Transfusion reaction: fever, dyspnea, TACO, TRALI, hemolysis

A 78-year-old man with heart failure is hospitalized for anemia and receives his second unit of packed red blood cells of the day. Forty minutes after the start, he says he is cold and begins to shiver. The nursing technician measures his vital signs: temperature 38.6 °C, which was 36.8 °C before the unit, oxygen saturation 89 percent, which was 96, blood pressure 178/96 mmHg and respiratory rate 26. He is more short of breath and coughing. The nurse stops the transfusion. The scene is fictional and was written for teaching.

This text uses the scenario as a setting for clinical reasoning in nursing. The trap is to treat everything as a "febrile reaction", give an antipyretic and restart the unit. Fever, shortness of breath and a change in blood pressure during a transfusion have several causes, and some kill within hours. The text does not replace your institution's hemovigilance protocol or the guidance of the transfusion service. If you play the case of the day on NEXO, you will recognize the challenge: overlapping clues and a decision that cannot wait.

Key points

• New symptoms during the unit or in the following hours should be treated as a transfusion reaction until proven otherwise.
• The first step is the same for all: stop the transfusion, keep the venous access and check the patient's and the unit's identification.
• High blood pressure, jugular venous distension and a history of heart disease point to circulatory overload (TACO).
• Low blood pressure and fever with pulmonary edema point to transfusion-related acute lung injury (TRALI).
• In TRALI, a diuretic can worsen hypotension; in TACO, it is part of the treatment.
• In anaphylaxis, intramuscular adrenaline is the first-line treatment.

Why this is a reasoning scenario

Serious transfusion reactions are uncommon, but circulatory overload is common enough to be part of routine practice. A meta-analysis of studies with active surveillance estimated TACO at 22.2 per 1000 transfused patients and 2.2 per 1000 units, and notes that it is one of the main causes of transfusion-related deaths reported to the American drug agency (White et al., 2025). In a medical intensive care unit, TACO appeared in 6 percent of transfused patients (Li et al., 2011).

The people at the patient's side in the first minutes are almost always the nursing team. They measure vital signs before, during and after the unit, notice the change and decide to stop. They are also the ones who keep the unit and the tubing for investigation and notify the transfusion service. A report from the British hemovigilance system SHOT suggests that part of the circulatory overloads would be preventable with better assessment before transfusion and better monitoring during it (Bolton-Maggs and Cohen, 2013).

What the scene teaches

The scene trains three habits. The first is to stop the unit at any change, without waiting for the diagnosis. The second is to read the signs together: blood pressure, temperature, saturation and cardiac history say different things. The third is to communicate in a structured way and preserve the material for investigation. The post on clinical decision-making discusses how to act with incomplete information.

What counts as a transfusion reaction

Transfusion reactions are classified as immediate when they appear in the first 24 hours after the start of the transfusion and as delayed when they appear after that (Soares et al., 2024). A review estimates the overall incidence of reactions at about 1 percent, with mortality of 1 in every 200 thousand to 420 thousand units in severe reactions (Wang et al., 2022). In a hemovigilance study of 19,800 units at a teaching hospital in India, fever was the most common symptom, followed by chills and shivering (Krishnamurthy et al., 2020).

The International Society of Blood Transfusion and the international hemovigilance network define febrile non-hemolytic reaction as a temperature of 38 °C or higher, or a rise of more than 1 °C from the previous value, during the transfusion or up to 4 hours afterward, after excluding hemolysis, bacterial contamination and other causes (Wang et al., 2022). The same review advises considering a septic reaction when the patient does not improve after the bag is stopped or an antipyretic is given, when the temperature rises 2 °C or more, or when new signs of bacterial infection appear (Wang et al., 2022). The patient in the scene rose 1.8 °C. But febrile reaction is a diagnosis of exclusion: before accepting it, hemolysis, bacterial contamination and TRALI must be ruled out.

