Molecular assays as tools to facilitate new discoveries and to enhance immunohematology in daily transfusion practice

The practice of transfusion medicine saves lives, but approximately 2-4% of transfused patients develop alloantibodies against red blood cell antigens, becoming alloimmunized. The alloimmunization index is 10 times higher in transfusion-dependent patients such as those with sickle cell anemia or thalassemia. The determination of red blood cell phenotype by hemagglutination in alloimmunized patients can be lengthy, complex, and produce results difficult to interpret. The elucidation of the molecular basis for most red cell antigens in recent years allows the use of molecular assays to determine the presence or absence of alleles for various blood groups (genotype) and predict the red cell phenotype. Genotype determination can be used to resolve complex cases where serological determination of the blood recipients' phenotype is impaired either by lack of reagents or by other limitations of hemagglutination due to the presence of alloantibodies in the patient's blood. In those instances, the determination of genotype helps to predict the red cell antigen that can be expressed, providing a more thorough characterization of the blood type. Often blood group genotyping in the care of transfusion-dependent patients is of great clinical benefit because it allows for the use of better-matched blood, reducing the risk of hemolytic transfusion reactions, especially delayed transfusion reactions due to existing alloantibodies, and prevents new alloimmunization events. The prevention of hemolytic reactions can by itself reduce transfusion requirements by ensuring better survival of the transfused erythrocytes and decreasing the risk of other transfusion adverse reactions such as potential exposure to infectious diseases and transfusion-related acute lung injury (1-3). There is solid evidence indicating that matching genotype can provide an extra layer of safety and efficacy to the care of transfusion-dependent and/or chronically transfused patients. The use of genotype is also cost-effective in terms of time and resources associated with complex serologic workups and a higher number of transfused red blood cell units. Molecular testing is rapidly advancing and offers tremendous help as a powerful tool with potential advantages in the identification of rare red blood cell donors and finding antigen matches for chronically transfused patients. However, it should be noted that, regardless of the test protocols used, genotyping predicts a blood type but does not determine the phenotype the way serologic tests do. In some instances, the genotype will not correlate with the serotype because the simple presence of a gene does not mean that the gene will be expressed as an antigen on …