Transfusion reaction

Mr. Topesh Patle

Introduction

  • Blood transfusion is a life-saving therapeutic procedure widely used in medical and surgical practice, but it is not without risk.
  • A transfusion reaction refers to any adverse clinical event occurring during or after the transfusion of whole blood or blood components, irrespective of its severity.
  • Transfusion reactions may be mild, moderate, or life-threatening, ranging from simple febrile or allergic reactions to severe complications such as acute hemolytic reaction, sepsis, TRALI, and circulatory overload.
  • These reactions can occur due to immune-mediated mechanisms (e.g., ABO incompatibility, alloantibody formation) or non-immune causes (e.g., bacterial contamination, volume overload, mechanical hemolysis).
  • Based on timing, transfusion reactions are classified into acute reactions (occurring during transfusion or within 24 hours) and delayed reactions (developing days to weeks later).
  • Acute hemolytic transfusion reaction, most commonly due to ABO mismatch, is a medical emergency associated with high morbidity and mortality if not promptly recognized and managed.
  • Clinical manifestations of transfusion reactions are often non-specific and may mimic other acute conditions such as sepsis, allergic reactions, or cardiac failure, making diagnosis challenging.
  • Therefore, immediate clinical assessment combined with systematic laboratory investigation is essential to confirm the diagnosis, identify the underlying cause, and guide appropriate management.
  • Laboratory evaluation plays a crucial role in:
    • Detecting blood group incompatibility
    • Identifying immune or non-immune hemolysis
    • Assessing severity and complications such as DIC or renal failure
    • Preventing recurrence in future transfusions
  • A well-defined transfusion reaction investigation protocol also supports hemovigilance systems, improves transfusion safety, and enhances overall quality of patient care.

 

Etiology

I. Immune-Mediated Causes

These reactions occur due to antigen–antibody interactions between donor blood components and the recipient.

1. ABO Incompatibility

  • Most common and most severe cause of acute hemolytic transfusion reaction
  • Occurs due to clerical errors, mislabeling, or incorrect patient identification
  • Naturally occurring IgM antibodies activate complement
  • Leads to intravascular hemolysis, shock, DIC, and acute renal failure

2. Rh Incompatibility

  • Occurs mainly in Rh-negative recipients receiving Rh-positive blood
  • Usually causes delayed hemolytic transfusion reactions
  • Mediated by IgG antibodies
  • Less severe than ABO mismatch but clinically significant

3. Alloantibodies Against Minor Blood Group Antigens

  • Antibodies against Kell, Duffy, Kidd, MNS systems
  • Develop following previous transfusions or pregnancy
  • Responsible for delayed hemolytic transfusion reactions (DHTR)
  • Often missed during routine compatibility testing

4. Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

  • Caused by:
    • Recipient antibodies against donor leukocytes
    • Cytokines accumulated during blood storage
  • Common with platelet and whole blood transfusions

5. Allergic Reactions

  • Due to hypersensitivity to donor plasma proteins
  • Range from mild urticaria to severe anaphylaxis
  • More common with plasma-rich products

6. Anaphylactic Reaction

  • Seen in patients with IgA deficiency
  • Caused by anti-IgA antibodies reacting with donor IgA
  • Rapid onset with bronchospasm, hypotension, shock

7. Transfusion-Related Acute Lung Injury (TRALI)

  • Caused by donor anti-leukocyte or anti-HLA antibodies
  • Leads to immune-mediated pulmonary capillary damage
  • Results in non-cardiogenic pulmonary edema

 

II. Non-Immune-Mediated Causes

These reactions are not antibody-mediated and result from physical, chemical, or biological factors.

1. Bacterial Contamination of Blood Products

  • Commonly associated with platelets (stored at room temperature)
  • Caused by improper collection or storage
  • Leads to septic transfusion reaction
  • Presents with high fever, hypotension, shock

2. Mechanical Hemolysis

  • Caused by:
    • Use of small-gauge needles
    • Faulty transfusion pumps
    • Excessive pressure during transfusion
  • Leads to non-immune intravascular hemolysis

3. Thermal Injury

  • Transfusion of overheated or improperly warmed blood
  • Causes RBC membrane damage and hemolysis

4. Chemical Hemolysis

  • Occurs due to contamination with:
    • Hypotonic solutions
    • Drugs or IV fluids
  • Results in RBC destruction

5. Transfusion-Associated Circulatory Overload (TACO)

  • Caused by rapid or excessive transfusion volume
  • Common in:
    • Elderly
    • Pediatric patients
    • Cardiac or renal failure patients
  • Results in cardiogenic pulmonary edema

 

III. Metabolic and Storage-Related Causes

These occur due to biochemical changes in stored blood.

