Free ASCP MLS Blood Banking Exam Mock Test – Part 59: Other Blood Group Systems

• Kell system antibodies (like anti-K) are almost always immune-mediated (resulting from transfusion, pregnancy, or transplant).

• They are IgG (mostly IgG1 and IgG3) and react at 37°C.

• They do not occur naturally and are not cold-reactive.

• They are clinically significant — can cause HDFN and acute/delayed hemolytic transfusion reactions.

Other options:

• a) Naturally occurring and IgM → False; Kell antibodies are not naturally occurring.

• c) Cold-reactive and complement-binding → False; Kell antibodies are warm-reactive.

• d) Clinically insignificant → False; they are highly significant.

• Lewis antibodies (anti-Leᵃ and anti-Leᵇ) are:

  • Typically IgM

  • Cold-reactive (optimal reaction at lower temperatures)

  • Generally not clinically significant for transfusion — they rarely cause hemolytic transfusion reactions or HDFN.

  • They may bind complement and cause in vitro hemolysis if fresh serum is used, but in vivo red cell destruction is uncommon.

Other options:

• b) Clinically significant and warm-reactive → False; they are not usually clinically significant and are cold-reactive.

• c) Complement-binding and hemolytic → They can bind complement and cause in vitro hemolysis, but this is not their primary characteristic; in vivo they are insignificant.

• d) IgG and reactive at 37°C → False; they are mostly IgM and react better at colder temperatures.

• Leᵃ is formed when the FUT3 (Lewis) gene acts on type 1 precursor chains, adding fucose.

• Leᵇ is formed when the individual is a secretor (has the FUT2 gene), which first makes H substance from type 1 chains, and then the Lewis gene adds another fucose to form Leᵇ.

• Thus, Leᵇ requires both the Secretor (H) gene and the Lewis gene, while Leᵃ requires only the Lewis gene.

Other options:

• b) Leᵃ is stronger in men → False; strength is not gender-dependent.

• c) Leᵇ reacts only at 4°C → False; Lewis antibodies can react at higher temperatures too.

• d) Leᵃ is not adsorbed onto red cells → False; both Leᵃ and Leᵇ are adsorbed from plasma.

• Anti-I is a common cold-reactive autoantibody.

• In infectious mononucleosis (caused by Epstein–Barr virus), patients often produce a transient cold agglutinin with anti-I specificity.

• This anti-I is typically IgM and can cause mild to moderate hemolytic anemia.

Let’s check the other options:

• a) Associated with warm AIHA → No, anti-I is a cold antibody; warm AIHA is usually associated with IgG antibodies against Rh antigens.

• c) Detected at 37°C in normal individuals → No, anti-I reacts best at cold temperatures (0–4°C), not at 37°C in normal people.

• d) Usually IgG → No, anti-I is typically IgM.

Let’s go through the options for the K (KEL1) antigen:

• a) It is absent from the red cells of neonates — False.
  K antigen is well developed at birth and can be detected on neonatal red cells.

• b) It is strongly immunogenic — True.
  After the ABO and Rh systems, K is one of the most immunogenic red cell antigens in transfusion medicine.

• c) It is destroyed by proteolytic enzymes — False.
  K antigen is part of the Kell glycoprotein, which is sensitive to some reducing agents (like DTT) but not destroyed by proteolytic enzymes (ficin, papain, etc.).

• d) It has a frequency of 50% in the random population — False.
  The K antigen frequency is about 9% in Caucasians, lower in other populations — far from 50%.

• TRALI (Transfusion-Related Acute Lung Injury) is caused by antibodies in donor plasma reacting with recipient leukocytes, leading to neutrophil activation and pulmonary capillary leakage.

• Antibodies implicated in TRALI:

  • HLA class I and II – against recipient leukocytes.

  • HNA (Human Neutrophil Antigens) – neutrophil-specific antibodies.

  • Neutrophil-specific antigens – subset of HNA antibodies.

• ABO antibodies – cause hemolytic transfusion reactions, but do not cause TRALI.

• The K (KEL1) antigen is highly immunogenic, meaning that after exposure (e.g., through transfusion or pregnancy), there is a high likelihood of antibody production.

