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Definition

Febrile nonhemolytic transfusion reaction (FNHTR) is a fever (≥1°C increase from baseline) that occurs within 4 hours of transfusion and that is not associated with hemolysis or signs of allergic reaction.

Risk factors

 Hypersensitivity to donor leukocytes

 Crossmatch‐incompatible blood

 In humans, blood product storage is associated with accumulation of proinflammatory cytokines and FNHTR

Pathogenesis

Fever and allergic reactions are the most common complications of blood and plasma transfusion in veterinary patients [1, 9]. Leukocytes in the transfused blood may incite febrile reaction. Acute allergic reactions can also occur, most often a type I immune‐mediate hypersensitivity to plasma components. In human patients, febrile nonhemolytic reactions occur in 0.1–1.0% of transfusions and incidence of allergic reaction is reported at 1–3% [2]. In a retrospective study of blood transfusions in canine patients, there was a complication rate of approximately 25%, with fever (12%) and hemolysis (6%) being the most common [3].

Prevention

In an experimental study with healthy horses, crossmatch incompatibility was predictive of febrile reaction, so using crossmatch compatible blood should limit the risk of FNHTR [6]. Plasma proteins are thought to be one stimulus allergic transfusion reactions, so washing the RBCs may reduce the risk of allergic reaction. This author has used the technique of washing donor RBCs to eliminate an allergic reaction in a horse that had a moderate allergic reaction to blood from multiple different crossmatch‐compatible donors. Leukoreduction has been shown to lower the risk of inflammatory reaction in an experimental study with healthy dogs, so this could also be considered if a febrile reaction is noted [10]. Premedication with antihistamines has been shown to decrease the incidence of acute allergic reactions in dogs receiving transfusions [11].

Diagnosis and monitoring

Clinical signs of allergic reaction can include urticaria, piloerection, facial swelling, and fever. Severe anaphylactic allergic reactions will cause hypotension and shock, and may cause death. FNHTR is characterized by fever without other clinical signs. However, fever is also associated with acute hemolytic reaction, allergic reaction, and bacterial contamination, so careful investigation and close monitoring are warranted whenever fever is associated with transfusion.

Treatment

Febrile reactions are usually self‐limiting. Treatment with antipyretics such as nonsteroidal anti‐inflammatory drugs (e.g. flunixin meglumine, 1.1 mg/kg IV) is indicated with high or symptomatic fevers. When in doubt, the transfusion should be stopped while the cause of the fever is investigated. Mild allergic reactions, such as urticaria, can be treated with antihistamines (e.g. diphenhydramine, 1.1 mg/kg IM) and temporary interruption of the transfusion. Any signs of anaphylactic reaction warrant immediate discontinuation of the transfusion and treatment with epinephrine (0.01–0.02 mg/kg IV).

Expected outcome

FNHTR is usually self‐limiting. There is a risk of recurrence with subsequent transfusions. Mild allergic reactions can usually be treated successfully. Anaphylactic reactions may be fatal.