Blood transfusion begins with safe donor selection and testing. In the United States, the blood supply and transfusion are highly regulated. Blood transfusion safety is multifaceted, whereby each of the elements of the blood safety value chain, spanning donor recruitment and qualification, to collection, blood processing, testing, transfusion practice, and posttransfusion surveillance, must be optimized to minimize risk. Pathogen inactivation is a promising approach to decrease bacterial contamination of platelets, inactivate parasites and viruses, and decrease risks associated with emerging and unidentified pathogens. This article offers an overview of blood donor infectious and noninfectious testing in the United States.
The safety of the blood supply in the United States is regulated primarily by the US Food and Drug Administration (FDA).
Donor testing is preceded by donor screening, education, and questioning, to exclude donors with an increased risk of infections. Testing of the donated blood has 2 steps: (1) serologic testing to type and screen and label the collected blood product, and (2) comprehensive infectious diseases testing.
Transfusion-transmitted infection (TTI) as defined by the FDA is a pathogen transmissible through blood transfusion that is known to be fatal, life threatening, or cause severe impairment.
The overall estimated risk of TTIs in the United States is extremely low. However, infection transmission can still occur, particularly during early in infection when the test is negative, either when the pathogen is not yet detectable or before development of antibodies (ie, the preseroconversion window period). With the use of improved and sensitive testing methods such as minipool nucleic acid testing, the estimated window period has been reduced for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus.
Pathogen inactivation is a powerful technique that has been shown to minimize the risk of bacterial sepsis from platelets. In vitro data suggest that Pathogen inactivation can reduce the residual risk of known TTIs and of many emerging potential pathogens.
Blood transfusion begins with safe donor selection and testing. In the United States, the blood supply and transfusion are highly regulated, most importantly by the Food and Drug Administration (FDA). Blood transfusion safety is multifaceted, whereby each of the elements of the blood safety value chain, spanning donor recruitment and qualification, to collection, blood processing, testing, transfusion practice, and posttransfusion surveillance, need to be optimized to mitigate risk. This article offers an overview of blood donor testing in the United States.
All blood donations in the United States undergo a determination of ABO blood group and Rh(D) antigen typing. In addition, blood products are tested for clinically significant red blood cell antibodies. Each collected product gets extensively tested using serologic (tube, gel, and/or solid phase) and molecular methods. For certain populations (eg, sickle cell population), the red blood cell (RBC) products can also undergo extended phenotyping. Molecular testing has grown significantly in recent years and is particularly important in performing these extended phenotypes. This testing is for the procurement of antigen-matched blood in patients with special transfusion needs (eg, alloimmunization, rare phenotypes).
Blood products collected from donors are labeled with their specific ABO and Rh(D) +/− type before release to the inventory. ABO testing is a 2-step process, wherein donor RBCs are incubated with anti-A and anti-B sera to detect the presence of A and or B antigens, referred to as forward or front typing. The donor serum/plasma is subsequently evaluated for reciprocal antibodies using A1 and B reagent red cells (eg, anti-A antibodies are expected in blood group B individuals), referred to as back or reverse typing. If the results of these 2 steps of the ABO tests are not in concordance (eg, if the forward typing suggests blood group A, whereas the serum grouping suggests blood group AB), an ABO discrepancy has occurred. Any discrepancies between the forward and back types need to be resolved before issuing of the blood product. Molecular methods can be helpful in resolving some of these discrepancies.
The donors are also tested for D antigen to determine their Rh-positive or Rh-negative status. Rh(D) is the most immunogenic and clinically significant RBC antigen among non-ABO antigens. Alloimmunization to the D antigen can result in both hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. Most D-positive people express D antigen strongly on their RBCs, causing a robust reaction at the immediate-spin phase when tested with anti-D reagents. However, some individuals have altered expression of Rh(D) and are not easily detected. These individuals include insufficient quantity of D antigen (quantitative deficiency or weak D) or mutations in Rh(D) genes causing changes in epitopes on RBC surface (qualitative deficiency or partial D), and are referred to as D variants. These donors undergo weak-D testing, where they are tested for the D antigen at the anti-human globulin (or Coombs) phase. Weak-D testing identifies donors with low D antigen expression, altered D expression, or truly absent D antigen (weak D, partial D, and deletion respectively) using serologic methodology before giving a Rh(D) status (positive or negative) to a blood product. Some weak-D donors, if incorrectly labeled as D negative, can alloimmunize a D-negative recipient. Serologic methods for Rh(D) typing, although robust and inexpensive, can result in variable reactivity of Rh(D) compared with ABO blood groups. This variable reactivity is due in part to the multitude of reagents available. Different manufacturers target different variants/epitope in their monoclonal blends. These reagents are based on the most common variants overall, but the prevalence of variants can differ according to the genetic makeup of a given population. Many blood centers perform Rh(D) testing using a combination of these reagents in order to detect as many D antigens/variants as possible. Rh(D) typing by molecular methods can overcome these pitfalls and also avoid wastage of donor product inadvertently labeled as D negative (when weak D or partial D).
Antibody screening of the donor product is typically performed on an automated platform along with ABO and Rh(D). RBC alloantibodies are identified in less than 1% of US donors and are more common in donors with previous pregnancy or transfusion. , , Use of blood components with RBC alloantibodies is at the discretion of the transfusion services as stipulated by institutional policies.