ABO Blood Group System

Function

ABO Antigens and Antibodies

Individuals are classified into 4 main groups—A, B, O, and AB—based on the agglutination patterns of their red blood cells (RBCs). The ABO blood group system consists of A and B antigens on RBCs and their corresponding antibodies in the sera of individuals who who lack those antigens.[1][2] ABO antigens are present on the surface of RBCs and on the surfaces of other tissues and secretions. Anti-A and anti-B antibodies are naturally produced by immunocompetent individuals starting at approximately 6 months of age.[3][4]

The A and B blood group antigens are oligosaccharide antigens generated by reactions catalyzed by glycosyltransferases. The expression of these antigens determines the blood type of the patient. The human ABO gene, located on chromosome 9, spans over 18 kb and comprises seven coding exons. Functional A and B alleles encode specific glycosyltransferases that synthesize the A and B antigens, respectively. The A and B genes encode transferases with different sugar specificities due to nucleotide substitutions leading to amino acid substitutions. The O genes are inactive because they do not produce functional enzymes.

Group O individuals have an H gene on chromosome 19, forming the H-antigen. This antigen is a precursor oligosaccharide needed to form the A and B antigens. H antigens are abundantly noted in type O individuals. If the A and B genes are both present, some of the H becomes A, and some become B, forming the AB group. If the H gene is defective or absent, the H antigen cannot be formed, and, therefore, A or B cannot be formed. The consequence is a rare phenotype known as the Bombay phenotype. Patients with the Bombay phenotype have antibodies in the plasma similar to those in the plasma of type O individuals, but they also have clinically significant anti-H antibodies.[3][5][4]

Subgroups of ABO blood group system have also been identified based on the pattern and degree of agglutination using reference antibodies and RBCs. Subgroups are distinguished by decreased amounts of A, B, or O (H) antigens on the RBCs. Blood type A has the most variation with different subgroups; type A1 has the standard amount of antigen A, with decreasing amounts of this antigen noted in the subsequent subtypes.[5]

Issues of Concern

Discrepancies in Blood Typing

Before a blood transfusion, ABO typing is routinely conducted to ensure the safest possible transfusion. This process involves forward typing, which tests for the presence of A and B antigens on RBCs, and reverse typing, which tests anti-A and anti-B antibodies in the patient's plasma. These tests are performed to confirm the individual's blood type. However, discrepancies may occur between forward and reverse typing. The discordance can be due to a lack or excess of antigens or antibodies. If a discrepancy is found, the first step is to perform confirmatory assessments to evaluate for any errors in testing or technical problems. Various clinical scenarios can also explain these discrepancies.

In forward typing, the patient's RBCs are mixed with commercial antisera. Weaker RBC agglutination than expected (weak or missing reactivity) can occur in cases of A or B subgroups. Additional RBC reactivity on forward typing can occur in cases of acquired B phenomenon. The acquired B phenotype occurs in cases where bacterial enzymatic changes lead to the conversion of N-acetylgalactosamine (A antigen) into galactose (B antigen). This phenomenon has been reported in cases of bacterial infections and colorectal malignancy.[6][7] 

Reverse ABO typing involves mixing a patient's plasma with commercial reagent RBCs. Possible causes of weaker than expected plasma reactivity include immunosuppression, very young or old age, hypogammaglobulinemia, and prior treatment with rituximab. Unexpected or extra reactivity detected in reverse typing can be observed in patients who have received intravenous immune globulin or non–ABO-matched plasma products.[8]

Choosing the Safest Blood Products

In the simplest terms, individuals with type O blood are considered universal donors for RBCs, whereas those with type AB blood are universal recipients of RBCs from patients with any ABO blood type. Type AB plasma is compatible with all other ABO blood types. However, multiple clinical considerations and exceptions must be accounted for when selecting the safest and most appropriate blood products for a patient.

Although the ABO antigen is fully developed at birth, newborns do not start producing antibodies until 3 to 6 months. The antibodies present in the serum of newborns younger than 4 months are passively transferred from the mother. Therefore, when a blood transfusion is ordered for an infant younger than 4 months, the mother's blood type must be considered.[9] Forward typing is performed to determine a newborn's blood type, but reverse typing is not performed in infants during the first few months of life. 

