4.6 - Transfusion Reactions

A patient had a transfusion reaction to packed RBCs. The MLS began the laboratory investigation of the transfusion reaction by assembling pre- and post-transfusion specimens and all paperwork and computer printouts. What should the MLS do next?

A. Perform a DAT on the post-transfusion sample

B. Check for clerical error(s)

C. Repeat ABO and Rh typing of patient and donor units

D. Perform an antibody screen on the post-transfusion

B. Check for clerical error(s)

• First step in any transfusion reaction investigation is to verify patient and unit identification to rule out clerical or labeling errors — the most common and most dangerous cause of transfusion reactions.

• After clerical accuracy is confirmed, proceed in the following order:

  1. Check for clerical errors (patient ID, unit tags, records)

  2. Perform a DAT on the post-transfusion sample

  3. Compare pre- and post-transfusion plasma for hemolysis

  4. Repeat ABO/Rh typing on patient and donor units

  5. Repeat antibody screen / crossmatch if needed

Summary
Always check for clerical errors first in a transfusion reaction — they’re the most common cause and guide the next investigation steps (DAT → hemolysis check → ABO/Rh → antibody workup).

What is the pathophysiological cause surrounding anaphylactic & anaphylactoid reactions?

A. Ab in pt's serum is detected 3 to 7 days after transfusion & is attached to donor RBCs

B. Donor plasma has reagins (IgE or IgA) that combine with allergens in pt's plasma

C. Pt is deficient in IgE and develops IgE antibodies via sensitization as a result of transfusion or pregnancy

D. Pt is deficient in IgA and develops IgA antibodies via sensitization as a result of transfusion or pregnancy

D. Patient is deficient in IgA and develops IgA antibodies via sensitization as a result of transfusion or pregnancy

• Anaphylactic and anaphylactoid transfusion reactions most often occur in patients who are IgA-deficient and have developed anti-IgA antibodies.

• When transfused with blood products containing IgA, these antibodies trigger severe systemic allergic reactions, often within minutes of transfusion.

• Mechanism: Type I hypersensitivity — preformed IgE or IgG anti-IgA antibodies bind donor IgA → mast cell degranulation, histamine release, and anaphylaxis.

Summary
IgA-deficient patients with anti-IgA antibodies can have anaphylactic reactions when exposed to donor IgA, due to immune complex–mediated hypersensitivity.

A patient has a hemolytic reaction to blood transfused 8 days ago. What is the most likely cause?

A. Immediate, nonimmunologic, probably as a result of volume overload

B. Delayed immunologic, probably as a result of an antibody such as Anti-Jka

C. Delayed nonimmunologic, probably as a result of iron overload

D. Immediate, immunologic, probably as a result of clerical error, ABO incompatibility

B. Delayed immunologic, probably as a result of an antibody such as Anti-Jkᵃ

• Timing (≈8 days post-transfusion) indicates a delayed hemolytic transfusion reaction (DHTR).

• Caused by anamnestic (secondary) immune response to an RBC alloantigen from prior exposure (transfusion or pregnancy).

• Kidd (Jkᵃ, Jkᵇ) antibodies are classic culprits — they often evanesce below detection but reappear after re-exposure, causing extravascular hemolysis days later.

Summary
Delayed immunologic hemolysis (DHTR) 5–14 days post-transfusion is typically due to Kidd antibodies (e.g., Anti-Jkᵃ) from a secondary immune response.

What may be found in the serum of a person who is exhibiting signs of transfusion-related acute lung injury (TRALI)?

A. RBC alloantibody

B. IgA antibody

C. Antileukocyte antibody

D. Allergen

C. Antileukocyte antibody

• TRALI (Transfusion-Related Acute Lung Injury) occurs when donor plasma contains antileukocyte antibodies (most often anti-HLA or anti-HNA) that react with the recipient’s leukocytes.

