Alloimmunisation

When to suspect this adverse reaction

Alloimmunisation results in the stimulation of alloantibodies to red cell antigens, human leucocyte antigens (HLA) or human platelet antigens (HPA).
 
Acute or delayed haemolytic transfusion reactions commonly result from alloimmunisation by transfused red cells that are serologically incompatible with the patient. 

Post-transfusion purpura (PTP) can also occur as a consequence of the development of HPA antibodies during previous pregnancy or transfusion.

Alloimmunisation against HLA antigens is also implicated in transplant rejection, febrile non-haemolytic reactions, TRALI and platelet refractoriness.

Usual causes

Approximately 1% of red cell transfusions are associated with alloantibody formation, but the rate may be much higher (up to 30%) in frequently transfused patients, such as those with sickle cell disease and thalassaemia. 
 
HLA and HPA antibody formation may lead to platelet refractoriness, where less than an expected rise in platelet count is seen after a platelet transfusion. This may occur in about 25-70% of patients receiving multiple red cell and platelet transfusions. 

Other sensitising events include pregnancy or following a transplant.  

Investigation

Obtain the patient’s history for details of any previous transfusions, transplantation or pregnancies. 

Repeat the patient’s blood group and perform an antibody screen on their plasma to detect clinically significant red cell antibodies. The DAT is usually positive following red cell alloimmunisation.  

Testing for HLA or HPA antibodies may be required in suspected PTP or platelet refractoriness. 

What to do

Stop transfusion immediately and follow other steps for managing suspected transfusion reactions.

Alloimmunisation can’t be completely prevented. Treatment depends on the type and severity of the transfusion reaction, with most reactions being mild. 

If a red cell alloantibody is identified, antigen-negative blood should be selected if further transfusion is needed.  

With patients requiring long-term transfusion support, e.g. those with thalassaemia, giving phenotyped-matched red cells early in their treatment course may reduce the risk of further antibody development. 

 In Australia, all cellular blood components are leucodepleted, with most white cells being removed by filtration, reducing the risk of HLA sensitisation. 
 
To reduce the risk of TRALI, plasma for fresh frozen plasma and cryoprecipitate is only accepted from males, and apheresis platelets are only collected from males and nulliparous women.  

The patient should also be notified if they are alloimmunised, and this should also be recorded in their medical records, for management of subsequent transfusion or future pregnancies.

Updated June 2025