Transfusion Reactions

BSH Guideline on the investigation and management of acute transfusion reactions. Published: Apr 2023.

NHS Scotland GGC – Blood Transfusion – Transfusion Reaction Management. Last revised: Oct 2015.

Article Last Updated:19/02/2026

Acute Transfusion Reactions

Acute transfusion reactions are those occurring within 24 hours of transfusion.

Acute Haemolytic Transfusion Reaction (AHTR)

Definition

AHTR is a life-threatening immune-mediated reaction occurring within 24 hours

Caused by pre-existing antibodies rapidly destroying transfused donor RBCs
Resulting in intravascular haemolysis

Aetiology

AHTR is usually caused by ABO blood group incompatibility

Mediated by pre-existing IgM antibodies

The unintentional transfusion of ABO-incompatible blood components is classified as a Never Event in the NHS.

Clinical Manifestation

By definition, AHTR occurs within 24 hours after the transfusion. Symptoms can present very quickly after transfusion:

Loin pain classically
- Abdominal / chest / muscle / bone pain is also possible
Dyspnoea and respiratory distress
Hypotension, tachycardia, shock
Systemic upset: significant fever (see green box below), rigours, chills, nausea, profound ‘sense of impending doom‘
Haemoglobinuria (dark urine)

AHTR can precipitate renal failure and DIC.

If the patient has a significant fever (defined as $\geq 3 9^{\circ}$ C or $\geq2^{\circ} C rise from baseline), one must consider more serious causes like:$

Acute haemolytic transfusion reaction, or
Bacterial contamination

In contrast, if the patient has an isolated, mild fever (< $3 9^{\circ}$ C and <2 $^{\circ}$ C rise from baseline) → febrile non-haemolytic transfusion reaction is more likely

Investigation and Diagnosis

The following tests should be performed if AHTR is suspected:

Standard investigations (FBC, U&Es, LFTs)
Repeat crossmatch
Direct Coombs test (on both pre and post-transfusion samples)
Haemolysis markers (LDH, haptoglobin)
Urinalysis (to check for haemoglobinuria)
Coagulation screen (to check for DIC)
Blood cultures (to exclude sepsis)

Key findings seen in AHTR:

+ve Direct Coombs test – major diagnostic marker
Anaemia
Markers of haemolysis (low haptoglobin, high LDH, high unconjugated bilirubin, haemoglobinuria)

Management

Immediate emergency actions:

Stop the transfusion (and do NOT restart it)
Disconnect the blood unit and the giving set
Established new venous access if possible (to ensure no residual blood in the original line is accidentally infused)
Perform identity check (verify the patient’s details against their identity band and the compatibility label on the blood unit)

After the immediate emergency actions → resuscitation

A-E assessment and approach
Call for help
1st line: aggressive fluid resuscitation (usually with 0.9% saline)
Provide inotropic / renal support as required
If bacterial contamination cannot be definitively excluded → give broad-spectrum antibiotics

Febrile Non-Haemolytic Transfusion Reaction (FNHTR)

Definition

FNHTR is an immune-mediated transfusion reaction, occurring within 24 hours of transfusion.

FNHTR is common, affecting up to 1 in 100 red cell transfusions and 1 in 5 platelet transfusions.

Aetiology

FNHTR is mediated via two principal pathways that produce an inflammatory response in the recipient:

The accumulation of pro-inflammatory cytokines in the blood product during storage
Recipient antibodies reacting with donor leukocyte antigens

Clinical Manifestation

Classically, FNHTR presents as isolated, mild fever (defined as < $3 9^{\circ}$ C and <2 $^{\circ}$ C rise from baseline), with the patient feeling otherwise well.

If the patient has a significant fever (defined as $\geq 3 9^{\circ}$ C or $\geq2^{\circ} C rise from baseline), one must consider more serious causes like:$

Acute haemolytic transfusion reaction, or
Bacterial contamination

Less commonly, FNHTR may present with systemic symptoms such as chills, rigours, myalgia, nausea, or vomiting.

