Page 2021 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 119

TRANSFUSION REACTIONS TO BLOOD AND CELL

THERAPY PRODUCTS

William Savage

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A transfusion reaction can be defined broadly as any untoward clinical transfused. Transfusing as little as 30 cm of incompatible blood can
event that is the consequence of infusing a blood or cell therapy be fatal, and there is a direct relationship between increasing volumes
product. Transfusion reactions are classified by how close to transfu- of incompatible blood transfused and mortality.
sion they occur (timing), how much morbidity is caused (severity), In IgM-mediated ABO-incompatible transfusion reactions, acti-
how strong the causal association of the event is with transfusion vation of the complement cascade generates anaphylatoxins C3a and
(imputability), and how closely the reactions fit a consensus defini- C5a, which lead to capillary leak, hypotension, and phagocyte and
tion of a transfusion reaction type. Every year, approximately 40 mast cell activation. Furthermore, the deposition of C3b on the RBC
fatalities attributable to transfusion are reported to the US Food and membrane increases extravascular hemolysis. Excessive terminal
Drugs Administration (FDA). complement activation results in C5b-9 membrane attack complexes
It is important to recognize that many transfusion reactions can overwhelming complement regulatory factors on the RBC membrane
mimic pathology unrelated to transfusion. The differential diagnosis leading to osmotic lysis. Plasma heme also induces renal vasoconstric-
of any untoward clinical event should always consider adverse sequelae tion through nitric oxide scavenging.
of transfusion, even when transfusion occurred weeks earlier. This In addition to complement components, cytokines also play a role
chapter will review the presentation, mechanisms, and management in the clinical syndrome, including fever. For example, interleukin
of transfusion reactions (Table 119.1). Approximate risks of selected (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α have pyrogenic
transfusion reactions are shown in Fig. 119.1. activity; IL-8 is a neutrophil chemotactic and activating factor. These
four cytokines have been generated in various in vitro models of
intravascular hemolysis and IgG-mediated RBC incompatibility.
HEMOLYTIC TRANSFUSION REACTIONS TNF-α induces tissue factor expression on endothelium while
decreasing thrombomodulin, which contributes to disseminated
Hemolytic transfusion reactions are caused by the immune-mediated intravascular coagulation (DIC). TNF-α also promotes endothelin
clearance of transfused red blood cells (RBCs). Immune-mediated production, which promotes renal vasoconstriction. The clinical
hemolysis can be classified clinically according to the timing of the variability of hemolytic transfusion reactions is explained in part by
reaction (acute or delayed) and mechanistically by site of hemolysis the relative balance of cytokine production in the transfusion recipi-
(intravascular with terminal complement activation or extravascular ent. Factors that increase the circulating levels of proinflammatory
1,2
with phagocytosis in liver and spleen, Table 119.2). Although cytokines and chemokines often result in more severe reactions.
hemolytic transfusion reactions are mechanistically considered An acute intravascular hemolytic transfusion reaction is a medical
immune-mediated in most cases, thermal, osmotic, infectious, and emergency. Initial clinical symptoms can include fever and chills,
mechanical destruction of RBCs also can lead to acute hemolysis. shortness of breath, chest pain, dizziness, and back or flank pain.
Some patients report feeling anxiety or pain or warmth ascending
ACUTE INTRAVASCULAR HEMOLYTIC from the site of infusion. Often the first sign of an immediate hemo-
lytic transfusion reaction is fever. Therefore RBC transfusions must
TRANSFUSION REACTIONS be stopped and evaluated by blood bank testing when fever develops
(≥1°C). The transfused incompatible RBCs undergo complement-
Acute hemolytic reactions are those that occur typically during or mediated osmotic lysis, producing hemoglobinemia and hemoglobin-
immediately after incompatible RBCs are transfused into a patient uria. Cardinal signs of an acute intravascular hemolytic transfusion
who already possesses the corresponding antibody. ABO-incompatible reaction are the presence of red plasma (hemoglobinemia) and red/
RBC transfusion is the prototypical example of an acute, intravascular dark urine (hemoglobinuria). Acute transfusion reactions can quickly
hemolytic transfusion reaction. ABO antibodies are spontaneously progress to shock and acute renal failure. Many patients, curiously
occurring immunoglobulin (Ig) M and IgG antibodies to foreign A even anephric patients, often complain of lower back pain. It is
and B blood group antigens. IgM antibodies efficiently fix comple- speculated that this symptom is caused by ischemic muscle pain or
ment after binding to ABO-incompatible RBCs and are responsible vasospasm, rather than by kidney pain from developing renal failure.
for initiating the hemolytic and inflammatory cascades that cause a Laboratory tests for hemolysis can be useful if there is clinical
clinically significant acute intravascular hemolytic transfusion reac- ambiguity about the type of reaction and useful for guiding ongoing
tion. Such a reaction could occur, for example, after transfusion of A management of severe hemolytic reactions. Because most ABO-
RBCs into an O recipient who has significant amounts of circulating incompatible transfusion reactions are caused by errors in safety
anti-A (see box titled “Acute Hemolytic Transfusion Reaction”). Acute systems, an important initial evaluation is confirmation of blood
hemolytic reactions can also occur with incompatible plasma transfu- incompatibility and determination of where an error occurred. There
sion. Because of limited platelet inventories, platelet components with may be a systemic error that could put other patients at risk. Labora-
incompatible plasma to the recipient are frequently transfused, for tory findings include hemoglobinuria, hemoglobinemia, and a hap-
example an O platelet with anti-A transfused into an A recipient. This toglobin level that is low to undetectable. During the hemolytic
plasma incompatibility (i.e., minor incompatibility) can occasionally episode, the bilirubin (especially indirect bilirubin) usually increases
result in acute, ABO-incompatible hemolytic reactions. only modestly (2–3 mg/dL) if the patient has normal liver function.
Factors that determine the severity of hemolysis include the Because of the lysis of RBCs, levels of lactate dehydrogenase (LDH)
antibody titer, antibody avidity, antibody subtype, antigen density on may rise markedly. If the patient shows no signs of cardiovascular
the RBC membrane, and volume and rate of incompatible blood instability and if hemostatic and renal function is unchanged at least

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