• It is the third most immunogenic antigen after ABO and Rh D.

• Even a single exposure can provoke anti-K formation in K-negative individuals.

Other options:

• a) It’s present in high frequency → False; K antigen has a low frequency (~9% in Caucasians).

• b) It’s easily destroyed by enzymes → False; Kell antigens are resistant to proteolytic enzymes (but sensitive to DTT).

• d) It is a cold-reactive antigen → False; anti-K is IgG and reacts at 37°C.

• The S and s antigens are part of the MNS blood group system, along with M and N.

• M and N are located on glycophorin A, while S and s are located on glycophorin B.

Other options:

• a) Kell – Includes K, k, Kpᵃ, Kpᵇ, etc.

• c) Duffy – Includes Fyᵃ, Fyᵇ.

• d) P – Includes P1, P, Pᵏ (globoside system).

• Lewis antigens (Leᵃ and Leᵇ) are not intrinsic to the red cell membrane but are adsorbed from the plasma onto red cells.

• They are glycolipids synthesized in tissues and secreted into body fluids (plasma, saliva).

• Red cell Lewis phenotype can change if plasma environment changes (e.g., after transfusion).

Other options:

• a) Duffy – Intrinsic transmembrane protein.

• c) Kidd – Intrinsic red cell urea transporter.

• d) Lutheran – Intrinsic red cell membrane protein.

• Anti-M antibodies are often naturally occurring (can appear without previous red cell exposure).

• They are typically IgM and react best at cold temperatures (room temperature or below).

• They are not usually clinically significant for transfusion, but rare IgG anti-M can cause HDFN or hemolytic transfusion reactions.

Other options:

• b) Warm-reactive IgG → False; most are cold-reactive IgM, though IgG can occur.

• c) Clinically significant in all patients → False; most are not significant.

• d) Found only after transfusion → False; they can occur naturally.

• The M and N antigens are part of the MNS blood group system (ISBT 002).

• They are located on glycophorin A of the red cell membrane.

• The MNS system also includes other antigens such as S, s, and many variants.

Other options:

• b) Kidd – Includes Jkᵃ and Jkᵇ.

• c) Lewis – Includes Leᵃ and Leᵇ.

• d) Lutheran – Includes Luᵃ and Luᵇ.

• Anti-Fy3 is an antibody directed against a common epitope on the Duffy glycoprotein that is present when either Fyᵃ or Fyᵇ is expressed.

• It will react with Fy(a+b+), Fy(a+b–), and Fy(a–b+) phenotypes because all of these have the Duffy glycoprotein.

• It will NOT react with Fy(a–b–) phenotype cells, because these completely lack the Duffy glycoprotein (and are therefore resistant to Plasmodium vivax).

• As of the most recent update (2023/2024), the International Society of Blood Transfusion (ISBT) recognizes 44 human blood group systems.

• This number has increased over the years as new systems are discovered and defined.

The other options are too low:

• a) 10 – Far too low (this was the number known many decades ago).

• b) 20 – Still too low.

• d) 15 – Also too low.

• The Duffy antigen (Fy) acts as a receptor for Plasmodium vivax merozoites to invade red blood cells.

• Individuals with the Fy(a–b–) phenotype lack this receptor and are therefore resistant to P. vivax malaria.

• This phenotype is very common in people of African descent, which explains the lower incidence of P. vivax malaria in Africa.

Other options:

• a) Hepatitis B virus – Not related to Duffy antigen.

• c) Cytomegalovirus – Not related.

• d) Epstein–Barr virus – Not related.

• The McLeod phenotype is a result of mutations in the XK gene, which codes for the Kx protein.

• The Kx protein is linked to the Kell glycoprotein on the red cell membrane.

• In McLeod syndrome, absence or defect of Kx causes weak expression of all Kell system antigens.

• This is associated with chronic granulomatous disease (CGD) when the XK mutation occurs together with a mutation in the closely linked CYBB gene on the X chromosome.

Other options:

• Duffy, Kidd, and Lutheran are not affected in McLeod syndrome.

• Jkᵃ and Jkᵇ are the antithetical antigens of the Kidd blood group system (ISBT 009).

• They are carried on the urea transporter (UT-B1) in the red cell membrane.

