Delayed Haemolytic Transfusion Reaction

Delayed haemolytic transfusion reaction is destruction of transfused red cells by an antibody that became undetectable before transfusion and rises quickly after re-exposure to the antigen (an anamnestic response). It usually occurs 3 to 14 days after transfusion, and sometimes up to 28 days. The usual antibodies are directed against Kidd, Duffy, Rh and Kell antigens.

Clinical features. Unexplained fall in haemoglobin or failure to rise after transfusion, fever, jaundice, dark urine, fatigue, and a new positive direct antiglobulin test with a new red cell antibody. Many reactions are mild and found only on laboratory tests, and some are severe with renal failure.

Classification.

• Delayed haemolytic transfusion reaction: clinical or laboratory evidence of haemolysis with a new antibody.

• Delayed serological transfusion reaction: a new antibody and positive direct antiglobulin test without haemolysis.

• Hyperhaemolysis (especially in sickle cell disease): destruction of both transfused and the patient's own red cells, with haemoglobin falling under the pre-transfusion level, and often without a detectable new antibody.

Risk factors. Previous transfusion or pregnancy, sickle cell disease, thalassaemia, multiple transfusions, and care in several hospitals without shared records.

Special groups. Patients with sickle cell disease have high rates of alloimmunisation and a risk of hyperhaemolysis, and need extended phenotype matching.

Differential diagnosis.

• Ongoing haemolysis from the underlying disease (sickle cell crisis, autoimmune haemolytic anaemia, glucose-6-phosphate dehydrogenase deficiency, malaria).

• Bleeding, sepsis and drug induced haemolysis.

• Acute haemolytic reaction (earlier onset).

• Passenger lymphocyte syndrome (after transplant) and disseminated intravascular coagulation.

Initial assessment. Symptoms, temperature, jaundice, urine colour, haemoglobin trend compared with the expected rise, and review of transfusion history and previous antibodies, including from other hospitals.

Immediate actions in order.

1. Stop any transfusion in progress.

2. Assess the patient: airway, breathing, circulation, urine output, and signs of haemolysis, with senior help for severe features.

3. Keep intravenous access with 0.9% sodium chloride and maintain hydration and urine output.

4. Recheck identity of the recent units and the records, and compare the transfusion history.

5. Inform the blood bank and the responsible clinician, and send a new sample.

6. Do not give further red cells until the blood bank has identified the antibody and provided compatible units.

Investigations.

• Direct antiglobulin test, antibody screen and identification (with eluate), repeat group and crossmatch against pre- and post-transfusion samples.

• Full blood count and reticulocyte count, bilirubin, lactate dehydrogenase, haptoglobin, plasma free haemoglobin, urinalysis for haemoglobin, urea and creatinine.

• Compare with previous antibody records, and in sickle cell disease check for hyperhaemolysis (fall in haemoglobin under pre-transfusion level, reticulocytopenia, low haemoglobin A fraction).

Definitive management.

• Mild cases: observe, maintain hydration and monitor haemoglobin, bilirubin and renal function.

• Transfusion only when life-threatening anaemia occurs, using antigen negative, crossmatch compatible red cells selected by the blood bank, and with careful monitoring.

• Renal complications: maintain fluids and urine output, treat hyperkalaemia, and arrange renal support when needed.

• Hyperhaemolysis: avoid further transfusion unless life-threatening, because it can worsen haemolysis. Give intravenous immunoglobulin (for example 1 g/kg daily for 2 days) with corticosteroid (for example prednisolone 1 mg/kg daily), and use erythropoiesis stimulating agents and iron in selected cases. Specialist agents (rituximab, complement inhibitors) are directed by haematology.

• Support and monitor patients with sickle cell disease for crisis and organ damage.

Reporting. Report to the transfusion service and haemovigilance system, and add the new antibody to the patient's permanent record.

Prevention.

• Obtain full transfusion and antibody history, including from other hospitals, and check the blood bank record before each request.

• Provide antigen negative blood for every antibody ever identified, even when it is no longer detectable.

• Extended phenotype or genotype matching for patients likely to need repeated transfusion.

• Give the patient a transfusion card with phenotype and antibodies, and share records between hospitals.

• Review all patients 1 to 2 weeks after transfusion (symptoms and haemoglobin) when at risk.