Rh Blood Group System (M) Flashcards
Rh specific Ags reside on what?
Proteins
Where do ABO and Hh Ags reside?
Carbohydrates
What are the characteristics of Rh Ags?
1) These are very immunogenic
2) These are distinct from ABO Abs
What is the order of immunogenicity of Rh Ags?
D -> c -> E -> C -> e
When are Rh Ags produced?
These are produced after exposure to foreign RBCs
Production is caused when person lacking Ag is exposed to Ag foreign to their system
What are the characteristics of Rh blood grp?
1) It is the 2nd most impt blood grp system after ABO
2) It is a complex blood grp system composed of over 50 different RBC Ags
What is the term for individuals who lack RhD?
Rh negative
What is the term for individuals who possess RhD?
Rh positive
True or False
Determining the presence / absence of RhD is critical in pretransfusion testing
True
Who are the persons who described a hemolytic transfusion rxn in an obstetrical pt?
1) Levine
2) Stetson
Who are the persons who reported on an Ab made by guinea pigs and rabbits when they are transfused w/ Rhesus macaque monkey RBCs?
1) Landsteiner
2) Wiener
Accdg to research, what blood grp is the primary cause of hemolytic disease of fetus and newborn (HDFN or erythroblastosis fetalis) and a significant cause of hemolytic transfusion rxns?
Rh blood grp
How are Rh Abs produced?
These are produced due to sensitization
*Rh Abs are considered as what type of Ig?
IgG (subclasses 1 - 4)
What are the characteristics of Rh Abs?
1) These do not usually bind complement
2) These react optimally at 37 DC after antiglobulin testing
3) It can cross the placenta
*What are the Ig subclasses that are of greatest clinical significance (in connection to Rh Abs)?
1) IgG1
2) IgG3
*IgA and transient IgM forms
What are the 4 schemes for nomenclature of Rh blood grp system?
1) Fisher-Race
2) Wiener
3) Rosenfield
4) ISBT
What is the other term for Fisher-Race nomeclature?
DCE terminology
Who are the persons behind the Fisher-Race nomenclature?
1) Fisher
2) Race
What did Fisher and Race postulated?
They postulated that the Ags of the system were produced by 3 closely linked sets of alleles
What is the simplified concept of Fisher-Race?
Each gene was responsible for producing a product (/ Ag) on the RBC surface
The phenotype of a given RBC is defined by what?
Defined by the presence of D, C, c, E, and e expression
What is phenotype?
It is the Ags expressed on the RBC detected by typing
True or False
In Fisher-Race, D, C / c, and E / e genes have close linkage
True
What are the Ags produced (w/c are present on the RBC’s surface) by the ff genes:
1) D gene
2) C / c gene
3) E / e gene
1) D
2) C / c
3) E / e
True or False
In Fisher-Race, each gene produces 1 product
True
What are the rules for Fisher-Race nomenclature?
1) Ags have same designations as genes. Genes are italicized
2) “d” refers to the absence of D Ag
3) “-“ represents other missing Ags
4) Haplotypes are inherited from each parent
Provide an ex of applying the Fisher-Race nomenclature
Genotype: DCe / dce
Phenotype (Ags produced): D, C, c, and e
In Fisher-Race, what is the Rh Ag frequency in the Caucasian population?
1) D: 85% (Rh [+])
2) Absence of D: 15% (Rh [-])
3) C: 70%
4) E: 30%
5) c: 80%
6) e. 98%
What is haplotype?
It is the complement of genes inherited from either parent
In Fisher-Race, what is the most common haplotype for whites and asians?
DCe
In Fisher-Race, what is the most common haplotype for blacks?
Dce
What are the 2 types of Rh phenotypes (in Fisher-Race)?
1) Rhnull
2) Rhmod
What is Rhnull?
A pt is expressing no Rh Ags on their RBC’s
What is Rhmod?
A pt has weakened expression of Rh Ags
How is Rhmod expressed and provide an ex?
It is expressed w/ parenthesis
Ex. (D), (C), (e)
What is the other term for Wiener nomenclature?
Rh-Hr terminology
What did Wiener believed?