Other options:

• a) Kell – Includes K, k, Kpᵃ, Kpᵇ, etc.

• b) Duffy – Includes Fyᵃ, Fyᵇ, etc.

• d) Lutheran – Includes Luᵃ, Luᵇ, etc.

• After ABO and Rh, the Kell system (especially anti-K) is considered the most clinically significant in transfusion medicine.

• Anti-K can cause severe hemolytic transfusion reactions (HTR) and hemolytic disease of the fetus and newborn (HDFN).

• It is highly immunogenic and often leads to strong IgG antibodies.

Other options:

• a) Kidd – Clinically significant (especially delayed HTR), but not ranked above Kell.

• c) Duffy – Can cause HTR and HDFN, but less immunogenic than Kell.

• d) MNS – Anti-M is often not clinically significant; anti-S and anti-s can be significant but less common than Kell.

• Kidd antibodies (anti-Jka, anti-Jkb) are IgG and often react weakly in vitro, making them sometimes hard to detect.

• However, they are potent complement activators, and in the presence of fresh complement, they can cause in vitro hemolysis.

• Clinical significance: Kidd antibodies are notorious for causing delayed hemolytic transfusion reactions and in vivo hemolysis.

• Other options:

  • Anti-Leᵃ – usually IgM, clinically insignificant, rarely causes hemolysis.

  • Anti-K – IgG, clinically significant, but does not usually cause complement-mediated hemolysis.

  • Anti-Fyᵃ – IgG, can cause hemolysis in vivo, but less efficient at activating complement in vitro compared to Kidd.

• Le(a–b+) phenotype requires:

  • Lewis gene (FUT3) – to produce the Lewis fucosyltransferase

  • Secretor gene (FUT2) – to produce H substance, which is then converted to Leᵇ

• Without the Lewis gene → Le(a–b–)

• Without the Secretor gene → Le(a+b–)

• With both genes → Le(a–b+)

• Paroxysmal cold hemoglobinuria (PCH) is associated with the Donath-Landsteiner antibody.

• This is an IgG autoantibody that has specificity for the P antigen (also known as globoside).

• It binds to red cells in the cold and fixes complement; upon warming, complement-mediated hemolysis occurs, leading to hemoglobinuria.

Other options:

• a) I – Associated with cold agglutinin disease (IgM anti-I).

• b) i – Also associated with cold agglutinins (less common).

• d) Leᵇ – Not associated with PCH.

• Anti-K is highly immunogenic and is the most common cause of HDFN outside the ABO and Rh systems.

• It can cause severe HDFN, including hydrops fetalis, by suppressing fetal erythropoiesis in addition to hemolysis.

• Anti-K is considered second only to anti-D in clinical significance for HDFN in populations where D-negative women are immunized.

Other options:

• a) Fyᵇ – Less immunogenic; rarely causes severe HDFN.

• c) Jkᵃ – Can cause HDFN but usually mild.

• d) S – Can cause HDFN but less common and severe than anti-K.

• The Duffy blood group system includes the Fyᵃ and Fyᵇ antigens.

• The Fy(a–b–) phenotype is very common among people of African descent (> 68% in African Americans).

• This phenotype results from a mutation in the Duffy promoter that prevents Duffy antigen expression on red cells.

• The Duffy antigen (Fy) is a receptor for Plasmodium vivax; without it, the red cells are resistant to invasion by this malaria parasite.

The other options do not match:

• Lu(a–b–) is very rare and not linked to malaria resistance.

• Jk(a–b–) causes urinary concentrating defects but not malaria resistance.

• K–k– is extremely rare and unrelated to malaria.

• Anti-K is highly clinically significant and can cause:

  • Immediate hemolytic transfusion reactions (if high titer)

  • Delayed hemolytic transfusion reactions

  • Severe Hemolytic Disease of the Fetus and Newborn (HDFN)

Other options:

• a) Anti-Fyᵃ – Can cause delayed reactions, but less commonly immediate severe reactions.

• c) Anti-Jkᵃ – Primarily causes delayed hemolytic reactions; immediate reactions are rare.

• d) Anti-Leᵃ – Usually not clinically significant; rarely causes hemolytic reactions.

