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Transfusion reactions

16 min

Skills you'll build4 skills
  • Perform the laboratory checks for a suspected transfusion reaction
  • Tell TRALI from circulatory overload by blood pressure, BNP, and fluid balance
  • Distinguish delayed serologic change from delayed hemolytic injury
  • Investigate suspected bacterial contamination of a transfused component

At the bench: Perform and document the laboratory workup of a transfusion reaction

Try first

Try first

A nurse calls: 15 minutes into a red-cell unit, the patient has chills and a temperature 1.5 °C above baseline. The transfusion is stopped, and the bag and a postreaction specimen come to the transfusion service. What does the laboratory check first?

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

The first checks

When a reaction is called in, the bedside team stops the transfusion and sends back the bag, the tubing and a postreaction specimen. Keep all of them for the investigation.1 The laboratory workup follows a set order:1

  1. Clerical check. Compare the patient's identifiers, the unit label and the compatibility record.
  2. Visual check. Compare the color of the postreaction plasma with the prereaction specimen.
  3. Direct antiglobulin test (DAT) on the postreaction specimen, and repeat ABO typing on that specimen and on the unit.
  4. Hemolysis markers as the findings require: urine hemoglobin, lactate dehydrogenase (LDH), bilirubin and haptoglobin.

A negative DAT leaves immune hemolysis possible. Incompatible cells may already be destroyed, or too few coated cells may remain to detect. A postreaction DAT stronger than the prereaction one, or a mixed-field DAT, requires an eluate.1

Bacterial contamination

A temperature rise of 2 °C or more with rigors or hypotension points to bacterial contamination. Platelets stored at room temperature carry the highest risk. Bacterial screening or pathogen reduction lowers that risk, and a screened unit can still be contaminated.2 The laboratory cultures the patient and the component, Gram stains the component, and calls the collecting facility so it can retrieve the other components from that donation.1,2

TRALI and TACO

Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) both cause hypoxemia and pulmonary edema. The associated findings help distinguish them.1,3

FindingTRALITACO
OnsetDuring or within 6 hoursDuring or within 12 hours
Blood pressureOften lowOften high
Volume overloadAbsent, or not the main explanationPresent: raised B-type natriuretic peptide (BNP) and positive fluid balance

No single finding distinguishes them, and the two can occur together. Report suspected TRALI to the collecting facility at once.1,2

Delayed reactions

An IgG antibody can rise 2 to 14 days after a new exposure to a red-cell antigen, classically in the Rh, Kidd, Duffy or Kell systems. A new antibody with a positive DAT and no sign of red-cell destruction is a delayed serologic reaction. An unexplained fall in hemoglobin, with rising bilirubin and LDH and falling haptoglobin, indicates a delayed hemolytic reaction. In both cases, the antibody is added to the patient's record and applies to every future unit.1,4

Follow the bench demonstration

Sources for this step
References
  1. Bloch EM, Campbell-Lee S, McKenna DH Jr, Montemayor-Garcia C, Schwartz J, Shaz B, Storry J, eds. Technical Manual. 22nd ed. AABB; 2026.
  2. Association for the Advancement of Blood & Biotherapies, American Red Cross, America's Blood Centers, Armed Services Blood Program. Circular of Information for the Use of Human Blood and Blood Components. June 2024. Accessed September 27, 2026.
  3. Vlaar APJ, Toy P, Fung M, et al. A consensus redefinition of transfusion-related acute lung injury. Transfusion. 2019;59(7):2465-2476. doi:10.1111/trf.15311
  4. Centers for Disease Control and Prevention. National Healthcare Safety Network. Biovigilance Component Hemovigilance Module Protocol. Version 3.0. January 2026. Accessed September 27, 2026.

Watch one

Read each decision and its explanation.