Wiener believed that there was 1 gene responsible for defining Rh that produced an agglutinogen containing a series of blood factors
In Wiener, the Rh gene produced what?
Produced at least 3 factors within an agglutinogen
The agglutinogen may be considered as what?
As the phenotypic expression of the haplotype
In Wiener, each factor is what?
Each factor is an Ag recognized by an Ab
In Wiener, Abs can recognize what?
Can recognize single / multiple factors or Ags
True or False
Fisher-Race nomenclature may be converted to Wiener nomenclature and vice versa
True
What is the theory of Wiener?
3 Ags produced by single gene (Rh^0)
What are the Ags of Wiener?
1) Rh0
2) Rh1
3) Rh2
4) Rhz
5) rh
6) rh’
7) rh’’
8) rhy
What are the 2 types of designations in Wiener nomenclature?
1) Longhand designation
2) Shorthand designation
What are the 3 agglutinogen produced by Rh^0 gene?
1) Factor Rh0
2) Factor hr’
3) Factor hr’’
What are the corresponding Rh factors (present on the RBCs surface) of the ff agglutinogen:
1) Factor Rh0
2) Factor hr’
3) Factor hr’’
1) Rh0
2) hr’
3) hr’’
What is the principle of Wiener’s agglutinogen theory?
Ab will recognize each factor within the agglutinogen
What are the rules (for writing genes) for Wiener nomenclature?
1) R = represents presence of D
r= represents absence of D
2) Ags have same designations as genes. Genes are italicized, w/ subscripts written as superscripts (Rh^0, Rh^1, Rh^2, Rh^z, rh, rh’, rh’’, rh^y)
-> rules for writing genes
What are the rules for writing Wiener (longhand designation)?
1) Rh0 refers to “D”
2) Single prime (‘) refers to “C or c”
3) Double prime (‘’) refers to “E or e”
4) If “r” precedes “h” (rh’ or rh’’), we are referring to the uppercase “C and E”
5) If “h” precedes “r” (hr’ or hr’’), we are referring to the lowercase “c and e”
Provide an ex whereas the rules for writing Wiener (longhand) is applied
Dce -> Rh0hr’hr’’
What are the rules for Wiener (shorthand designation)?
1) “R” denotes presence of “D”, “r” denotes absence
2) “C” denoted by subscript “1 (one)” or by a single prime (‘)
3) “E” denoted by subscript “2 (two)” or by a double prime (‘’)
4) When both “C and E” are uppercase, the subscript “z” or superscript “y” is used
5) When both “c and e” are lowercase, the subscript “0” or no superscript is used
6) Subscripts are used w/ uppercase “R”, while superscripts and primes w/ lowercase “r”
Provide an ex whereas the rules for writing Wiener (shorthand) is applied
R1 -> DCe
What is the theory of Rosenfield nomenclature?
No genetic basis
Simply states presence or absence of Rh Ags
What are the rules for writing Rosenfield nomenclature?
1) Minus sign (-) before the number designates absence
2) If an Ag hasn’t been tested for, its number will not appear
3) Designations:
- > D: Rh1
- > C: Rh2
- > E: Rh3
- > c: Rh4
- > e: Rh5
Provide an ex whereas Rosenfield nomenclature is applied
D + , C + , E + , c - , e - -> Rh: 1, 2, 3, -4, -5
Summary of Wiener terminology
Ag
1) Rh0
2) Rh1
3) Rh2
4) Rhz
5) rh
6) rh’
7) rh’’
8) rh^y
Longhand
1) Rh0hr’hr’’
2) Rh0rh’hr’’
3) Rh0hr’rh’’
4) Rh0rh’rh’’
5) hr’hr’’
6) rh’hr’’
7) hr’rh’’
8) rh’rh’’
Shorthand
1) R0
2) R1
3) R2
4) Rz
5) r
6) r’
7) r’’
8) r^y
Fisher-Race
1) Dce
2) DCe
3) DcE
4) DCE
5) dce
6) dCe
7) dcE
8) dCE
What is the meaning of ISBT?
International Society of Blood Transfusion Committee
ISBT formed what?
