Acute Haemolytic Transfusion Reaction

Acute haemolytic transfusion reaction is rapid destruction of transfused red cells by antibodies in the recipient, most dangerously ABO incompatibility, which is nearly always caused by an identification error. Symptoms appear within minutes of the start of the transfusion (often after only 5 to 15 mL), and the severity is related to the volume transfused, so early stopping saves life.

Clinical features. Fever, chills and rigors, flushing, anxiety or sense of doom, pain at the infusion site, chest, back or loin, nausea and vomiting, tachycardia, hypotension, dark or red urine, oliguria, and bleeding or oozing from disseminated intravascular coagulation. In anaesthetised patients, the only signs may be unexplained hypotension, bleeding and haemoglobinuria.

Classification.

• Immune, intravascular: ABO incompatibility (IgM anti-A or anti-B, complement mediated), with other antibodies (Kidd, Kell, Duffy, Rh) causing haemolysis that may be intravascular or extravascular.

• Non-immune haemolysis: damage to red cells from heat, freezing, hypotonic fluid, mechanical devices, drugs or bacterial contamination (this is discussed as a differential).

Pathophysiology. Complement activation, release of free haemoglobin and cytokines, activation of coagulation and kinin systems, shock, disseminated intravascular coagulation and acute kidney injury.

Risk factors. Wrong blood in tube, bedside identification failure, emergency transfusion with poor identification, unconscious patient, multiple patients, and fatigue or interruption.

Differential diagnosis.

• Bacterial contamination with septic shock and haemolysis.

• Non-immune haemolysis: overheated blood, hypotonic fluid (5% dextrose or sterile water), mechanical damage, drugs.

• Anaphylaxis.

• Transfusion related acute lung injury and circulatory overload (respiratory presentations).

• Febrile non-haemolytic reaction (diagnosis of exclusion, only when no other features).

• Haemolysis from an underlying disease (autoimmune haemolytic anaemia, sickle cell disease, glucose-6-phosphate dehydrogenase deficiency, malaria) or from drugs.

• Haemorrhage and sepsis not related to transfusion.

Initial assessment. Airway, breathing, circulation, vital signs, urine colour and volume, oozing, and consciousness. Presence of fever, pain, hypotension and dark urine together makes haemolytic reaction very likely, so assume haemolysis until excluded and act on that while tests are pending.

Key early findings. Pink plasma in a post-reaction sample (free haemoglobin), haemoglobinuria, fall in haemoglobin, positive direct antiglobulin test, mismatch of group on repeat testing, and a clerical discrepancy.

Immediate actions in order.

1. Stop the transfusion and clamp the line.

2. Assess the patient: airway, breathing, circulation, disability and exposure, and call senior help and intensive care early.

3. Keep intravenous access with a new giving set and 0.9% sodium chloride.

4. Recheck identity of patient, unit label and tag, and look for a clerical error. Consider that another patient may have received the wrong unit.

5. Inform the blood bank and the responsible clinician at once, and return the unit and set.

6. Do not restart the transfusion. Do not transfuse other units until the blood bank has confirmed compatibility.

Resuscitation.

• Intravenous 0.9% sodium chloride in boluses (for example 1 to 2 L initially in an adult, with reassessment), aiming at urine output over 100 mL/hour (1 mL/kg/hour in children), and haemodynamic stability.

• Noradrenaline for persistent hypotension after fluids.

• Furosemide 40 to 80 mg intravenously (0.5 to 1 mg/kg in children) if urine output remains low after volume restoration, and not as a substitute for fluids.

• Treat disseminated intravascular coagulation with products for bleeding: platelets, plasma and cryoprecipitate, directed by results.

Investigations.

• Clerical check of all documentation and unit labels.

• Repeat ABO and RhD on the pre-transfusion and post-reaction samples, repeat antibody screen and crossmatch, and direct antiglobulin test.

• Visual check of plasma for haemolysis, plasma free haemoglobin, haptoglobin, bilirubin, lactate dehydrogenase, full blood count, coagulation and fibrinogen, urea, creatinine, electrolytes (especially potassium), and urinalysis for haemoglobin.

• Blood cultures from the patient and culture of the unit.

• Repeat creatinine, potassium and coagulation every 2 to 4 hours initially.

Definitive management.

• Intensive care for shock, renal impairment and coagulopathy, with renal replacement therapy if there is refractory hyperkalaemia, acidosis, fluid overload or established renal failure.

• Maintain urine output, correct potassium and acidosis, and treat bleeding.

• Exchange transfusion is considered in severe cases when a large volume of incompatible blood has been given, at a specialist's direction.

• Further transfusion: group O red cells or red cells compatible with the recipient, as selected by the blood bank, once the cause is clear.

If another patient may be affected. Alert the clinical team of the other patient at once so that their transfusion is stopped and assessed, and so that both patients are managed.

Prognosis. Mortality is related to the volume of incompatible blood given. Early recognition and stopping within minutes greatly reduces the risk of renal failure and death.

Reporting. Immediate report to the transfusion service and the haemovigilance system as a serious event, with a full investigation (root cause analysis), disclosure to the patient and family, and review by the hospital transfusion committee.

Prevention.

• Correct sampling with bedside labelling, never pre-labelling.

• Two person bedside check before every unit, or a validated electronic system.

• Care in emergency transfusion with emergency identifiers.

• Staff training, avoidance of interruptions during checks and audit of the process.

• For non-ABO immune haemolysis: antibody screening, careful record review and antigen negative units.