1. Citrate Toxicity

  • Citrate used as anticoagulant binds calcium
  • Causes hypocalcemia, especially in massive transfusion
  • Leads to paresthesia, tetany, arrhythmias

2. Hyperkalemia

  • Potassium leaks from stored RBCs
  • Risk increased in massive or rapid transfusions
  • Particularly dangerous in neonates and renal failure patients

3. Hypothermia

  • Infusion of cold blood products
  • Can cause cardiac arrhythmias and coagulopathy

 

IV. Procedural and Clerical Errors

  • Incorrect patient identification
  • Wrong labeling of samples
  • Errors in blood grouping or crossmatching
  • Transfusion of wrong blood component
  • Failure to follow transfusion protocols
    ➡ Most preventable cause of serious transfusion reactions

V. Patient-Related Risk Factors

  • Previous transfusions
  • History of transfusion reactions
  • Pregnancy (alloimmunization)
  • IgA deficiency
  • Cardiac or renal disease
  • Immunocompromised state

 

Epidemiology

Distribution by Type of Transfusion Reaction

  • Febrile Non-Hemolytic Transfusion Reactions (FNHTR)
    • Most common transfusion reaction
    • Occurs in 0.1–1% of red cell transfusions
    • Higher incidence with platelet transfusions
    • Frequency reduced significantly by leukoreduction
  • Allergic Reactions
    • Occur in 1–3% of plasma-containing transfusions
    • Mostly mild (urticaria, itching)
    • Severe anaphylactic reactions are very rare
  • Acute Hemolytic Transfusion Reactions (AHTR)
    • Incidence: ~1 in 38,000–70,000 transfusions
    • Most commonly caused by ABO incompatibility
    • Majority due to clerical or identification errors, not laboratory testing failure
  • Delayed Hemolytic Transfusion Reactions (DHTR)
    • Under-reported due to delayed onset
    • Incidence increases in multiply transfused patients
    • Common in patients with hematologic disorders
  • Transfusion-Related Acute Lung Injury (TRALI)
    • One of the leading causes of transfusion-related mortality
    • Incidence: 1 in 5,000–10,000 transfusions
    • Risk higher with plasma-rich components
    • Reduced by use of male-only plasma donors
  • Transfusion-Associated Circulatory Overload (TACO)
    • Incidence: 1–8% in high-risk populations
    • Now reported as the most common cause of transfusion-related death in many hemovigilance systems
    • Frequently underdiagnosed
  • Septic (Bacterial) Transfusion Reactions
    • Rare but highly fatal
    • More common with platelet transfusions due to room-temperature storage
    • Estimated incidence: 1 in 100,000–250,000 transfusions

Population-Based Risk Distribution

  • Higher risk groups include:
    • Elderly patients
    • Neonates and pediatric patients
    • Patients with cardiac or renal disease
    • Immunocompromised individuals
    • Patients receiving massive or repeated transfusions
  • Gender differences:
    • TRALI historically more common with plasma from multiparous female donors
    • Risk reduced with revised donor selection policies

Component-Specific Epidemiology

  • Platelets:
    • Highest rate of transfusion reactions (febrile and septic)
  • Plasma:
    • Higher risk of allergic reactions and TRALI
  • Packed Red Cells:
    • Most commonly associated with hemolytic reactions

Geographical and System-Based Factors

  • Incidence varies by:
    • Transfusion practices
    • Hemovigilance reporting systems
    • Quality control measures
  • Developed countries report higher incidence due to better surveillance, not necessarily higher true rates

 

Pathophysiology

I. Immune-Mediated Transfusion Reactions

These occur due to antigen–antibody interactions between donor blood components and recipient immune system.