The Committee on Terminology for Red Cell Surface Antigens
What is the mandate of ISBT?
To establish a uniform nomenclature that is both eye- and machine-readable and is in keeping w/ the genetic basis of blood grps
What did ISBT adopted?
A six-digit number for each authenticated Ag belonging to a blood grp system
In the six-digit number, what is the meaning of the ff:
1) 1st 3 numbers
2) Remaining 3 numbers
1) It represents the system
2) It represents the antigenic specificity
What is the principle of the 6-digit # of ISBT (for Rh blood grp)?
Number 004 was assigned to the Rh blood grp system, and then each Ag assigned to the Rh system was given a unique number to complete the 6-digit computer #
Provide an ex whereas ISBT is applied
004 was assigned to Rh blood grp system
ex. Rh1 -> “D” -> 004001
ISBT is similar w/ Rosenfield, what are the only differences and provide an ex?
1) RH instead of Rh
2) Takes genetics into account. Characters are italicized, followed by a space or an asterisk, and then numbers of the Ags are separated by commas
Ex. Rh1 -> DCe and RH 1, 2, 5 or RH*1 ,2, 5
Determining probably or predicted genotypes was useful for what?
Parentage studies (relationship testing)
What are the considerations for zygosity testing (molecular testing)?
1) There are substantial differences in phenotypes and predicted genotypes of various populations
2) These differences must be remembered when trying to locate compatible blood for recipients w/ unusual or multiple Rh Abs
The 2 theories of Rh genetic control were initially postulated to explain what?
To explain genetically the results of serologic and biochemical studies in the Rh system
*What are the 2 theories of Rh genetic control?
1) Wiener postulated that a single gene produces a single product that contains separately recognizable factors
2) Fisher and Race proposed that the Rh locus contains 3 distinct genes that control production of their respective Ags
In connection to RH genes, Tippett correctly proposed what?
Proposed that 2 closely linked genes located on chromosome 1 control expression of Rh proteins (namely RHD and RHCE)
What does the gene RHD code?
It codes for the presence / absence of the RhD protein
What does the gene RHCE code?
Either the ff polypeptides:
1) RhCe
2) RhcE
3) Rhce
4) RhCE
What is the other gene impt to Rh Ag expression?
RHAG gene
Where is RHAG gene located?
On chromosome 6
What is the product of RHAG gene?
Rh-associated glycoprotein (RhAG)
RhAG is termed as what?
Coexpressor
What must be present for successful expression of the Rh Ags?
RhAG
True or False
By itself RhAG does not express any Rh Ags
True
What is the result when mutations in the RHAG gene occur?
It results in missing or significantly altered RhD and RhCE proteins, affecting Ag expression
*In connection to RH genes, what should be considered?
Rhnull phenotype
What is Rhnull?
No Rh Ags expressed on RBC’s
Rh-positive individuals inherit what and what is its result?
Inherit 1 or 2 codominant RHD genes, w/c result in expression of RhD Ag and are typed Rh-positive
In addition to the RHD gene(s), what genes are inherited?
2 RHCE genes are inherited, 1 from each parent
Rh-negative individuals can arise from at least what?
From at least 3 different mutations
The mutations (where Rh [-] individuals can arise) are most often found in who?
Found in individuals falling into 3 different ethnic bgs
What are the 3 ethnic bgs where the mutations are most often found?
1) European ethnicity
2) African ethnicity
3) Asian ethnicity
What are the characteristics of Rh Ags?
1) These are non-glycosylated (no carbohydrates) proteins
2) These reside on transmembrane proteins
3) These are integral part of the RBC membrane
4) Only small loops of Rh proteins are exposed on the surface of the RBC
5) The number of D Ag sites vary depending on Rh phenotype
*What are the characteristics of RhD and RhCE proteins, and RhAG?
1) They are exclusively on RBCs
2) They may also act as molecular transporters
As transmembrane proteins (RhD and RhCE proteins), what is their role?
They play a role in maintaining the structural integrity of the RBC
Some individual’s RBCs possess what?
Weaker expression of D Ag
Some individual’s RBCs possess weaker expression of D Ag that requires what?
