Description
- Immune destruction of transfused red cells within 24 hours of transfusion (usually within minutes)
- Almost always ABO incompatibility from a clerical/administrative error - patient or sample misidentification, mislabelled tube, wrong unit collected, wrong patient bedside check
- *Not a failure of the laboratory. A failure of identification.*
- The classic triad in a conscious patient: fever, loin/back pain, and a sense of impending doom
- In an anaesthetised or unconscious patient: hypotension, oozing from wounds, and haemoglobinuria may be the only signs
- Volume matters - as little as 10-30 mL of incompatible blood can be fatal
Epidemiology
- ~1 in 40,000-80,000 units transfused; fatal ABO-incompatible transfusion ~1 in 1.5 million units
- Peak risk situations: emergency and out-of-hours transfusion, theatre, multiple simultaneous transfusions on a ward, patients unable to state their own name
- *Incidence has fallen with barcode/electronic bedside identification systems, not with better serology*
Aetiopathogenesis2 exam ›
The immunology
- Naturally occurring anti-A and anti-B are IgM (Landsteiner's law - present without prior exposure, from environmental carbohydrate antigens)
- IgM is pentameric -> highly efficient complement fixation
- -> full complement cascade to C5b-9 membrane attack complex
- -> intravascular haemolysis - free haemoglobin in plasma and urine
- Simultaneously:
- C3a, C5a anaphylatoxins -> mast cell degranulation, hypotension, bronchospasm
- Cytokine storm (TNF, IL-1, IL-8) -> fever, shock
- Tissue factor exposure and stroma release -> DIC
- Free haemoglobin scavenges nitric oxide -> vasoconstriction; and causes direct tubular toxicity with renal vasoconstriction -> AKI
Contrast with delayed reactions
| Acute (ABO) | Delayed | |
|---|---|---|
| Antibody | IgM | IgG (Kidd, Kell, Rh, Duffy) |
| Complement | Fully activated -> MAC | Not to completion |
| Site of destruction | Intravascular | Extravascular (splenic macrophages) |
| Onset | Minutes to hours | 2-10 days |
| Severity | Life-threatening | Usually mild |
Non-immune haemolysis - the mimic
- Mechanical (roller pump, pressure infusion through a small cannula), thermal (overheated or frozen unit), osmotic (co-infused hypotonic fluid such as 5% glucose), bacterial contamination
- Same laboratory picture of haemolysis but with a negative DAT and a compatible crossmatch
Diagnosis
Clinical
- Fever and rigors, loin/back or chest pain, restlessness, "feeling of impending doom"
- Hypotension, tachycardia, flushing, dyspnoea
- Haemoglobinuria - red or dark urine
- Bleeding/oozing from cannula and wound sites (DIC)
- Oliguria, jaundice within hours
- *Under anaesthesia: unexplained hypotension, haemoglobinuria and diffuse bleeding*
Investigations
- *First: recheck the patient's wristband against the unit and the compatibility label - and check whether another patient on the ward has received the wrong unit*
- DAT (direct antiglobulin test) - positive (may be negative if all incompatible cells are already destroyed)
- Free plasma haemoglobin - pink/red plasma; haemoglobinuria
- LDH high, haptoglobin undetectable, unconjugated bilirubin high, Hb falls without an obvious source of bleeding
- Repeat group and screen on a fresh sample + re-crossmatch of the implicated unit
- Coagulation screen, fibrinogen, D-dimer, platelets - for DIC
- UEC and urine output - AKI
- Blood cultures from patient and unit (to exclude bacterial contamination)
- Return the unit and giving set to the blood bank
Differential
- Bacterial contamination/septic transfusion reaction - high fever, rigors, shock, positive unit culture
- FNHTR - fever only, no haemolysis, no hypotension
- TRALI - hypoxaemia with bilateral infiltrates
- Anaphylaxis - urticaria, angioedema, bronchospasm; afebrile
- Non-immune haemolysis (mechanical/thermal/osmotic) - negative DAT
Management
*An emergency. Stop, resuscitate, protect the kidneys, and find out whether someone else is also getting the wrong blood.*
A. Immediate
1. STOP the transfusion immediately - do not flush the line contents in
2. Change the giving set, keep the line with 0.9% sodium chloride
3. ABC - oxygen, IV access, monitoring
4. Recheck identity: patient wristband vs unit vs compatibility label
5. Alert the blood bank urgently - another mislabelled sample may mean a second patient is at risk right now
6. Return the unit and giving set; send the investigations above
B. Resuscitation and organ protection
- Aggressive IV crystalloid - target urine output >1-1.5 mL/kg/h
- Maintaining renal perfusion is the single most effective intervention
- Vasopressors for persistent hypotension; ICU involvement
- Loop diuretic only once intravascularly replete, to maintain output
- *Urinary alkalinisation and mannitol are no longer recommended*
- Treat hyperkalaemia (from lysed cells)
- DIC: product support for bleeding - platelets >50, cryoprecipitate for fibrinogen <1.5 g/L, FFP for prolonged PT/APTT
- Renal replacement therapy if refractory AKI, hyperkalaemia or fluid overload
- Further transfusion only if essential, and then group O RhD-negative, fully crossmatched, after the blood bank has resolved the discrepancy
C. Do NOT
- Do not restart the transfusion under any circumstances
- Do not give the remaining unit to another patient
- Do not treat with corticosteroids or antihistamines as primary therapy (no role in a complement-mediated haemolytic reaction)
D. Governance - as important as the clinical response
- Mandatory incident report and root cause analysis; report to the haemovigilance programme
- Open disclosure to the patient/family
- *System prevention beats individual vigilance*: barcode/electronic patient identification, two-sample rule for a first-time group, single-nurse bedside checks replaced by electronic verification, never pre-labelling tubes away from the bedside
Associations
- ABO incompatibility from misidentification (the dominant cause)
- RhD and other clinically significant antibodies in previously alloimmunised patients
- DIC and acute kidney injury - the two lethal complications
- Bacterial contamination of the unit (differential and occasional co-existence)
- Hyperhaemolysis syndrome in sickle cell disease - Hb falls below the pre-transfusion level; further transfusion worsens it; treat with steroid + IVIG, not more blood
- Passenger lymphocyte syndrome after ABO-minor-mismatched solid organ or stem cell transplant
- Massive transfusion, emergency O-negative release, theatre and out-of-hours transfusion
Natural history & complications
- Severity is dose-dependent - the volume of incompatible blood infused before recognition determines outcome
- Mortality ~10-20% overall for ABO-incompatible transfusion, higher when >200 mL is infused
- Survivors: haemolysis stops once the incompatible cells are cleared (hours), but AKI and DIC evolve over the following days
- Most AKI is reversible with prompt fluid resuscitation
Complications
- Acute kidney injury requiring dialysis
- DIC with major haemorrhage
- Shock, multi-organ failure, death
- Hyperkalaemia and arrhythmia
- Alloimmunisation - future crossmatching becomes difficult
- *Institutional* - the reaction is a sentinel event; the underlying identification failure will recur unless the system is changed
7 of 7 sections written · drafted 2026-09-04