1. Acute Hemolytic Transfusion Reaction (AHTR)

Mechanism:

  • Occurs most commonly due to ABO incompatibility
  • Recipient has preformed IgM antibodies against donor RBC antigens
  • IgM antibodies rapidly activate the complement system

Pathophysiological Events:

  • Complement activation → intravascular hemolysis
  • Rapid destruction of donor RBCs
  • Release of:
    • Free hemoglobin
    • LDH
    • Potassium
  • Hemoglobin binds haptoglobin → depletion
  • Free hemoglobin filtered by kidneys → hemoglobinuria
  • Nitric oxide scavenging → vasoconstriction
  • Cytokine release → fever, hypotension
  • Severe cases → DIC, acute renal failure, shock

2. Delayed Hemolytic Transfusion Reaction (DHTR)

Mechanism:

  • Occurs days to weeks after transfusion
  • Due to IgG alloantibodies formed against minor blood group antigens
  • Common antigens: Kell, Kidd, Duffy

Pathophysiological Events:

  • Antibody-coated RBCs removed by macrophages
  • Extravascular hemolysis (spleen and liver)
  • Gradual fall in hemoglobin
  • Mild jaundice and anemia
  • Usually less severe but clinically significant

3. Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

Mechanism:

  • Recipient antibodies against donor leukocytes
  • Cytokines (IL-1, IL-6, TNF-α) accumulated during blood storage

Pathophysiology:

  • Cytokine release causes:
    • Fever
    • Chills
    • Rigors
  • No RBC destruction
  • Common with platelet transfusions

4. Allergic Transfusion Reaction

Mechanism:

  • IgE-mediated hypersensitivity to donor plasma proteins

Pathophysiology:

  • Mast cell degranulation
  • Histamine release
  • Causes:
    • Urticaria
    • Pruritus
    • Flushing

5. Anaphylactic Transfusion Reaction

Mechanism:

  • Occurs in IgA-deficient recipients
  • Recipient anti-IgA antibodies react with donor IgA

Pathophysiology:

  • Massive mediator release
  • Vasodilation and bronchoconstriction
  • Rapid onset of:
    • Hypotension
    • Bronchospasm
    • Shock

6. Transfusion-Related Acute Lung Injury (TRALI)

Mechanism (Two-Hit Hypothesis):

  • First hit: Recipient clinical condition primes pulmonary neutrophils
  • Second hit: Donor anti-HLA or anti-neutrophil antibodies activate neutrophils

Pathophysiological Events:

  • Neutrophil activation in pulmonary capillaries
  • Endothelial damage
  • Capillary leak
  • Non-cardiogenic pulmonary edema
  • Acute hypoxemia within 6 hours

II. Non-Immune-Mediated Transfusion Reactions

These reactions occur without antigen–antibody interactions.

1. Transfusion-Associated Circulatory Overload (TACO)

Mechanism:

  • Rapid or excessive transfusion volume
  • Compromised cardiac or renal function

Pathophysiology:

  • Increased intravascular volume
  • Elevated pulmonary capillary pressure
  • Cardiogenic pulmonary edema
  • Hypertension and respiratory distress

2. Septic Transfusion Reaction

Mechanism:

  • Bacterial contamination of blood products
  • More common in platelets (room temperature storage)

Pathophysiology:

  • Endotoxin release
  • Systemic inflammatory response
  • Cytokine storm
  • Septic shock and multiorgan failure

3. Mechanical Hemolysis

Mechanism:

  • Physical damage to RBCs due to:
    • Small-bore needles
    • Faulty pumps
    • Excessive pressure

Pathophysiology:

  • RBC membrane rupture
  • Non-immune intravascular hemolysis

4. Thermal and Chemical Hemolysis

Thermal Injury:

  • Overheating blood damages RBC membranes

Chemical Injury:

  • Hypotonic fluids or drug contamination
  • Causes RBC lysis

III. Metabolic and Storage-Related Pathophysiology

1. Citrate Toxicity

  • Citrate binds calcium
  • Leads to hypocalcemia
  • Causes paresthesia, tetany, arrhythmias

2. Hyperkalemia

  • Potassium leaks from stored RBCs
  • Dangerous in neonates and renal failure

3. Hypothermia

  • Cold blood infusion
  • Causes arrhythmias and coagulopathy

 

