Beyond the ABO and Rh systems, there are more than 60 recognized blood group systems, each with unique antigens that may cause immune responses during transfusion or pregnancy.
This chapter introduces the clinically significant non-ABO/Rh blood group systems, such as Kell, Kidd, Duffy, MNS, Lewis, Lutheran, and P, which play important roles in immunohematology and patient safety.
These systems are essential for antibody identification, compatibility testing, and the prevention of hemolytic transfusion reactions.
Topics Covered in This Chapter
- Overview of major blood group systems:
- Kell System (K, k, Kp, Js)
- Kidd System (Jkᵃ, Jkᵇ)
- Duffy System (Fyᵃ, Fyᵇ)
- MNS System (M, N, S, s, U)
- Lewis System (Leᵃ, Leᵇ)
- Lutheran and P Systems
- Antigen frequencies and genetic inheritance
- Clinical significance and transfusion reactions
- Antibody characteristics (IgG/IgM, complement activation, enzyme reactivity)
- Identification and interpretation of non-ABO/Rh antibodies
Why It Matters
Although less common than ABO or Rh incompatibility, antibodies from these systems can cause delayed hemolytic transfusion reactions (DHTR) and hemolytic disease of the newborn (HDN).
Recognizing their serologic patterns is essential for safe transfusion practices and advanced antibody identification workups.
Learning Outcomes
After studying this section, learners should be able to:
- Interpret serologic test results related to these systems.
- Identify the major non-ABO/Rh blood group systems and their key antigens.
- Recognize the clinical significance of antibodies in each system.
- Understand antigen frequencies and inheritance patterns.
4481 MCQs (4481-4540):
- The K (KEL1) antigen is characterized by which of the following?
a) It is absent from the red cells of neonates
b) It is strongly immunogenic
c) It is destroyed by proteolytic enzymes
d) It has a frequency of 50% in the random population - Which of the following phenotypes is most commonly found in the African American population and confers resistance to Plasmodium vivax malaria?
a) Lu(a-b-)
b) Jk(a-b-)
c) Fy(a-b-)
d) K-k- - Antibodies in the Kidd (JK) blood group system are most associated with which of the following?
a) Immediate hemolytic transfusion reactions
b) Hemolytic Disease of the Fetus and Newborn (HDFN)
c) Delayed hemolytic transfusion reactions
d) Allergic transfusion reactions - Proteolytic enzyme treatment of red blood cells will typically destroy which of the following antigens?
a) Jkᵃ
b) E
c) Fyᵃ
d) k - An individual has been sensitized to the k antigen and has produced anti-k. What is the most probable KEL genotype for this individual?
a) KK
b) Kk
c) kk
d) K₀K₀ - Which of the following antibodies is most likely to show a dosage effect?
a) Anti-Leᵃ
b) Anti-P1
c) Anti-M
d) Anti-Fyᵃ - The red cells of a nonsecretor (se/se) will most likely type as:
a) Le(a-b-)
b) Le(a+b+)
c) Le(a+b-)
d) Le(a-b+) - Anti-Fy3 will fail to react with which of the following red cells?
a) Fy(a+b+)
b) Fy(a+b-)
c) Fy(a-b+)
d) Fy(a-b-) - Which of the following statements is true about the Lewis system?
a) Lewis antigens are well developed at birth
b) Lewis antibodies are often IgG and cause HDFN
c) Lewis antigens are absorbed from the plasma onto the red cell membrane
d) Lewis antibodies are typically clinically significant - The McLeod phenotype, associated with chronic granulomatous disease (CGD), is characterized by a weak expression of which blood group system antigens?
a) Duffy
b) Kidd
c) Kell
d) Lutheran - Which of the following antibodies is usually an IgM cold agglutinin and is considered clinically insignificant?
a) Anti-K
b) Anti-Jkᵃ
c) Anti-P1
d) Anti-Fyᵃ - Paroxysmal cold hemoglobinuria (PCH) is associated with an autoantibody that has specificity for which antigen?
a) I
b) i
c) P
d) Leᵇ - Which of the following blood group systems is most commonly associated with platelet refractoriness and Febrile Non-Hemolytic Transfusion Reactions (FNHTR)?
a) Rh
b) Kell
c) HLA
d) Kidd - A patient with the rare p phenotype would likely have an antibody with which specificity?
a) Anti-P1
b) Anti-P
c) Anti-PP1Pᵏ
d) Anti-Pᵏ - Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is most frequently caused by maternal antibodies against which antigen?
a) HLA-A
b) HPA-1a
c) HPA-5b
d) ABO - Which of the following is a characteristic of anti-I?
a) It is often associated with warm autoimmune hemolytic anemia
b) It is found in the serum of patients with infectious mononucleosis
c) It is detected at 37°C in the serum of normal individuals
d) It is usually an IgG antibody - Which of the following antigens is destroyed by treatment of red cells with proteolytic enzymes such as ficin or papain?
