Extensive red blood cell matching considering patient alloimmunization risk.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) transfusions pose a risk of alloantibody development in patients. For patients with increased alloimmunization risk, extended preventive matching is advised, encompassing not only the ABO-D blood groups but also the most clinically relevant minor antigens: C, c, E, e, K, Fya, Fyb, Jka, Jkb, S and s. This study incorporates patient-specific data and the clinical consequences of mismatching into the allocation process. MATERIALS AND METHODS: We have redefined the MINimize Relative Alloimmunization Risks (MINRAR) model to include patient group preferences in selecting RBC units from a finite supply. A linear optimization approach was employed, considering both antigen immunogenicity and the clinical impact of mismatches for specific patient groups. We also explore the advantages of informing the blood bank about scheduled transfusions, allowing for a more strategic blood distribution. The model is evaluated using historical data from two Dutch hospitals, measuring shortages and minor antigen mismatches. RESULTS: The updated model, emphasizing patient group-specific considerations, achieves a similar number of mismatches as the original, yet shifts mismatches among patient groups and antigens, reducing expected alloimmunization consequences. Simultaneous matching for multiple hospitals at the distribution centre level, considering scheduled demands, led to a 30% decrease in mismatches and a 92% reduction in shortages. CONCLUSION: The reduction of expected alloimmunization consequences by incorporating patient group preferences demonstrates our strategy's effectiveness for patient health. Substantial reductions in mismatches and shortages with multi-hospital collaboration highlights the importance of sharing information in the blood supply chain.

Acute haemolytic transfusion reaction after transfusion of fresh frozen plasma in a neonate-Preventable by using solvent/detergent-treated pooled plasma?

BACKGROUND: Plasma is a commonly used blood product and is available in the form of fresh frozen plasma (FFP) or pooled solvent/detergent-treated plasma. In the Netherlands, solvent/detergent-treated plasma has become the standard product in the adult population since several years, but for neonatal use, FFP remains the product of preference. DESCRIPTION: A preterm neonate developed lung bleeding at day 8 postpartum, for which intubation and mechanical ventilation was required and transfusions with packed red blood cells and plasma, in the form of FFP, were given. Five hours after transfusion, a red discoloration of the urine occurred. An acute haemolytic transfusion was suspected, confirmed by laboratory investigations (fast decrease in haemoglobin, increased free haemoglobin, decreased haptoglobin, increased lactate dehydrogenase and a positive direct antiglobulin test [IgG 2+]). Additional research showed that the FFP product contained nonspecific auto-antibodies that reacted with the transfused erythrocytes, most test erythrocytes and the donor's own erythrocytes. CONCLUSION: A neonate experienced an acute haemolytic reaction, most probably caused by administrating a FFP product containing auto-antibodies. If transfused with solvent/detergent-treated plasma, such antibodies would have been diluted or captured. This case adds a new argument to the discussion on expanding the use of solvent/detergent-treated plasma to the paediatric population.

Mapping anticipated advantages and disadvantages of implementation of extensive donor genotyping: A focus group approach.

BACKGROUND AND OBJECTIVES: Current genotyping techniques allow typing of all relevant red cell, human leukocyte and platelet antigens in a single analysis. Even genetic markers related to donor health can be added. Implementation of this technology will affect various stakeholders within the transfusion chain. This study aims to systematically map the anticipated advantages and disadvantages of a national rollout of blood group genotyping of donors, which will affect the availability of rare donors and the implementation of an extensively typed blood transfusion policy. MATERIALS AND METHODS: Two focus-group sessions were held with a wide representation of stakeholders, including representatives of donor and patient organisations. A dedicated software tool was used to collect the reflections of participants on genotyping for blood group antigens and extensive matching. Additionally, stakeholders and experts discussed various prepared propositions. All information collected was categorised. RESULTS: From 162 statements collected, 59 statements (36%) were labelled as 'hopes' and 77 (48%) as 'fears'. Twenty-six (16%) statements remained unlabelled. The statements were divided in 18 categories under seven main themes: patient health, genotyping, privacy issues and ethical aspects, donor management, inventory management and logistics, hospital and transfusion laboratory and general aspects. The discussion on the propositions was analysed and summarised. CONCLUSION: Stakeholders believe that a genotyped donor pool can result in a reduction of alloimmunization and higher availability of typed blood products. There are concerns regarding logistics, costs, consent for extended typing, data sharing, privacy issues and donor management. These concerns need to be carefully addressed before further implementation.

Preventing alloimmunization using a new model for matching extensively typed red blood cells.