• This interaction triggers neutrophil activation and capillary leakage in the lungs, leading to acute pulmonary edema within 1–6 hours of transfusion.

• Donor antileukocyte antibodies are most often found in multiparous women due to prior sensitization from pregnancy.

Summary
In TRALI, antileukocyte antibodies (anti-HLA or anti-HNA) in donor plasma react with recipient WBCs, causing acute lung injury.

Which type of transfusion reaction occurs in about 1% of all transfusions, results in a temperature rise of greater than 1C above 37C associated with blood component transfusion, and is not related to the patient's medical condition?

A. Immediate hemolytic

B. Delayed hemolytic

C. Febrile nonhemolytic reaction

D. TRALI

C. Febrile nonhemolytic reaction

• Occurs in ~1% of transfusions, typically within the first few hours of transfusion.

• Defined as a temperature rise >1 °C above 37 °C without other identifiable cause.

• Caused by:
  • Recipient antibodies reacting with donor leukocytes or platelets, or
  • Cytokines accumulating in stored blood components.

• Reaction is benign but uncomfortable and treated symptomatically (e.g., acetaminophen).

Summary
A febrile nonhemolytic transfusion reaction causes a >1 °C fever increase, affects ~1% of transfusions, and is due to cytokines or leukocyte antibodies, not hemolysis.

What would be the result of group A blood given to a group O patient?

A. Nonimmune transfusion reaction

B. Immediate hemolytic transfusion reaction

C. Delayed hemolytic transfusion reaction

D. Febrile nonhemolytic transfusion reaction (FNTR)

B. Immediate hemolytic transfusion reaction

• Group O recipients have naturally occurring anti-A and anti-B (IgM) antibodies in their plasma.

• Transfusing group A RBCs introduces A antigens, which react immediately with the recipient’s anti-A, causing complement activation and intravascular hemolysis.

• This is a severe, acute, immune-mediated reaction that can lead to renal failure, DIC, and death if not promptly recognized.

Summary
Group A blood → group O patient = immediate immune hemolytic reaction due to anti-A–mediated complement activation and RBC destruction.

All of the following are part of the preliminary evaluation of a transfusion reaction, except:

A. Check pre- and post-transfusion samples for color of serum

B. Perform ABO and Rh recheck

C. Perform DAT on the post-transfusion sample

D. Perform a panel on pre- and post-transfusion samples

D. Perform a panel on pre- and post-transfusion samples

• Preliminary evaluation of a suspected transfusion reaction includes:
  • Clerical check for ID or labeling errors
  • Visual hemolysis check — compare pre- and post-transfusion plasma for pink/red discoloration
  • Repeat ABO/Rh typing on patient and donor units
  • DAT on the post-transfusion sample to detect in vivo sensitization

• Performing an antibody panel is not part of the initial workup — it’s only done if hemolysis or incompatibility is suspected after preliminary testing.

Summary
Antibody panel testing is not part of the preliminary transfusion reaction evaluation — it’s performed only if further investigation is warranted.

Patient DB received 2 units of group A-positive RBCs 2 days ago. Two days later, he developed a fever and appeared jaundiced. His blood type was A positive. A transfusion reaction workup was ordered. There were no clerical errors detected.  A post transfusion specimen was collected an a DAT performed.  The DAT result was positive with monospecific anti-IgG.  The plasma was also hemolyzed.  An antibody screen and panel studies revealed the presence of anti -Jkb in the post transfusion specimen.  The antibody screen on the pre-transfusion specimen was negative.  Which of the following explains the positive DAT?

