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Y3S2 - Foundations of Haematology > T3 - Rh and Other Blood Groups > Flashcards

T3 - Rh and Other Blood Groups Flashcards

1
Q

Dosage Effect of Antigen Expression

A

With some blood group antigens, an individual who is homozygous for the antigen will express more of that antigen compared to someone who is heterozygous
It is said that the homozygote has “double dose” expression of the antigen on their RBCs

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2
Q

Dosage

A

Dosage refers to how antibodies react to antigens which demonstrate a dosage effect
Some antibodies react stronger to cells which have homozygous expression of the target antigen
These antibodies are said to demonstrate dosage
- e.g. anti-Jka demonstrates dosage as it reacts stronger to cells which have homozygous expression of Jka

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3
Q

Rh Blood Group System

A

After ABO, it is the most clinically important blood group
- antigens are highly immunogenic
- antibodies can cause HTR and HDNB
Consists of 5 major antigens (C, c, D, E, e) and over 50 antigens in total
- there is no “d” antigen
- well developed at birth
- enhanced by enzyme treatment

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4
Q

Rh Genetics

A

Two closely linked loci, RHD and RHCE encode the antigens
- found on chromosome 1
RHD encodes the D antigen
RHCE encodes the C, c, E, e antigens
- C and c, and E and e, are antithetical pairs
- antithetical pair - a pair of antigens encoded by different alleles of a single gene
Antigens are co-dominantly expressed

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5
Q

D Antigen Genetics

A

Presence of at least one D allele = D antigen
Absence of D allele = D not expressed (i.e. ‘d’)
D antigen differs from CE protein by 35 aa
Contains at least 30 different epitopes
- epitope - specific antibody binding site
For these reasons, the D antigen is highly immunogenic

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6
Q

C, c, E and e Genetics

A

C and c differ by 6 nucleotides, resulting in 4 amino acid changes
- serine => proline @ aa 103 is the most important
E and e differ by a single nucleotide, resulting in a single amino acid change
- proline => alanine @ aa 226
Results in 4 main alleles:
- RHce
- RHCe
- RHcE
- RHCE

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7
Q

Rh Inheritance

A

Rh genes are inherited as a haplotype
- haplotype - a group of genes inherited from a single parent
One set of RHD and RHCE genes from one parent, the second set from the other
Offspring’s genotype is written as the haplotype inherited from each parent, separated by a forward slash
- e.g. DCe/dce

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8
Q

Four Different Systems of Rh Nomenclature

A

Fisher-Race
Wiener
Rosenfield
ISBT

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9
Q

Rh Nomenclature - Fisher-Race

A

Each antigen is represented by a letter
- C, c, D, E, e
- d is used to represent ‘absence of D’. There is no d antigen
A haplotype is written as a triplet of letters
- e.g. dce, DCe
A genotype is written as the two inherited haplotypes, separated by a forward slash
- e.g. DCe/dce
Phenotype written as corresponding antigens that are expressed on the RBCs
- e.g. DCe/dce = DCce

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10
Q

Rh Nomenclature - Wiener

A

Uses a series of R/r and numbers/primes (‘) to represent the haplotype/genotype/phenotype
System relates to the Fisher-Race nomenclature
R = D antigen expressed
r = absence of D antigen
Big C plus little e = R1 or r’
Little c plus big E = R2 or r’’
Little c plus little e = R0 or r (no prime)

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11
Q

Rh Antibodies

A 
Immune
Usually IgG
Don’t bind complement
React optimally @ 37oC
Detect using the indirect antiglobulin test (IAT)
Anti –C, -c, -E, -e demonstrate dosage
Highly clinically significant
- haemolytic transfusion reactions (usually extravascular)
- haemolytic disease of the newborn
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12
Q

Weak D

A

Expression of the entire D antigen is decreased
RBCs with weak D give weaker reactions during testing
Reaction strength is technique dependent
As individuals with weak D express the complete D antigen, they are considered Rh(D) positive

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13
Q

Partial D

A

Regions of RHD are replaced by regions of RHCE => protein product is missing part of the D antigen
Individuals expressing partial D are considered either Rh(D) negative OR Rh(D) positive, depending on the whether they are a recipient or donor
Recipient:
- partial D individuals express an incomplete D antigen
- they can produce an anti-D antibody if exposed to the complete D antigen
- should be typed as Rh(D) neg and administered Rh(D) neg blood
Donor:
- the partial D antigen is immunogenic to a Rh(D) neg recipient
- it can stimulate the production of anti-D, and can cause HTRs
- should be typed as Rh(D) pos

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14
Q

Kell Blood Group

A

Blood group consists of two major antigens

  • K and k
  • protein
  • antithetical pair expressed in a co-dominant fashion
  • well developed at birth
  • K is highly immunogenic
  • not destroyed by enzymes, but are by reducing agents such as DTT or AET
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15
Q

Kell Blood Group Antibodies

A 
Anti-K
- usually IgG
- best detected at 37°C using the IAT
- can cause HTR and HDNB
- finding compatible blood for someone with an anti-K antibody is usually easy
Anti-k
- very rare
- usually IgG
- best detected at 37°C using the IAT
- can be difficult to find compatible blood
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16
Q

Kidd Blood Group

A

Two major antigens:

  • Jka and Jkb
  • protein
  • antithetical pairs expressed in a co-dominant fashion
  • well developed at birth
  • poor immunogens
  • enhanced by enzyme treatment
17
Q

Kidd Blood Group Antibodies

A

Anti-Jka and anti-Jkb

  • usually IgG
  • best detected at 37°C using the IAT
  • can be difficult to work with: (often weak, demonstrate dosage and can be found in combination with other aby’s)
  • titre quickly declines in vivo
  • unstable on storage
  • common cause of delayed HTR, rarely cause HDNB
18
Q

MNS Blood Group

A

Consists of 5 major antigens:
- M, N, S, s, U
- protein
M/N are expressed on glycophorin A (GPA)
- antithetical pair, co-dominantly expressed
- destroyed after enzyme treatment
S/s and U are expressed on glycophorin B (GPB), as is U
- S/s are antithetical, co-dominantly expressed
- S/s are destroyed after enzyme treatment (except trypsin)
- U is not destroyed by enzyme treatment

19
Q

MNS Antibodies

A 
Anti-M and anti-N
- usually naturally occurring antibodies that react below 37°C
- IgM or IgG
- anti-M demonstrates dosage
- don’t react with enzyme treated cells
- not clinically significant unless reactive @ 37°C
Anti-S and anti-s
- IgG
- best detected at 37°C using the IAT
- demonstrate dosage
- don’t react with enzyme treated cells
- can cause HTR and HDNB
- can be difficult to find compatible units for individual w/ anti-s
20
Q

Duffy Blood Group

A

Two major antigens:

  • Fya and Fyb
  • antithetical pairs expressed in a co-dominant fashion
  • well developed at birth
  • destroyed after enzyme treatment
21
Q

Duffy Blood Group Antibodies

A

Anti-Fya and anti-Fyb

  • best detected at 37°C using the IAT
  • demonstrate dosage
  • don’t react with enzyme treated cells
  • anti-Fya more common than anti-Fyb
  • cause HTR and mild to severe HDNB

Y3S2 - Foundations of Haematology (24 decks)

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