Evaluation of Transfusion Reaction

I. Immediate Clinical Evaluation

  • Stop the transfusion immediately at the first suspicion of a reaction
  • Maintain IV access with normal saline
  • Record:
    • Time of onset of symptoms
    • Type and volume of blood component transfused
    • Vital signs (temperature, BP, pulse, respiratory rate, oxygen saturation)
  • Assess for life-threatening features:
    • Hypotension or shock
    • Respiratory distress
    • Chest or back pain
    • Hemoglobinuria
    • Altered mental status
    • Signs of anaphylaxis

II. Bedside and Clerical Evaluation

  • Recheck patient identity:
    • Wristband
    • Blood bag label
    • Compatibility tag
  • Verify:
    • Patient name and ID number
    • Blood group and Rh type
    • Unit number and expiry date
  • Clerical error is the most common cause of fatal transfusion reactions, especially ABO mismatch

III. Sample Collection for Laboratory Evaluation

The following must be sent immediately to the laboratory:

  • Patient’s post-transfusion blood sample (EDTA and plain)
  • Remaining donor blood unit with tubing
  • Patient’s urine sample (if hemolysis suspected)
  • Pre-transfusion sample (if available for comparison)

IV. Basic Laboratory Evaluation

1. Repeat ABO and Rh Typing

  • Performed on:
    • Patient sample
    • Donor unit
  • Confirms or excludes ABO/Rh mismatch

Interpretation:

  • Any discrepancy strongly suggests acute hemolytic transfusion reaction

2. Repeat Crossmatch

  • Major crossmatch (recipient serum vs donor RBCs)

Interpretation:

  • Incompatible crossmatch → immune incompatibility
  • Compatible crossmatch → consider minor antigen mismatch or non-immune causes

3. Direct Antiglobulin Test (DAT / Direct Coombs Test)

  • Detects antibodies or complement bound to RBCs

Interpretation:

  • Positive DAT → immune-mediated hemolysis
  • Negative DAT → non-immune hemolysis or non-hemolytic reaction

4. Visual Inspection for Hemolysis

  • Centrifuged plasma examined for color

Findings:

  • Pink/red plasma → hemoglobinemia
  • Clear plasma → hemolysis unlikely

Urine Examination:

  • Red/brown urine with no RBCs → hemoglobinuria

V. Hemolysis Workup

Performed when hemolytic reaction is suspected:

  • Hemoglobin & Hematocrit
    • Unexpected fall post-transfusion suggests hemolysis
  • Serum Bilirubin
    • Raised indirect bilirubin → hemolysis
  • Lactate Dehydrogenase (LDH)
    • Elevated due to RBC destruction
  • Serum Haptoglobin
    • Low or absent in intravascular hemolysis
  • Reticulocyte Count
    • Elevated in delayed hemolytic reactions

VI. Evaluation for Complications

1. Renal Function Tests

  • Serum creatinine
  • Blood urea
  • Urine output monitoring

Purpose: Detect acute kidney injury due to hemoglobinuria

2. Coagulation Profile

  • PT
  • aPTT
  • D-dimer
  • Fibrinogen

Purpose: Identify disseminated intravascular coagulation (DIC) in severe hemolysis

VII. Evaluation for Infectious (Septic) Transfusion Reaction

Indicated when high fever, chills, or shock is present:

  • Blood cultures:
    • From patient
    • From donor blood unit
  • Gram stain of blood product if available

Positive cultures confirm bacterial contamination, a medical emergency

VIII. Evaluation for Pulmonary Transfusion Reactions

1. TRALI Evaluation

  • Acute respiratory distress within 6 hours
  • Chest X-ray: bilateral pulmonary infiltrates
  • Normal cardiac function
  • Exclusion of fluid overload

2. TACO Evaluation

  • Signs of volume overload
  • Raised BP, JVP
  • Pulmonary edema on chest X-ray
  • Response to diuretics

IX. Immunohematological Evaluation

  • Antibody screening and identification
  • Detection of alloantibodies against minor blood group antigens
  • Comparison with previous transfusion history

X. Documentation and Reporting

  • Record all clinical findings and laboratory results
  • Report reaction to:
    • Blood bank
    • Transfusion committee
    • Hemovigilance system
  • Label patient records clearly for future transfusion precautions

