L.3 Rh Blood Group System

Question 1

What discovery did Levine & Stetson make in 1939?

Answer 1

They discovered that the sera of most women who gave birth to infants with hemolytic disease contained an antibody that reacted with the red cells of the infant and with the red cells of 85% of Caucasians.

Question 2

What did Landsteiner and Wiener discover in 1940?

Answer 2

They discovered that injecting blood from the monkey Macacus rhesus into rabbits and guinea pigs resulted in an antibody that agglutinated rhesus (Rh) red cells.

Question 3

How were donors classified based on the agglutination of Rh red cells?

Answer 3

Donors whose cells were agglutinated were termed Rh positive; those whose cells were not agglutinated were termed Rh negative.

Question 4

What is the relationship between the antibody obtained by Landsteiner and Wiener and the antibody recognized in human hemolytic disease?

Answer 4

The antibody reacts with an antigen (LW) that is different but closely related to the one recognized in human hemolytic disease.

Question 5

What can happen if a mother is Rh-negative and the baby is Rh-positive?

Answer 5

The mother’s immune system could attack the baby’s blood cells.

Question 6

What is the next important antigen in transfusion practice after A and B?

Answer 6

Antigen D.

Question 7

What percentage of D negative individuals form Anti-D after a D+ to D- transfusion?

Answer 7

Approximately 80%.

Question 8

What percentage of cases result in Anti-D formation when a D+ baby is delivered to a D- mother?

Answer 8

16%.

Question 9

What change occurred 20 years after the discovery of Rh incompatibility in pregnancy?

Answer 9

Effective treatment became available.

Question 10

Why is the Rh status of mothers-to-be checked during pregnancy?

Answer 10

To identify those at risk of hemolytic disease of the newborn (HDN).

Question 11

What is matched in all blood transfusions?

Answer 11

The Rh status.

Question 12

How many main Rh antigens are in the Rh blood group system?

Answer 12

5 main Rh antigens: D, C, c, E, e.

Question 13

Which Rh antigen is the most important?

Answer 13

Antigen D (RhD).

Question 14

What type of proteins are the RhD and RhCE?

Answer 14

Transmembrane, multipass proteins that are integral to the RBC membrane.

Question 15

How are Rh proteins different from most cell surface molecules?

Answer 15

They are not glycosylated but are closely related to a RBC membrane glycoprotein called RhAG.

Question 16

How many times do the polypeptides of Rh proteins span the membrane?

Answer 16

12 times.

Question 17

Approximately how many amino acids do the Rh proteins have?

Answer 17

Approximately 417 amino acids.

Question 18

What are the two loci that encode the Rh blood group?

Answer 18

Two tightly linked loci on chromosome 1

Codominant alleles located next to each other on the chromosome.

Question 19

What does the RHD gene encode?

Answer 19

RhD antigens

The RHD gene is responsible for producing the RhD antigen found on red blood cells.

Question 20

What does the RHCE gene encode?

Answer 20

RhCE antigens

The RHCE gene produces the RhCE antigen, which is also found on red blood cells.

Question 21

What are the two historic genetic theories related to Rh antigens?

Answer 21

Fischer-Race theory and Wiener theory

Fischer-Race theory suggests Rh antigens are controlled by 3 closely linked loci, while Wiener theory states they are controlled by alleles at one gene locus.

Question 22

What is the symbol used to indicate deletion of the RHD gene in D negative individuals?

Answer 22

dd

This symbol indicates the absence of the RhD antigen.

Question 23

How do the polypeptides encoded by RHD and RHCE differ?

Answer 23

By 36 amino acids

Differences at key residue positions determine serologic typing to be C or c, E or e.

Question 24

What polymorphism most commonly arises from a deletion of the entire RHD gene?

Answer 24

D/d polymorphism

This leads to the absence of the RhD antigen.

Question 25

How does the C/c polymorphism arise?

Answer 25

From 4 SNPs causing 4 amino acid changes ## Footnote One of the SNPs (S103P) determines the C or c antigen specificity.

Question 26

What causes the E/e polymorphism?

Answer 26

A single SNP (676G->C) ## Footnote This SNP results in a single amino acid change (A226P).