• Proteolytic enzymes (such as ficin, papain, bromelin) destroy certain blood group antigens, including those in the Duffy system (Fyᵃ and Fyᵇ).

• Enzyme treatment typically enhances the reactivity of some other antigens (like Rh, Kidd), but destroys M, N, Fyᵃ, and Fyᵇ.

Let’s check the options:

• a) Jkᵃ – Not destroyed; enzymes may actually enhance Kidd system reactivity.

• b) E – Not destroyed; Rh antigens are generally resistant or enhanced.

• c) Fyᵃ – Destroyed by enzyme treatment.

• d) k – Not destroyed; Kell system antigens are sensitive to DTT but not to proteolytic enzymes.

• Parvovirus B19 uses the P antigen (also known as globoside) as its cellular receptor to infect red cell precursors.

• Individuals who lack the P antigen (very rare p phenotype) are resistant to parvovirus B19 infection.

Other options:

• a) P1 – Not the receptor for parvovirus B19.

• c) Pk – Intermediate in biosynthesis of P, but not the primary receptor.

• d) p – This is the phenotype lacking P antigen, not the antigen itself.

• K₀ (Kell null) red cells lack all Kell system antigens.

• Dithiothreitol (DTT) is a reducing agent that destroys Kell system antigens by breaking disulfide bonds in the Kell glycoprotein.

• Treating normal red cells with DTT can create in vitro K₀-like cells for antibody identification (e.g., to confirm anti-Kpᵇ by showing loss of reactivity after DTT treatment).

Other options:

• a) Ficin – A proteolytic enzyme; affects MNS, Duffy, but not Kell antigens.

• b) Chloroquine diphosphate – Used to remove IgG from red cells (for phenotyping in the presence of IgG coating), not to destroy Kell antigens.

• d) Polyethylene glycol (PEG) – An enhancement medium for antibody detection, not for antigen destruction.

• The LW (Landsteiner–Wiener) blood group system has antigens LWᵃ and LWᵇ.

• Key points:

  • LWᵃ is a high-prevalence antigen, present on most red cells.

  • Expression of LW antigens is enhanced on D-positive cells, not reduced.

  • LW antibodies are usually IgG, react best at the antiglobulin (AHG) phase, not at room temperature.

  • Rh-null cells are usually LW(a+b+), not LW(a-b-).

• Kidd (JK) antibodies (anti-Jkᵃ and anti-Jkᵇ) are well known for causing delayed hemolytic transfusion reactions (DHTR).

• They often drop to very low or undetectable levels in the plasma after initial immunization, making pre-transfusion antibody screens sometimes negative.

• Upon re-exposure to the antigen during transfusion, a rapid anamnestic response occurs, leading to antibody production and destruction of transfused red cells days after the transfusion.

• They are not a common cause of severe immediate hemolytic reactions, significant HDFN, or allergic reactions.

• Lewis antigens are glycolipids produced by tissue cells (especially gastrointestinal) and secreted into plasma.

• They are adsorbed onto the red cell membrane from the plasma.

• Their formation depends on the interaction of two genes:

  • FUT3 (Lewis gene) – Encodes a fucosyltransferase that adds fucose to precursor substance to form Leᵃ.

  • FUT2 (Secretor gene) – Encodes a fucosyltransferase that makes H substance; if present, Leᵇ is formed.

Other options:

• a) Genes on the X chromosome → False; Lewis gene (FUT3) is on chromosome 19.

• c) Structural proteins on the red cell membrane → False; they are adsorbed glycolipids, not intrinsic proteins.

• d) Inheritance through mitochondrial DNA → False.

• Lutheran antibodies (anti-Luᵃ and anti-Luᵇ) are often naturally occurring (can appear without prior red cell exposure).

• They are typically IgM and react best at room temperature or below.

• They are generally not clinically significant and rarely cause hemolytic transfusion reactions or HDFN.

Other options:

• b) Clinically significant and IgG → False; they are usually not significant and are IgM.

• c) Complement-binding → Some may bind complement, but it’s not a defining feature.

• d) IgE and heat-labile → False; not IgE.

• The p phenotype (also called globoside-deficient) results from the lack of P, P1, and Pᵏ antigens due to a defect in the synthesis of the globoside series.

