The Rh Blood Group System is the second most clinically significant blood group system after ABO. It plays a vital role in transfusion medicine and hemolytic disease of the newborn (HDN). This chapter explores the genetics, antigenic structure, and clinical implications of Rh typing — a cornerstone of safe blood transfusion and pregnancy management.
Understanding the Rh system enables laboratory professionals to prevent alloimmunization, ensure accurate crossmatching, and recognize complex serologic patterns in Rh variants.
Topics Covered in This Chapter
- History and discovery of the Rh system
- Major Rh antigens: D, C, c, E, e
- Genetics and inheritance models (Fisher-Race and Wiener theories)
- Rh antigen structure and expression
- Weak D and partial D variants
- Rh antibodies and their clinical significance
- Rh typing methods and interpretation
- Hemolytic Disease of the Newborn (HDN) related to Rh incompatibility
Why It Matters
The Rh system determines an individual’s Rh-positive or Rh-negative status, which is essential for transfusion compatibility and maternal-fetal safety.
Failure to detect weak D or partial D variants can result in alloimmunization and life-threatening transfusion reactions.
Learning Outcomes
After studying this section, learners should be able to:
- Describe the genetic and antigenic basis of the Rh system.
- Identify Rh antigens and antibodies of clinical importance.
- Explain the concept and detection of weak D and partial D variants.
- Understand the role of the Rh system in hemolytic disease of the newborn.
60 MCQs (4421 – 4480):
- An individual’s red blood cells give the reactions with Rh antisera shown in this table: anti-D (4+), anti-C (3+), anti-E (0), anti-c (3+), anti-e (3+). The individual’s most probable genotype is:
a) DCe/DcE
b) DcE/dce
c) Dce/dce
d) DCe/dce - In an emergency situation, Rh-negative red cells are transfused into an Rh-positive person of the genotype CDe/CDe. The first antibody most likely to develop is:
a) Anti-c
b) Anti-d
c) Anti-e
d) Anti-E - A patient’s red cells type as positive with anti-C, anti-D, anti-E, anti-c, and anti-e. Which is the most probable genotype?
a) R₁R₁
b) R₁R₂
c) R₀R₀
d) R₂R₂ - Before labeling a blood donation as Rh-negative, what additional test must be performed after initial negative reactions with anti-D?
a) Test donor RBCs with anti-A,B
b) Test donor RBCs with anti-H
c) Perform weak D testing on donor RBCs
d) Test donor serum with A₂ cells - The phenomenon of an Rh-positive person whose serum contains anti-D is best explained by:
a) Gene deletion
b) Missing antigen epitopes
c) Trans position effect
d) Gene inhibition - A mother is Rh-negative and the father Rh-positive. Their baby is Rh-negative. It may be concluded that:
a) The father is homozygous for D
b) The mother is heterozygous for D
c) The father is heterozygous for D
d) At least one of the three Rh typings must be incorrect - A mother has the red cell phenotype D+C+E–c–e+ with anti-c in her serum. The father has the phenotype D+C+E–c+e+. The baby is Rh-negative and not affected with HDN. What is the baby’s most probable Rh genotype?
a) r’r’
b) r’r
c) R₁R₁
d) R₁r - Which of the following phenotypes will react with anti-f?
a) rr
b) R₁R₁
c) R₂R₂
d) R₁R₂ - A patient’s red blood cells gave the reactions shown in this table: anti-D (+), anti-C (+), anti-E (+), anti-c (+), anti-e (+), anti-f (0). The most probable genotype of this patient is:
a) R₁R₂
b) R₂r
c) R₀r
d) R₂R₂ - A woman types as Rh-positive. She has an anti-c titer of 32 at AHG. Her baby has a negative DAT and is not affected by HDN. What is the father’s most likely Rh phenotype?
a) rr
b) r’r
c) R₁r
d) R₂r - A donor is tested with Rh antisera with the results shown in this table: anti-D (+), anti-C (+), anti-E (0), anti-c (+), anti-e (+). What is his most probable Rh genotype?
a) R₁R₁
b) R₁r
c) R₀r
d) R₂r - Which of the following Rh antigens has the highest frequency in the Caucasian population?
a) D
b) E
c) C
d) e - The Rh-negative phenotype results from the complete deletion of what gene(s)?
a) RHD and RHce
b) RHCE
c) RHD
d) RHD and RHCE - A patient received 2 units of Rh-positive blood emergently 2 years ago. The patient is Rh-negative. What antibody is most likely to be present now?
a) Anti-E
b) Anti-D
c) Anti-C
d) Anti-e - Which of the following is the most immunogenic blood group antigen?
a) Fyᵃ
b) K
c) Jkᵇ
d) D - A patient with a suspected warm autoantibody often demonstrates an antibody with which specificity?