Question 27

What is the relationship between the D antigen's immunogenicity and the RhD protein?

Answer 27

The RhD protein is quite 'foreign' to those lacking it ## Footnote This foreignness likely contributes to its immunogenicity.

Question 28

What type of antibodies are produced against the 5 Rh antigens?

Answer 28

IgG type ## Footnote These antibodies are highly immunogenic and reactive at 37°C.

Question 29

What is the main effect of Rh antibodies in transfusion reactions?

Answer 29

Causing significant hemolytic transfusion reactions ## Footnote They can also lead to Hemolytic disease of newborns.

Question 30

How do Rh antibodies mediate RBC destruction?

Answer 30

Via macrophages in the spleen (extravascular hemolysis) ## Footnote Rh antibodies rarely bind complement.

Question 31

What test is best for detecting Rh antibodies?

Answer 31

Indirect antiglobulin test (Coombes test) ## Footnote This test is used for identifying the presence of Rh antibodies.

Question 32

What type of blood is sometimes given when anti-E antibody is identified?

Answer 32

E-negative AND c-negative blood ## Footnote A weak anti-c antibody is often seen with anti-E antibody.

Question 33

What antibodies have been involved in hemolytic transfusion reactions?

Answer 33

Anti-D, anti-C, anti-E, anti-e ## Footnote Particularly involved in delayed reactions.

Question 34

What typically causes delayed transfusion reactions?

Answer 34

A secondary immune reaction to a foreign RBC antigen previously encountered ## Footnote Prior exposure can occur through pregnancy or previous blood transfusions.

Question 35

What type of hemolysis is most common in delayed transfusion reactions?

Answer 35

Extravascular hemolysis ## Footnote It is slower, longer in duration, and symptoms are less pronounced compared to acute reactions.

Question 36

What is the primary cause of Haemolytic Disease of Foetus and Newborn?

Answer 36

Rhneg woman giving birth to a Rhpos fetus ## Footnote Mother's immune system produces Anti-D antibodies against fetal RBCs.

Question 37

Which antibody type is produced first in Haemolytic Disease of Foetus and Newborn?

Answer 37

IgM antibodies ## Footnote Cannot cross placental barriers.

Question 38

What happens during isotype switching in Haemolytic Disease of Foetus and Newborn?

Answer 38

IgG antibodies are produced ## Footnote These can cross the placenta and attack fetal RBCs.

Question 39

What does the International Society of Blood Transfusion (ISBT) do?

Answer 39

Attempts to standardize nomenclature ## Footnote Assigns six-digit numbers to each blood group specificity.

Question 40

What does the ISBT number 004 refer to?

Answer 40

The Rh system ## Footnote Other numbers refer to the Rosenfield system.

Question 41

What typically causes weak D antigens?

Answer 41

A single amino acid switch in the transmembrane region of the RhD protein ## Footnote Disrupts RhD protein insertion into the RBC membrane.

Question 42

How do RBCs with weak D antigens typically test?

Answer 42

Positive only by IAT ## Footnote Often associated with the cDe haplotype.

Question 43

In which population are weak D antigens more common?

Answer 43

The black population ## Footnote Formation of anti-D is prevented, allowing patients to receive D-positive blood.

Question 44

What causes partial D antigens?

Answer 44

Creation of a hybrid RhD and RhCE protein ## Footnote Lacks several epitopes found on the complete RhD protein.

Question 45

What should individuals with partial D antigens avoid?

Answer 45

Receiving Rh D-positive blood ## Footnote They may produce anti-D toward the missing part.

Question 46

What characterizes individuals with the Rh null phenotype?

Answer 46

They have RBCs that do not express any of the Rh antigens ## Footnote Caused by the deletion of RHAG.

Question 47

What are the consequences of the absence of the Rh complex?

Answer 47

Alters RBC shape, increases osmotic fragility, shortens lifespan ## Footnote Results in a usually mild hemolytic anemia.

Question 48

What risk do Rh null individuals face regarding transfusions?

Answer 48

They may produce antibodies against several of the Rh antigens ## Footnote Can develop Anti-Rh29, antibodies to 'total' Rh antigens.