• Individuals with the p phenotype naturally produce a potent IgM antibody called anti-PP1Pᵏ (historically known as anti-Tjᵃ).

• This antibody reacts with all red cells except those of the very rare p phenotype, making it clinically significant.

Other options:

• a) Anti-P1 – Found in P1-negative individuals (common), not the p phenotype.

• b) Anti-P – Found in Pᵏ phenotype individuals, not the p phenotype.

• d) Anti-Pᵏ – Not relevant to p phenotype.

• Paroxysmal cold hemoglobinuria (PCH) is associated with the Donath-Landsteiner antibody, which is an IgG autoantibody with specificity for the P antigen (globoside).

• This antibody binds to red cells in the cold, fixes complement, and upon warming causes intravascular hemolysis.

Other options:

• b) P1 – Not associated with PCH.

• c) S – Part of MNS system, unrelated.

• d) Leᵃ – Lewis system, unrelated.

• Kpᵃ (KEL3) and Kpᵇ (KEL4) are antithetical antigens in the Kell blood group system.

• They are located on the Kell glycoprotein along with other Kell antigens like K, k, Jsᵃ, Jsᵇ.

Other options:

• a) Kidd – Includes Jkᵃ and Jkᵇ.

• c) Lutheran – Includes Luᵃ and Luᵇ.

• d) Duffy – Includes Fyᵃ and Fyᵇ.

• In FNAIT, the newborn has thrombocytopenia due to maternal alloantibodies against fetal platelet antigens (most often HPA-1a).

• Maternal platelets are the preferred treatment because they lack the target antigen and are not susceptible to the maternal antibody.

• They must be washed and irradiated to remove maternal plasma (which contains the antibody) and prevent transfusion-associated graft-versus-host disease.

Other options:

• a) Random donor platelets – Likely to be destroyed by the maternal antibody.

• b) Paternal platelets – Would likely have the offending antigen and be destroyed.

• d) Granulocyte transfusions – Not indicated for FNAIT.

• Proteolytic enzymes (ficin, papain, bromelin, trypsin) alter or destroy certain red cell antigens by cleaving protein structures on the membrane.

• S antigen (MNS system) is enzyme-sensitive and is destroyed or weakened by enzyme treatment.

• Other options:

  • K (Kell system) – generally resistant to enzyme treatment.

  • Jka (Kidd system) – resistant to enzymes.

  • E (Rh system) – resistant to enzymes.

Let’s check each option:

• a) Lewis antigens are well developed at birth → False. Lewis antigens are poorly developed at birth and may not be detectable until several months of age.

• b) Lewis antibodies are often IgG and cause HDFN → False. Lewis antibodies are typically IgM and do not cause Hemolytic Disease of the Fetus and Newborn because the antigens are poorly developed on fetal/neonatal red cells and are not synthesized by the fetus.

• c) Lewis antigens are absorbed from the plasma onto the red cell membrane → True. Lewis substances are glycolipids produced by tissue cells and secreted into plasma, where they adsorb onto red cells.

• d) Lewis antibodies are typically clinically significant → False. Most Lewis antibodies (anti-Leᵃ, anti-Leᵇ) are not considered clinically significant for transfusion because they often do not cause reduced red cell survival.

• The Cartwright (Yt) blood group system antigens (Ytᵃ and Ytᵇ) are carried on acetylcholinesterase, an enzyme anchored to the red cell membrane.

• This enzyme’s function in red cells is not fully understood, but it may have a role in regulating acetylcholine.

Other options:

• b) Alkaline phosphatase – Not associated with a known blood group system.

• c) Lactate dehydrogenase – A cytoplasmic enzyme, not a red cell surface antigen carrier.

• d) Glycophorin A – Carries M/N antigens (MNS system).

• The Colton blood group system antigens (Coᵃ, Coᵇ) are located on aquaporin-1 (AQP1), a water channel protein.

• The Co(a–b–) null phenotype results from mutations in the AQP1 gene, causing absence of the Colton antigens.

• Individuals with this phenotype have a subclinical reduction in red cell water permeability but are generally healthy.

Other options:

• a) Glucose transporter – Carries the GLUT1 protein (associated with the Gill blood group system).