a) I
b) P
c) Rh
d) Leᵃ - Which of the following genes on chromosome 1 encodes for the four common antigen combinations ce, cE, Ce, and CE?
a) RHD
b) RHCE
c) RHD and RHCE
d) RHd and RHce - A mother is group A, D-negative with anti-D in her serum. Her newborn is group O, D-negative with a 4+ DAT. From this information, which test result is questionable?
a) Paternal D type
b) Newborn D type
c) Maternal ABO type
d) Newborn DAT - Blood selected for an intrauterine transfusion for HDFN due to anti-D must be:
a) Group O, Rh-negative, Irradiated, CMV safe
b) Group O, Rh-positive, Irradiated, CMV safe
c) Group A, Rh-negative, Irradiated, CMV safe
d) Group AB, Rh-positive, Irradiated, CMV safe - The purpose of performing weak D testing on a donor unit is to:
a) Identify partial D antigens
b) Prevent the recipient from making anti-D
c) Prevent HDFN in future pregnancies
d) Identify the correct genotype of the donor - A patient types as D-negative but has a history of making anti-D. This patient is most likely:
a) A weak D phenotype
b) A partial D phenotype
c) An Rh-null phenotype
d) Genetically Rh-negative - Which of the following statements is true about the G antigen?
a) It is present only when the D antigen is present
b) It is present on red cells possessing either C or D
c) It is a low-frequency antigen
d) It is the product of the RHCE gene alone - In a delayed hemolytic transfusion reaction caused by Rh antibodies, the red cell destruction is primarily:
a) Intravascular, due to complement activation
b) Extravascular, via the reticuloendothelial system
c) Due to direct agglutination in the bloodstream
d) Caused by neutrophil-mediated destruction - Which of the following Rh antibodies is most commonly involved in Hemolytic Disease of the Fetus and Newborn (HDFN)?
a) Anti-C
b) Anti-D
c) Anti-E
d) Anti-e - A patient’s phenotype is D+C+E-c+e+. The most probable genotype is:
a) R₁R₁
b) R₁r
c) R₀r
d) R₂r - Rh immune globulin (RhIG) would NOT be indicated in an Rh-negative woman who has a(n):
a) First trimester abortion
b) Husband who is Rh-positive
c) Anti-D titer of 1:4096
d) Positive direct antiglobulin test - The “rosette” test is used to:
a) Determine the Rh genotype of a fetus
b) Screen for a large fetomaternal hemorrhage (FMH)
c) Identify Rh antibodies in maternal serum
d) Confirm the presence of the D antigen on red cells - A Kleihauer-Betke stain of a postpartum blood film revealed 0.3% fetal cells. What is the estimated volume (mL) of the fetomaternal hemorrhage expressed as whole blood?
a) 5
b) 15
c) 25
d) 35 - A fetomaternal hemorrhage of 48 mL of fetal Rh-positive whole blood has been detected in an Rh-negative woman. How many vials of Rh immune globulin should be given?
a) 0
b) 1
c) 2
d) 3 - Rhₙᵤₗₗ red cells are also:
a) LW(a-b-)
b) Fy(a-b-)
c) K–k–
d) Jk(a-b-) - 1. The Rh blood group system was first discovered during studies involving which animals?
a) Mice
b) Monkeys
c) Rabbits
d) Guinea pigs - The most immunogenic Rh antigen is:
a) C
b) c
c) D
d) E - The Rh system antigens are located on which type of molecule?
a) Glycoprotein
b) Lipoprotein
c) Transmembrane protein
d) Glycolipid - The Fisher-Race terminology expresses the Rh genotype using:
a) Letters (D, C, E, c, e)
b) Numbers (1, 2, 3, 4, 5)
c) Greek symbols
d) Numeric codes only - The Wiener system uses which notation for Rh genes?
a) RhA, RhB
b) R¹, R², r, etc.
c) DCE notation
d) R₀, R₁, R₂ - An individual with genotype R₁r has which antigens on their red cells?
a) D, C, e
b) C, c, e
c) D, c, E
d) D, E, e - The absence of all Rh antigens results in which rare condition?
a) Rh null phenotype
b) Rh negative
c) Weak D variant
d) Partial D phenotype - The gene responsible for the production of Rh antigens is located on:
a) Chromosome 1
b) Chromosome 4
c) Chromosome 6
d) Chromosome 19 - Which antigen determines Rh-positive or Rh-negative status?
a) C
b) E
c) D
d) e - Which test is used to detect weak D antigen expression?
a) Direct antiglobulin test (DAT)
b) Indirect antiglobulin test (IAT)
c) Crossmatch test
d) Immediate-spin phase only - Weak D expression is most commonly due to:
a) Reduced number of D antigen sites
b) Presence of anti-D antibodies
c) Excess antigen–antibody complexes
d) Plasma protein interference
12. Partial D individuals: - Lack some D epitopes and can make anti-D
b) Have excess D antigen sites
c) Are the same as weak D
d) Cannot form antibodies - Which of the following best describes Rh antibodies?