BACKGROUND AND OBJECTIVES: Alloimmunization is a well-known adverse event associated with red blood cell (RBC) transfusions, caused by phenotype incompatibilities between donor and patient RBCs that may lead to haemolytic transfusion reactions on subsequent transfusions. Alloimmunization can be prevented by transfusing fully matched RBC units. Advances in RBC genotyping render the extensive typing of both donors and patients affordable in the foreseeable future. However, the exponential increase in the variety of extensively typed RBCs asks for a software-driven selection to determine the 'best product for a given patient'. MATERIALS AND METHODS: We propose the MINimize Relative Alloimmunization Risks (MINRAR) model for matching extensively typed RBC units to extensively typed patients to minimize the risk of alloimmunization. The key idea behind this model is to use antigen immunogenicity to represent the clinical implication of a mismatch. Using simulations of non-elective transfusions in Caucasian donor and patient populations, the effect on the alloimmunization rate of the MINRAR model is compared with that of a baseline model that matches antigens A, B and RhD only. RESULTS: Our simulations show that with the MINRAR model, even for small inventories, the expected number of alloimmunizations can be reduced by 78.3% compared with a policy of only matching on antigens A, B and RhD. Furthermore, a reduction of 93.7% can be achieved when blood is issued from larger inventories. CONCLUSION: Despite an exponential increase in phenotype variety, matching of extensively typed RBCs can be effectively implemented using our MINRAR model, effectuating a substantial reduction in alloimmunization risk without introducing additional outdating or shortages.

Reduction of anti-K-mediated hemolytic disease of newborns after the introduction of a matched transfusion policy: A nation-wide policy change evaluation study in the Netherlands.

BACKGROUND: During pregnancy, maternal red blood cell (RBC) antibodies can lead to life-threatening fetal hemolysis and anemia. Women can become immunized by a pregnancy or an unmatched transfusion. Our aim was to quantify the effect of a nationwide K-matched transfusion policy for women of childbearing age potential to prevent K-immunization in pregnancy. STUDY DESIGN AND METHODS: In this nation-wide policy change evaluation study we determined the occurrence of RBC antibodies before and after introduction of a K-matched transfusion policy and evaluated the cause K alloimmunization 10 years after introduction of this measure. K-matched transfusion for females under 45 years of age is advised in the Dutch transfusion guideline since 2004. We used laboratory data from pregnancies with RBC antibodies identified in the period 1999-2018 obtained as part of a population-based screening program in the Netherlands. RESULTS: Tests of 36 286 pregnancies produced a positive antibody screening result which concerned anti-K in 1550 pregnancies. The occurrence of anti-K decreased from 67.9 to 20.2 per 100 000 pregnancies. The relative risk reduction was 0.70 which largely exceeded the relative risk reduction of 0.27 for antibodies against RBC antigens for which no preventive matching is required. The number of pregnancies at risk for anti-K-mediated disease decreased from 9.7 to 4.2 per 100 000 pregnancies. CONCLUSIONS: A K-matched transfusion policy is associated with a major decrease in a number of pregnant women with anti-K and pregnancies at risk for anti-K-mediated disease. A relatively simple measure is now shown to impact prevention of hemolytic disease in the fetus and newborn.

Development and validation of a universal blood donor genotyping platform: a multinational prospective study.

Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non-self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates. This DNA-based test is capable of simultaneously typing most clinically relevant red blood cell (RBC), human platelet (HPA), and human leukocyte (HLA) antigens. Validation was performed, using samples from 7927 European, 27 South Asian, 21 East Asian, and 9 African blood donors enrolled in 2 national biobanks. We illustrated the usefulness of the platform by analyzing antibody data from patients sensitized with multiple RBC alloantibodies. Genotyping results demonstrated concordance of 99.91%, 99.97%, and 99.03% with RBC, HPA, and HLA clinically validated typing results in 89 371, 3016, and 9289 comparisons, respectively. Genotyping increased the total number of antigen typing results available from 110 980 to >1 200 000. Dense donor typing allowed identification of 2 to 6 times more compatible donors to serve 3146 patients with multiple RBC alloantibodies, providing at least 1 match for 176 individuals for whom previously no blood could be found among the same donors. This genotyping technology is already being used to type thousands of donors taking part in national genotyping studies. Extraction of dense antigen-typing data from these cohorts provides blood supply organizations with the opportunity to implement a policy of genomics-based precision matching of blood.

A Conceptual Framework for Optimizing Blood Matching Strategies: Balancing Patient Complications Against Total Costs Incurred.

Alloimmunization is currently the most frequent adverse blood transfusion event. Whilst completely matched donor blood would nullify the alloimmunization risk, this is practically infeasible. Current matching strategies therefore aim at matching a limited number of blood groups only, and have evolved over time by systematically including matching strategies for those blood groups for which (serious) alloimmunization complications most frequently occurred. An optimal matching strategy for controlling the risk of alloimmunization however, would balance alloimmunization complications and costs within the entire blood supply chain, whilst fulfilling all practical requirements and limitations. In this article the outline of an integrated blood management model is described and various potential challenges and prospects foreseen with the development of such a model are discussed.