Individuals exposed to red blood cell alloantigens through transfusion, pregnancy or transplantation may produce antibodies against the alloantigens. Alloantibodies can pose serious clinical problems such as delayed haemolytic reactions and logistic problems, for example, to obtain timely and properly matched transfusion blood for patients in which new alloantibodies are detected.
The authors hypothesise that the particular clinical conditions (eg, used medication, concomitant infection, cellular immunity) during which transfusions are given may contribute to the risk of immunisation. The aim of this research was to examine the association between clinical, environmental and genetic characteristics of the recipient of erythrocyte transfusions and the risk against erythrocyte alloimmunisation during that transfusion episode.
Methods and analysis Study design
Incident case–cohort study.
Secondary care, nationwide study (within the Netherlands) including seven hospitals, from January 2005 to December 2011.
Consecutive red cell transfused patients at the study centres.
The study cohort comprises of consecutive red blood cell transfused patients at the study centre.
Patients with transfusions before the study period and/or pre-existing alloantibodies.Cases defined as first time alloantibody formers; Controls defined as transfused individuals matched (on number of transfusions) to cases and have not formed an alloantibody.
Logistic regression models will be used to assess the association between the risk to develop antibodies and potential risk factors, adjusted for other risk factors.
Ethics and dissemination
Approval at each local ethics regulatory committee will be obtained. Data will be coded for privacy reasons. Patients will be sent a letter and an information brochure explaining the purpose of the study. A consent form in presence of the study coordinator will be signed before the blood taking commences. Investigators will submit progress summary of the study to study sponsor regularly. Investigators will notify the accredited ethics board of the end of the study within a period of 8 weeks.
Identifying transfusion-related risk factors of alloimmunisation against red blood cell (RBC) antigens.
Identifying clinical risk factors of alloimmunisation against RBC antigens.
Identifying environmental and genetic risk factors of alloimmunisation against RBC antigens.
Alloimmunisation against RBC transfusion is a clinically relevant problem faced by transfusion specialists.
Identifying a high-risk group of responders who form allantibodies against transfused RBCs would be the next step towards transfusion of complete phenotyped matched RBC.
In synergy with other ongoing studies, cost-effectiveness of a phenotyped matched RBC approach will be assessed.
Strengths and limitations of this study
Multicentre, matched case–cohort design.
Good representative sample of controls from large base cohort of general population.
Cases and controls matched on the number of RBC transfusions.
Possibility that patients entering cohort have had transfusions prior to start of study period in other hospitals/non-study centres.
Previous pregnancies in women could play a role in alloimmunisation. Retrospective data will not allow for a comprehensive check on previous pregnancies.
There could be a few cases selected who are booster/secondary alloimmune responders, instead of first time ever alloantibody formers.