Non-immunological transfusion reactions

  • Circulatory overload: This can be produced in young animals or patients with cardiovascular disease. Normovolemic adult patients can also develop circulatory overload if transfused with large amounts of blood. The clinical signs are cardiovascular in nature (coughing, tachypnea, dyspnea and tachycardia). In severe cases, pulmonary edema, congestive heart failure, and vomiting may occur. This reaction can be minimized by using appropriate component therapy and slow infusion rates (especially in small or compromised patients). If the reaction occurs, the transfusion should be stopped and furosemide given.

  • Hemolysis: Non-immunological hemolysis of erythrocytes occurs secondary to bacterial contamination, inappropriate administration, mishandling and use of out-dated products. Mechanical hemolysis can occur with infusion through small needles or catheters, plugged lines or rapid infusion. Some peristaltic pumps can also cause mechanical hemolysis. Overheating (> 37 C) or freezing of erythrocytes will also cause hemolysis as will administration of red cells with hypotonic solutions (such as 5% dextrose in water). Non-immunological hemolysis can be prevented by paying close attention to handling and administration of whole blood and blood products.

  • Bacterial contamination: Blood is an excellent culture medium. Infusion of gram-negative bacteria (dead or alive) will result in endotoxic shock, with clinical signs of fever, hypotension, hemolysis, vomiting, diarrhea and DIC. Contaminated blood is usually dark or discolored and may contain bubbles, particulate material or clots. If a reaction occurs, the transfusion should be ceased and the bag cultured and gram-stained. Supportive care is then instituted, however the prognosis is poor. Contamination can be kept to a minimum by the use of aseptic techniques (for blood transfusion collection from the donor and for administration) and by completing a transfusion over 3 to 4 hours.

  • Hypocalcemia: Hypocalcemia can result from citrate toxicity, which chelates calcium. In the absence of liver disease (which metabolizes citrate to bicarbonate), clinically significant hypocalcemia is unlikely to occur. In animals without liver disease, rapid transfusion of large amounts of plasma products may overwhelm the liver's ability to remove the citrate. In one study in dogs, citrated blood or fresh frozen plasma was associated with ionized hypocalcemia in all cases, especially those transfusions associated with > 40% blood replacement (the number of dogs showing clinical signs of hypocalcemia was not stated). Clinical signs of citrate toxicity include tremors, tetany, vomiting and ventricular arrythmias. Hypocalcemia is rapidly reversible by slowing or temporarily ceasing the transfusion. Calcium gluconate infusions can be used in severe cases.

  • Coagulopathy: Massive transfusions of stored blood (which lacks platelets and factors V, VIII and IX) may result in a coagulopathy. Furthermore, diluting packed red cells in solutions containing calcium may cause in vitro clotting. This can be avoided by diluting packed red cells in sterile isotonic (0.9%) saline.

  • Hyperammonia and acidosis: Erythrocytes are rich in ammonia and ammonia levels increase in stored whole blood. This can cause ammonia toxicity, although this is thought to only occur in animals with significant liver disease (which are unable to metabolize the ammonia).

    The pH of stored blood decreases with storage due to anaerobic metabolism of glucose, with lactic and pyruvic acid production. Massive transfusions may lead to post-transfusional acidosis, but this is exceedingly rare as the liver converts these acids into bicarbonate (thus offsetting the acidosis).

  • Hypothermia: Significant hypothermia can result if transfusing whole blood which has not been warmed. This will especially occur in small or young animals.

  • Embolism: Microaggregates of platelets, leukocytes and fibrin, which form in whole blood stored for more than 7 days, may be associated with pulmonary thromboembolism (although this is controversial). These range in size from 20 to 120 um and may not removed by standard filters (approximately 150 um). The use of small (20 to 40 um) filters is not recommended, because it may slow down the transfusion needlessly.

  • Disease transmission: Infectious agents, including heartworm microfilaria, spirochetes (Borrelia), rickettsia (Ehrlichia), and viruses (FIV and FeLV) can be transmittted from the donor to the recipient. All donors should be negative on serology for these diseases. Other infectious diseases that can be transmitted with whole blood transfusions include Babesia and Hemobartonella (there is a high incidence of seropositivity for Babesia in retired racing Greyhounds, a favored breed for blood donation). Carrier animals are almost impossible to detect using routine blood examination (as the organisms are sequestered in the spleen). In order to identify or eliminate carriers, some people splenectomize or administer immunosuppressive doses of corticosteroids to inhouse donors. These procedures will induce a parasitemia as illustrated in the image to the right. However, this cannot be justified in outpatient (client-owned) donors. Newer PCR-based detection techniques for Hemobartonella have been developed and will identify carriers. Therefore, whenever possible, donors should be screened for these diseases as well.

  • Hemosiderosis: Iron overload from massive transfusions of whole blood or blood products is a rare complication.