An indirect antiglobulin test to detect the D Ag
*Weak D Ag is denoted as what?
D^u
Where are individuals w/ altered D Ag categorized?
They are categorized into diff phenotypes defined as weakened D
*C in trans to RHD
Weak D has what?
Fewer D Ags in #
What is the event present in partial D?
D epitope is missing or altered
Del is common and rare in who?
Common in Asians
Rare in whites
Most Rh Abs are what?
IgG
Most Rh Abs w/c are IgG react optimally at what temp?
37 DC
Also, most Rh Abs can react optimally at what circumstance?
After AHG testing
When are Rh Abs usually produced?
These are usually produced following exposure to foreign RBCs
Rh Abs may show what?
Dosage
Rh Abs are enhanced when testing w/ what?
Enzyme-treated RBCs
What are the subclasses of Rh Abs?
1) IgG1
2) IgG2
3) IgG3
4) IgG4
Among all the Ig subclasses of Rh Abs, what Ig subclasses are of the greatest clinical significance?
1) IgG1
2) IgG3
RBCs coated w/ IgG1 and IgG3 are rapidly cleared from the circulation by what?
RES
What are the characteristics of Rh Abs?
1) They often persist for yrs
2) They do not bind complement
3) They can cross the placenta
4) They are transplacental IgG
In terms of Rh typing rgnts, the what rgnt is the goal to be used?
Rgnt anti-D
What is the action of rgnt anti-D?
It will allow for typing individual’s RBCs as quickly and accurately as typing for ABO
*What are the characteristics of Rh typing rgnts (rgnt anti-D)?
These rgnts may be:
1) High-protein-based
2) Low-protein-based
3) Saline-based
4) Chemically modified
5) Monoclonal
6) Blends of monoclonals
What is the most immunogenic Ag outside the ABO system?
D Ag
Since the D Ag is the most immunogenic Ag outside the ABO system, what should be done to avoid the occurrence of transfusion rxns?
Careful review of the medical history for pregnancy or transfusion of products containing RBCs
*What are the clinical results / manifestations, as well as the results for test of a pt w/ transfusion rxn due to the action of D Ag?
1) Unexplained fever
2) Mild bili elevation
3) Decrease in hgb
4) Decrease in haptoglobin
5) DAT is usually (+)
*What are the tests that can be done to determine the presence of D Ag?
1) Ab screen may demonstrate circulating Ab
2) Elution studies may be helpful
What is the characteristic of HDFN caused by Rh Abs?
It is often severe
The Rh Ags are well developed on what cells?
Fetal cells
What is Rh-immune globulin?
It is a purified preparation of IgG anti-D
Rh-immune globulin is given to what pts?
It is given to D-negative woman during pregnancy and after delivery of a D-positive fetus
Rh-immune globulin is effective only in preventing what condition?
RhD HDFN
If a pt lacks all Rh Ags on their RBCs, the pt has what disorder / syndrome?
Rhnull syndrome
What is present if a pt is Rhmod phenotype?
The pt have a partial suppression of RH gene expression caused by mutations in the RHAG gene
What will happen when the resultant RhAG protein is altered?
Normal Rh Ags are also altered often causing weakened expression of the normal Rh and LW Ags
True or False
The Landsteiner Weiner (LW) system dates from the time when Rh Ags were 1st recognized
True
In LW blood grp system, what is recognized many yrs later?
It was recognized that the 2 Abs were not identical
Who are the persons who described anti-rhesus?
1) Landsteiner
2) Wiener
Anti-rhesus was renamed as what?
Renamed as anti-LW in their honor
True or False
Phenotypically, there is no similarity between the Rh and LW systems
False, because phenotypically, there is a similarity between the Rh and LW systems
What are the characteristics of anti-LW?
1) It reacts strongly w/ most D-positive RBCs
2) It reacts weakly (sometimes not at all) w/ Rh (-) RBCs
3) It never reacts w/ Rhnull cells
4) It usually shows stronger (+) rxns w/ D-positive RBCs than w/ D-negative adult RBCs
5) It reacts equally well w/ cord cells regardless of their D type
