Transfusion With Alloantibodies or Autoimmune Haemolysis

Alloantibodies form after exposure to foreign red cell antigens through transfusion or pregnancy, and cause haemolysis when antigen positive red cells are given. Autoimmune haemolytic anaemia involves antibodies against the patient's own red cells, which makes pretransfusion testing difficult because the patient's plasma reacts with all donor cells. The risk is that a clinically significant alloantibody is masked by the autoantibody and a delayed or acute haemolytic reaction follows.

Warm autoimmune haemolytic anaemia. IgG antibodies, positive direct antiglobulin test for IgG with or without C3, reaction with all red cells.

Cold agglutinin disease. IgM antibodies, reaction at low temperature, complement mediated haemolysis, a positive direct antiglobulin test for C3.

Paroxysmal cold haemoglobinuria. Biphasic IgG antibody (Donath Landsteiner), often after infection in children.

Special groups. Patients with sickle cell disease and thalassaemia are at high risk of alloimmunisation, and women who have had pregnancies are at risk. Antigen negative blood may be scarce in East Africa, so early planning is needed.

Alloantibodies.

• Check records for previous antibodies. Antibodies can fall under the detection limit, and re-exposure to the antigen causes a rapid rise and delayed haemolysis days later.

• For identified clinically significant antibodies, provide antigen negative red cells, crossmatch compatible by antiglobulin technique, for the life of the patient.

• Extended phenotyping or genotyping for patients likely to need repeated transfusion (sickle cell disease, thalassaemia) reduces future immunisation.

Autoimmune haemolytic anaemia.

• Transfuse only when the anaemia is life-threatening or symptomatic (for example haemoglobin under 5 to 6 g/dL, or higher with cardiac ischaemia, shock or heart failure). Do not withhold transfusion in life-threatening anaemia because of positive crossmatches.

• Alloantibodies are present in a substantial minority of patients, so absorption studies, or use of genotype matched antigen negative units, are needed when laboratory resources allow.

• Haemoglobin should be raised only to a safe level, not to normal.

Red flags. Rapid fall in haemoglobin, haemoglobinuria, jaundice, rising lactate dehydrogenase and bilirubin, falling haptoglobin, and fever or back pain during transfusion.

Alloantibodies.

1. Notify the blood bank of antibody history at the first request.

2. Allow additional time for antigen negative selection.

3. In emergencies, medical staff weigh the risk of delay against the risk of haemolysis; ABO compatible, antigen unknown units may be given with close monitoring.

4. Give units slowly and monitor.

Warm autoimmune haemolytic anaemia.

• Treat the cause: prednisolone about 1 mg/kg daily (as a usual initial dose), with second line immunosuppression such as rituximab, and intravenous immunoglobulin in selected cases.

• Transfuse the least incompatible units, matched for Rh (C, c, E, e) and K if possible, one unit at a time, slowly.

• Monitor for haemolysis during and after transfusion.

Cold agglutinin disease. Keep the patient and the room warm, use a blood warmer, and avoid cold fluids and cold products. Treat the cause.

Paroxysmal cold haemoglobinuria. Supportive care, warm products and treat the infection.

Monitoring. Vital signs, urine colour, haemoglobin, bilirubin, lactate dehydrogenase and haptoglobin, and a direct antiglobulin test after transfusion.

Complications. Acute and delayed haemolytic reactions, worsening haemolysis, renal failure, and new alloantibodies.

Referral and escalation. Urgent haematology and blood bank involvement. Reference laboratory referral for extended testing may take days, so initiate early.

Disposition. Record the antibodies in the patient's record and give the patient written information about their antibody status for future care.