a) K
b) Jkᵃ
c) E
d) S - The Lutheran null phenotype, Lu(a-b-), is inherited as what type of trait?
a) Autosomal dominant
b) Autosomal recessive
c) X-linked dominant
d) X-linked recessive - Which of the following antibodies is most likely to cause in vitro hemolysis when fresh complement is present?
a) Anti-Leᵃ
b) Anti-K
c) Anti-Fyᵃ
d) Anti-Jkᵃ - hich of the following is a high-incidence antigen?
a) K
b) Jkᵃ
c) Vel
d) Leᵃ - Antibodies to which of the following systems are NOT implicated in Transfusion-Related Acute Lung Injury (TRALI)?
a) HLA
b) HNA
c) ABO
d) Neutrophil-specific antigens - Inheritance of the rare Mᵏ gene results in the deletion of glycophorin A and B. Which antigen would NOT be expressed?
a) Kₓ
b) Enᵃ
c) S
d) G - Which of the following is the preferred treatment for a newborn with Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)?
a) Random donor platelets
b) Paternal platelets, washed
c) Maternal platelets
d) Granulocyte transfusions - The Diego blood group system antigens are carried on which red cell membrane protein?
a) Glycophorin A
b) Band 3
c) Aquaporin
d) Decay-accelerating factor (DAF) - Which of the following antibodies is typically IgG and reactive at the antiglobulin phase, but its reactivity is enhanced by treating red cells with proteolytic enzymes?
a) Anti-M
b) Anti-Fyᵃ
c) Anti-Leᵃ
d) Anti-S - The Colton null phenotype, Co(a-b-), is associated with a defect in which red cell channel?
a) Glucose transporter
b) Urea transporter
c) Water channel (aquaporin-1)
d) Anion exchanger (Band 3) - Which of the following statements is true about the LW blood group system?
a) D-positive red cells express less LW antigen than D-negative cells
b) Rhₙᵤₗₗ red cells are also LW(a-b-)
c) LW antibodies generally react best at room temperature
d) The LWᵃ antigen is a high-prevalence antigen - A patient with warm autoimmune hemolytic anemia (WAIHA) has an autoantibody that demonstrates Rh specificity. What is the most appropriate course of action when crossmatching blood?
a) Select Rh-null blood
b) Select units that are phenotypically matched to the patient
c) Use only saline-washed red cells
d) Select units that are incompatible at 37°C - The Cartwright (Yt) blood group system antigens are located on which membrane-bound enzyme?
a) Acetylcholinesterase
b) Alkaline phosphatase
c) Lactate dehydrogenase
d) Glycophorin A - Which of the following blood group chemicals is used to produce K₀ (Kell null) red cells for serological testing?
a) Ficin
b) Chloroquine diphosphate
c) Dithiothreitol (DTT)
d) Polyethylene glycol (PEG) - How many major blood group systems are currently recognized by the International Society of Blood Transfusion (ISBT)?
a) 10
b) 20
c) Over 30
d) 15 - The second most clinically significant blood group system after ABO and Rh is:
a) Kidd
b) Kell
c) Duffy
d) MNS - The K antigen in the Kell system is highly immunogenic because:
a) It’s present in high frequency
b) It’s easily destroyed by enzymes
c) It stimulates strong immune responses after exposure
d) It is a cold-reactive antigen - Antibodies in the Kell system are usually:
a) Naturally occurring and IgM
b) Immune-stimulated and IgG
c) Cold-reactive and complement-binding
d) Clinically insignificant - Which of the following blood group systems is associated with delayed hemolytic transfusion reactions?
a) Lewis
b) P
c) Kidd
d) MNS - The Jkᵃ and Jkᵇ antigens belong to which blood group system?
a) Kell
b) Duffy
c) Kidd
d) Lutheran - Kidd antibodies are notorious because they:
a) Are easily detected in screening tests
b) Often cause mild transfusion reactions only
c) May drop below detectable levels and cause delayed reactions
d) Are naturally occurring - The Fyᵃ and Fyᵇ antigens are part of the:
a) Duffy system
b) Lewis system
c) MNS system
d) Kell system - Individuals who are Fy(a–b–) are resistant to infection by:
a) Hepatitis B virus
b) Plasmodium vivax malaria
c) Cytomegalovirus
d) Epstein–Barr virus - Duffy antigens are destroyed by:
a) Enzymes such as papain and ficin
b) Heat
c) Chemicals such as EDTA
d) Low ionic strength solution - Which blood group system includes antigens that are found in secretions and plasma?