a) Naturally occurring IgM
b) Immune-stimulated, usually IgG
c) Complement-fixing IgA
d) Cold-reactive antibodies - Rh antibodies react best at which temperature?
a) 4°C
b) 22°C
c) 37°C
d) Room temperature only - The D antigen is inherited in which pattern?
a) Autosomal recessive
b) Autosomal dominant
c) X-linked
d) Polygenic - The term “Rh negative” indicates:
a) Absence of all Rh antigens
b) Absence of D antigen only
c) Weak expression of E antigen
d) Lack of both C and E antigens - Which Rh phenotype is most common among Caucasians?
a) R₁r
b) R₀r
c) R₂r
d) rr - The presence of anti-D antibodies in an Rh-negative pregnant woman may cause:
a) ABO incompatibility
b) Hemolytic disease of the newborn (HDN)
c) Iron deficiency anemia
d) Polycythemia - Rh antibodies can cause:
a) Delayed hemolytic transfusion reactions
b) Febrile non-hemolytic reactions only
c) Platelet clumping
d) Leukopenia - The Du antigen is another term historically used for:
a) Weak D expression
b) Rh null phenotype
c) Partial D
d) Anti-D antibody - What reagent is used to confirm weak D positivity after incubation?
a) Anti-human globulin (AHG)
b) Anti-C3 reagent
c) Anti-IgM reagent
d) Enzyme solution - Rh antibodies are usually detected during which testing phase?
a) Immediate-spin
b) 37°C incubation
c) Room temperature
d) Saline phase only - Which of the following Rh genotypes is homozygous for D?
a) R₁r
b) R₂R₂
c) rr
d) R₀r - Which antigen combination is most likely found in genotype R₀r?
a) D, c, e
b) C, e
c) D, C, E
d) c, E - The Rh null phenotype may be associated with:
a) Spherocytosis and hemolytic anemia
b) Increased antibody production
c) Leukopenia
d) Plasma protein defects - Which enzyme can enhance Rh antigen reactivity?
a) Trypsin
b) Papain
c) Pepsin
d) Amylase - Rh antibodies generally do NOT cause:
a) Transfusion reactions
b) Hemolytic disease of the newborn
c) Complement-mediated lysis
d) In vivo sensitization - In the Wiener system, R₂ corresponds to which Fisher-Race genotype?
a) DCe
b) DcE
c) Dce
d) dCe - What is the purpose of Rh immune globulin (RhIG)?
a) To stimulate D antigen production
b) To prevent Rh-negative mothers from forming anti-D
c) To treat D-positive newborns
d) To increase antibody titer - In serologic testing, Rh antibodies are best detected using:
a) Enzyme phase
b) Antiglobulin (AHG) phase
c) Immediate-spin phase
d) Saline-only test
📌 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:
- d) DCe/dce
- a) Anti-c
- b) R₁R₂
- c) Perform weak D testing on donor RBCs
- b) Missing antigen epitopes
- c) The father is heterozygous for D
- a) r’r’
- a) rr
- a) R₁R₂
- b) r’r
- b) R₁r
- d) e
- c) RHD
- b) Anti-D
- d) D
- c) Rh
- b) RHCE
- b) Newborn D type
- a) Group O, Rh-negative, Irradiated, CMV safe
- b) Prevent the recipient from making anti-D
- b) A partial D phenotype
- b) It is present on red cells possessing either C or D
- b) Extravascular, via the reticuloendothelial system
- b) Anti-D
- b) R₁r
- c) Anti-D titer of 1:4096
- b) Screen for a large fetomaternal hemorrhage (FMH)
- b) 15
- d) 3
- a) LW(a-b-)
- b) Monkeys
- c) D
- c) Transmembrane protein
- a) Letters (D, C, E, c, e)
- b) R¹, R², r, etc.
- a) D, C, e
- a) Rh null phenotype
- a) Chromosome 1
- c) D
- b) Indirect antiglobulin test (IAT)
- a) Reduced number of D antigen sites
- a)Lack some D epitopes and can make anti-D
- b) Immune-stimulated, usually IgG
- c) 37°C
- b) Autosomal dominant
- b) Absence of D antigen only
- a) R₁r
- b) Hemolytic disease of the newborn (HDN)
- a) Delayed hemolytic transfusion reactions
- a) Weak D expression
- a) Anti-human globulin (AHG)
- b) 37°C incubation
- b) R₂R₂
- a) D, c, e
- a) Spherocytosis and hemolytic anemia
- b) Papain
- c) Complement-mediated lysis
- b) DcE
- b) To prevent Rh-negative mothers from forming anti-D
- b) Antiglobulin (AHG) phase
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