However, to be classified as FNHTR, there must be:

NO Haemolysis (no loin pain / jaundice / haemoglobinuria)
NO Allergic features (no pruritus, urticaria, angioedema)
NO respiratory distress (no dyspnoea, drop in SpO₂)

Management

Immediate action: stop the transfusion and assess the patient

Subsequent management depends on the severity of the reaction:

Severity	Definition	Management
Mild	Mild fever (< $3 9^{\circ}$ C and <2 $^{\circ}$ C rise from baseline), or The patient is otherwise well	Give oral paracetamol, and Restart the transfusion at a slower rate
More severe	Significant fever ( $3 9^{\circ}$ C or $\geq2^{\circ} C rise from baseline), or$ The patient is unwell	Stop the transfusion permanently Seek urgent review – consider the possibility of more serious reactions (e.g. AHTR, bacterial contamination)

Bacterial Contamination

Definition

Bacterial contamination is a rare but life-threatening acute transfusion reaction caused by the presence of bacteria in a blood component prior to its administration.

It is more frequent with platelet products, since they are stored at room temperature (which facilitates bacterial growth).

Clinical Manifestation

Onset is typically rapid and severe:

Significant fever (≥ $3 9^{\circ}$ C or $\geq2^{\circ} C rise from baseline)$
Chills and rigours
Hypotension, shock

Before transfusion, the unit might show unusual clumps, particulate matter, or discolouration, which are suggestive of contamination

Investigation and Diagnosis

Blood cultures + return the blood unit to the laboratory for urgent cultures
FBC
U&E
Coagulation screen

Management

Immediate action: stop the transfusion

Subsequent management:

Broad spectrum IV antibiotics
Aggressive fluid resuscitation

Allergic Reactions

Definition

Allergic reactions are a common complication of blood transfusion, ranging from mild skin rashes to life-threatening anaphylaxis.

Aetiology

Primary mechanism: allergenic substances (typically plasma proteins) within the donor component reacts with pre-existing IgE antibodies in the recipient (type 1 hypersensitivity).

Platelet products are associated with the highest rates of allergic reactions, due to its higher plasma volumes (and the allergens are found in the plasma).

Anaphylactic reactions have been rarely linked to severe congenital IgA deficiency. These patients would have developed anti-IgA antibodies that react when they encounter IgA in the donor’s plasma.

However, the link between IgA deficiency and anaphylactic reactions remains unclear, as many IgA-deficient patients never experience a reaction.

Clinical Manifestation

Allergic reactions to blood transfusion can present with varying severity:

Severity of reaction	Clinical features
Mild	Characterised by isolated cutaneous features: Urticaria Pruritus Skin rash
Moderate to severe	Characterised by the presence of cutaneous features, and Angioedema Wheezing Dyspnoea Hypoxia
Anaphylaxis	Rapid onset of any of the ABC problems: A: angioedema, stridor, drooling B: wheezing, stridor, hypoxia, dyspnoea C: hypotension, ↓ GCS

Investigation and Diagnosis

The extent of testing depends on the severity of the reaction:

Severity of reaction	Investigations
Mild	No investigations are required
Moderate to severe	Standard tests FBC U&E LFT Respiratory screen Oxygen saturation Chest X-ray
Anaphylaxis	Serial mast cell tryptase IgA levels (to identify patients with IgA deficiency)

Severity of reaction

Investigations

Mild

No investigations are required

Moderate to severe

Standard tests

Respiratory screen

Oxygen saturation
Chest X-ray

Anaphylaxis

Serial mast cell tryptase
IgA levels (to identify patients with IgA deficiency)

Management

Management also depends on the severity of the reaction:

Severity of reaction	Management
Mild	Immediate action: stop the transfusion to assess the patient If the patient is otherwise well: Give antihistamine (e.g. chlorphenamine) Restart the transfusion at a slower rate and under direct observation
Moderate to severe	Immediate action: stop the transfusion permanently (do NOT restart it) Subsequent management: Give antihistamine (e.g. chlorphenamine) Supplementary oxygen as required Consider bronchodilators
Anaphylaxis	Immediate action: stop the transfusion permanently (do NOT restart it) and call the resuscitation team Subsequent management: IM adrenaline immediately Fluid resuscitation High flow oxygen Also see the Anaphylaxis article for the full management algorithm

Severity of reaction

Management

Mild

Immediate action: stop the transfusion to assess the patient

If the patient is otherwise well:

Give antihistamine (e.g. chlorphenamine)
Restart the transfusion at a slower rate and under direct observation

Moderate to severe

Immediate action: stop the transfusion permanently (do NOT restart it)

Subsequent management:

Give antihistamine (e.g. chlorphenamine)
Supplementary oxygen as required
Consider bronchodilators

Anaphylaxis

Immediate action: stop the transfusion permanently (do NOT restart it) and call the resuscitation team

Subsequent management:

IM adrenaline immediately
Fluid resuscitation
High flow oxygen

Also see the Anaphylaxis article for the full management algorithm

Transfusion-Related Acute Lung Injury (TRALI)

Definition

TRALI is an immune-mediated transfusion reaction, defined as non-cardiogenic pulmonary oedema occurring within 6 hours of a transfusion.

