Key Facts

Transfusion reactions encompass a spectrum of adverse events occurring during or after blood product administration. Correct patient identification and bedside checks are the most important preventive measures.

Epidemiology

• ~2.5 million red cell units transfused annually in the UK
• FNHTR: 1-3% of transfusions
• Allergic reactions: 1-3% (mild), anaphylaxis rare
• TACO: most reported serious reaction in SHOT reports
• TRALI: incidence reduced since 2003 (male-only plasma policy)
• Acute haemolytic reactions: ~1:38,000 transfusions; most due to clerical error

Aetiology

Immunological:

• Acute haemolytic: ABO incompatibility (IgM anti-A/B → complement activation → intravascular haemolysis)
• Delayed haemolytic: alloantibody development (Rh, Kell, Kidd, Duffy) – days to weeks post-transfusion
• Febrile non-haemolytic: recipient antibodies to donor leucocyte antigens or cytokines in stored products
• Allergic/anaphylactic: reaction to donor plasma proteins; IgA deficiency with anti-IgA
• TRALI: donor anti-HLA/anti-HNA antibodies → neutrophil activation → pulmonary endothelial damage

Non-immunological:

• TACO: fluid overload (elderly, cardiac/renal disease)
• Bacterial contamination: platelets (room temperature storage) > red cells
• Transfusion-associated GvHD: donor lymphocytes attack recipient tissues (prevented by irradiation)
• Iron overload: chronic transfusion-dependent patients

Pathophysiology

• Acute haemolytic: IgM anti-A/B activates complement cascade → intravascular haemolysis → haemoglobinaemia, haemoglobinuria → DIC, renal failure, shock
• TRALI: two-hit model – underlying patient condition (infection, surgery) primes neutrophils; donor antibodies activate them → capillary leak in lungs
• TACO: excess intravascular volume → raised hydrostatic pressure → pulmonary oedema

Acute Haemolytic Reaction (Minutes-Hours)

• Fever, rigors
• Loin/back pain
• Hypotension, tachycardia
• Dark urine (haemoglobinuria)
• DIC: oozing from lines, widespread bleeding
• Under GA: unexplained hypotension and oozing

Febrile Non-Haemolytic Reaction

• Temperature rise ≥1°C during or shortly after transfusion
• Rigors, chills
• No haemodynamic instability

Allergic/Anaphylactic

• Mild: urticaria, pruritus
• Severe/anaphylaxis: bronchospasm, angioedema, hypotension, cardiovascular collapse

TRALI

• Acute dyspnoea and bilateral pulmonary infiltrates within 6 hours of transfusion
• Hypoxaemia (PaO₂/FiO₂ <300)
• No evidence of fluid overload

TACO

• Dyspnoea, orthopnoea
• Raised JVP, peripheral oedema
• Hypertension (unlike TRALI)
• BNP elevated (distinguishes from TRALI)

Red Flags

• Any new symptom during transfusion → reassess urgently
• Fever + hypotension → acute haemolytic reaction or bacterial contamination until proven otherwise
• Acute dyspnoea during/after transfusion → TRALI, TACO, or anaphylaxis

Immediate (for any suspected reaction)

• STOP transfusion but keep IV line open
• Check patient identity against unit label – exclude clerical error
• Observations: temperature, BP, HR, SpO₂, respiratory rate
• Visual check: plasma colour (pink = haemolysis), urine colour

Bloods

• Repeat group and screen (fresh sample)
• Direct antiglobulin test (DAT/Coombs): positive in immune-mediated haemolysis
• FBC: repeat for Hb, platelet count
• LDH, bilirubin, haptoglobin: haemolysis screen
• Coagulation screen + fibrinogen: DIC assessment
• U&Es: renal function
• Blood cultures (from patient AND blood product bag): if bacterial contamination suspected
• BNP/NT-proBNP: elevated in TACO, normal/low in TRALI
• Mast cell tryptase: if anaphylaxis suspected (serial – baseline, 1h, 24h)
• IgA levels: if recurrent allergic reactions (IgA deficiency)

Imaging

• CXR: bilateral infiltrates (TRALI), pulmonary oedema (TACO)
• ABG: assess oxygenation

Special Tests

• Return blood product bag and giving set to transfusion laboratory
• HLA/HNA antibody testing (donor): if TRALI suspected
• SHOT reporting: all serious adverse events

Acute Haemolytic Reaction

• STOP transfusion immediately
• Maintain IV access with 0.9% saline
• Aggressive fluid resuscitation to maintain renal perfusion
• Contact haematology and transfusion lab urgently
• Send repeat crossmatch, DAT, haemolysis screen
• Monitor for DIC – treat with blood products as needed
• Renal support if AKI develops

Febrile Non-Haemolytic Reaction

• Slow or stop transfusion depending on severity
• Paracetamol 1g PO/IV for symptomatic relief
• Exclude haemolytic reaction and sepsis
• If mild, may cautiously restart transfusion at slower rate
• Future transfusions: consider leucodepleted products (standard in UK since 1999)

Allergic/Anaphylactic

• Mild (urticaria): stop transfusion, give chlorphenamine 10mg IV, restart cautiously
• Anaphylaxis: IM adrenaline 0.5mg (500mcg 1:1000), ABC approach, IV fluids, hydrocortisone 200mg IV, chlorphenamine 10mg IV
• Future: washed red cells or IgA-depleted products if IgA-deficient

TRALI

• Stop transfusion
• Supportive care: oxygen, may require mechanical ventilation
• Avoid diuretics (not fluid overload)
• Typically resolves within 48-72 hours with supportive care
• Report to transfusion lab – donor investigation required

TACO

• Slow/stop transfusion
• Sit patient upright
• IV furosemide 40-80mg
• Oxygen as needed
• Future: slower transfusion rate (1 unit over 3-4 hours), diuretic cover, single-unit transfusions

Referral Criteria

• All suspected acute haemolytic reactions → transfusion laboratory + haematology
• TRALI → critical care + transfusion medicine
• Report to SHOT (Serious Hazards of Transfusion) reporting scheme

• Acute haemolytic reaction: mortality 5-10% if severe (renal failure, DIC)
• FNHTR: excellent prognosis, self-limiting
• TRALI: mortality 5-10%; most patients recover within 48-72 hours with supportive care
• TACO: mortality ~5%; higher in elderly and those with cardiac/renal disease
• Anaphylaxis: excellent prognosis if treated promptly
• Delayed haemolytic reactions: usually mild, self-limiting; may cause unexplained Hb drop days post-transfusion

TRALI vs TACO Differentiation

Transfusion Reaction Summary