Platelets have ABO antigens, but the expression is variable; these antigens are only strongly expressed in a small subset of individuals. However, platelets are suspended in plasma that contains ABO antibodies. The plasma accompanying the platelets may cause hemolysis if the plasma is not compatible with the recipient's RBCs.[10] In the emergency setting for the bleeding patient requiring blood products, group AB plasma and group O-negative RBCs have been traditionally transfused to minimize the risk of ABO incompatibility and avoid delays while blood typing is being performed. Group AB plasma does not contain anti-A or anti-B antibodies and is therefore compatible with all ABO blood groups. However, the availability of AB plasma is limited. Newer methods for treating patients without a known ABO blood type in emergencies include transfusing type A plasma and using low-titer group O whole blood. Although transfusion of even a small amount of ABO-incompatible red blood cells can lead to severe hemolysis and morbidity, clinically significant hemolysis has not been described in cases of type A plasma or low-titer group O whole blood transfusions into patients for whom these products are ABO-incompatible.[11]

Clinical Significance

Although the distribution of ABO phenotypes varies among different ethnic and racial groups, blood type O is generally the most common worldwide, followed by types A and B. Type B is more common in the Asian population. Blood type AB is the rarest of the ABO phenotypes.[12] ABO antigens are not only found on RBCs but are also expressed on the surface of many different types of human cells. The importance of ABO blood type antigens stretches beyond transfusion medicine, as many reports suggest the involvement of the ABO system in several disease processes. ABO blood groups have been linked with the susceptibility to various diseases, including hematologic disorders, cancer, infections, and cardiovascular diseases.[13]

Clinically significant antibodies can lead to adverse events during transfusion and can also lead to hemolytic disease of the fetus and newborn after placental transmission from mother to fetus. Hemolytic disease of the newborn occurs due to incompatibility between the blood of the mother and the baby. Antibodies from the mother cross the placenta during pregnancy and attack the baby's RBCs. ABO incompatibility between mother and infant can cause hemolysis and hyperbilirubinemia in the infant. Hemolytic disease of the newborn caused by ABO incompatibility is usually less severe than that caused by incompatibility because fetal RBCs express fewer ABO blood group antigens compared to adults. In addition, ABO blood group antigens are found on various tissues, which decreases the likelihood that ABO antibodies bind to their targets on fetal RBCs. The degree of severity of hemolysis varies greatly. Hemolytic disease of the newborn can occur with the first pregnancy and has a high recurrence rate.[14][15][16] 

A hemolytic transfusion reaction is a type of reaction that can occur with the transfusion of blood products. Acute hemolytic transfusion reactions most commonly occur with transfusion of RBCs, although they can develop with transfusions of other blood products. An acute hemolytic transfusion reaction occurs within 24 hours of the transfusion. Acute hemolytic reactions are most often caused by ABO incompatibility between the donor and recipient blood group systems. The classic presentation of acute hemolytic transfusion reaction includes fever, red or brown urine, and back or flank pain. However, not all patients present in this way; other symptoms that may be noted include hypotension, chills, renal failure, and disseminated intravascular coagulation.[17] 

Once an acute hemolytic transfusion reaction is suspected, the transfusion should be immediately stopped. The most common cause of death during a transfusion is a clerical error, which occurs when an incompatible unit of blood is transfused; therefore, it is essential to rule out such errors and confirm that the correct blood product was administered to the intended patient. The remaining blood product and a sample of patient blood should be sent to the blood bank for repeat ABO testing. Cross-matching should be repeated, and further laboratory evaluation should include assessment for renal failure, hemoglobinemia, hemoglobinuria, disseminated intravascular coagulation, and hemolysis. Treatment for an acute hemolytic transfusion reaction is mainly supportive care, and specific treatments are determined by the specific complications noted.

Enhancing Healthcare Team Outcomes

The discovery of the ABO system has led to increased safety in the transfusion of blood products. Understanding the ABO blood group system is essential to ensure appropriate blood products are administered to patients. Healthcare practitioners must be familiar with proper product selection based on ABO typing and be able to recognize the clinical manifestations of ABO incompatibility. Understanding the ABO blood system, preventing complications through proper blood product administration, and quickly identifying signs or symptoms of ABO incompatibility enhance patient care and reduce morbidity.

Collaboration between the bedside care team and the blood bank is essential to ensure safe transfusion practices and minimize complications. The blood bank team must determine the most appropriate blood product to release. Communication from the clinical team is necessary to provide clinical background and information regarding adverse transfusion-related events to the blood bank team. Safe transfusion depends on the collaboration of clinicians, advanced care practitioners, nurses, and technologists to minimize risk and optimize patient care.