Even with modern testing and compatibility procedures, transfusion reactions can still occur and may lead to severe, sometimes fatal, complications. This chapter explains the types, causes, and management of transfusion reactions as well as the pathophysiology of hemolytic disease of the newborn (HDN).
Understanding these conditions enables laboratory and clinical professionals to identify, investigate, and prevent transfusion-related complications effectively.

Topics Covered in This Chapter
- Types of transfusion reactions:
- Acute hemolytic transfusion reaction (AHTR)
- Delayed hemolytic transfusion reaction (DHTR)
- Febrile non-hemolytic transfusion reaction (FNHTR)
- Allergic and anaphylactic reactions
- Transfusion-related acute lung injury (TRALI)
- Transfusion-associated circulatory overload (TACO)
- Bacterial contamination and transfusion-transmitted infections
- Investigation and laboratory workup of suspected transfusion reactions
- Hemolytic Disease of the Newborn (HDN):
- Pathophysiology and immune mechanisms
- Rh and ABO incompatibility
- Prenatal testing and monitoring (antibody titers, amniocentesis)
- Postnatal diagnosis and management (DAT, exchange transfusion, RhIG prophylaxis)
- Prevention strategies and hemovigilance programs
Why It Matters
Prompt recognition and investigation of transfusion reactions are vital for patient safety.
Understanding HDN and its prevention through Rh immunoglobulin (RhIG) administration remains one of the most significant achievements in transfusion medicine.
This knowledge ensures laboratory scientists contribute to safe transfusion practices and maternal-fetal health care.
Learning Outcomes
After studying this section, learners should be able to:
- Identify and classify various transfusion reactions.
- Describe the laboratory evaluation process for suspected transfusion reactions.
- Explain the pathophysiology and management of hemolytic disease of the newborn.
- Implement prevention strategies such as RhIG administration.
- Understand hemovigilance and quality reporting systems.
60 MCQs (4781 – 4840):
- A patient immediately develops flushing, fever, shaking chills, and back pain during a transfusion. The plasma hemoglobin is elevated. Laboratory investigation would most likely show:
a) An error in Rh typing
b) An error in ABO grouping
c) Presence of anti-Fyᵃ
d) Gram-negative bacteria in the blood bag - Hemolytic Disease of the Newborn (HDN) caused by ABO incompatibility is most often seen in infants of which group of mothers?
a) Group A
b) Group B
c) Group AB
d) Group O - A patient becomes mildly jaundiced and experiences a drop in hemoglobin 5 days after a transfusion. The most likely explanation is:
a) A febrile non-hemolytic transfusion reaction
b) A delayed hemolytic transfusion reaction
c) Transfusion-associated circulatory overload (TACO)
d) An allergic reaction - Which of the following maternal antibodies is most likely to cause severe Hemolytic Disease of the Fetus and Newborn (HDFN)?
a) Anti-Leᵃ
b) Anti-P1
c) Anti-K
d) Anti-M - The direct antiglobulin test (DAT) in a case of ABO Hemolytic Disease of the Newborn is typically:
a) Strongly positive (4+)
b) Weakly positive or negative
c) Positive with complement only
d) Negative - What is the primary treatment goal for a patient experiencing an acute hemolytic transfusion reaction?
a) Administer antihistamines to reduce urticaria
b) Reverse hypotension and minimize renal damage
c) Reduce fever with antipyretics
d) Perform an exchange transfusion - Which of the following is a symptom of Transfusion-Related Acute Lung Injury (TRALI)?
a) Hypertension and bradycardia
b) Hives and itching
c) Dyspnea and hypoxemia within 6 hours of transfusion
d) Generalized edema and headache - Posttransfusion purpura (PTP) is most frequently caused by an antibody against which antigen?
a) HLA
b) HPA-1a
c) ABO
d) KEL - A febrile non-hemolytic transfusion reaction (FNHTR) is characterized by:
a) A temperature rise of 1°C or more with no other cause
b) Hemoglobinuria and renal failure
c) Hypotension and wheezing
d) Generalized bleeding and shock - Which of the following strategies has been useful in reducing the incidence of TRALI?
