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horses with hemorrhagic anemia receiving blood transfusions [1]. It is likely that these horses were transfused during or soon after the episode of hemorrhage, so the pre‐transfusion PCV may have been relatively high due to splenic contraction and incomplete volume resuscitation.

      Acute hemolytic reactions can be severe and may lead to organ failure and death. If recognized early, outcome can be good, especially if a compatible donor is identified. Horses may develop RBC antibodies after transfusion, without any clinical signs. These horses may develop acute hemolysis with subsequent transfusions, and broodmares may have RBC antibodies in their colostrum, leading to neonatal isoerythrolysis in the foal [8].

       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.

       Definition

      Transfusion‐related acute lung injury (TRALI) is a new onset of bilateral pulmonary infiltrates within 6 hours of transfusion. TRALI follows the criteria for acute lung injury (ALI), defined as acute onset respiratory difficulty with evidence of pulmonary capillary leakage, no evidence of left atrial hypertension, and PaO2/FiO2 of less than 300 mmHg [12]. TRALI is an important cause of transfusion‐related mortality in humans. TRALI has been described in dogs but has not been reported in horses. Nonetheless, it is an important potential adverse reaction to consider and include in the list of differential diagnoses for dyspnea or hypoxemia after transfusion.

       Risk Factors

       Leukocyte antibodies in the donor may react with leukocyte antigens in the recipient, leading to sequestration and activation of neutrophils in lung tissue.

       Activation of cytokines and lipids may also cause damage to the pulmonary vascular endothelium.

       Activation of neutrophils related to infection, inflammation, or trauma may be the “first hit” prior to the “second hit” of the transfusion.

       Pathogenesis

      Activation of neutrophils (see above) leads to damage to the pulmonary capillary endothelium, with subsequent capillary leak. Priming of the neutrophils may occur from an initial event (e.g. trauma, surgery, infection). Activation of the neutrophils in the pulmonary endothelium then occurs secondary to transfusion‐related immune stimulation.

       Prevention

      Leukocyte antibodies in donor blood can be reduced by processing whole blood into packed RBCs and by washing RBCs.

       Diagnosis

      Clinical signs of TRALI include hypoxemia, cyanosis, tachypnea, and tachycardia, usually within 6 hours of transfusion. Volume overload, allergic reaction, and systemic inflammatory response syndrome should also be considered as differential diagnoses.

       Treatment

      Hypoxemic patients should be treated with supplemental oxygen. Conservative fluid therapy is indicated to reduce the risk of volume overload.

       Expected outcome

      TRALI is usually self‐limiting in humans, with recovery in 48 to 96 hours, although mortality is reported as high as 25% [13]. The incidence of TRALI in dogs appears to be low (3.7%) and not significantly different than the incidence of ALI in critically ill dogs that have not received transfusions [14].

      Volume Overload

       Definition

      Volume overload, or transfusion‐associated circulatory overload (TACO), is recognized when signs of respiratory distress and pulmonary edema occur after a large volume transfusion.

       Risk factors

       Large volume of whole blood given to normovolemic patient

       Total dose (ml/kg) of blood products was a risk factor in a study of dogs receiving packed RBC transfusions [15].

       Large volume of crystalloid or colloid fluids administered in addition to blood transfusion

       Preexisting

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