When the signs appear

Each reaction has a typical window. TRALI, by the 2019 consensus definition, appears up to 6 hours after the transfusion (Vlaar et al., 2019). Acute hemolytic reaction usually appears in the first 24 hours and may begin with fever, chills and shortness of breath (Wang et al., 2022). Anaphylaxis appears within minutes. That is why the first 15 minutes of each bag deserve close observation, but surveillance continues after the infusion ends.

The first minutes: nursing management

A nursing simulation scenario validated by experts describes the expected sequence in the face of chills and tachycardia during the bag: call for help, measure vital signs, stop the drip, keep venous access with 0.9 percent saline, call the physician and activate the hematology team (Soares et al., 2024). The same authors note that wrong identification of the recipient and wrong labeling of the sample are the most common errors in reported events (Soares et al., 2024). In the scene, the nurse closes the tubing, keeps the catheter with saline, calls the medical team and checks the name, date of birth and bag number against the wristband and the prescription.

What to do in sequence

• Stop the transfusion and do not disconnect the venous access.
• Measure temperature, blood pressure, heart rate, respiratory rate and oxygen saturation again.
• Give oxygen if saturation has dropped and raise the head of the bed if there is shortness of breath.
• Check patient identification, blood type and bag number.
• Notify the medical team and the transfusion service.
• Keep the bag and tubing, closed, for investigation, according to protocol.
• Collect the samples requested by the transfusion service and record the volume infused.

The check that prevents the worst error

The British SHOT system divides reported events into three groups: those caused by error, which should be preventable; those caused by unpredictable reactions; and an intermediate group of complications that can be avoided with better assessment before transfusion and better monitoring, which includes circulatory overload (Bolton-Maggs and Cohen, 2013). The same article shows that transfusion goes through many steps and professionals, from donor identification to the bedside check, and that monitoring and recognition of adverse events are the responsibility of nurses, midwives and physicians (Bolton-Maggs and Cohen, 2013). Each step is a chance for error and also a barrier.

In practice, the bedside check compares the wristband, the prescription and the bag label, with the patient stating their own name when able. When a reaction appears, this check is repeated. If there is any discrepancy, the transfusion service must know immediately, because another patient may be receiving the wrong bag. SHOT also notes that TACO symptoms can overlap with those of TRALI and transfusion-associated dyspnea (Bolton-Maggs and Cohen, 2013), which reinforces the idea of not closing the diagnosis too early.

Communicate clearly

Structured communication helps the team decide fast. An example: "78-year-old patient with heart failure, second unit of red blood cells, 40 minutes of infusion. Chills, temperature 38.6, saturation 89 on room air, pressure 178/96, respiratory rate 26, crackles at the bases. Transfusion stopped, access maintained, oxygen started, identification checked. I request evaluation now." The message brings the time, the signs, what has already been done and the request. The post about interprofessional clinical reasoning discusses how nursing, medicine and the blood bank decide together.

Fever, shortness of breath and high blood pressure: the hypotheses

In the scene, there are four clues that pull in different directions: fever with chills, falling saturation, high blood pressure and a history of heart failure. The table organizes the hypotheses.

Hypothesis	Clues in favor	What weighs against or remains to be confirmed
TACO	High blood pressure, heart failure, second unit, crackles	Fever is less typical
TRALI	Fever, hypoxemia, pulmonary edema	In TRALI the pressure usually falls
Acute hemolytic reaction	Fever and chills may be the only initial signs	Identification check and agency tests
Bacterial contamination of the unit	High fever and chills	Hypotension, cultures of the patient and of the unit
Febrile non-hemolytic reaction	Fever during the unit	Only after ruling out the others
Anaphylaxis	Shortness of breath	No urticaria, no wheezing, no hypotension

Table sources: (Wang and colleagues, 2022) and (Desai and colleagues, 2022). The post about differential diagnosis with clues shows how to organize this list when time is short.

The most important point of the reasoning is that the hypotheses do not exclude each other. A patient with heart disease can have TACO and another reaction at the same time, and fever does not rule out overload. That is why nursing does not need to close the diagnosis to act. It needs to stop, stabilize, document and call in whoever investigates.

