Transfusion Reactions

Chapter 46


Transfusion Reactions



A transfusion reaction can be defined as any unexpected patient sign or symptom during or following the transfusion of a blood product. Transfusion reactions may be acute or delayed, immune or nonimmune mediated, and clinically insignificant or potentially life threatening. Mild reactions include allergic and febrile reactions that occur with ~1% of transfusions. Potentially fatal reactions are rare and include transfusion-related acute lung injury (TRALI), acute hemolytic transfusion reactions (AHTRs), septic reactions, and anaphylaxis.


Both mild and serious transfusion reactions can occur even when procedures are followed appropriately. Such reactions to blood products occur with a predictable frequency (Table 46.1). Additional laboratory testing by the blood bank is often required to determine the etiology of the suspected transfusion reaction, the specifics of which take into account the type of blood product transfused. For example, TRALI can occur with any plasma-containing product (fresh frozen plasma [FFP], units of packed red blood cells [RBCs], and platelet concentrates), whereas AHTRs occur most frequently with RBC products.



In the context of transfusion reactions, this chapter only considers those that are acute. Indications for transfusions are discussed elsewhere (see Chapter 19). Also discussed elsewhere are acute reactions of particular concern with massive transfusion, including hypocalcemia and other electrolyte and metabolic disorders (see Chapter 39) and hypothermia (see Chapter 55).



Definitions and Pathophysiologic Mechanisms



Transfusion-Related Acute Lung Injury (TRALI)


TRALI is now considered to be the most common cause of fatal transfusion reactions. Approximately 43% of transfusion fatalities reported to the Food and Drug Administration (FDA) are attributed to TRALI. The precise pathophysiology of TRALI remains debated and appears to be multifactorial. Classically TRALI has been thought to occur when antibodies in donor plasma bind to recipient granulocytes via human leukocyte antigens (HLAs) or granulocyte-specific alloantigens, and then activate the granulocytes causing degranulation within the lung vasculature. The degranulation in turn triggers acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). However, cases of TRALI based on clinical and radiographic findings have occurred in the absence of demonstrable anti-granulocyte antibodies. Thus, the exact mechanisms that lead to TRALI remain incompletely understood.



Acute Hemolytic Transfusion Reactions (AHTR)


Approximately 23% of transfusion fatalities reported to the FDA are due to acute hemolysis of RBCs (i.e., AHTRs). AHTRs occur when antibodies against RBC antigens strongly fix complement and produce brisk intravascular hemolysis. The activation of complement triggers the coagulation cascade and elevated bradykinin. Brisk hemolysis also leads to the formation of RBC membrane fragments (stroma) and tissue factor. Together, these responses can lead to hypotension, renal failure, disseminated intravascular coagulation (DIC), and bleeding. Hypotension occurs from elevated bradykinin and tumor necrosis factor alpha (TNF-α). Renal failure may occur because of reactive renal splanchnic vasoconstriction after bradykinin release and acute renal tubular necrosis from toxicity of the RBC stroma. Historically it was thought that AHTRs resulted from clerical errors leading to the transfusion and subsequent destruction of ABO-incompatible blood by recipient IgM anti-carbohydrate antibodies. However, FDA data indicate that fatal AHTRs can also be caused by certain complement-fixing IgG antibodies directed against protein antigens on the RBC surface, such as those in the Kidd blood group system.



Febrile Transfusion Reactions


Transfusion of blood products that contain leukocytes, such as platelets and less frequently RBCs, can be associated with an isolated rise in body temperature as the apoptotic white blood cells (WBCs) release cytokines. Cytokine release may be enhanced when the recipient contains anti-leukocyte antibodies that cross-link the transfused WBCs (leukoagglutinins). These reactions are classified as febrile nonhemolytic transfusion reactions when other causes of fever have been ruled out. Febrile reactions occur in ~1% of transfusions in which the transfused blood products have not undergone either prestorage or bedside leukoreduction filtration. The incidence of febrile nonhemolytic transfusion reactions have been reduced in frequency because of the adoption of “universal leukoreduction” programs by many blood collection centers.



Allergic and Anaphylactic Reactions


Allergic reactions occur in 1% to 3% of transfusions. Anaphylaxis occurs with 1 in 20,000-50,000 transfusions. These reactions occur when antibodies exist against soluble plasma proteins introduced by any plasma-containing blood product. The actual protein antigen that causes the reaction is generally not identified and this type of reaction is often idiosyncratic, specific to a particular donor/recipient pair who are unlikely to cross paths again. The one notable exception is when plasma containing IgA antibodies serves as the allergen, upon transfusion into an IgA-deficient patient. In the most severe cases, anaphylaxis can occur when the recipient has high titer IgE antibodies against IgA. Fortunately, most IgA-deficient recipients are incompletely deficient in IgA and thus are not at risk for anaphylaxis. Mild reactions are generally limited to urticaria.



Septic Reactions


Approximately 5% of fatal transfusion reactions are due to bacterial contamination of blood products. Platelet products are most often implicated because they are stored at room temperature (red cells are stored refrigerated and FFP is stored frozen). The incidence of fatal transfusion reactions resulting from bacterial contamination reported to the FDA has decreased since implementation of bacterial culturing of apheresis platelet products.


Bacteria can contaminate blood products because of their presence on skin plugs or from transient bacteremia in blood donors. Among platelet products, pooled platelet products derived from whole blood donations (versus apheresis collection) have the highest contamination rate because they come from four to six donors. Though most common gram-positive bacteria cause septic transfusion reactions, products contaminated with gram-negative bacteria can cause the most serious reactions partly because of endotoxin. RBC products rarely cause sepsis, but when occurring, bacteria such as Yersinia enterocolitica, which grow well in the cold, may be responsible.


The parasite Babesia microti has been identified as the most frequent cause of transfusion transmitted microbial infection that led to death in 2007-2011. These infections do not cause acute transfusion reactions as generally it takes ~2-10 weeks for the parasite to replicate to significant levels for symptoms to appear.


< div class='tao-gold-member'>

Jul 7, 2016 | Posted by in CRITICAL CARE | Comments Off on Transfusion Reactions

Full access? Get Clinical Tree

Get Clinical Tree app for offline access