– Example: DCe/dce
Can safely transfuse D positive blood components.
Mohammed Laqqan
22 - -DDuu Variant (Partial D) Variant (Partial D)
The D- Ag consists of at least 4 parts Missing one or more PARTS (epitopes) of the D
antigen remaining Ag is weakly expressed Alloantibodies are produced to the missing parts Du variants should receive Rh –ve blood when
transfused
Mohammed Laqqan
Partial D: Multiple epitopes make up D antigen. Each color represents a different epitope of the D antigen.
The difference between Patient A and Patient B is a single epitope of the D antigen. The problem is that Patient B can make an antibody to Patient A even though both appear to have the entire D antigen present on their red blood cell’s using routine anti-D typing reagents..
A.
B. Patient B lacks one D epitope.
Mohammed Laqqan
33 - -Hereditary DHereditary Duu (Genetically Transmissible) (Genetically Transmissible)
The RHD gene codes for weakened expression of D antigen in this mechanism.
– D antigen is complete, there are just fewer D Ag sites on the rbc. Quantitative!
– Common in Black population (usually Dce haplotype). Very rare in White population.
Agglutinate weakly or not at all at immediate spin phase. Agglutinate strongly at AHG phase. Can safely transfuse D positive blood components.