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Chapter 119 Transfusion Reactions to Blood and Cell Therapy Products 1799
splenectomy may also be useful. Patients with acute bleeding and supernatant of an RBC unit can reach 7 mEq at the end of storage.
needing platelet support should receive platelets without the platelet- Neonates and children can receive transfusions of up to 20 mL/kg
specific antigen, if possible. If random donor platelets are given, RBC for routine transfusions over 3–4 hours without concern for
patients can develop severe reactions, including allergic reactions. hyperkalemia. For large volume transfusions or transfusion in the
Recurrence of PTP is rare. setting of hyperkalemia, fresher or washed RBC components can be
requested. As there is increased potassium leakage from RBCs after
exposure to 25 Gy of radiation to prevent posttransfusion GVHD, a
Hypothermia maximum 28-day shelf life from the day of irradiation is imposed on
this blood component.
Hypothermia can occur with rapid infusion of large quantities of
refrigerated (1–6°C) blood, such as in cases of rapid and massive
transfusions. Rapid infusion of blood (1 unit every 5 minutes) may Iron Overload
lower the temperature of the sinoatrial node to less than 30°C, at
which point ventricular fibrillation may occur. Hypothermia also Iron loading from RBC transfusion is not categorized as a transfusion
induces coagulopathy, possibly attributed to inefficient enzymatic reaction, but it is a common adverse consequence of chronic RBC
activity below physiologic temperatures. Use of warming devices may transfusion. One milliliter of RBCs at a hematocrit of a typical RBC
reduce the incidence of coagulopathies associated with major trauma unit contains approximately 0.75 mg of iron. A unit of blood with
and also help to overcome cardiac complications. Most transfusions 300 mL of RBCs thus contains approximately 225 mg of iron, and
need not be given this rapidly. For routine transfusion, blood does 4 units of blood contain ~1 g of iron, roughly the amount stored in
not have to be warmed. Indeed, overwarming a unit of blood can the bone marrow. Men and nonmenstruating women lose only
cause RBC thermal injury and produce hemolysis, DIC, or shock. approximately 1 mg of iron each day. Continued use of transfusion
If blood is to be warmed, the temperature must be monitored and therapy in individuals with a hemolytic anemia, such as those with
kept below a level that could cause hemolysis. Usually, this is less than thalassemia or sickle cell disease, in which iron is not lost from the
42°C. Heating blood under running hot tap water or heating in a body but is recycled, can thus result in the accumulation of excessive
microwave device is unacceptable. tissue stores of iron. Over long periods, the iron that is stored in
parenchymal cells results in oxidative injury and organ failure, par-
ticularly in the heart, liver, and endocrine organs. Iron chelation
Electrolyte Toxicity therapy is now widely used to mitigate positive iron balance. The
availability of oral iron chelators such as deferasirox and deferiprone
Citrate, a component of the preservative solution used in blood provides expanded access to iron chelation therapy.
storage, functions as an anticoagulant by chelating calcium and
interfering with the coagulation cascade. Rapid transfusion of citrated
blood is associated with a drop in ionized calcium levels. Citrate- Air Emboli
containing blood products, however, are routinely infused without
any problem because the citrate is rapidly metabolized to bicarbonate. Since the replacement of evacuated glass bottles by plastic blood bags,
In patients with normal liver function, citrate infusion is unlikely to the risk for air embolism from phlebotomy or transfusion has virtually
produce reactions. Mild to severe citrate toxicity can be seen, however, disappeared from transfusion practice. Air, however, still may be
in individuals undergoing therapeutic apheresis when citrate is infused into patients by the roller pumps contained in various transfu-
infused to anticoagulate blood flowing through the instrument and sion devices, especially apheresis machines and intraoperative salvage
large volumes of citrated RBCs or plasma are simultaneously machines. All such devices currently manufactured, however, contain
reinfused. air-in-line sensors. However, any operators using this equipment must
The effects of hypocalcemia range from mild circumoral paresthe- be well trained and remain alert to the potential risk for air emboliza-
sias to frank tetany. However, severe citrate toxicity, even with massive tion at all times while the patient is being treated. Patients who receive
transfusion, is rare. More commonly, the reaction is mild and self- air intravenously experience acute cardiopulmonary insufficiency. The
limiting and can be treated by merely slowing the rate of reinfusion. air tends to lodge in the right ventricle, preventing blood from enter-
If prolonged QT intervals or signs of tetany are seen, calcium can be ing the pulmonary circulation. Acute cyanosis, pain, cough, shock,
administered. Calcium need not be infused routinely, even after and arrhythmia may occur, and death may result unless immediate
large-volume blood transfusions. However, it is prudent to monitor action is taken. The patient should be placed head-down on the left
calcium status in patients undergoing massive transfusion and patients side; this may displace the air bubble from the pulmonary valve. Use
at risk for hypocalcemia arising from citrate toxicity. Under no cir- and removal of central lines may also pose a risk for air embolism.
cumstances should calcium be added to a unit of blood or a line used
for blood infusion because it would recalcify the unit and cause clots
to form. In addition to the effects on calcium, the metabolism of Complications Associated With Massive Transfusion
citrate also can result in a metabolic alkalosis because of the genera-
tion of large amounts of bicarbonate. Massive transfusion is variably defined as the transfusion of one whole
Citrate also chelates magnesium, so correction of the hypocalcemia blood volume within 24 hours, 4 units of RBCs in 1 hour with
may require infusion of magnesium, as well. Actual clinical complica- anticipation of more blood needed, or transfusion of 50% of total
tions of transfusion-induced hypomagnesemia, however, have not blood volume in 3 hours. Common problems associated with massive
been well documented other than in cases of apheresis. transfusion include coagulopathy, hypothermia, and metabolic
Hyperkalemia caused by infusion of stored blood is a rare occur- abnormalities.
rence. Although hyperkalemia is often thought to be a problem in Coagulopathy of massive transfusion is multifactorial and can
massive transfusion, development of hypokalemia is of greater have devastating consequences. Classically the coagulopathy associ-
concern. With storage, leakage of potassium from RBCs to the ated with massive transfusion was thought to be attributable solely
extracellular fluid occurs. However, after infusion the RBCs reverse to consumption of factors owing to ongoing hemorrhage and/or
the biochemical storage lesion by restoring the Na-K ATP membrane dilution owing to the large volume of fluids and RBCs typically
pump, and intracellular potassium levels are restored. As the citrate infused. However, the understanding of hemostasis in massive trans-
is metabolized to bicarbonate, the blood becomes alkalotic, contrib- fusion now includes a form of coagulopathy that occurs before coagu-
uting to hypokalemia. In massive transfusion, it is not uncommon lation factors and platelets are consumed. Early coagulopathy,
for this to result in the need for administration of potassium. described primarily in the setting of trauma, is driven by tissue
Depending on the storage solution, the potassium content in the hypoperfusion and increased fibrinolysis. Early coagulopathy is not

