Acute Hemolytic Transfusion Reactions

Incidence

Studies from the REDS III database showed that in 2013–14, AHTRs comprised 0.41% of all reported adverse effects to transfusion. Per the National Blood Collection and Utilization Surveys, 2013 and 2015, AHTRs were estimated to have occurred less than 100 times annually at a national level. Between fiscal year (FY) 2002 and 2015, the number of AHTR resulting in fatalities has decreased. In FY2015, there were two reported ABO hemolytic transfusion fatalities (5% of confirmed transfusion-associated fatalities), and four non-ABO hemolytic transfusion fatalities (11% of confirmed transfusion-associated fatalities).

Mistransfusion may range from being asymptomatic in approximately 50% of recipients to death in 2-7% of ABO-incompatible recipients. Volume of incompatible blood transfused and antibody titer likely play a role in recipient signs/symptoms. While, transfusion of as little as 30 mL of incompatible RBCs has been reported to result in fatality, in other cases, large volumes have been transfused with no or minor symptoms.

Transfusion of ABO-Incompatible RBCs

Transfusion of ABO-incompatible RBCs is most associated with mistransfusion event, which is the “transfusion of a unit of blood that has been ‘incorrectly typed, labeled crossmatched, or issued,’ or the transfusion of ‘correctly typed, labeled, crossmatched, and issued’ unit of blood that is administered to the incorrect patient.” Thus, transfusion service errors (typing, labeling, crossmatching, and issuing), and patient identification errors (patient sampling for blood typing, or patient and unit identification at the time of transfusion [at the bedside]), can lead to mistransfusion.

Transfusion errors are a sentinel event (an unexpected occurrence resulting in death or serious adverse event or risk thereof) according to the Joint Commission that must be reported. A sentinel event requires root cause analysis to identify what happened, why it happened, and what factors (human, equipment, and/or environmental) contributed to its occurrence. In addition, an action plan must be developed to reduce risk of event reoccurring.

Transfusion of Non-ABO-Incompatible RBCs to Alloimmunized Recipients

Recipients may develop non-ABO antibodies when exposed to RBC antigens (also known as alloimmunization). These antibodies may make future RBC transfusions incompatible. In extremely rare circumstances, non-ABO-incompatible blood is administered knowingly. These include emergent clinical situations where the best available RBC product is incompatible with recipient’s plasma, and the product is either not available or there is not enough time to identify antibody specificity and/or obtain antigen negative product. In other circumstances, AHTR due to non-ABO-incompatible blood occurs because the patient’s antibody was not identified before transfusion. This may be due to false-negative antibody identification test (indirect antiglobulin test [IAT]), lack of antibody presence detection by IAT, or not enough time to perform IAT.

Transfusion of Significant Amounts of Incompatible Plasma

Transfusion of incompatible plasma most often occurs with administration of out-of-group platelets, most commonly group O platelet to group A recipient, which may result in AHTR. Passive ABO antibodies can also occur in administration of non-ABO identical whole blood or plasma product, which often result in a positive DAT and rarely in a severe AHTR. Non–group O platelet units are rarely associated with AHTR. Increased use of single-donor apheresis platelets in the United States, coupled with low availability of type-specific apheresis platelets, has likely led many adult hospital transfusion services to issue ABO-mismatched platelets that contain large plasma volumes and potentially high titers of isohemagglutinins. In the United Kingdom, all blood donations undergo anti-A IgM testing and those with titers >100 are labeled accordingly, and hospital transfusion services are aware to transfuse to only group O recipients. Most US hospital transfusion services do not routinely measure isohemagglutinin titers (IgM or IgG) before transfusing ABO-mismatched platelets or plasma, although this practice is becoming more standard and blood centers are performing titers and labeling products as high titer accordingly. The majority use “critical titer” of 100 for anti-A/B at room temperature. Notably, direct correlation between hemoglobin loss and rising anti-A/B titers was demonstrated: larger decrease in hemoglobin value was observed as titers increased from undetectable to low (32 or less) to high (512 or more). Thus, high-titer products should be limited to ABO-compatible recipients.