a) Duffy
b) Lewis
c) Kidd
d) Lutheran - Lewis antigens are formed by:
a) Genes on the X chromosome
b) Transferase enzymes in plasma, then adsorbed onto red cells
c) Structural proteins on the red cell membrane
d) Inheritance through mitochondrial DNA - The Lea and Leb antigens differ because:
a) Only Leb requires the H gene for expression
b) Lea is stronger in men
c) Leb reacts only at 4°C
d) Lea is not adsorbed onto red cells - The Lewis antibodies are generally:
a) Clinically insignificant and cold-reactive
b) Clinically significant and warm-reactive
c) Complement-binding and hemolytic
d) IgG and reactive at 37°C - The M and N antigens belong to which system?
a) MNS
b) Kidd
c) Lewis
d) Lutheran - The S and s antigens are part of the same system as:
a) Kell
b) M and N
c) Duffy
d) P - M and N antigens are destroyed by:
a) Enzymes like ficin and papain
b) Heat only
c) Acids
d) Formaldehyde - Anti-M antibodies are usually:
a) Naturally occurring, cold-reactive IgM
b) Warm-reactive IgG
c) Clinically significant in all patients
d) Found only after transfusion - Which antigen is a high-frequency antigen in the Kell system?
a) K
b) k
c) Kpᵃ
d) Jsᵃ - The Lutheran system antibodies (Luᵃ and Luᵇ) are usually:
a) Naturally occurring and IgM
b) Clinically significant and IgG
c) Complement-binding
d) IgE and heat-labile - Which antibody is known to cause both immediate and delayed hemolytic transfusion reactions?
a) Anti-Fyᵃ
b) Anti-K
c) Anti-Jkᵃ
d) Anti-Leᵃ - The P system antigen associated with parvovirus B19 infection is:
a) P1
b) P
c) Pk
d) p - The antigen associated with paroxysmal cold hemoglobinuria (PCH) is:
a) P
b) P1
c) S
d) Lea - Which antibody reacts best at 37°C and is often detected in the AHG phase?
a) Anti-M
b) Anti-Leᵃ
c) Anti-K
d) Anti-P1 - The Kpᵃ and Kpᵇ antigens belong to which system?
a) Kidd
b) Kell
c) Lutheran
d) Duffy - Which antigen combination occurs together on the same red cell membrane in most individuals?
a) M and N
b) K and k
c) S and s
d) All of the above - Which blood group system antigens are located on glycoprotein A and B?
a) Kidd
b) MNS
c) Duffy
d) Lewis - The Lewis phenotype Le(a–b+) indicates:
a) Presence of both Le and Se genes
b) Absence of both genes
c) Only Le gene present
d) Only Se gene present - The antigen that is strongly immunogenic and often second only to D in causing HDFN is:
a) Fyᵇ
b) K
c) Jkᵃ
d) S - The MNS system antibodies can sometimes show:
a) Dosage effect
b) No serologic reaction
c) Weak reactions only at cold temperatures
d) No enzyme sensitivity
📌 How to Use This Practice Set
- Answer each question before checking the key.
- Focus on why the correct answer is right and the others are wrong.
- Use this set as timed practice to simulate the real exam environment.
Answer Key
Answer Key:
- b) It is strongly immunogenic
- c) Fy(a-b-)
- c) Delayed hemolytic transfusion reactions
- c) Fyᵃ
- c) kk
- d) Anti-Fyᵃ
- c) Le(a+b-)
- d) Fy(a-b-)
- c) Lewis antigens are absorbed from the plasma onto the red cell membrane
- c) Kell
- c) Anti-P1
- c) P
- c) HLA
- c) Anti-PP1Pᵏ
- b) HPA-1a
- b) It is found in the serum of patients with infectious mononucleosis
- d) S
- b) Autosomal recessive
- d) Anti-Jkᵃ
- c) Vel
- c) ABO
- c) S
- c) Maternal platelets
- b) Band 3
- d) Anti-S
- c) Water channel (aquaporin-1)
- d) The LWᵃ antigen is a high-prevalence antigen
- b) Select units that are phenotypically matched to the patient
- a) Acetylcholinesterase
- c) Dithiothreitol (DTT)
- c) Over 30
- b) Kell
- c) It stimulates strong immune responses after exposure
- b) Immune-stimulated and IgG
- c) Kidd
- c) Kidd
- c) May drop below detectable levels and cause delayed reactions
- a) Duffy system
- b) Plasmodium vivax malaria
- a) Enzymes such as papain and ficin
- b) Lewis
- b) Transferase enzymes in plasma, then adsorbed onto red cells
- a) Only Leb requires the H gene for expression
- a) Clinically insignificant and cold-reactive
- a) MNS
- b) M and N
- a) Enzymes like ficin and papain
- a) Naturally occurring, cold-reactive IgM
- b) k
- a) Naturally occurring and IgM
- b) Anti-K
- b) P
- a) P
- c) Anti-K
- b) Kell
- d) All of the above
- b) MNS
- a) Presence of both Le and Se genes
- b) K
- b) Ka) Dosage effect
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