 

Diagnosis 

I. Basis of Diagnosis

Diagnosis is established on the following pillars:

  • Temporal relationship between transfusion and onset of symptoms
  • Clinical manifestations during or after transfusion
  • Laboratory evidence of hemolysis, immune reaction, infection, or overload
  • Exclusion of alternative causes (sepsis, cardiac failure, drug reactions)

II. Clinical Diagnostic Criteria

A transfusion reaction should be suspected when any of the following occur during or within hours of transfusion:

  • Fever (≥1°C rise)
  • Chills or rigors
  • Hypotension or shock
  • Chest, back, or flank pain
  • Dyspnea, hypoxia
  • Dark or red urine
  • Rash, urticaria, bronchospasm
  • Sudden respiratory distress
  • Unexplained bleeding or oozing

👉 Early recognition is critical, especially for acute hemolytic reactions.

III. Laboratory Diagnosis (Core Diagnostic Tests)

1. Repeat ABO and Rh Typing

  • Confirms or excludes ABO/Rh incompatibility
  • Any discrepancy between patient and donor blood groups is diagnostic of mismatched transfusion

2. Direct Antiglobulin Test (DAT / Direct Coombs Test)

Diagnostic Role:

  • Detects antibodies or complement attached to RBCs

Interpretation:

  • Positive DAT → immune-mediated hemolytic transfusion reaction
  • Negative DAT → excludes immune hemolysis but not non-immune causes

3. Evidence of Hemolysis (Diagnostic Panel)

Diagnosis of hemolytic transfusion reaction is supported by:

  • Hemoglobinemia (pink/red plasma)
  • Hemoglobinuria (dark urine without RBCs)
  • ↓ Hemoglobin / Hematocrit
  • ↑ Indirect bilirubin
  • ↑ LDH
  • ↓ Serum haptoglobin

Presence of these findings strongly confirms acute hemolytic transfusion reaction.

4. Crossmatch Re-testing

  • Incompatible crossmatch → confirms immune incompatibility
  • Compatible crossmatch → suggests minor antigen reaction or non-immune cause

IV. Diagnosis of Specific Transfusion Reactions

1. Acute Hemolytic Transfusion Reaction

Diagnostic Features:

  • Onset: During or within hours
  • Positive DAT
  • Laboratory evidence of intravascular hemolysis
  • Often due to ABO mismatch

2. Delayed Hemolytic Transfusion Reaction

Diagnostic Features:

  • Onset: Days to weeks after transfusion
  • Gradual fall in hemoglobin
  • Positive DAT
  • Newly detected alloantibodies

3. Febrile Non-Hemolytic Transfusion Reaction

Diagnostic Features:

  • Fever and chills only
  • No laboratory evidence of hemolysis
  • Normal DAT
  • Diagnosis of exclusion

4. Allergic Transfusion Reaction

Diagnostic Features:

  • Urticaria, itching, flushing
  • Normal laboratory tests
  • Diagnosis based on clinical presentation

5. Anaphylactic Reaction

Diagnostic Features:

  • Sudden hypotension, bronchospasm, shock
  • Occurs within minutes
  • Often in IgA-deficient patients
  • Diagnosis is primarily clinical

6. Septic Transfusion Reaction

Diagnostic Features:

  • High fever, hypotension, shock
  • Positive blood cultures from:
    • Patient
    • Donor blood unit
  • Diagnosis confirms bacterial contamination

7. TRALI (Transfusion-Related Acute Lung Injury)

Diagnostic Criteria:

  • Acute respiratory distress within 6 hours
  • Hypoxemia
  • Bilateral pulmonary infiltrates on chest X-ray
  • Normal cardiac function
  • No evidence of fluid overload

8. TACO (Transfusion-Associated Circulatory Overload)

Diagnostic Criteria:

  • Signs of volume overload
  • Hypertension, raised JVP
  • Pulmonary edema on chest X-ray
  • Improves with diuretics
  • Evidence of cardiac dysfunction

V. Differential Diagnosis 

  • Sepsis unrelated to transfusion
  • Acute cardiac failure
  • Drug-induced reactions
  • Pulmonary embolism
  • Acute respiratory distress syndrome (non-transfusion related)