Dolores Reagan, 68 (MRN 4418270), is 25 minutes into a red-cell unit on the surgical floor. Her temperature rises from 36.8 °C to 38.6 °C, and she reports back pain. The nurse stops the transfusion and sends the bag, the tubing, a postreaction EDTA specimen and a urine specimen. Her pretransfusion specimen is still in the transfusion service refrigerator.

What does the workup show?

  1. Clerical check: the tag on the bag reads Doris Pipkin, MRN 4481207. The unit was prepared for another patient. Notify the transfusion service physician now and continue the workup.

    A wrong patient or wrong unit is the most preventable cause of a hemolytic reaction, and finding one changes everything that follows.

  2. Visual check: the postreaction plasma is pink-red, and the pretransfusion plasma is straw-colored.

    Free hemoglobin that was absent before the transfusion points to red cells destroyed after it began.

  3. DAT on the postreaction specimen: negative.

    Incompatible cells destroyed in the bloodstream leave few coated cells behind, so a negative DAT does not end the workup.

  4. Repeat ABO typing: her postreaction specimen types as group O, and the segment from the unit types as group A.

    Typing both the patient and the unit shows whether she received ABO-incompatible red cells.

  5. Hemolysis markers: the urine is positive for hemoglobin, and LDH and bilirubin are above her pretransfusion values.

    Hemolysis markers confirm red-cell destruction and give the physician a baseline for follow-up.

The workup shows an acute hemolytic transfusion reaction from ABO incompatibility: a group A unit prepared for another patient reached a group O patient. The results go to the transfusion service physician, and the event is investigated and reported under the facility's procedure.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

After a suspected hemolytic reaction, the clerical check shows no error, the postreaction plasma is more hemolyzed than the prereaction specimen, and the postreaction direct antiglobulin test (DAT) is negative. What does the laboratory do next?

Incorrect. A negative DAT alone does not identify a nonimmune cause. Bag and tubing samples and a review of storage, warming, and infusion equipment are used to investigate that possibility. Immune hemolysis stays possible until the workup is complete.

Correct. Incompatible cells can be destroyed quickly, or the remaining coating can fall below the assay's sensitivity, so a negative DAT leaves immune hemolysis possible. Repeat ABO testing of the postreaction sample and the implicated unit, with hemolysis markers and urine hemoglobin, continues the workup.

Incorrect. The DAT detects antibody or complement on the red cells and gives no information about how the sample was drawn. Hemolysis that rose after the transfusion is investigated as possible destruction in the patient until the workup shows otherwise.

Hint
  1. Ask what could make a DAT negative even when incompatible cells were transfused.
  2. Cells destroyed in the bloodstream leave nothing on the remaining cells for the DAT to detect. Ask which step checks, without the DAT, whether she received ABO-incompatible cells.

Review Immediate response and basic workup

Problem 2 of 3 · Hints available

Two hours into a plasma transfusion, a recipient develops hypoxemia and bilateral pulmonary edema. Which set of findings most supports transfusion-associated circulatory overload (TACO) over transfusion-related acute lung injury (TRALI)?

Incorrect. Hypotension without evidence of circulatory overload supports TRALI. TACO usually presents with hypertension and signs of volume excess.

Correct. Hypertension, a raised B-type natriuretic peptide (BNP) or NT-proBNP, and fluid-overload evidence together support TACO. No single finding establishes the category, and overlap is recorded when both processes appear.

Incorrect. A cognate donor antibody supports an immune TRALI mechanism and does not address volume overload. TRALI and TACO can also occur together.

Hint
  1. TACO means the circulation received more volume than the heart could handle.
  2. Blood pressure tends to move in opposite directions in TRALI and TACO. Ask which way it moves when the circulation is overloaded.

Review Acute reactions

Problem 3 of 3 · On your own

Thirty minutes into an apheresis platelet unit that tested negative for bacteria, a patient's temperature rises from 37.0 °C to 39.4 °C with rigors, and the blood pressure falls to 86/48 mm Hg. The clerical check matches, and the postreaction plasma shows no hemolysis. What does the laboratory do next?

