Non-immune mediated-haemolysis
When to suspect this adverse reaction
The symptoms vary depending on the degree of haemolysis and the amount of component transfused.
Most non-immune-mediated haemolysis situations are benign, but life-threatening haemolysis with severe anaemia and renal failure may occur.
Patients often present with fever and increased pulse rate. Transfused patients may develop haemoglobinuria and haemoglobinaemia.
The incidence of acute non-immune-mediated haemolysis is rare.
Usual causes
Causes of non-immune-mediated red cell haemolysis include:
- inadvertent freezing of red cells (transporting directly on ice or storage in freezer)
- incomplete deglycerolisation of frozen red cells
- transfusing red cells under pressure through a small-bore needle
- using a rapid pressure infuser
- overheating of red cells due to improper storage
- medical device malfunctions (blood warmers or cell savers) or use of hot water baths and microwaves to warm blood
- simultaneous infusion of red cells through the same tubing with hypotonic solutions or pharmacological agents
- bacterial contamination of the red cell unit
- transfusion of outdated red cells
- the patient’s underlying disease or condition, and
- patient (or transfused red cells) have an intrinsic membrane defect e.g. G6PD deficiency.
Investigations
Rule out immune haemolysis by performing a direct antiglobulin test (DAT) and repeating the patient’s ABO group.
Test the transfused unit for haemolysis.
Perform a root-cause analysis (RCA) to identify and eliminate the cause.
What to do
Stop the transfusion immediately and follow other steps for managing suspected transfusion reactions.
Seek urgent medical assistance. Maintain blood pressure and renal output. Induce diuresis with intravenous fluids and diuretics.
This may become a medical emergency so support blood pressure and maintain an open airway.
Do not administer additional blood components until cleared by a haematologist or Transfusion Service Provider.
Updated June 2025