Other Blood Group Systems, Part 2 PDF

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Summary

Kell Blood Group System (ISBT 006)- Discovered in 1946 by Coombs, Mourant and Race. - Kell remained a two-antigen system until other antithetical antigens named Kpa, Kpb, Jsa, and Jsb were discovered. Today it consists of 32 high and low incidence antigens - In 1957, the Kell null phenotype was disc...

Description

MLSC-3200, Transfusion Science Kell Blood Group System (ISBT 006) -

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Discovered in 1946 by Coombs, Mourant and Race. Kell remained a two-antigen system until other antithetical antigens named Kpa, Kpb, Jsa, and Jsb were discovered. Today it consists of 32 high and low incidence antigens In 1957, the Kell null phenotype was discovered (K0). In 1961, the McLeod phenotype was discovered. The development of Kell antigens is controlled by two co-dominant genes (K and k). The K antigen in present in about 9% of the population, while the k antigen is present in about 99.8% of the population. Rare samples have been found to lack both genes (Kell null). There are three major allelic pairs of genes. o K and k o Kpa and Kpb o Jsa and Jsb The resulting Kell antigen is a combination of these three pairs of genes. The K antigens are sensitive to treatment with sulfhydryl reagents. If exposed, the reagent breaks the disulphide bonds to create an RBC that lacks the Kell antigen. Reagents include 2-ME, DTT, and AET. The K antigen is almost immunogenic as the D antigen and are expressed on RBCs as early as 10 months after birth. Phenotyping Frequency o K-k+, 91% of Whites and 98% of Blacks. High frequency. o K+k-, 0.2% of Whites and rare in Blacks. o K+k+, 8.8% in Whites and 2% in Blacks. o Kp(a+b-), rare in Whites and 0% in Blacks. o Kp(a-b+), 97.7% in Whites and 100% in Blacks. High frequency. o Kp(a+b+), 2.3% in Whites and rare in Blacks. o Js(a+b-), 0% in Whites and 1% in Blacks. o Js(a-b+), 100% in Whites and 80% in Blacks. High Frequency. o Js(a+b+), rare in Whites and 19% in Blacks.

Kell Antibodies -

Anti-K, the most common antibody after the ABO/Rh antibodies. Primarily made of IgG, but Anti-Kell IgM has been seen in bacterial infection. These antibodies react in the antiglobulin phase and binds complement. Anti-K is not affected by routine enzymes and shows dosage (hetero/homozygous expression strength differs). Can cause severe hemolytic transfusion reactions and HDFN when it crosses the placenta. Anti-k, Anti-Kpa- Jsb, very rarely seen in patients since most people possess their corresponding antigens on their RBCs.

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Anti-Jsa, Anti-Kpa, have a very low frequency antigens, so the exposure to them is minimal. Results in these antibodies being rare in patients.

Anti-K and Pregnancy -

Kell-related issues can occur in a K- mother having a child with a K+ father. Pregnancy is not an efficient immunizer in this situation, resulting in the HDFN more often being mild. However, it can still be severe in some cases. Patients will be monitored for Anti-K using antibody titres, have their MCA-PSV tested (monitors fetal blood flow from mother), and may be monitored for cardiocentesis.

Kell and The MacLeod Phenotype -

Affects males since the inheritance is X-linked and comes from a carrier mother. This is a rare phenotype that is characterized by a weak expression of k, Kpa and Jsb. These patients can make Anti-Kx and Anti-Km antibodies against their own antigens, which will harm the patient. McLeod Syndrome, associated with chronic granulomatous disease and muscular abnormalities that intensify as time goes on. Blood smear shows acanthocytosis, reticulocytotic, reduced serum haptoglobin, anisocytosis and increased osmotic fragility. o Granulomatous Disease, patient WBCs lack NADPH which results in them being able to only engulf microorganisms and not destroy them. Results in increased susceptibility to normal flora infections and recurring infections.

Cross-Matching Blood for Kell -

Anti-K Positive, units selected for transfusion are required to be negative for the K antigen and crossmatch compatible. Anti-k Positive, units selected for transfusion are required to be negative for the k antigen. However, the incidence of k- blood is very rare (0.2%), so finding a donor can be problematic. May have to resort to CBS, patient’s family members or, if possible, autologous units.

Duffy Blood Group System (ISBT 008) -

Discovered in 1950 when Mr. Duffy, a multiple transfused hemophilic, was found to have anti-Fya. In 1951, anti- Fyb discovered, which in turn led to the discovery of Fy b. The antigen is produced by two co-dominant allelic genes ( Fya and Fyb). A third allele results in the null phenotype Fy(a-b-) (common in Blacks). Additional antigens associated with the system include Fy3, Fy4, Fy5, Fy6, and Fyx. Duffy antigens can be identified on fetal RBCs as early as 6 weeks after birth. They also don’t store well in saline and elute from RBCs in low pH/low ionic strength medium.

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Duffy antigens are also destroyed by common proteolytic enzymes such as ficin, papain, bromelin and ZZAP. Phenotyping Frequency, Duffy null is most commonly found in the Black population and Duffy positive-homozygous is most commonly found in the White population. Duffy can help us determining paternity. Works the same way as typically co dominant inherited genes.