a) Using Fresh Frozen Plasma from male donors
b) Pre-medicating with acetaminophen
c) Using leukoreduced blood products
d) Slowing the infusion rate - In a delayed hemolytic transfusion reaction, the antibody is typically detectable:
a) 3-6 hours after transfusion
b) 2 days to 2 weeks after transfusion
c) 60-90 days after transfusion
d) Immediately after the transfusion is started - An obstetrical patient has had 3 pregnancies: first baby healthy, second jaundiced requiring exchange, third stillborn. The most likely cause is:
a) ABO incompatibility
b) Rh incompatibility
c) Congenital spherocytosis
d) Immune deficiency disease - Which of the following is the most appropriate initial step when a transfusion reaction is suspected?
a) Slow the infusion and monitor the patient
b) Stop the transfusion and keep the IV line open with saline
c) Administer epinephrine and call the physician
d) Send a post-transfusion sample to the lab immediately - Which of the following laboratory results would be most indicative of an acute hemolytic transfusion reaction?
a) Positive direct antiglobulin test on post-transfusion sample
b) Elevated plasma hemoglobin and hemoglobinuria
c) Positive antibody screen
d) Elevated bilirubin 24 hours post-transfusion - For an Rh-negative mother who has not been previously immunized, Rh immune globulin (RhIG) should be administered after which of the following?
a) Delivery of an Rh-negative infant
b) Delivery of an Rh-positive infant
c) A positive antibody screen for anti-D
d) A positive direct antiglobulin test on the mother - Graft-versus-host disease (GVHD) in a transfusion recipient is prevented by:
a) Leukocyte reduction of blood components
b) Irradiation of blood components
c) Washing of blood components
d) Using CMV-safe blood products - Which of the following symptoms is characteristic of an anaphylactic transfusion reaction?
a) Fever and chills
b) Hypotension, bronchospasm, and no fever
c) Hypertension and tachycardia
d) Generalized edema and dark urine - The Kleihauer-Betke test is used to:
a) Identify fetal red cells in maternal circulation
b) Determine the blood type of a fetus
c) Detect maternal antibodies in cord blood
d) Diagnose Hemolytic Disease of the Newborn - A patient develops hives and itching during a transfusion. This is most consistent with which type of reaction?
a) Febrile non-hemolytic
b) Allergic
c) Hemolytic
d) TRALI - Which of the following is a potential complication of massive transfusion?
a) Hypercalcemia
b) Citrate toxicity and hypocalcemia
c) Hyperkalemia from stored platelets
d) Iron deficiency - Which of the following blood group systems is most commonly associated with delayed hemolytic transfusion reactions?
a) Lewis
b) Kidd
c) P
d) I - In a case of suspected HDN, what significant information can be obtained from the baby’s blood smear?
a) Estimation of WBC and platelet counts
b) Presence of spherocytes
c) Absolute lymphocyte count
d) Immature neutrophil count - The purpose of performing an antibody titer on serum from an immunized pregnant woman is to:
a) Identify the antibody specificity
b) Identify candidates requiring additional fetal monitoring
c) Decide if the baby needs an intrauterine transfusion
d) Determine if early induction of labor is indicated - Which of the following transfusion reactions is characterized by high fever, shock, hemoglobinuria, DIC, and renal failure?
a) Bacterial contamination
b) Circulatory overload
c) Febrile non-hemolytic
d) Allergic - Rh immune globulin administration 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 - What is the most frequent transfusion-associated disease complication?
a) Cytomegalovirus (CMV)
b) Syphilis
c) Hepatitis
d) HIV-1/2 - A patient develops fever, watery diarrhea, skin rash, and elevated liver enzymes 9 days after an HLA-matched platelet transfusion. This may indicate:
a) Transfusion-associated hepatitis
b) Transfusion-associated graft-versus-host disease (TA-GVHD)
c) Anaphylactic reaction
d) Sepsis from bacterial contamination - Which of the following patients is at highest risk for developing transfusion-associated graft-versus-host disease (TA-GVHD)?
a) A full-term infant
b) A patient receiving blood from a first-degree relative
c) A patient with a positive direct antiglobulin test
d) A patient with a history of febrile reactions - In treating hyperbilirubinemia in HDN, phototherapy is used to:
a) Break down conjugated bilirubin
b) Prevent further hemolysis of fetal red cells
c) Convert unconjugated bilirubin to a nontoxic, water-soluble form
d) Stimulate liver enzyme production - A fetomaternal hemorrhage of 35 mL of whole blood is detected. How many vials of RhIG are required?
