Transfusion Reactions and Procedure

How to Cite This Chapter: Morin P-A, Ning S, Łętowska M, Rosiek A. Transfusion Reactions and Procedure. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed April 16, 2024.
Last Updated: October 19, 2023
Last Reviewed: October 19, 2023
Chapter Information


Adverse reactions:

1) Acute transfusion reactions (Table 1, Table 2) occur during transfusion or shortly after its completion (within 24 hours). The reactions may be:

a) Immunologic, including acute hemolytic reactions, febrile nonhemolytic reactions, transfusion-related acute lung injury, and minor or major allergic reactions.

b) Nonimmunologic, including posttransfusion sepsis, transfusion-associated circulatory overload (TACO), hypotensive reactions (related or not related to angiotensin-converting enzyme inhibitor [ACEI] use), complications of massive transfusion (hypocalcemia, hypothermia, coagulopathy), and rarely nonimmune hemolysis and air embolism.

2) Delayed transfusion reactions may occur within days, months, or even years after transfusion and include alloimmunization to red cell antigens, delayed hemolytic reaction, posttransfusion graft-versus-host disease, and posttransfusion purpura. Transmission of viruses (eg, hepatitis B, hepatitis C, HIV, human T-lymphotropic virus, West Nile virus), protozoa (eg, malaria, Chagas disease), or prions (variant Creutzfeldt-Jakob disease) may occur but risks are low with current donor testing and blood manufacturing methods. Iron overload may be a complication of chronic transfusion therapy.

Symptoms of acute transfusion reactions:

1) Fever (the most frequent manifestation of hemolytic reactions).

2) Rigors without elevated body temperature.

3) Pain at the site of IV access, chest pain, abdominal pain, or lower back pain (this may be a sign of acute hemolytic reaction).

4) Sudden blood pressure changes. Hypotension with concomitant fever and rigors may be a feature of septic shock or acute hemolytic reaction. Symptoms of shock without fever may indicate anaphylactic reaction.

5) Respiratory distress with dyspnea, tachypnea, wheezing, and hypoxemia.

6) Cutaneous changes, for instance, urticaria, pruritus, erythema, or localized edema.

7) Nausea, vomiting.

8) Dark urine (this can be the first symptom of acute hemolytic reaction in patients undergoing general anesthesia).

9) Bleeding.

Management of transfusion reactions: For all transfusion reactions:

1) Stop the transfusion immediately.

2) Confirm the identity of the patient and the blood product to assess for clerical errors.

3) Maintain venous access.

4) Measure body temperature, pulse, respiratory rate, blood pressure, and oxygen saturation.

5) Notify the transfusion medicine laboratory using the appropriate mechanism.

Further management of specific reactions and symptoms: Table 1.


Equipment required for blood transfusion:

1) A standard single-use transfusion set with a microaggregate filter (this is required for transfusion of cellular blood components, frozen plasma [FP], and cryoprecipitate).

2) A blood warmer with a thermometer and an alarm system in the case of rapid transfusions.


1. Plan the transfusion rate according to the clinical condition of the patient:

1) In the case of a massive hemorrhage, rapid packed red blood cell (PRBC) transfusion and a blood warmer may be necessary.

2) In the case of a risk of volume overload, particularly in patients with cardiac dysfunction, renal impairment, and aged >70 years, reduce the transfusion rate (up to a maximum of 4 hours) and consider pretransfusion furosemide.

3) In a stable patient, 1 unit of PRBCs can be usually transfused over 120 minutes, 1 adult platelet dose over 60 minutes, and 1 unit of plasma over 30 to 120 minutes.

4) The transfusion time of 1 unit of PRBCs, platelet concentrate, or plasma should not be >4 hours.

2. Start the transfusion, in most cases at a rate of 4 to 5 mL/min, and ensure constant patient supervision for the first 15 minutes of the transfusion. Decrease the transfusion rate if necessary.

3. After 15 minutes from the start of the transfusion, repeat vital signs and record the results. Ensure further monitoring throughout the procedure and for 12 hours after its completion.