Duffy Antibodies -

Predominantly IgG, bind complement, inhibited by enzymes and show dosage. These antibodies react best at 37 degrees following IAT since they are IgG. Cause HDFN and delayed HTR. o Delayed HTR, after the primary exposure to the antigen, the level of the antibody can decrease to a non-detectable level. This may result in a false negative AntiDuffy reaction. If these patients are given Duffy positive blood, the anti-Duffy antibodies will rise quickly to cause HTR. This is known as an anamnestic response.

Duffy and Malaria -

In 1975, Miller and colleagues reported that Duffy null individuals, mostly Blacks, were resistant to malarial infection. Later on, it was learned that Fya and Fyb served as receptors for the invasion of malarial parasites. The absence of these receptors conferred the resistance to malaria seen in the Black population with Fy(a-b-) phenotypes.

Crossmatching Duffy Blood -

Anti-Fya and Anti-Fyb, units selected for transfusion must be antigen negative and IAT crossmatch compatible.

Kidd Blood Group System (ISBT 009) -

Discovered in 1951 by Dr. Allen when a new antibody in the serum of Mrs. Kidd was found. Her child subsequently suffered from HDFN. The antibody is called Kidd which was then shortened to Jk, chosen from the father’s initials (John Kidd). A year later, another antibody was discovered and called anti-Jkb. Kidd only involves three genes and is the most straight-forward blood group. Jka and Jkb are products of two co-dominant genes (Jka and Jkb). Most people have both antigens.

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Rare examples of Jk null phenotype individuals are often reported from Polynesia, South America, India or Filipino descent. This occurs when a silent Jk gene is inherited from each parent. Phenotyping Frequency, the presence of antigens is typically evenly distributed between the entire population. However, the null phenotype is rare in Blacks and Whites, while being more common in Polynesians.

Kidd Antibodies -

Primarily IgG, react best at 37 degrees following IAT testing, enhanced by enzymes, bind complement, and cause hemolysis of antigen positive cells in vivo/vitro. Show dosage when a single and double dose antigen positive RBCs are used. Anti- Jka occurs most commonly than anti Jkb, although both are rare in general. These antibodies cause HDFN when they cross the placenta. It is also notorious for delayed HTR (even more than Duffy Abs). These antibodies will deteriorate rapidly after exposure to undetectable levels and will rise quickly in the presence of its corresponding antigen (anamnestic response). Usually associated with the presence Rh antibodies.

Crossmatching Kidd Blood -

Anti-Jka or Anti-Jkb Positive, units selected for transfusion must be antigen negative and IAT crossmatch compatible.

The Lutheran Blood Group System (ISBT 005) -

Discovered in 1945, the Anti-Lua antibody was found in a patient with lupus who underwent a recent transfusion with this low incidence antigen. The system is made up of 24 antigens of high incidence with corresponding antibodies infrequently encountered. There are two primary antigens, Lua and Lub, which are produced by allelic co-dominant genes. These antigens are poorly developed at birth and reach adult levels at 15 years of age. The Lu locus is found on chromosome 19 and linked to the Se locus. Phenotyping Frequency, the most popular phenotype is Lu(a-b+), with 92% of the population having this phenotype.

MLSC-3200, Transfusion Science Lutheran Antibodies -

Anti-Lua, may be present without immune RBC sensitization. It may be either IgG, IgM or IgA. Some bind complement without in vitro hemolysis. Usually go undetected in routine testing because most reagent cells are Lu(a-). Since most people are Lu(a-b+), those who have the antibody will not react with our RBCs. This Ab reacts optimally at RT in vitro and is known for giving mixed field reactions. Not clinically significant in transfusion but can cause mild cases of HDFN. Anti-Lub, this is a rare IgG Ab due to the high incidence of the Lub antigen. Clinically significant since it can cause HTR and HDFN. Also shows mixed field reactions.

Cross matching Lutheran Blood -

Antisera for Lua and Lub are not routinely available for typing donor units. As a result, units selected for transfusion must be IAT crossmatch compatible and are not required to be negative for the corresponding antigen.

Cold Reacting Antibodies (IgM) -

Anti-Lea Anti-Leb Anti-I Anti-P1 Anti-M Anti-A,B,H Anti-N Use the acronym LIiPMABHN to memorize these.

Warm Reacting Antibodies -

Rh Antibodies Kidd Antibodies Kell Antibodies Duffy Antibodies S,s, and U Antibodies All IgG, clinically significant, and can cause HTR and HDFN. Patients with these antigens require antigen negative cells that are crossmatch compatible.

Antibody Enzyme Activity -

Enzyme Enhanced, Kidd, Rh, Lewis, I, and P. Enzyme Destroyed, Duffy, M, N, S and s. Enzymes that interact with antibodies include Papain, Bromelin, Ficin and Trypsin. Kell antibodies are unaffected by enzymes.

MLSC-3200, Transfusion Science Dosage Antibodies -

Kidd Duffy Rh MNS Kidds and Duffy the Monkey (RH) eat lots of M&Ns. These antibodies show different dosage based on antigens being able to be inherited heterozygously/homozugously....