Chapter 6 Rh Blood Group System Flashcards
After ABO what is the 2nd most important blood group system?
Rh blood group system.
What does Rh positive mean?
A person has a D antigen on their RBCs.
There are more than 50 antigens identified in the system. D is the most clinically significant.
What is the most immunogenic antigen?
D antigen.
How much blood with D antigen can it take to stimulate an immune response?
Exposure to less than 0.1 mL can stimulate a response. This can occur through transfusion or while delivering a baby (or a traumatic pregnancy).
What are the 5 major Rh antigens (out of 50)?
D, C, E, c, e
What makes the Rh antigens different than most other antigens or is noteworthy?
Most RBC antigens include carbohydrates in their make-up but Rh antigens are only proteins.
Also it loops the membrane 12 times in short loops of amino acids on the exterior (no CHO). Therefore it is an integral part of the RBC and maintains its integrity.
What determines what antigens are present in the Rh system?
The antigen varies between two amino acids on specific spots in the long chain. This determines what antigens are present based on the genetic material inherited.
What antigens are antitheticals in the Rh system?
C, c, E, and e.
What type of genes control the expression of all Rh antigens?
Two closely linked genes (co-dominant alleles):
1. RHD gene - determines the expression of the D antigen.
2. RHCE gene: determines the expression of C, c, E, and e antigens.
What is the Fisher-Race terminology for the Rh antigens?
- Each gene expresses an antigen that is given the same letter as the italicized letter of the gene name (e.g., the C gene produces the C antigen).
- Order of genes is usually DCE (may be CDE)
- 8 possible set of genes inherited (from one parent):
Dce, DCe, DcE, DCE
dce, dCe, dcE, dCE
What is the wiener terminology based on?
8 alleles exist at the single Rh gene locus.
R0, R1, R2, Rz, r, r’, r”, ry
(subscripts, see slide 14)
Each gene encodes an agglutinogen (made of factors) that correlates with Rh antigens.
What is an agglutinogen?
A group of antigens or factors.
What (in general) is Rosenfield terminology for the Rh antigen system?
Indicates phenotype information more suited for computerized data entry.
Antigens are designated by number
Rh1:D
Rh2:C
Rh3:E
Rh4:c
Rh5:e
Example:
D+, C+, E–, c+, e+ is written as Rh:1,2,–3,4,5
What is the ISBT terminology?
International Society of Blood Transfusion
Attempts to standardize nomenclature
Six-digit numbers are assigned to each blood group specificity
The numbers 004 refer to the Rh system. The other numbers refer to the Rosenfield system (e.g., C antigen is RH2)
Example: ISBT number for the C antigen is 004002
How can genotypes be predicted without doing a molecular study?
Race can be used to predict the most probable genotype after the phenotype (i.e. antigen type) is determined.
What occurs after the immediate spin with a weak D antigen in phenotype testing?
A weak D may look negative with anti-D after immediate spin.
What do you do if you discover a weak D?
Follow through test into IAT phase for both D tube and Rh C tubes.
Antisera contains IgM and IgG.
What test can identify a weak D antigen?
RBCs that test positive only by the indirect antiglobulin test (IAT) are called Weak D antigens.
New monoclonal reagents have enhanced the detection of weak D antigens without the IAT.
What are the theories on the causes of a weak D expression?
There are three different theories of inheritance patterns:
1. Inherited Genetic Coding
2. Gene Position Effect
3. Partial D (also referred to as D mosaic)
What is the genetic reason for the weak D antigen (mutations that alter amino acids)?
Due to inheritance of a weaker form of the D antigen, often the cDe haplotype (R0)
Mutations that alter amino acids at the molecular level
More common in the black population (23%)
IAT is usually required to detect the weak antigen
Describe how position effect can cause a weak D antigen?
The D antigen may appear weak when the C antigen is inherited trans to D (2%)
Ce (r’) gene is paired with either Cde (R1) or cDe (R0)
How do newer monoclonal antisera blends help discover weak D when due to C trans to D?
Increased sensitivity of newer Anti-D are usually positive in the immediate spin phase
Patients are considered weak D positive and are able to receive D-positive blood
What does it mean to have a partial D antigen?
Individuals are D positive but are missing parts of the D antigen (partial D antigen)
When exposed to the “whole D antigen,” individuals may produce anti-D toward the missing part.
What can make you suspect a partial D antigen on a patient?
When a patient is D-positive but makes anti-D and it does not react with his or her own RBC.
When are you required to test for weak D? Not to?
Required to test all D negative results for weak D antigen if they are initially non-reactive on:
1. All donor blood
2. Pregnant females
3. Newborns from Rh negative mothers.
Don’t necessarily test recipients, just give them D negative blood (unless workplace has different policy).
