Alloimmunisation against blood group antigens. The balance between patients’ need and supply of matched red cells

Alloimmunization, the formation of antibodies against minor RBC blood group antigens, is the most frequent adverse event after RBC transfusion, observed in approximately 20% of multiple transfused patients. While completely matched donor blood would prevent alloimmunization, this is practically impossible because of a) restricted availability of completely matched donor blood, b) costs and c) logistic problems. The general consensus is that extended matching is only cost-effective in patients at high risk of alloimmunization. However, ideas about the balance between the benefit of extended matching and the related costs are gradually changing. Dutch CBO transfusion guidelines have in 2011 extended the advice for more extensive preventive matching of blood types between patient and donor for additional categories of patients.
This research program focuses on methods to achieve comprehensive cost-efficient full donor typing in order to fulfill the increasing demand of hospitals for more extensively typed donor blood.

The program consists of three projects:
1. BloodMatch Benefits
2. BloodMatch Availability
3. BloodMatch Supply

Project 1. BloodMatch Benefits; The effect of donor and patient’s risk factor steered extended matching and new blood group typing platforms

At present the current transfusion practice is mainly aimed to prevent the adverse health effects of immunization (i.e. haemolytic transfusion reactions and haemolytic disease of the fetus and newborn) rather than preventing immunization itself. Approximately 20% of multiple transfused patients become immunized against multiple different blood group antigens, which makes the identification of compatible donor blood laborious, costly and sometimes impossible. 
Ongoing research will lead to a growing ability to identify patients who are at higher risk for alloimmunization. Together with previously developed high throughput blood group genotyping assays, which allow better matching of donor and recipient, a survey on the feasibility of a preventive (patient-risk adapted) matching strategy is justified. This project will provide the scientific basis for this new transfusion strategy, including associated cost effects. 

Study objectives

Get insight in the effect of preventive matching by comparing various strategies for prevention of development of transfusion-induced clinically relevant alloantibodies.
Examine the relative contribution of (previously identified) environmental and genetic (including ethnic background) factors of the development of alloantibodies after red blood cell transfusion (R-Fact)
Evaluate whether genotyping compared to phenotyping may be used to compose a comprehensively typed donor cohort to be used to prevent alloimmunization. Data derived from objective 1 and 2 will be used to resolve this objective. Also cost-effectiveness of genotyping will be part of the research question (in collaboration with project 3).
Evaluate current practices of inventory management of hospital transfusion laboratories and the issuing locations of Sanquin Blood Bank with regard to (extended) phenotyped red blood cell units for the purpose of preventive red blood cell matching
Analyze all costs caused by transfusion-induced alloimmunizatioN

Project 2. BloodMatch Availability; Donor recruitment and retention in minority populations

In the Netherlands, a broad variety of ethnic minority populations exist, and patients from these populations more frequently are negative for common blood group antigens or have uncommon combinations of alloantibodies. To secure the supply of compatible RBC and stem cells for these patients it is important to enable donor selection from a diverse donor population and increase the variety of blood types in our donor base.

Study objectives

Analysis of blood group antigen frequencies in Dutch ethnic minority populations.
Development, implementation and evaluation of effective and efficient recruitment and retention strategies for ethnic minority populations, most relevant in terms of rare blood type matching.

Project 3. BloodMatch Supply: Optimizing inventory of red blood cells by development of a comprehensive blood supply management model

This project aims to develop a blood supply management model that will link donor selection and screening efforts directly to recipient benefits which allows optimization of screening strategies.


The Dutch CBO transfusion guideline advises more extensive preventive matching strategies for a range of patient groups. The targets set for the number of typed donors for a range of antigens that are used at Sanquin’s National Screening Laboratory (NSS), have been formulated before the launch of the newest CBO guideline and are based on expert opinions only. This project aims to collect and combine all available information on the antibody formation, patient risk, it’s mitigation by blood type matching and subsequent implications on blood supply management (donor availability, operational feasibility and costs) in order to select an integrated optimal blood matching strategy.

Study objectives

The development of a blood supply management model that enables calculation of the subset and number of typed donors needed to guarantee a sufficient and most cost-effective supply of typed red blood cells for patients groups that are at risk for developing blood group antibodies. The project will be integrating the outcomes from the other two subprojects.

Research staff (alphabetic order)

  • JG van der Bom, Centre of Clinical Transfusion Research
  • M de Haas, Dept of Immunohematological Diagnostic Services
  • EMJ Huis in 't Veld, Dept of Donor Studies
  • K van den Hurk, Dept of Donor Studies
  • M Janssen, Dept of Transfusion Technology Assessment
  • EF Klinkenberg, Dept of Donor Studies
  • MMW Koopman, Unit Transfusion Medicine, Blood Bank division
  • W de Kort, Dept of Donor Studies
  • MGJ van Kraaij, Unit Transfusion Medicine, Blood Bank division
  • H Schonewille, Dept of Experimental Immunohematology
  • CE van der Schoot, Dept of Experimental Immunohematology
  • B Veldhuisen, Dept of Experimental Immunohematology
  • JJ Zwaginga, Centre of Clinical Transfusion Research