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(.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 the red blood cell membrane. A large number of
genetic events may silence or weaken the expression of antigens encoded by an allele. Thus,
the profile of a gene needs to be completely elucidated, and appropriate assays need to be
performed to look for genetic changes that may alter the predicted phenotype.This field is growing exponentially and molecular events associated with the specific
expression of most alleles have been identified for all described blood group systems in
various ethnic groups. Therefore, molecular methods must be used with caution in antigen
and antibody investigations because the serological problem may involve the inheritance of
a null allele, a hybrid gene or a new variant.Genetic analysis of blood group variants within a given population is an important step
that provides basic knowledge and ultimately increases the accuracy of prediction of red
cell phenotype by genotype determination.The Kell blood group is very relevant in transfusion practice because it is highly
immunogenic, frequently causes alloimmunization and may cause hemolytic disease of the
fetus and newborn (HDFN)(. Kell antigen
phenotyping is hampered by technical limitations and genotyping can be of great assistance
to solve this problem. The development of easy and efficacious strategies for KEL
genotyping is fundamental to provide the needed information about the allelic frequency in
multiethnic populations and to identify individuals with rare genotypes such as K*1/K*1 and
K*3/K*3(.The more we know about the frequency and molecular background of variants in a given
population, the more accurate will be genotype/phenotype results, and the better will be
the care provided for those in need.