VI. Diagnostic Documentation

  • Diagnosis must be:
    • Clearly documented in patient records
    • Communicated to blood bank
    • Reported under hemovigilance programs
  • Patient should be labeled as “history of transfusion reaction” for future transfusions

 

Complications

I. Hematological Complications

1. Acute Intravascular Hemolysis

  • Massive destruction of donor red blood cells
  • Commonly due to ABO incompatibility
  • Leads to:
    • Hemoglobinemia
    • Hemoglobinuria
    • Severe anemia
  • Can rapidly progress to shock and multiorgan failure

2. Delayed Hemolytic Anemia

  • Occurs days to weeks after transfusion
  • Due to alloantibody-mediated destruction of transfused RBCs
  • Causes:
    • Gradual fall in hemoglobin
    • Jaundice
    • Reticulocytosis
  • Often underdiagnosed

3. Disseminated Intravascular Coagulation (DIC)

  • Triggered by severe hemolysis or septic transfusion reactions
  • Widespread activation of coagulation cascade
  • Leads to:
    • Consumption of clotting factors
    • Bleeding from multiple sites
    • Microvascular thrombosis

II. Renal Complications

1. Acute Kidney Injury (AKI)

  • Caused by:
    • Hemoglobin-induced tubular injury
    • Hypotension and renal ischemia
  • Common in acute hemolytic reactions
  • May progress to:
    • Oliguria or anuria
    • Need for dialysis

III. Cardiovascular Complications

1. Shock

  • Can be:
    • Hypovolemic
    • Septic
    • Anaphylactic
  • Results from massive cytokine release or hemolysis
  • Presents with hypotension and poor tissue perfusion

2. Transfusion-Associated Circulatory Overload (TACO)

  • Causes acute cardiac decompensation
  • Leads to:
    • Pulmonary edema
    • Hypertension
    • Heart failure exacerbation
  • Common in elderly and pediatric patients

IV. Pulmonary Complications

1. Transfusion-Related Acute Lung Injury (TRALI)

  • One of the leading causes of transfusion-related mortality
  • Causes:
    • Acute hypoxemic respiratory failure
    • Non-cardiogenic pulmonary edema
  • Often requires:
    • Mechanical ventilation
    • ICU admission

2. Acute Respiratory Failure

  • Can occur secondary to:
    • TRALI
    • TACO
    • Anaphylaxis
  • May progress to acute respiratory distress syndrome (ARDS)

V. Infectious Complications

1. Septic Shock

  • Due to bacterial contamination of blood products
  • Rapid onset with:
    • High fever
    • Hypotension
    • Multiorgan dysfunction
  • High mortality if not treated promptly

2. Secondary Infections

  • Immunomodulation following transfusion
  • Increased susceptibility to nosocomial infections

VI. Metabolic and Electrolyte Complications

1. Hyperkalemia

  • Due to potassium leakage from stored RBCs
  • Can cause:
    • Cardiac arrhythmias
    • Cardiac arrest

2. Hypocalcemia

  • Caused by citrate toxicity in massive transfusions
  • Leads to:
    • Tetany
    • Arrhythmias
    • Hypotension

3. Hypothermia

  • Rapid infusion of cold blood products
  • Results in:
    • Cardiac arrhythmias
    • Coagulopathy

VII. Immunological Complications

1. Alloimmunization

  • Development of antibodies against RBC antigens
  • Complicates future transfusions
  • Increases risk of delayed hemolytic reactions

2. Anaphylaxis

  • Severe, rapid hypersensitivity reaction
  • Can cause:
    • Airway obstruction
    • Circulatory collapse
  • Potentially fatal without immediate treatment

VIII. Mortality

  • Severe transfusion reactions can be fatal
  • Leading causes of transfusion-related death include:
    • TRALI
    • TACO
    • Acute hemolytic transfusion reactions
    • Septic reactions

 

MCQs

1. A transfusion reaction is best defined as:

A. Any infection transmitted by blood
B. Any adverse event during or after transfusion
C. Only immune-mediated complications
D. Only fatal reactions