Aetiology

TRALI is caused by an interaction between donor neutrophil antibodies and recipient leucocytes → triggering an inflammatory process that increases vascular permeability.

TRALI occurs more commonly with:

Plasma-rich components (e.g. fresh frozen plasma, platelets)
Patients who are already systemically unwell

Clinical Manifestation

Symptoms are rapid onset, and occurs within 6 hours (most commonly the first 2 hours):

Severe dyspnoea (worse with lying down)
Hypoxia
Hypotension
Fever and systemically unwell

For any patient presenting with respiratory symptoms not caused by allergy or anaphylaxis (i.e. suspected TRALI / TACO), the standard investigations are:

Chest X-ray – 1st line in ALL patients
NT-pro BNP levels
Echocardiography

The following features help differentiate between TRALI and TACO:

Feature	TRALI	TACO
Type of reaction	Immune-mediated lung injury	Non-immune volume overload
Primary pathology	Non-cardiogenic pulmonary oedema	Cardiogenic pulmonary oedema
Clinical feature	Severe dyspnoea
Clinical feature	Fever No signs of circulatory overload: Hypotension Normal JVP Auscultation: diffuse bilateral crackles	Signs of circulatory overload: Hypertension Raised JVP S3 gallop Auscultation: bi-basal crackles
Chest X-ray	Bilateral infiltrates / Pulmonary oedema
Chest X-ray	Normal heart size No effusions	Cardiomegaly Pleural effusions
NT-proBNP	Normal or low	Raised
Echocardiography	Normal cardiac function Normal capillary wedge pressure	Evidence of volume overload: Dilated left atrium ↑ LV filling pressure
Pulmonary capillary wedge pressure (PCWP)*	Normal	Raised (indicating cardiogenic pulmonary oedema)
Response to diuretics	No improvement (may worsen TRALI)	Rapid improvement

*While pulmonary wedge pressure is a key physiological factor in distinguishing these conditions, it is generally described as a characteristic finding rather than a routine diagnostic measurement. In practice, non-invasive tests (chest X-ray, NT-proBNP, and echocardiography) are preferred over invasive wedge pressure measurement.

Management

Immediate action: stop the transfusion

Management is primarily supportive

High-flow oxygen
Ventilatory support
Fluid resuscitation

It is important to avoid diuretics, as it tends to worsen TRALI.

However, diuretics are the mainstay of management of TACO.

Transfusion-Associated Circulatory Overload (TACO)

Definition

TACO is a non-immune mediated transfusion reaction, characterised by acute fluid overload and cardiogenic pulmonary oedema occurring within 6 hours of a transfusion.

Aetiology

TACO is primarily caused by fluid overload

Mechanism: fluid overload → ↑ intravascular hydrostatic pressure → ↑ left atrial pressure → cardiogenic pulmonary oedema
Risk is significantly increased with
- Large transfusion volumes or rapid infusion rates
- Elderly patients
- Pre-existing heart failure or kidney disease

Clinical Manifestation

Symptoms are rapid onset, and occurs within 6 hours:

Severe dyspnoea (worse with lying down)
Hypoxia
Features of fluid overload
- Hypertension
- Raised JVP
- S3 gallop

For any patient presenting with respiratory symptoms not caused by allergy or anaphylaxis (i.e. suspected TRALI / TACO), the standard investigations are:

Chest X-ray – 1st line in ALL patients
NT-pro BNP levels
Echocardiography

The following features help differentiate between TRALI and TACO:

Feature	TRALI	TACO
Type of reaction	Immune-mediated lung injury	Non-immune volume overload
Primary pathology	Non-cardiogenic pulmonary oedema	Cardiogenic pulmonary oedema
Clinical feature	Severe dyspnoea
Clinical feature	Fever No signs of circulatory overload: Hypotension Normal JVP Auscultation: diffuse bilateral crackles	Signs of circulatory overload: Hypertension Raised JVP S3 gallop Auscultation: bi-basal crackles
Chest X-ray	Bilateral infiltrates / Pulmonary oedema
Chest X-ray	Normal heart size No effusions	Cardiomegaly Pleural effusions
NT-proBNP	Normal or low	Raised
Echocardiography	Normal cardiac function Normal capillary wedge pressure	Evidence of volume overload: Dilated left atrium ↑ LV filling pressure
Pulmonary capillary wedge pressure (PCWP)*	Normal	Raised (indicating cardiogenic pulmonary oedema)
Response to diuretics	No improvement (may worsen TRALI)	Rapid improvement