A febrile nonhemolytic reaction is called only after contamination is ruled out. A rise of 2.4 °C with rigors and hypotension fits sepsis, and screening lowers the risk without removing it.

Dismissed sepsis because a component had bacterial screening

Bacterial screening lowers contamination risk without removing it, and room-temperature platelets remain the highest-risk component. Dismissing a high fever and rigors because the platelets were tested delays the patient and component cultures and the call to the collecting facility, which retrieves the other components from that donation.

The component is the likely source, and the other components from that donation may still be in use elsewhere. Waiting delays the notification that allows them to be retrieved.

The clerical check matched, and the plasma shows no hemolysis. The fever and hypotension point to bacteria, which ABO typing cannot detect.

The rise of 2.4 °C with rigors and hypotension points to contamination. The component culture and Gram stain look for the organism, and the collecting facility retrieves the other components from that donation.

Review Bacterial contamination

Use it

Read the case evidence, then make each decision. The step is complete without it.

  • Gloria Bufford, 58 (MRN 5230418), received two red-cell units after hip surgery. Her pretransfusion antibody screen was negative.
  • Eight days later she returns tired and slightly jaundiced, with no sign of bleeding.
  • Today's antibody screen is positive, and the panel identifies anti-Jka.
  • Her DAT is positive with anti-IgG, weak and mixed field. Anti-C3d is negative.
TestResultPreviousReference intervalFlag
Hemoglobin7.4 g/dL LowDay 1: 10.1 g/dL10.1 g/dLDay 112.0–15.5 g/dL12.0–15.5Low
Total bilirubin3.2 mg/dL HighDay 1: 0.8 mg/dL0.8 mg/dLDay 10.1–1.2 mg/dL0.1–1.2High
Lactate dehydrogenase540 U/L HighDay 1: 210 U/L210 U/LDay 1140–280 U/L140–280High
Haptoglobin<10 mg/dL LowDay 1: 120 mg/dL120 mg/dLDay 130–200 mg/dL30–200Low

Specimen: H 15, L 10, I 3. EDTA whole blood and serum, day 8 after transfusion

Decision 1 of 3

How is the event classified?

A serologic reaction has no evidence of red-cell destruction. Her hemoglobin fell 2.7 g/dL with no bleeding, and her bilirubin, LDH and haptoglobin all changed in the direction expected with hemolysis.

An acute reaction begins during the transfusion or within 24 hours. This one appeared 8 days later, the time an anamnestic IgG antibody needs to rise.

A new anti-Jka and a mixed-field DAT show the antibody coating transfused cells. The hemoglobin fall and the hemolysis markers show those cells being destroyed.

Her pretransfusion screen was negative, and the antibody appeared after the transfusion. Kidd antibodies often fall below detection and return quickly after a new exposure.

Review Delayed reactions

Decision 2 of 3

Which test shows what is coating her transfused red cells?

A polyspecific DAT shows that something coats the cells. It cannot identify the antibody.

The eluate removes the antibody from the coated cells. Testing it against panel cells shows whether the coating is the anti-Jka found in her plasma.

The plasma panel already found anti-Jka. It shows antibody in the plasma. The question is what is bound to the cells.

Review Immediate response and basic workup

Decision 3 of 3

What happens to the anti-Jka result?

Kidd antibodies often fade below detection. A record that lapses would let the next unit be Jk(a+), and the antibody would return within days.

A new antibody is recorded whether or not hemolysis occurs. A serologic reaction changes every future unit selection too.

The antibody stays on her record after it falls below detection. Every future red-cell unit is Jka-negative and antiglobulin-crossmatched, even when her screen is negative.

Review Unit selection and availability

The anti-Jka and the mixed-field DAT, with no other findings, would fit a delayed serologic reaction. The hemoglobin fall of 2.7 g/dL without bleeding, with raised bilirubin and LDH and a haptoglobin below 10 mg/dL, shows the transfused cells being destroyed.

For reference

Sources checked