Delayed Serologic Transfusion Reaction

Delayed serologic transfusion reaction is the appearance of a new red cell alloantibody (with a positive direct antiglobulin test in some cases) 3 to 14 days after transfusion, without clinical or laboratory evidence of haemolysis. When haemolysis is present it is called a delayed haemolytic transfusion reaction.

Epidemiology. New alloantibodies develop in about 1 in 100 to 1 in 1,000 transfused patients, and delayed haemolytic reactions in about 1 in 2,500 to 1 in 11,000 transfusions. Rates are higher in sickle cell disease, thalassaemia and other patients transfused regularly, and in multiparous women.

Antibodies involved. Rhesus (E, c, C), Kidd (Jka, Jkb), Kell (K), Duffy (Fya, Fyb) and MNS (S, s) are the commonest.

Pathophysiology. A secondary (anamnestic) immune response occurs in a patient previously immunised, whose antibody level has fallen under the detection limit at pre-transfusion testing. After re-exposure to the antigen, antibody titre rises over 3 to 14 days and coats donor red cells. If haemolysis occurs it is mostly extravascular, but Kidd antibodies can cause intravascular lysis.

Serologic reactions are usually asymptomatic. Haemolytic reactions give fever, malaise, jaundice, dark urine, unexplained fall in haemoglobin, dyspnoea, rising lactate dehydrogenase and bilirubin, and rarely acute kidney injury, shock or DIC.

Red flags.

• Falling haemoglobin 3 to 14 days after transfusion.
• Sickle cell disease with pain crisis or hyperhaemolysis after transfusion.
• Dark urine, jaundice or new fever.

Repeat blood group and antibody screen, direct antiglobulin test (often positive with IgG and complement) and antibody identification (with eluate from the patient's red cells). Check haemoglobin, reticulocytes, bilirubin, lactate dehydrogenase, haptoglobin, free haemoglobin, urinalysis and creatinine. Review the blood film (spherocytes). Compare with the pre-transfusion sample.

Differential diagnosis. Autoimmune haemolytic anaemia, hyperhaemolysis in sickle cell disease, ongoing bleeding, drug induced haemolysis, sepsis and sickle cell crisis.

Serologic reaction without haemolysis. No treatment. Identify the antibody, record it, give the patient an antibody card and flag the laboratory record. Future transfusion needs antigen negative units and full crossmatch. Antibody screen after each transfusion in at risk patients.

Delayed haemolytic reaction.

• Check haemoglobin and haemolysis markers daily until stable.
• Maintain hydration (0.9% sodium chloride 1 to 2 L over 24 hours as tolerated) and monitor urine output and renal function.
• Transfuse antigen negative, crossmatch compatible red cells only if symptomatic anaemia or physiological need, because further transfusion can worsen haemolysis (sickle cell disease carries a risk of hyperhaemolysis).
• Corticosteroid (prednisolone 1 mg/kg daily) and intravenous immunoglobulin 1 g/kg daily for 2 days are used in severe cases with specialist advice.
• Folic acid 5 mg daily.
• Treat acute kidney injury and DIC as indicated.

Prevention in patients with sickle cell disease and thalassaemia. Extended phenotype matching (Rhesus, Kell, Kidd, Duffy, MNS) of red cells for regular transfusion, antibody history shared across hospitals, and transfusion only when needed.

Reporting. Notify the transfusion service and haemovigilance scheme.

Monitoring. Haemoglobin, bilirubin, lactate dehydrogenase, reticulocytes, creatinine and urine colour for 14 days.

Referral and escalation. Haematology and transfusion medicine. Intensive care for shock or renal failure.

Special groups. In sickle cell disease and thalassaemia, seek specialist advice before any further transfusion. In pregnancy, antibodies may cause haemolytic disease of the foetus and newborn, so inform obstetrics.