TACO and TRALI side by side

TACO and TRALI cause pulmonary edema and shortness of breath in the hours after transfusion, but they have different mechanisms and treatments. An educational case summarizes the differences (Desai and colleagues, 2022).

Feature	TRALI	TACO
Blood pressure	Hypotension	Hypertension
Other signs	Fever, tachycardia	Jugular distension, edema
BNP	No elevation	Significant elevation
Radiograph	Diffuse bilateral infiltrate without enlargement of the cardiac area	Alveolar and interstitial edema, pleural effusion, enlarged cardiac area
Mechanism	Immune, donor antibodies	Volume or speed beyond cardiac reserve
Treatment	Support with oxygen and ventilation	Diuretic and oxygen

Table source: (Desai and colleagues, 2022).

TRALI criteria

The 2019 consensus redefinition describes type I TRALI, in patients without a risk factor for acute respiratory distress syndrome, with acute onset, PaO2/FiO2 ratio of 300 mmHg or less or saturation below 90 percent on room air, bilateral pulmonary edema on imaging, absence of left atrial hypertension or, if present, not being the main cause, and onset within 6 hours after transfusion (Vlaar and colleagues, 2019). Type II TRALI includes patients with a risk factor or with a mild syndrome already present (Vlaar and colleagues, 2019). Treatment is supportive, and diuretics should be avoided (Yu and Lian, 2023). TRALI is one of the main causes of transfusion-related death (Kim and Na, 2015).

The role of natriuretic peptide

A systematic review of biomarkers found that a ratio of NT-proBNP after and before transfusion above 1.5 favors TACO, and that BNP below 300 pg/mL or NT-proBNP below 2000 pg/mL make TACO unlikely (Klanderman and colleagues, 2019). The test does not decide on its own, but it helps the team separate the two hypotheses.

Who is at higher risk of TACO

In the intensive care study, patients with TACO had a more positive fluid balance, received more plasma and were transfused faster; prior left ventricular dysfunction had an odds ratio of 8.23 (Li et al., 2011). The 2025 meta-analysis cites heart and kidney disease, advanced age and positive balance among the risk factors (White et al., 2025). In a rat study, transfusion speed raised filling pressure more than volume did (Klanderman et al., 2022), and another rat study tested prophylactic furosemide (Klanderman et al., 2022b); the animal data did not become a rule for people, but they reinforce attention to speed. In treatment, TACO usually improves quickly with a diuretic, and a diuretic can be considered before future transfusions (Desai et al., 2022).

Hemolysis, sepsis and anaphylaxis

Acute hemolytic reaction

Acute hemolytic reaction usually comes from ABO incompatibility, almost always due to an error in identifying the sample, the bag or the patient (Desai et al., 2022). The patient may have fever, chills, lower back pain, nosebleed, pain at the access site, hypotension and kidney failure (Desai et al., 2022). It can start with fever, chills and shortness of breath, and then show lower back pain, hemoglobin in the urine, kidney failure and shock (Wang et al., 2022). That is why checking identification right after stopping the bag is not bureaucracy. Measuring and recording urine output and the appearance of the urine helps the team notice kidney injury early; testing the urine for hemoglobin is part of the laboratory workup (Krishnamurthy et al., 2020).

Bacterial contamination

The septic reaction usually presents with fever and chills and signs of a systemic inflammatory response, and the diagnosis uses culture and Gram stain (Wang et al., 2022). In the Indian hemovigilance study, the bag was inspected for hemolysis, clots and color change, and microbiological testing was done to rule out bacterial infection (Krishnamurthy et al., 2020). Nursing contributes by keeping the bag closed and recording the times.

Anaphylaxis

Allergic transfusion reactions range from isolated urticaria to anaphylaxis. A review of allergic transfusion reactions describes intramuscular or subcutaneous adrenaline as treatment and the intravenous route in shock (Hirayama, 2013). The 2020 World Allergy Organization guidance indicates intramuscular adrenaline in the anterolateral thigh, at a dose of 0.01 mg/kg, up to 0.5 mg in adults, which corresponds to 0.5 mL of the 1 mg/mL solution, repeated every 5 to 15 minutes if there is no response (Cardona et al., 2020). In the patient in the scene, the absence of urticaria, wheezing and hypotension makes anaphylaxis less likely, but the dose needs to be clear for those caring for transfusions.