Management

Immediate action: stop the transfusion

Subsequent management:

Oxygen therapy as needed
Loop diuretics (e.g. furosemide, bumetanide) – primary treatment for TACO (often given IV)

Delayed Transfusion Reaction

Delayed transfusion reactions are those occurring more than 24 hours after the transfusion (typically days to weeks later).

Delayed Haemolytic Transfusion Reaction (DHTR)

Definition

DHTR is an immune-mediated reaction occurring after 24 hours.

Aetiology

DHTR is caused by minor antigen mismatch in previously sensitised individuals (e.g. Kidd, Kell, Rh non-D)

Mediated by pre-existing IgG antibodies (alloimmunisation)
These antibodies against minor antigens are often not routinely screened for on pre-transfusion testing (usually only ABO and RhD are routinely screened for)

Clinical Manifestation

By definition, AHTR occurs 24 hours after the transfusion, typically 3-14 days after:

Fever
Jaundice
Dark urine (haemoglobinuria)
Symptoms of anaemia (e.g. fatigue, exertional dyspnoea)

Unexpected fall in Hb after an initial post-transfusion rise is a key feature

The following key features are ABSENT in DHTR, which helps differentiate from AHTR:

Flank pain
Respiratory distress
Shock / hypotension

Management

No specific management is required in most cases

Patient may require further transfusion if the Hb level falls significantly

Transfusion-Associated Graft Versus Host Disease (TA-GVHD)

Definition

TA-GVHD is a rare, life-threatening delayed immune transfusion reaction, where donor T lymphocytes attack the recipient’s tissue.

Aetiology

TA-GVHD is caused by viable donor T lymphocytes within the transfused blood product mounting an immune attack against host tissue.

Normally, recipient’s immune system will eliminate donor lymphocytes. TA-GVHD develops when the immune clearance fails, most commonly in:

Immunocompromised patients
HLA-matched or partially matched donors (e.g. transfusions from relatives – where donor cells evade immune recognition)

Note that GVHD most commonly occurs following allogeneic stem cell transplantation, TA-GVHD is rare.

Clinical Manifestation

Symptoms typically appear 1-6 weeks after the transfusion (median onset: 8-10 days):

Fever – often the first sign
Widespread erythematous rash (often maculopapular)
- Painful and/or pruritic
- Can progress to desquamation
GI manifestation: profuse diarrhoea, abdominal pain
Hepatic manifestation: jaundice, hepatitis derangement
Bone marrow manifestation: pancytopaenia

TA-GVHD is primarily a clinical diagnosis, supported by biopsy (usually of the skin, liver or GI mucosa).

Management

There are NO curative treatments, management is predominantly supportive

TA-GVHD is almost always fatal
Death typically occurs within 3 weeks of symptom onset

In the UK all cellular components except granulocytes are leukocyte depleted, which has already dramatically reduced the overall incidence of TA-GVHD.

However leukocyte depletion alone is NOT sufficient to prevent TA-GvHD in susceptible patients. Prevention requires irradiated blood products.

Key category of patients who require irradiated blood products: ^[Ref]

Intrauterine transfusion (RBCs and platelet)
Neonatal exchange blood transfusion
Immunocompromised patients
- Severe congenital T-lymphocyte immunodeficiency syndromes
- Recipient of haematopoietic stem cell transplantation
- Hodgkin’s lymphoma (any stage)

Post-Transfusion Purpura (PTP)

Definition

PTP is a rare but serious delayed transfusion reaction characterised by a sudden and profound drop in platelet count.

Aetiology

PTP is caused by a secondary immune response triggered by a transfusion, in a patient who has pre-existing anti-HPA antibodies.

Clinical Manifestation

Onset is characteristically ~7 days post-transfusion:

Profound thrombocytopaenia (often <10 x 10⁹/L)
Haemorrhage (common and can be severe)

Management

1st line: IV immunoglobulin

References

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