A, The donor cells had a positive DAT

B. The donor cells were polyagglutinable 

C. The donor cells were likely positive for the Jkb antigen

D. The recipient cells were likely positive for the Jkb antigen

C.  This is an example of an anamnestic reaction, where the patient was most likely exposed to the Jkb antigen at some point in his life, and upon reexposure to the antigen, the A titer rose to detectable levels.   This resulted in positive DAT and post transfusion AB screen results

A 68 year old female diagnosed with neutropenia and inflammation of the left hand was typed as A positive and recieved 1 packed RBC unit. The ab screen was negative, and crossmatch was compatible.During the transfusion, her pulse was 94, and BP rose from 114/59 mmHg to 132/64.  Temp rose from 37.1 to 37.8 60 minutes after starting transfusion and then to 38.3 upon completion.  A post transfusion specimen yielded plasma that was neither hemolyzed nor icteric, and a negative DAT.  Post transfusion urinalysis showed 1+ blood and protein with 10 RBC/high powered field.  The clerical check result was acceptable.  What type of reaction most likley occured as a result of transfusion?

A. allergtic

B. Circulatory Overload

C. Febrile nonhemolytic 

D. Delayed hemolytic 

C. Febrile nonhemolytic

• Key findings:
  • Temp rise from 37.1 → 38.3 °C (>1 °C increase) during transfusion
  • No hemolysis (plasma clear, DAT negative)
  • Normal clerical check
  • Mild RBCs/protein in urine = transient, nonspecific finding

• The patient’s fever without evidence of hemolysis or allergy fits a febrile nonhemolytic transfusion reaction (FNHTR).

• Mechanism: recipient antibodies to donor leukocytes or cytokines released during storage.

• TACO (circulatory overload) would present with respiratory distress, hypertension, pulmonary edema, not just fever.

Summary
>1 °C temperature rise + no hemolysis + negative DAT → Febrile nonhemolytic transfusion reaction (FNHTR) due to cytokine or leukocyte antibody response.

a 92 year old male diagnosed with anemia and episodes of frequent falling was typed as B neg and transfused with 1 unit of packed RBCs, also B negative.  He had not been recently transfused, and the antibody screen was negative.  During the transfusion, his temp rose from 36.2 to 35.4, his pulse from 96 to 124, respiration from 18- 20, and BP from 127/81 to 174/83.  he was transfused with 205 mL before a reaction was called by the transfusionist.  The post transfusion specimen DAT result was negative, the clerical check was acceptable.  Urinalysis showed 1+ blood with 5 RBCs microscopically.  Other symptoms included tachycardia and flushing.  What reaction had most likely taken place?

A. febrile nonhemolytic

B. Acute hemolytic

C. Anaphylactic

D. Volume Overload

D. Volume overload (TACO — Transfusion Associated Circulatory Overload)

• Key findings:
  • Marked BP rise (127/81 → 174/83) and tachycardia (96 → 124)
  • Flushing and mild dyspnea (↑ respirations)
  • No hemolysis (DAT negative, plasma clear, acceptable clerical check)
  • No fever — temp actually decreased slightly (36.2 → 35.4 °C)

• Mechanism: too rapid or excessive transfusion → volume overload, particularly in elderly or cardiac-compromised patients.

• FNHTR requires fever; anaphylaxis would involve hypotension and airway symptoms; acute hemolysis would show hemoglobinemia/hemoglobinuria and positive DAT.

Summary
Hypertension + tachycardia + no hemolysis + elderly patient → Transfusion-associated circulatory overload (TACO).

A 76-year-old female diagnosed with urosepsis was transfused with 2 units of packed RBCs. Her type was AB positive and she had a negative result on antibody screen. The units transfused were AB positive. Upon receiving the second unit, the patient became hypoxic with tachypnea. The clerical check result was acceptable, and the DAT was negative. She received 269 mL from the second unit before a reaction was called. Her temperature fell from 38°C to 36.4°C, her pulse increased from 72 to 90, and respirations rose from 35 to 41. Her BP was 110/70 mm Hg. The patient died approximately 12 hours after the reaction was called. What type of reaction was most likely present?