Step-by-step reasoning in the case

First, the stop: the nurse interrupts the bag upon seeing chills, fever and falling saturation, without waiting for the diagnosis.

Second, safety: the nurse keeps the access with saline and checks identification and the bag.

Third, support: the nurse offers oxygen, raises the head of the bed and measures the signs again.

Fourth, the reading: high blood pressure, jugular distension, crackles and heart failure point to TACO; fever keeps TRALI, hemolysis and contamination on the list.

Fifth, communication: the nurse notifies the medical team and the transfusion agency with a structured message.

Sixth, the investigation: the nurse keeps the bag and tubing, collects the requested samples and records the infused volume.

Seventh, follow-up: the nurse monitors urine output and signs, and documents the reaction in the hemovigilance system.

Common mistakes

The first mistake is giving an antipyretic and restarting the bag. Fever during transfusion calls for stopping and investigating.

The second mistake is disconnecting the access. It may be needed for fluids or medications.

The third mistake is giving a diuretic by reflex to every patient with shortness of breath. In TRALI with hypotension, it can worsen the picture.

The fourth mistake is discarding the bag. Without it, the investigation loses its main evidence.

The fifth mistake is transfusing a patient with heart failure quickly without assessing the risk of overload beforehand.

Preventing the next reaction

Before each transfusion, it is worth asking whether the patient has heart or kidney disease, what the fluid balance is like and whether the bag can run more slowly. Measuring vital signs before, in the first 15 minutes and at the end of each bag helps to notice the change early. The post about diagnostic pause shows how to stop and review a picture before going on.

After the episode

When the patient stabilizes, the work continues. Nursing records the time the bag was started, the time of the symptoms, the volume infused, the serial vital signs and the measures taken. This record feeds the notification to the hemovigilance system (Soares et al., 2024) and helps the team plan the next transfusions. If the leading hypothesis is TACO, the next bag can be prescribed with slower infusion and assessment of fluid balance (Li et al., 2011). If it is TRALI, the donor investigation is up to the hemotherapy service. Explaining to the patient and family what happened, in plain language, is also part of the care, and it reduces anxiety before a new transfusion, if one is needed.

How NEXO helps train this reasoning

To use the case of the day as training, try three habits. Before the first guess, ask which hypothesis would be the most dangerous to miss. With each clue, ask whether it changes the management or only the cause. After the result, note which sign you overvalued.

Three exercises with cases

Read the blood pressure. In each case with shortness of breath, ask what the blood pressure suggests.

Separate the timing. Note when each symptom started in relation to a procedure or medication.

Build the communication. Write the message you would pass to the team in four sentences.

The post about simulation of care shows how to train patient assessment, and the post about signs, symptoms and history shows how to read the patient's complaints. The post about case-based learning in clinical practice shows how cases help fix these habits, and the post about diagnostic uncertainty discusses how to decide when the data do not yet add up.

The limits on using the game are described on the NEXO Economy page. If you research the teaching of clinical reasoning, the page for Researchers explains how to get in touch. Professionals who write or review cases find information on Curator and on Creators, and institutions can learn about the proposal on the partnerships page.

Frequently asked questions

Is fever during transfusion always a febrile reaction?

No. Febrile non-hemolytic reaction is a diagnosis of exclusion, and hemolysis can also start with fever and chills (Wang et al., 2022).

How can TACO and TRALI be told apart at the bedside?

Blood pressure helps: hypertension and jugular venous distension suggest TACO; hypotension and fever suggest TRALI (Desai et al., 2022). BNP and the chest X-ray complete the assessment.

Can I give a diuretic?

In TACO, the diuretic is part of the treatment (Desai et al., 2022). In TRALI, it should be avoided (Yu and Lian, 2023). The decision is medical.

