Match study

Preventive extended red blood cell antigen MATCHing: when and how?


Red blood cell (RBC) alloimmunization after blood transfusion results form the genetic disparity between donor and recipient. After multiple transfusions, up to 60% of patients will develop alloantibodies. In >80% of cases, the antibodies are directed against clinically relevant C, c, E, K, Fya, Jka and S antigens. This high immunization rate led to the policy to prophylactically match RBC transfusions for C, c, E and K antigens in high risk haematological patients. In addition, to prevent haemolytic disease of the fetus and newborn, transfusions in women in their (pre-) fertile ages are matched for c and K antigens. For all other patients, RBC transfusions are only ABO-D compatible.When antibodies are detected in case of a subsequent transfusion event, RBCs also compatible with these antibodies are selected. This requires extensive and time consuming assays, which can cause delay of treatment and in case of multiple antibodies compatible blood may not be readily available.


A longer life expectancy is associated with an increased probability of repeat surgery or diseases, which in turn can increase the chance of multiple transfusion events. Except for particular populations, patients at risk for alloimmunization and the costs associated with it are unknown.

Prior to the availability of new technology enabling large-scale extended donor RBC antigen genotyping identification for which patients extensive matching is efficient and may be cost-effective is warranted.


This study investigates the benefits and costs of extended RBC antigen matching to prevent RBC alloimmunization. Preventive RBC matching is evaluated in two transfusion populations with different (random and high) risk for alloimmunization. This will provide information for an optimal strategy to apply preventive extended matching with respect to clinical benefits improving transfusion safety and cost-effectiveness.

Study design

Multicenter randomized controlled trial.

Study population

General transfusion population (men >18 years and women >45 years of age) requiring an elective RBC transfusion of ≤4 RBC units. Patients included in the study are stratified into two strata. The stratum is defined by transfusion history and the presence (high risk, n=230) or absence (random risk, n=890) of antibodies. By including these numbers of patients an 80% reduction in alloimmunization rate is anticipated (power 90, β 0.1).


Patients in both strata are randomized to receive standard ABO-D compatible or extended (C, c, E, e, K, Fya, Jka and S) compatible RBC products.

Main study parameters/endpoints


  • Incidence of alloimmunization in transfusion patients through preventive donor matching for clinically relevant antigens compared to standard matching.


  • Cost-analysis for current screen and match strategy compared to preventive matching in both strata.
  • Transfusion and/or medical delay in case of RBC alloimmunization.
  • Data on clinical and genetic factors associated with RBC alloimmunization.

Procedure of the research (study protocol)

Patients with an elective transfusion indication/request who fulfil the inclusion criteria are informed about the study and asked for informed consent by the local investigator. Patients are centrally randomised and subsequently transfused accordingly. Patients are followed-up for RBC allimmunization by blood-sampling and clinical data are gathered from the hospital files.

Exclusion criteria

  1. Men younger than 18 years and women younger than 45 years. The latter because they routinely receive K matched RBC transfusions
  2. Patients with an a priory indication for matched transfusions
  3. Patients with a pre-transfusion positive direct antiglobulin test
  4. Patients who are expected to receive more than 4 RBC units during the transfusion event or are expected to experience multiple transfusion events in the near (6 months) future
  5. Incapacitated patients or patients who cannot understand the information

Time schedule

After transfusion follow-up including blood-sampling takes place at three time points e.g. 7-10 days, 4-6 weeks and 4-6 months


  • H. Schonewille PhD
  • A. Brand MD PhD