A. Febrile
B. Symptoms not related to transfusion
C. Allergic
D. TRALI

B. Symptoms not related to transfusion

• Key findings:
  • Patient had urosepsis (a severe infection) — already predisposed to respiratory compromise.
  • Hypoxia, tachypnea, and fall in temperature (not rise) point to septic deterioration, not transfusion reaction.
  • DAT negative, clerical check acceptable, and no hemolysis — exclude hemolytic, allergic, or TRALI reactions.
  • Death 12 h later most consistent with progression of underlying infection, not transfusion-related pathology.

Summary
Clinical picture best explained by underlying urosepsis, not a true transfusion reaction — thus symptoms not related to transfusion.

A 52-year-old male received 2 units of packed RBCs as an outpatient in the intravenous (IV) therapy unit. He had had a head trauma 20 years ago and was quadriplegic. He had recurrent pneumonia and hematuria as a result of removal of a Foley catheter. His blood type was A positive, with previously identified anti-Fyᵃ. There was an ABO discrepancy, in that reverse typing with reagent A₁ cells was positive. The MLS attributed this reaction to Fyᵃ antigen being present on the reagent A₁ cells. The patient also had a cold autoantibody. Two units of A-positive packed cells were crossmatched that were Fyᵃ negative and were compatible. One unit was transfused at 11:30 a.m. without incident. The second unit was transfused at 2:16 p.m. and stopped at 3:55 p.m. because of reddish brown–tinged urine found in his collection bag. A post-transfusion specimen yielded a positive DAT and plasma that was grossly hemolyzed. A prewarm crossmatch was incompatible in both the pre- and post-transfusion specimens. Anti-E and anti-c were present in the post-transfusion specimen. What reaction was most likely present?

A. Acute hemolytic
B. Febrile
C. Allergic
D. TRALI

A. Acute hemolytic

• Key findings:
  • Reddish-brown urine → hemoglobinuria, a hallmark of intravascular hemolysis.
  • Grossly hemolyzed plasma and positive DAT confirm immune-mediated RBC destruction.
  • Newly formed Anti-E and Anti-c in post-transfusion sample → anamnestic (secondary) immune response causing acute hemolytic transfusion reaction.
  • Incompatible prewarm crossmatch supports presence of clinically significant antibodies.

• Mechanism: Recipient alloantibodies (Anti-E, Anti-c) reacting with donor RBCs → complement-mediated lysis.

Summary
Positive DAT + hemolyzed plasma + hemoglobinuria = Acute hemolytic transfusion reaction, due to newly formed Anti-E and Anti-c antibodies.

An 82-year-old male was admitted for renal failure. His type was B positive, and his antibody screen was negative. Two units of RBCs were ordered. The first unit was transfused at 1:00 p.m. without incident. The second was started at 4:15 p.m. and stopped at 5:12 p.m. after the nurse observed that the patient had died. Vital signs had been taken at 4:30 p.m. with no abnormalities. A transfusion reaction was called and the blood unit, tubing, and paperwork sent to the blood bank. There were no clinical manifestations noted on the paperwork, and no post-transfusion specimen was sent to the blood bank. What type of reaction most likely occurred?

A. Cause not related to transfusion
B. Acute hemolytic reaction
C. Anaphylactic reaction
D. Volume overload

A. Cause not related to transfusion

Unexpected Death During Transfusion

• Patient: 82-year-old male with renal failure, B+, Ab screen negative.

• Findings: No abnormal vitals before death, no hemolysis, no symptoms suggesting reaction, no post-specimen sent.

• Interpretation: Sudden death temporally associated with transfusion, but no evidence of hemolysis, allergy, pulmonary distress, or volume overload.

• Diagnosis: Cause not related to transfusion (coincidental event).

Context:
Fatal events during or after transfusion require investigation, but absence of clinical/laboratory evidence (normal vitals, negative DAT, no hemolyzed plasma) indicates non–transfusion-related death, possibly due to underlying disease (e.g., renal/cardiac failure).