Rh Blood Group System

when testing type, what antigen do the Rh refer to

D antigen

currently Rh consists of 61 different atigens, what are the main Rh antigens that we’re concerned about

D, C, E, c, and e

what chromosome are the Rh genes located on

two Rh genes on chromsome 1

what are the two genes responsible for the Rh expression in the Tippet Theory

RHD and RHCE

what does the RHD gene code for

the prescence of RhD protein

what does the RHCE gene code for

encodes CcEe proteins in four combinations (RhCe, RhcE, Rhce, and RhCE)

are RHD and RHCE codominant

yes, they produce antigens detectable on an RBC

what chromosome is the RHAG gene located on

chromsome 6

what does coexpressor mean in terms of the RHAG gene

the gene must be present for the successful expression of the Rh antigens, it can’t express antigens by itself

what does mutation of the RHAG gene most likely result in

affects antigen expression causing missing or altered RhD or RhCE proteins resulting in the Rh_null phenotype

four terminologies used to describe the Rh system

fisher-race DCE terminology

Wiener Rh-Hr terminology

rosenfield: alphanumeric terminology

international society of blood transfusion committee (ISBT) - numeric terminology

theory behind the fisher-race

Rh antigens are inherited as a gene complex or haplotype that code for three closely linked sets of alleles

each gene is responsible for producing an angtigen on the RBC surface

D gene inherited at one locus, C or c at second, and E or e at the third locus

order of genes in the fisher-race theory

DCE

what are the dominant and codominant genes in the fisher-race theory

D gene is dominant to the d gene

Cc and Ee are codominant

if the genes D, C, and e are inherited from both parents then how is the haplotype written

DCe (genotype is DCe/DCe)

theory behind the wiener theory

one gene is responsible for coding 3 different Rh antigen (one haplotype expresses 3 different antigens)

DCe

R¹

R¹

DCe

Ce

r’

r’

Ce

DcE

R²

R²

DcE

cE

r”

r”

cE

DCE

R^z

R^z

DCE

CE

r^y

r^y

CE

Dce

R^o

R^o

Dce

ce

r

r

ce

theory behind rosenfield nomenclature

a system that assigns a number to eacha ntigen of the Rh system in order of its duscovery or recognized relationship to the Rh system

advantage of using rosenfield nomenclature

expedites data entry and retrieval

how are the 5 antigens labeled in the rosenfield nomenclature

D = Rh1

C = Rh2

E = Rh3

c = Rh4

e = Rh5

theory behind the ISBT nomenclature

establishes a uniform nomenclature that is eye and machine-readable with the first 3 numbers being system specific and the last 3 antigenic specific

keeps with genetic basis of blood groups

DCe/ce

R¹r

DCe/DCe

R¹R¹

DCe/DcE

R¹R²

DcE/ce

R²r

DcE/DcE

R²R²

Dce/ce

R⁰r

Dce/Dce

R^oR^o

DCE/ce

R^z/r

ce/ce

rr

Ce/ce

r’r

Ce/Ce

r’r’

cE/ce

r”r

cE/cE

r”r”

Ce/cE

r’r”

CE/ce

r^yr

R¹r

DCe/ce

R¹R¹

DCe/DCe

R¹R²

DCe/DcE

R²r

DcE/ce

R²R²

DcE/DcE

R^or

Dce/ce

R^oR^o

Dce/Dce

R²r

DcE/ce

rr

ce/ce

r’r

Ce/ce

r’r’

Ce/Ce

r”r

cE/ce

r”r”

cE/cE

r’r”

Ce/cE

r^yr

CE/ce

purpose of the mandate in ISBT nomeclature

uniformity and bar code scannable

biochemsitry of an Rh antigen

non-glycosylated proteins (no carbohydrates)

very immunogenic

reside on transmembrane proteins

number of D antigen sites varies depending on Rh phenotype

has 61 different RBC antigens related to Rh blood group system

function of Rh antigen

to help maintain the structural integrity of the RBC membrane

act as molecular transporters (may transport ammonia)

might be CO₂ transporters

structure of the Rh antigen

small loops of Rh protein exposed on the surface of the RBC

chracteristics of the Rh antigen

only detected on the RBC

not soluble or expressed on other cells

integrated into the RBC membrane (passes through RBC wall 12 times)

present at birth

very immunogenic

potent to least potent immunogenicity of Rh antigens

D > c > E > C > e

how much exposure can stimulate the production of the Rh antibody

less than 0.1 mls of D positive blood stimulates antibody formation

antigen D frequency

about 90%

antigen C frequency

about 80%

antigen E frequency

about 75%

antigen c frequency

about 66%

antigen e frequency

about 98%

what are the 3 main variations of D that can lead to weaknened expression of D antigen

position effect

quantitative

partial D or D mosaic

what is the position effect in relation to weakened expression of the D antigen

the C and D are in a trans position

the position effect in relation to weakened expression of the D antigen causes what

a suppressive effect or interferes with the expression of the D antigen

the position effect in relation to weakened expression of the D antigen cannot be distinguished from genetic weak D without

molecular studies

the quantiative variation that leads to weakned D antigen due to fewer antigen sites is a result from

a mutation in the RHD gene (inherited) causing changes or deletions in amino acids present in the transmembrane

people with weak D rarely form

anti-D

the quantiative variant that has weak D due to fewer D antigen sites is mostly found in people of ___________ descent

african

the quantitative variation causing a weakned expression of D due to D_el causes what

the RBC expression of D antigen to be extremely low (low enough that it can’t be detected by routine serologic methods) and is only detected by adsorption/elution methods

the quantiative variation causing a weakned expression of D due to D_el occurs in

up to 30% of D negative people pf southeast asian descent (they do not make anti-D in response to transfusion or pregnancy)

rare in causcasions

the partial D variation aka D mosiac is caused by

a portion of the RHD gene being replaced by a portion of the RHCE gene causing individuals who are positive for D antigen to make alloantibodies after exposure

those who have partial D or D mosiac are missing parts of the D antigen complex so when exposed to a whole D antigen what happens

they can make an antibody to the part they’re missing (causing HTR and HDFN)

what immunoglobulin class do the Rh antibodies belong to

IgG

two most clinicially significant IgGs

IgG1 and IgG3

are Rh antibodies naturally occuring

no, only formed after exposure to foreign red cells (usually through transfusion or pregnancy)

are Rh antibodies clnically significant

yes, they recat optimally at 37 degrees celsius

do Rh antibodies show dosage

may show dosage

do Rh antibodies bind complement

no, hemolysis takes place extravascularly

can Rh cross the placenta and cause HDFN

yes

four pathophysiology steps that occur in HDFN

1. IgG anti-D are produced from previous exposure

2. IgG anti-D crosses the placenta into fetal circulation and coats the Rh D positive RBCs

3. the coated RBCs are hemolyzed in the spleen

4. the newborn’s immature liver can’t conjugate bilirubin which causes jaundice

five symptoms seen in a baby with HDFN

kernicterus (bilirubin in the brain)

jaundice

hepatosplenomegaly

hydrops fetaliz (bloated baby)

anemia

symptoms of a transfusion reaction associated with Rh antibodies

fever

mild bilirubin elevation

decreased in hgb and haptoglobin

DAT positive = elution studies for specificities

antibody screen will be positive

when can circulated antibody show up

10-14 days after primary exposure

1-7 days after secondary exposure