• b) Urea transporter – Carries the Kidd antigens (JK system).

• d) Anion exchanger (Band 3) – Carries the Diego blood group system antigens.

• The Mᵏ (Miltenberger) phenotype involves a rare mutation that results in the deletion of both glycophorin A (GPA) and glycophorin B (GPB).

• Consequences for blood group antigens:

  • S and s antigens are carried on GPB. If GPB is absent, S and s are not expressed.

  • Kx antigen – part of the Kell system, still present.

  • Enᵃ – high-incidence antigen, present.

  • G antigen – carried on GPA, so may be absent if GPA is deleted; however, the question focuses on antigens specifically affected by deletion of glycophorin B (GPB), which is S.

• MNS system antibodies (especially anti-S, anti-s, and some anti-M) can demonstrate a dosage effect — stronger reactivity with homozygous expression (e.g., SS vs. Ss) than with heterozygous expression.

• This is common with many blood group systems where antigen strength correlates with gene dose.

Other options:

• b) No serologic reaction → False; they do react.

• c) Weak reactions only at cold temperatures → Anti-M is often cold-reactive, but anti-S/s are IgG and react at 37°C.

• d) No enzyme sensitivity → False; MNS antigens (M, N, S, s) are sensitive to proteolytic enzymes.

• The k antigen (Cellano) is highly prevalent, present in ~99% of the population.

• For an individual to produce anti-k, they must lack the k antigen.

• Therefore, their red cell phenotype must be k-negative.

• The KEL genotype options:

  • KK → has K antigen, usually K-positive, k-positive as well.

  • Kk → has K and k antigens.

  • kk → lacks K antigen, but actually expresses k normally. Wait — let’s carefully check:

Let’s reason step by step:

• KEL system: two main antithetical antigens are K (KEL1) and k (KEL2).

• K is low frequency (~9%), k is high frequency (~99%).

• To make anti-k, a person must lack the k antigen, which is extremely rare.

• The genotype K₀K₀ is used to denote someone negative for both K and k.

• High-incidence antigens are present in >99% of the population.

• Vel is a high-incidence antigen; very few people lack it (Vel-negative phenotype is rare).

Other options:

• a) K – Low incidence (~9% in Caucasians).

• b) Jkᵃ – Relatively common (~77% in Caucasians) but not >99%.

• d) Leᵃ – Present in ~22% of Caucasians, not high incidence.

• Anti-K is typically an IgG antibody that reacts optimally at 37°C and is detected in the antiglobulin (AHG) phase of testing.

• It is immune-stimulated and clinically significant.

Other options:

• a) Anti-M – Usually IgM, reacts best at room temperature or below.

• b) Anti-Leᵃ – Usually IgM, reacts best at immediate spin or room temperature.

• d) Anti-P1 – Usually IgM, cold-reactive.

Each of these antigen pairs represents allelic antigens from the same blood group system, and most individuals express both members (one inherited from each parent):

• M and N (MNS system):

  • Found on glycophorin A.

  • Most people inherit one M and one N allele → express both M and N antigens.

• K and k (Kell system):

  • Codominant alleles on the Kell glycoprotein.

  • Most individuals are Kk, expressing both K and k antigens.

• S and s (MNS system):

  • Found on glycophorin B.

  • Most individuals are Ss, expressing both S and s antigens.

• Kidd antibodies (anti-Jkᵃ, anti-Jkᵇ) are known to decline rapidly after initial immunization and can become undetectable in routine antibody screening.

• Upon re-exposure to the antigen during transfusion, a strong anamnestic response occurs, leading to delayed hemolytic transfusion reactions (DHTR).

• This makes them particularly dangerous because pre-transfusion testing may miss them.

Other options:

• a) Are easily detected in screening tests → False; they are often missed.

• b) Often cause mild transfusion reactions only → False; they can cause severe hemolysis.

• d) Are naturally occurring → False; they are immune-stimulated.

• Kidd system antibodies (anti-Jkᵃ, anti-Jkᵇ) are notorious for causing delayed hemolytic transfusion reactions (DHTR).

• They often drop to undetectable levels between exposures, leading to negative pre-transfusion screens, but upon re-exposure, they can cause rapid anamnestic responses and hemolysis days after transfusion.