What could happen if you don’t follow-up with weak D testing?
- Donor blood - you would falsely call it Rh negative. You would give to Rh negative people that could be stimulated to form Anti-D.
- Pregnant females – if identified falsely as Rh negative, would be monitored closely and would receive RhIg unnecessarily
- Newborns from Rh negative mothers – if identified falsely as Rh negative the mother would not receive RhIg and may form Anti-D. This can can cause HDFN in subsequent pregnancies
What are cis-product antigens and what is the significance of it?
Two genes inherited on the same chromosome may form additional antigen products
Example: c and e antigens cause “f” to be inherited
Can illicit it’s own immune response
What genes code for the G antigen?
Almost all genes that code for the C or D antigen will code for the G antigen.
How can someone start producing anti-G antibody?
Anti-G antibody will mimic anti-D and anti-C antibodies. If an individual is negative for D and/or C and receives D-positive and/or C-positive blood, he or she may produce anti-G antibody (appears as anti-D or anti-C antibody).
What type of blood is given if a person has the anti-G antibody in their blood?
If anti-G antibody is present, give D-negative and C-negative blood
What gene is required for the Rh antigens to be present (besides those already discussed) and is a co-expresser?
Regulator gene for RhAG blood group system on chromosome 6 produces a similar protein structure as Rh but with a carbohydrate attached. It forms complexes with the Rh antigens on the membrane and must be present for successful expression of the Rh antigen (i.e. co-expressor).
What happens if mutations occur to the regulator gene on chromosome 6?
If mutations can occur such that there is no RhAG protein, and no RhD or RhCE expression.
What unusual RH phenotypes results in no reactions with anti-E, anti-e, anti-C, or anti-c?
D-deletion:
-D- or D–
Stronger D antigen activity
Transfuse only D-deleted cells
The RhCE genes are missing or non-functional
What is Rhnull and two genetic causes?
No Rh antigens
Two possible genetic mechanisms
1. Regulator gene: RHAG mutation causes no Rh gene expression
2. Amorph (r=) - means RHD gene is absent and lack of expression of RHCE gene causing no Rh protein production.
Impaired rbc membrane
What is the phenotype when most Rh antigen expression is missing?
Rhmod.
Similar to Rhnull
Most Rh antigen expression is missing; the RHAG gene also controls this phenotype
How soon after 1st and 2nd exposure are Rh antibodies produced?
Usually RBC stimulated
From pregnancy or transfusion
Ab’s produced within 120 days first exposure
Ab’s produced within 2-7 days on second exposure
What is the most typical antibody type produced in response to the Rh antigens?
Most are immunoglobulin G (IgG1)
Do Rh antibodies activate complement?
No they do not.
What Rh antibodies tend to be present in a person?
Often have antibodies to more than one Rh antigen
E-negative and c-negative blood is sometimes given when anti-E antibody is identified.
Weak anti-c antibody is often seen with anti-E antibody.
Why is it difficult to detect Rh antibodies in a person?
Rh antibody levels may be undetectable for years but produce a rapid response upon exposure to the antigen
Not likely to have any effect on the first transfusion
What is the result of a transfusion reaction?
Often causes extravascular hemolytic transfusion reaction
Removed by spleen = increased bilirubin, mild fever
Positive DAT
What situation causes Hemolytic disease of the Fetus and Newborn?
- HDFN may occur when a woman is Rh negative and the fetus/infant is Rh positive
- Antibodies may form during the first pregnancy
- Maternal antibodies may destroy fetal RBCs in subsequent pregnancies
What is done for a pregnant woman who is Rh negative to prevent HDFN?
Rh immune globulin will protect the mother from forming anti-D antibody
What is the LW blood group system and how does it related to the Rh blood group system?
LW antigens and antibodies are similar to Rh antigens, but are not genetically related
Anti-LW antibody will react with D-positive (strong) and D-negative (weak) cells
Alleles include Lwa, LWb, and LW (Note a & b are superscript).
The most common phenotype is LW(a+b–)
Why would you not want to form an anti-e?
You would not want to form an anti-e because if you needed a transfusion it would be hard to get blood without the e antigen because 98% of people have the e antigen.
What % of people have the D antigen versus not?
85% have the D antigen (inherited from one or both parents).
15% do not have the D antigen (inherited from both parents).
What % of people have the C antigen and the c antigen?
70% have the C antigen (inherited from one or both parents).
80% have the c antigen (inherited from one or both parents).
What percentage of people have the E antigen and the e antigen?
30% have the E antigen (inherited from one or both parents)
98% have e antigen (inherited from one or both parents).
