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First antigen discovered:
D antigen, Rh positive mean D-positive.
Tippet's theory on Rh gene:
Two loci on chromosome 1. RHD and RHCE.
RHCE is made up of:
4 different alleles. RHCE, RHCe, RHcE, and RHce.
Gene products are:
non-glycosylated proteins containing 417 amino acids.
Rh associated glycoprotein:
Not part of Rh blood group system. Coded for on chromosome 6. Absence in this gene causes absences in RHCE and RHD proteins.
Fisher-Race is also known as:
CDE terminology
Fisher-Race:
Phenotype expressed as CDE sequence with D sometimes missing if pt is D-negative.
Wiener is also known as:
Rh-Hr terminology.
Alexander Wiener postulated that:
one loci was responsible for Rh system expression.
Determining the genotype from the phenotype:
Can be done if you have phenotype of patient using commercial antisera and race of the patient.
D-antigen:
The most immunogenic, high ability to elicit immune response. This antigen concentration differs based upon phenotype.
Weak D (Du)
A weak form of the D antigen that may require indirect antiglobulin testing to detect.
Weak D genetics:
Some genes encode for weaker expression of the antigen. This is seen when antigen is inherited in trans to C-antigen.
Partial D/Mosiac D is:
When a persons are missing part of D-antigen complex. A type of weak D. The anti-D does not interact with their own partial antigen.
Significance of weak D:
Labeled as D-positive. Important to test all donors for weak D. Recipients do not need to be tested bc if they are D-neg, they will only receive D-neg units.
What is the flowchart for immunogenicity in the antigens of the Rh system?
D >c>E>C>e
G antigen:
Rh polypeptide with serine at position 103. Coded for by both RHD and RHCE genes.
Patients with G-antigen:
Can produce anti-G that mimics an anti-C and anti-D. Differentiation requires extensive testing. Simply look for C-neg and D-neg transfusion units.
Cw antigen:
Rare antigen in individuals of European and African ancestry. Can cause alloimmunization that leads to anti-Cw antibody in patients.
Compound antigens (cis product antigens):
An additional antigen product when two genes are inherited in cis position.
Examples of compound antigens are:
f-antigen is formed when c and e are in the cis positions. Ce-antigen is formed when C and e are inherited in cis form.
What to do with patient that has compound antigen?
Best to transfuse patient with units negative for one of the antigens that forms the compound of interest.
Partial deletions:
Patient is negative for C/c and-or E/e antigens. May or may not have D antigen activity. A dash mark is used to designate this. (cD- or -DEe as examples).
Rh null phenotype:
RHAG gene mutation (regulator type). Mutations in RHCE gene with RHD deletion and normal RHAG gene (amorphic type). Results in hemolytic anemia.
General characteristics of Rh antibodies:
'Unexpected antibodies', typically IgG that don't readily bind complement, can be enhanced by albumin, LISS, proteolytic enzymes, or PEG. Dosage reactions can be seen with C/c and E/e.
Rh system clinical considerations:
Second most significant blood group system. Can cause hemolytic transfusion reactions. Frequent case of hemolytic disease of the newborn.
High protein D typing reagent:
IgG anti-D in 20% protein dilution. A Rh control is required for this reagent to assure increased protein does not cause spontaneous agglutination of cells leading to false positives.
Low protein reagent:
Monoclonal or polyclonal IgM in 6% protein solution. IgM allows agglutination to occur at immediate spin without need for high albumin content. Can often detect weak D directly. Rh control needed for AB patients.
Chemically modified anti-D:
Largely outdated due to monoclonal antibodies. Chemically alter anti-D to allow agglutination directly without protein media.
Possible reason for FALSE POSITIVE reactions in Rh typing:
Contaminated reagents, abnormal proteins in patient/donor plasma causing rouleaux, use of wrong antiserum.
Possible reasons for FALSE NEGATIVE reactions in Rh typing:
Failure to add antiserum, use of wrong antiserum, red blood cell suspension too heavy, patient/donor RBCs with variant Rh antigen that does not react with antiserum.
LW blood group system:
Three alleles code for this system. Anti-LW with react with most D-pos cells.