✅ Answer: B

2. The most common cause of acute hemolytic transfusion reaction is:

A. Rh incompatibility
B. Minor blood group mismatch
C. ABO incompatibility
D. Leukocyte antibodies

✅ Answer: C

3. Acute hemolytic transfusion reaction is mainly mediated by:

A. IgG antibodies
B. IgE antibodies
C. IgM antibodies
D. IgA antibodies

✅ Answer: C

4. The primary mechanism of RBC destruction in ABO mismatch is:

A. Extravascular hemolysis
B. Intravascular hemolysis
C. Phagocytosis in spleen
D. Apoptosis

✅ Answer: B

5. Direct Antiglobulin Test (DAT) detects:

A. Free antibodies in serum
B. Antibodies bound to RBCs
C. Complement in plasma
D. Platelet antibodies

✅ Answer: B

6. A positive DAT indicates:

A. Non-immune hemolysis
B. Mechanical hemolysis
C. Immune-mediated hemolysis
D. Thermal injury

✅ Answer: C

7. Which finding is most characteristic of intravascular hemolysis?

A. Increased haptoglobin
B. Hemoglobinuria
C. Splenomegaly
D. Reticulocytopenia

✅ Answer: B

8. The earliest laboratory sign of hemolytic transfusion reaction is:

A. Raised bilirubin
B. Drop in hemoglobin
C. Hemoglobinemia
D. Reticulocytosis

✅ Answer: C

9. Serum haptoglobin levels in acute hemolysis are:

A. Increased
B. Normal
C. Decreased
D. Unchanged

✅ Answer: C

10. Delayed hemolytic transfusion reactions are usually mediated by:

A. IgM antibodies
B. IgG antibodies
C. IgE antibodies
D. IgA antibodies

✅ Answer: B

11. Delayed hemolytic transfusion reaction usually occurs:

A. Within 1 hour
B. Within 6 hours
C. 24–48 hours
D. Days to weeks later

✅ Answer: D

12. Which blood group system is commonly involved in delayed hemolytic reactions?

A. ABO
B. Rh only
C. Kell
D. Lewis

✅ Answer: C

13. Febrile non-hemolytic transfusion reaction is caused by:

A. ABO mismatch
B. Cytokines and leukocyte antibodies
C. Bacterial toxins
D. Plasma proteins

✅ Answer: B

14. FNHTR is most commonly associated with transfusion of:

A. Packed RBCs
B. Plasma
C. Platelets
D. Cryoprecipitate

✅ Answer: C

15. Leukoreduction mainly helps prevent:

A. TRALI
B. FNHTR
C. TACO
D. Anaphylaxis

✅ Answer: B

16. Allergic transfusion reactions are usually caused by:

A. RBC antigens
B. Platelet antigens
C. Plasma proteins
D. Bacterial endotoxins

✅ Answer: C

17. Severe anaphylactic reaction is commonly seen in patients with:

A. Hemophilia
B. Sickle cell disease
C. IgA deficiency
D. Iron deficiency anemia

✅ Answer: C

18. TRALI usually occurs within:

A. 24 hours
B. 12 hours
C. 6 hours
D. 72 hours

✅ Answer: C

19. TRALI is characterized by:

A. Cardiogenic pulmonary edema
B. Non-cardiogenic pulmonary edema
C. Pleural effusion
D. Pneumothorax

✅ Answer: B

20. The main pathogenic mechanism in TRALI is:

A. Volume overload
B. IgE-mediated allergy
C. Neutrophil activation in lungs
D. Hemoglobin toxicity

✅ Answer: C

21. TACO is primarily caused by:

A. Immune reaction
B. Bacterial contamination
C. Rapid volume overload
D. Cytokine release

✅ Answer: C

22. Which patient is at highest risk for TACO?

A. Young healthy adult
B. Trauma patient
C. Elderly with heart failure
D. Blood donor

✅ Answer: C

23. Septic transfusion reactions are most commonly associated with:

A. Whole blood
B. Packed RBCs
C. Platelets
D. Cryoprecipitate

✅ Answer: C

24. Platelets have higher risk of bacterial contamination because they are stored at:

A. −20°C
B. 2–6°C
C. Room temperature
D. 37°C

✅ Answer: C

25. The most important immediate step when transfusion reaction is suspected is:

A. Give antibiotics
B. Continue transfusion slowly
