**1. Introduction**

Blood transfusion saves lives in trauma situations and serves as a unique therapeutic treatment of various hematologic disorders where patients require lifelong regular transfusions to survive. However, in contrast to therapeutic drugs, blood cannot be manufactured and tested for quality control of purity, potency, and efficacy. Instead, each donation is a unique batch, most often single use, for which all characterization and quality assessment need to be performed individually even if several units are used in a single treatment. Since blood is a biological product, safety assessment must be done at multiple levels, including donor screening, blood collection, testing for infectious agents, blood cell typing and labeling. Checkpoints and quality control are also required at the time of transfusion to avoid human error and to guarantee that the right blood goes to the right person. Each step has its own characteristics and challenges. Screening involves the review of donor history that allows assessment for safety; requirements that need to be followed for blood collection to assure proper timing, storage, and processing so that the quality of the

product is not compromised; testing for infectious agents ensures a second layer of screening for pathogens that could be transmitted to the patient with an infected blood unit; testing for blood cell typing helps to avoid improper usage of the product since non-compatible blood can produce serious consequences and even fatalities; lastly, the transfusion process itself requires strict checkpoints to prevent the use of an incompatible unit in a given patient.

The scope of this chapter focuses on blood group typing and approaches to achieve better management and prevention of alloimmunization. We will provide an overview on the following topics: blood transfusion and risk of RBC alloimmunization; approaches for prevention of alloimmunization and improvement of transfusion therapy; serology and molecular typing methods and their use for RBC matching; current technologies for RBC genotyping; and standards for red cell antigens typing including scope, importance, and description of reference reagents available for use.