Other options:

• a) Lewis – Usually not clinically significant; rarely cause DHTR.

• b) P – Anti-P1 is typically not significant; anti-PP1Pᵏ can cause immediate, not delayed, reactions.

• d) MNS – Anti-M is often not significant; anti-S/s can cause DHTR but less commonly than Kidd.

• Anti-S (MNS system) is usually IgG and reacts best at the antiglobulin (AHG) phase.

• Its reactivity can be enhanced by proteolytic enzyme treatment (e.g., ficin, papain), which removes steric hindrance and exposes certain epitopes.

• Other options:

  • Anti-M – typically IgM, reacts at cold temperatures, and enzyme treatment usually destroys or weakens it.

  • Anti-Fyᵃ – IgG, enzyme-sensitive, so treatment destroys its antigen; reactivity is reduced.

  • Anti-Leᵃ – IgM, enzyme-sensitive; reactivity decreases with enzyme treatment.

• In the Kell blood group system:

  • K (KEL1) – low-frequency antigen (~9% in Caucasians).

  • k (Cellano, KEL2) – high-frequency antigen (~99% of the population).

  • Kpa – low-frequency antigen (~2%).

  • Jsa – very low-frequency antigen (~0.1%).

• Clinical significance:

  • Individuals lacking k are extremely rare, but if they produce anti-k, it can cause severe hemolytic transfusion reactions.

• In warm autoimmune hemolytic anemia (WAIHA), the patient produces IgG autoantibodies that often react with all red cells, including donor units, making crossmatching difficult.

• If the autoantibody shows Rh specificity, selecting blood that is negative for the corresponding Rh antigens (i.e., phenotypically matched) can help reduce hemolysis.

• Other options:

  • Rh-null blood – unnecessary unless the patient requires complete Rh antigen-negative blood; extremely rare.

  • Saline-washed red cells – may reduce plasma antibodies but does not solve the problem of autoantibodies.

  • Selecting units incompatible at 37°C – unsafe; only compatible units should be transfused.

• Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) occurs when maternal alloantibodies against fetal platelet antigens cross the placenta and destroy fetal platelets.

• In Caucasian populations, the most common cause is maternal anti-HPA-1a (about 80% of cases).

• The mother is usually HPA-1a negative and the father/fetus is HPA-1a positive.

Other options:

• a) HLA-A – HLA antibodies can cause platelet refractoriness in transfusion but are not the main cause of FNAIT.

• c) HPA-5b – The second most common cause in Caucasians, but far less frequent than HPA-1a.

• d) ABO – ABO incompatibility is not a common cause of FNAIT.

• The MNS blood group system antigens are located on:

  • Glycophorin A – carries M and N antigens

  • Glycophorin B – carries S, s, and other related antigens

Other options:

• a) Kidd – Located on the urea transporter (UT-B1).

• c) Duffy – Located on the Duffy glycoprotein (Fy), a chemokine receptor.

• d) Lewis – Not intrinsic to red cell membrane; glycolipids adsorbed from plasma.

• Duffy antigens (Fyᵃ and Fyᵇ) are destroyed by proteolytic enzymes like papain, ficin, and bromelin.

• This property is used in blood bank serology to help identify antibodies — if an antibody stops reacting with enzyme-treated cells, it may be anti-Fyᵃ or anti-Fyᵇ.

Other options:

• b) Heat – Not typically used to destroy Duffy antigens; heat can denature proteins but is not specific for Duffy.

• c) Chemicals such as EDTA – EDTA is an anticoagulant that chelates calcium; it does not destroy Duffy antigens.

• d) Low ionic strength solution – Used to enhance antibody uptake, not to destroy antigens.

• Anti-P1 is typically a naturally occurring IgM cold-reactive antibody.

• It reacts best at lower temperatures (e.g., 4°C) and often shows weak or no reactivity at 37°C.

• It is generally not clinically significant for transfusion, as it rarely causes hemolytic transfusion reactions.

Compare with the others:

• a) Anti-K – IgG, clinically significant.

• b) Anti-Jkᵃ – IgG, can cause delayed hemolytic transfusion reactions.

• d) Anti-Fyᵃ – IgG, clinically significant.