C. Stop transfusion
D. Send blood culture

✅ Answer: C

26. Pink-colored plasma after centrifugation indicates:

A. Lipemia
B. Icterus
C. Hemolysis
D. Infection

✅ Answer: C

27. Which laboratory test best confirms immune hemolysis?

A. ESR
B. DAT
C. PT
D. Bleeding time

✅ Answer: B

28. Which complication is most feared in acute hemolytic transfusion reaction?

A. Hypertension
B. Acute kidney injury
C. Hypoglycemia
D. Hypercalcemia

✅ Answer: B

29. Hemoglobinuria can lead to renal failure by causing:

A. Glomerulonephritis
B. Tubular obstruction
C. Immune complex deposition
D. Renal stones

✅ Answer: B

30. DIC in transfusion reaction occurs due to:

A. Platelet deficiency
B. Excess anticoagulant
C. Massive hemolysis and cytokine release
D. Vitamin K deficiency

✅ Answer: C

31. Reticulocyte count is increased in:

A. Acute hemolysis only
B. Delayed hemolytic reaction
C. FNHTR
D. Allergic reaction

✅ Answer: B

32. Which is NOT an immune-mediated transfusion reaction?

A. AHTR
B. DHTR
C. TACO
D. FNHTR

✅ Answer: C

33. Most fatal transfusion reactions are due to:

A. Laboratory testing error
B. Clerical error
C. Storage lesion
D. Expired blood

✅ Answer: B

34. Which antibody activates complement most efficiently?

A. IgG
B. IgA
C. IgE
D. IgM

✅ Answer: D

35. Raised LDH in transfusion reaction indicates:

A. Liver failure
B. RBC destruction
C. Infection
D. Renal failure

✅ Answer: B

36. Hypocalcemia in massive transfusion is due to:

A. Potassium
B. Citrate
C. Heparin
D. EDTA

✅ Answer: B

37. Hyperkalemia in transfusion is seen due to:

A. RBC lysis during storage
B. Plasma proteins
C. Citrate metabolism
D. Leukocytes

✅ Answer: A

38. Which investigation differentiates TRALI from TACO?

A. DAT
B. Chest X-ray
C. Cardiac function assessment
D. Blood culture

✅ Answer: C

39. Which transfusion reaction presents with urticaria and itching only?

A. FNHTR
B. Allergic reaction
C. TRALI
D. Septic reaction

✅ Answer: B

40. In septic transfusion reaction, blood culture is taken from:

A. Patient only
B. Donor unit only
C. Both patient and donor unit
D. Environment only

✅ Answer: C

41. Which is a delayed complication of transfusion?

A. TRALI
B. FNHTR
C. Alloimmunization
D. Anaphylaxis

✅ Answer: C

42. The most reliable method to prevent ABO mismatch is:

A. Antibody screening
B. Leukoreduction
C. Proper patient identification
D. Washed RBCs

✅ Answer: C

43. TRALI pulmonary edema is due to:

A. Increased hydrostatic pressure
B. Left ventricular failure
C. Capillary leak syndrome
D. Fluid overload

✅ Answer: C

44. Which transfusion reaction has the highest mortality?

A. FNHTR
B. Allergic reaction
C. TRALI
D. Delayed hemolysis

✅ Answer: C

45. Hemovigilance refers to:

A. Blood donation
B. Monitoring transfusion reactions
C. Crossmatching
D. Blood storage

✅ Answer: B

46. The most common transfusion reaction overall is:

A. AHTR
B. FNHTR
C. TRALI
D. Septic reaction

✅ Answer: B

47. Which test helps detect DIC?

A. ESR
B. Bleeding time
C. D-dimer
D. Hemoglobin

✅ Answer: C

48. Mechanical hemolysis is caused by:

A. Antibodies
B. Cytokines
C. Faulty transfusion equipment
D. Plasma proteins

✅ Answer: C

49. The most effective preventive measure for FNHTR is:

A. Washed RBCs
B. Leukocyte-reduced blood
C. Male-only plasma
D. Irradiated blood

✅ Answer: B

50. The single most important step to reduce transfusion reaction-related mortality is:

A. Expensive testing
B. Early diagnosis and prompt action
C. Universal plasma transfusion
D. Massive transfusion protocols

✅ Answer: B