4. Every blood or blood component transfusion should be recorded in the patient’s medical records.


Table 9.7-1. Acute transfusion reactions according to the cardinal symptoma

Differential diagnosis


Cause and clinical features



Cardinal symptom: fever 38°C-39°C without associated symptomsc

Febrile nonhemolytic transfusion reaction

1:300 RBCs

1:20 platelet pools

Inflammatory mediators within blood products; fever usually isolated

None required

– Transfusion may be restarted after medical evaluation

– Consider acetaminophen

Cardinal symptom: fever 39°C or with associated symptomsc

Febrile nonhemolytic transfusion reaction

As above

As above

– CBC, electrolytes, creatinine, bilirubin, LDH, haptoglobin, INR, PTT, fibrinogen

– Repeat group and screen, DAT

– Patient blood and blood product cultures

– Urinalysis

– Stop transfusion

– Consider acetaminophen for fever and meperidine for significant rigors

Acute hemolytic transfusion reaction

1:38,000 RBCs

Usually due to ABO incompatible transfusion (secondary to clerical errors), may be due to other alloantibodies; associated with dyspnea, back pain, dark urine, DIC, and renal failure

– Stop transfusion

– Check for clerical errors

– Maintain urine output

– Manage DIC and AKI

Bacterial sepsis

1:10,000 platelet pools

1:250,000 RBCs

Bacterial contamination of blood product; associated with usual symptoms and signs of sepsis

– Stop transfusion

– Start broad-spectrum antibiotics immediately (prior to culture results)

– Supportive care

Cardinal symptom: dyspnea


Likely underestimated; 1:700 to 1:13 recipients (typically older adults or those with compromised cardiac function)

Volume overload; inflammatory mediators likely contributive and blood product volume is not equivalent to crystalloids

– Chest x-ray

– Other tests as for fever and anaphylaxis, depending on additional clinical manifestations

– Stop transfusion

– Diuretics

– Supportive care

– Prevention is key


True incidence unknown; likely 1:10,000-1:100,000

ARDS secondary to transfusion; anti-HLA or anti-HNA antibodies in donor plasma incompatible with recipient; may be associated with hypotension, fever, and transient cytopenias

– Supportive care

– Diuretics usually administered because differentiation with TACO is difficult, but they are not effective

Bacterial contamination

As above


As above


As above


Acute hemolytic transfusion reaction

As above

As above


As above


As below

As below

As below

Cardinal symptom: urticaria (hives), itching, or rash

Minor allergic reaction

1:200 RBCs

1:30 platelets and plasma

Allergens in blood products, usually not identified; urticarial rash (<2/3 of body surface) or other isolated mucocutaneous symptoms

None required

– Transfusion may be restarted after medical evaluation

– Consider antihistamines


Major allergic reaction/anaphylaxis

Rare; true incidence unknown

Allergens in blood products, usually not identified; can be due to anti-IgA antibodies in IgA-deficient individuals; manifests as urticarial rash associated with other allergic symptoms (hypotension, airway obstruction, digestive symptoms)

– Anaphylaxis: IgA and haptoglobin; anti-IgA if IgA-deficient

– Other tests depending on associated symptoms (chest x-ray, blood cultures, hemolysis testing)

– Do not restart transfusion

– Usual management of anaphylaxis: epinephrine, glucocorticoids, antihistamines, supportive care

– IgA-deficient products may be provided if anti-IgA are identified

Cardinal symptom: hypotension

Acute hypotensive reaction


Bradykinin-induced hypotension, most common with ACEI use; isolated hypotension without other symptoms

No specific investigations

– Stop transfusion (resolves with cessation)

– Supportive care

a Main symptom usually associated with the reaction; other symptoms may be present.

b Incidence in Canada.

c Symptoms associated with fever that warrant further investigations include shaking/rigors/chills, hypotension, dyspnea, chest/back pain, tachycardia, nausea, vomiting, and hemoglobinuria.

ACEI, angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ARDS, acute respiratory distress syndrome; CBC, complete blood count; DAT, direct antiglobulin test; DIC, disseminated intravascular coagulation; HLA, human leukocyte antigen; HNA, human neutrophil antigen; INR, international normalized ratio; LDH, lactate dehydrogenase; PTT, partial thromboplastin time; RBC, red blood cell; TACO, transfusion-associated circulatory overload; TRALI, transfusion-related acute lung injury.

Table 9.7-2. Complications of massive transfusion





Citrate toxicity; citrate chelates calcium

IV calcium


Mostly dilutional; massive transfusion of PRBCs without platelets or plasma leads to loss of coagulation factors and platelets

Administration of other blood products (plasma, platelets, cryoprecipitate, or fibrinogen concentrate) in ratios or depending on laboratory results


PRBCs are stored at 4 degrees Celsius; rapid infusion may decrease body temperature

Use of blood warmers, patient warming

Acid-base disturbances

– Metabolic alkalosis may be due to metabolism of citrate to bicarbonate

– Metabolic acidosis is rare (due to acid pH of blood products)

Supportive care


Release of potassium from stored PRBCs (primarily in massive transfusions, in patients with impaired renal function, and in neonates)

Potassium monitoring; usual management

IV, intravenous; PRBC, packed red blood cell.

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