a) 1
b) 2
c) 3
d) 4 - A transfusion reaction is defined as:
a) Any adverse event associated with transfusion of blood or its components
b) Only hemolytic reactions caused by ABO incompatibility
c) Fever after surgery
d) Any allergic response unrelated to transfusion - The most common cause of fatal transfusion reactions is:
a) Clerical error leading to ABO incompatibility
b) Contaminated anticoagulant
c) Bacterial contamination of plasma
d) Wrong storage temperature - An acute hemolytic transfusion reaction usually occurs:
a) Within minutes of starting the transfusion
b) 24 hours after transfusion
c) 7 days after transfusion
d) 2 weeks after transfusion - The primary antibody responsible for acute hemolytic transfusion reactions is:
a) IgG
b) IgM anti-A or anti-B
c) IgA
d) IgE - The first step when a transfusion reaction is suspected is to:
a) Stop the transfusion immediately
b) Increase transfusion rate
c) Discard the blood bag
d) Add saline to the IV line - The clerical check during a transfusion reaction investigation verifies:
a) Patient identification and blood unit labeling
b) Bacterial contamination
c) Plasma protein content
d) Temperature control - The most frequent nonhemolytic transfusion reaction is:
a) Febrile nonhemolytic reaction
b) Hemolytic reaction
c) Anaphylactic reaction
d) Delayed hemolytic reaction - Febrile nonhemolytic reactions are commonly caused by:
a) Leukocyte antibodies reacting with donor WBCs
b) ABO incompatibility
c) Bacterial toxins
d) Platelet alloimmunization - Which type of transfusion reaction involves allergic symptoms such as urticaria and itching?
a) Acute hemolytic
b) Allergic reaction
c) Septic reaction
d) Delayed hemolytic - Anaphylactic transfusion reactions are often associated with:
a) IgA deficiency in the recipient
b) High bilirubin levels
c) Iron overload
d) Cold agglutinins - Bacterial contamination in blood products is most common in:
a) RBC units
b) Platelet concentrates
c) Cryoprecipitate
d) Plasma - Symptoms of bacterial contamination include:
a) Sudden chills, fever, and hypotension
b) Mild itching
c) Delayed hemolysis
d) Elevated bilirubin - Delayed hemolytic transfusion reactions typically occur:
a) Within 24 hours
b) 2–14 days after transfusion
c) 3–4 weeks after transfusion
d) Immediately after completion - The most common antibodies causing delayed hemolytic transfusion reactions are:
a) Anti-Jkᵃ, Anti-E, Anti-K
b) Anti-A and Anti-B
c) Anti-Leᵃ and Anti-M
d) Anti-P1 and Anti-I - Transfusion-associated circulatory overload (TACO) is caused by:
a) Rapid infusion of large blood volumes
b) ABO incompatibility
c) Iron deficiency
d) Leukocyte antibodies - Transfusion-related acute lung injury (TRALI) is caused by:
a) Donor anti-HLA or anti-neutrophil antibodies
b) ABO mismatch
c) Platelet transfusion only
d) Plasma protein deficiency - A characteristic feature of TRALI is:
a) Acute respiratory distress and pulmonary edema
b) High fever
c) Rash and hives
d) Hemoglobinuria - Post-transfusion purpura is associated with antibodies against:
a) Platelet antigen HPA-1a
b) Leukocytes
c) Plasma proteins
d) Hemoglobin - Iron overload is a complication of:
a) Multiple chronic transfusions
b) Single transfusion
c) Platelet transfusion
d) Plasma donation - The laboratory finding most consistent with an acute hemolytic transfusion reaction is:
a) Positive direct antiglobulin test (DAT)
b) Negative antibody screen
c) Normal plasma color
d) Elevated platelet count - In suspected hemolytic reactions, the plasma should be inspected for:
a) Free hemoglobin (pink/red discoloration)
b) Elevated bilirubin only
c) Increased viscosity
d) Coagulation factors - In a transfusion reaction workup, the first laboratory test performed is:
a) Direct antiglobulin test (DAT)
b) Antibody identification panel
c) Crossmatch
d) Urinalysis - Hemoglobinuria following transfusion indicates:
a) Intravascular hemolysis
b) Extrinsic anemia
c) Platelet destruction
d) Plasma protein deficiency - Delayed hemolytic transfusion reactions usually present with:
a) Mild jaundice and anemia
b) Shock and hypotension
c) Rash and hives
d) Severe hemoglobinemia - The most common cause of Transfusion-Associated Graft-vs-Host Disease (TA-GVHD) is:
a) Transfusion of non-irradiated blood to immunocompromised patients
b) Transfusion of plasma only
c) Platelet transfusion
d) ABO mismatch - The hallmark symptom of TA-GVHD is:
a) Skin rash, diarrhea, and pancytopenia
b) High fever only
c) Hemoglobinuria
d) Cold agglutination - The preventive measure for TA-GVHD is:
a) Irradiation of cellular blood components
b) Freezing red cells
c) Leukoreduction
d) Washing plasma - The major cause of transfusion-associated sepsis is:
a) Bacterial contamination of platelet units
b) ABO incompatibility
c) Allergic reaction
d) Cold autoantibody - In hemolytic disease of the newborn (HDN), maternal antibodies are most commonly directed against:
a) Rh (D) antigen
b) ABO antigen
c) Kell antigen
d) Duffy antigen - The most effective method to prevent HDN due to anti-D is:
a) Administration of Rh immune globulin (RhIG) to Rh-negative mothers
b) Transfusing O-positive blood during pregnancy
c) Giving corticosteroids after delivery
d) Delaying labor
📌 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) An error in ABO grouping
- d) Group O
- b) A delayed hemolytic transfusion reaction
- c) Anti-K
- b) Weakly positive or negative
- b) Reverse hypotension and minimize renal damage
- c) Dyspnea and hypoxemia within 6 hours of transfusion
- b) HPA-1a
- a) A temperature rise of 1°C or more with no other cause
- a) Using Fresh Frozen Plasma from male donors
- b) 2 days to 2 weeks after transfusion
- b) Rh incompatibility
- b) Stop the transfusion and keep the IV line open with saline
- b) Elevated plasma hemoglobin and hemoglobinuria
- b) Delivery of an Rh-positive infant
- b) Irradiation of blood components
- b) Hypotension, bronchospasm, and no fever
- a) Identify fetal red cells in maternal circulation
- b) Allergic
- b) Citrate toxicity and hypocalcemia
- b) Kidd
- b) Presence of spherocytes
- b) Identify candidates requiring additional fetal monitoring
- a) Bacterial contamination
- c) Anti-D titer of 1:4096
- c) Hepatitis
- b) Transfusion-associated graft-versus-host disease (TA-GVHD)
- b) A patient receiving blood from a first-degree relative
- c) Convert unconjugated bilirubin to a nontoxic, water-soluble form
- b) 2
- a) Any adverse event associated with transfusion of blood or its components
- a) Clerical error leading to ABO incompatibility
- a) Within minutes of starting the transfusion
- b) IgM anti-A or anti-B
- a) Stop the transfusion immediately
- a) Patient identification and blood unit labeling
- a) Febrile nonhemolytic reaction
- a) Leukocyte antibodies reacting with donor WBCs
- b) Allergic reaction
- a) IgA deficiency in the recipient
- b) Platelet concentrates
- a) Sudden chills, fever, and hypotension
- b) 2–14 days after transfusion
- a) Anti-Jkᵃ, Anti-E, Anti-K
- a) Rapid infusion of large blood volumes
- a) Donor anti-HLA or anti-neutrophil antibodies
- a) Acute respiratory distress and pulmonary edema
- a) Platelet antigen HPA-1a
- a) Multiple chronic transfusions
- a) Positive direct antiglobulin test (DAT)
- a) Free hemoglobin (pink/red discoloration)
- a) Direct antiglobulin test (DAT)
- a) Intravascular hemolysis
- a) Mild jaundice and anemia
- a) Transfusion of non-irradiated blood to immunocompromised patients
- a) Skin rash, diarrhea, and pancytopenia
- a) Irradiation of cellular blood components
- a) Bacterial contamination of platelet units
- a) Rh (D) antigen
- a) Administration of Rh immune globulin (RhIG) to Rh-negative mothers
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Top 8 Medical Laboratory Scientist (MLS) Exams that are recognized globally and can help professionals validate their credentials and enhance their career opportunities:
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- Exam Name: MLS(ASCP)
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