What is the adrenaline dose in anaphylaxis?

0.01 mg/kg intramuscularly in the thigh, up to 0.5 mg in adults, repeated every 5 to 15 minutes if needed (Cardona et al., 2020).

For how long should the patient be monitored after the bag?

Reactions in the first 24 hours are classified as immediate (Soares et al., 2024), and TRALI can appear up to 6 hours later (Vlaar et al., 2019).

Final checklist

• I assessed the risk of overload before starting the bag.
• I measured vital signs before, in the first 15 minutes and during the transfusion.
• I stopped the transfusion at the first new sign.
• I kept the venous access with saline solution.
• I checked the identification of the patient and of the bag.
• I gave oxygen and called the medical team and the transfusion service.
• I saved the bag and the tubing for investigation.
• I monitored urine output and vital signs over the following hours.
• I reported the reaction to the hemovigilance system.

Want to practice your reasoning with progressive clues? Play the case of the day.

References

1. Bolton-Maggs PH, Cohen H. Serious Hazards of Transfusion (SHOT) haemovigilance and progress is improving transfusion safety. Br J Haematol. 2013. PMID 24032719.
2. Cardona V, Ansotegui IJ, Ebisawa M, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020. PMID 33204386.
3. Desai DS, Shah KS, Shah SA. Educational Case: Transfusion reactions: Transfusion associated circulatory overload vs transfusion-related acute lung injury. Acad Pathol. 2022. PMID 35770198.
4. Hirayama F. Current understanding of allergic transfusion reactions: incidence, pathogenesis, laboratory tests, prevention and treatment. Br J Haematol. 2013. PMID 23215650.
5. Kim J, Na S. Transfusion-related acute lung injury; clinical perspectives. Korean J Anesthesiol. 2015. PMID 25844126.
6. Klanderman RB, Bosboom JJ, Migdady Y, et al. Transfusion-associated circulatory overload-a systematic review of diagnostic biomarkers. Transfusion. 2019. PMID 30488959.
7. Klanderman RB, Wijnberge M, Bosboom JJ, et al. Differential effects of speed and volume on transfusion-associated circulatory overload: A randomized study in rats. Vox Sang. 2022. PMID 34396543.
8. Klanderman RB, Bosboom JJ, Veelo DP, et al. Prophylactic furosemide to prevent transfusion-associated circulatory overload: a randomized controlled study in rats. Sci Rep. 2022. PMID 35840620.
9. Krishnamurthy AV, Mathialagan J, Raghavan ATMV, Srinivasan S. Analysis of Patterns of Adverse Transfusion Reactions and Management: A Novel Initiative toward Hemovigilance in a Teaching Hospital of South India. J Lab Physicians. 2020. PMID 32905365.
10. Li G, Rachmale S, Kojicic M, et al. Incidence and transfusion risk factors for transfusion-associated circulatory overload among medical intensive care unit patients. Transfusion. 2011. PMID 20723173.
11. Soares FMM, Dutra SVO, Lima GK, Rodrigues ABFL, Magalhães DS, et al. Development and Content Validation of a Nursing Clinical Simulation Scenario on Transfusion Reaction Management. Int J Environ Res Public Health. 2024. PMID 39200652.
12. Vlaar APJ, Toy P, Fung M, et al. A consensus redefinition of transfusion-related acute lung injury. Transfusion. 2019. PMID 30993745.
13. Wang H, Ren D, Sun H, Liu J. Research progress on febrile non-hemolytic transfusion reaction: a narrative review. Ann Transl Med. 2022. PMID 36660666.
14. White SK, Walker BS, Potter S, Anderson D, Metcalf RA. Estimating the incidence of transfusion-associated circulatory overload using active surveillance: A systematic review and meta-analysis. Transfusion. 2025. PMID 40342068.
15. Yu Y, Lian Z. Update on transfusion-related acute lung injury: an overview of its pathogenesis and management. Front Immunol. 2023. PMID 37251400.