• Fyᵃ and Fyᵇ are the main antithetical antigens of the Duffy blood group system (ISBT 008).

• The Duffy glycoprotein is a receptor for Plasmodium vivax malaria parasites.

• The Fy(a–b–) phenotype is common in people of African descent and confers resistance to this form of malaria.

Other options:

• b) Lewis system – Includes Leᵃ and Leᵇ.

• c) MNS system – Includes M, N, S, s, etc.

• d) Kell system – Includes K, k, Kpᵃ, Kpᵇ, etc.

• M and N antigens are located on glycophorin A, which is sensitive to proteolytic enzymes.

• Treatment with ficin, papain, or bromelin destroys M and N antigen activity.

• This is used in serological testing to help identify antibodies — loss of reactivity after enzyme treatment suggests anti-M or anti-N.

Other options:

• b) Heat only – Not typically used to destroy M/N; heat can denature proteins but is not specific.

• c) Acids – Not standard for antigen destruction in blood bank testing.

• d) Formaldehyde – Can modify red cell antigens but is not routinely used for this purpose.

A dosage effect means the antibody reacts more strongly with red cells that are homozygous for the corresponding antigen than with cells that are heterozygous.

Let’s check each option:

• a) Anti-Leᵃ – Lewis antibodies (anti-Leᵃ) generally do not show a clear dosage effect because Lewis antigens are not intrinsic to the red cell membrane but are adsorbed from plasma.

• b) Anti-P1 – Anti-P1 often shows variable reactivity, but not a consistent dosage effect based on zygosity because P1 antigen strength is influenced by factors other than gene dose.

• c) Anti-M – Anti-M can show dosage in some cases, but many examples react well regardless of zygosity; it’s not the most classic example.

• d) Anti-Fyᵃ – Anti-Fyᵃ is well known for showing a strong dosage effect — it reacts more strongly with Fy(a+b–) cells than with Fy(a+b+) cells.

• The Lutheran blood group system (Luᵃ and Luᵇ) is controlled by the LU gene on chromosome 19.

• The null phenotype Lu(a-b-) occurs when an individual inherits two nonfunctional LU alleles, meaning it is autosomal recessive.

• Characteristics:

  • Extremely rare.

  • Individuals may produce anti-Luᵃ or anti-Luᵇ if exposed to the antigen via transfusion.

• Other options:

  • Autosomal dominant – would require only one allele; not applicable.

  • X-linked – Lutheran system is not X-linked.

• Platelet refractoriness occurs when transfused platelets fail to produce the expected rise in platelet count.

• The most common cause is alloimmunization to HLA (Human Leukocyte Antigen) class I antigens on donor platelets.

• Febrile Non-Hemolytic Transfusion Reactions (FNHTR) are also frequently caused by HLA antibodies reacting with donor leukocytes or platelets.

• Other options:

  • Rh, Kell, Kidd – primarily relevant to red blood cells and hemolytic reactions, not platelet refractoriness.

• The Diego blood group system antigens (including Diᵃ, Diᵇ, Wrᵃ, etc.) are located on Band 3, the red cell anion exchange protein (AE1).

• Band 3 is important for CO₂ transport and red cell structural integrity.

Other options:

• a) Glycophorin A – Carries M/N antigens.

• c) Aquaporin – Carries Colton antigens.

• d) Decay-accelerating factor (DAF) – Carries Cromer antigens

• Lewis antigens (Leᵃ and Leᵇ) are not directly produced by red cell precursors, but are absorbed from the plasma onto the red cell membrane.

• Their formation depends on the interaction of the FUT3 (Lewis gene) and FUT2 (Secretor gene) enzymes:

  • Nonsecretor (se/se) → no H substance secreted in body fluids → cannot make Leᵇ.

  • If the Lewis gene (FUT3) is active, the person makes Leᵃ antigen in secretions, which gets adsorbed onto RBCs.

  • So phenotype: Le(a+b–).

• Le(a–b+) requires being a secretor (to make H, then Leᵇ).

• Le(a–b–) occurs if the Lewis gene itself is inactive (FUT3 deficient).

• Le(a+b+) is rare and usually temporary, seen in infants or some populations.