Risk factors
Foals <7 days [31]
Patients that have received multiple previous transfusions
Multiparous mares
Hypernatremic animals
Pathogenesis
The immunogenicity of blood products stems from proteins and from other cellular material not completely removed during production. Generally hemolytic transfusion reactions are the result of antibodies in the recipient plasma reacting with the erythrocytes of the donor. These types of reaction should therefore not occur if the plasma is free of red blood cells. Minor reactions can occur when antibodies present in the plasma of the donor react with the red blood cells of the recipient. Non‐hemolytic febrile reactions are thought to occur due to leukocyte antigens on transfused lymphocytes, granulocytes or platelets and antibodies in previously sensitized recipients. Urticarial reactions are not well understood but are believed to occur due to proteins in the donor blood and antibodies in the recipient blood. There is usually not a specific antigen against which the recipient is reacting. Systemic anaphylaxis is the most severe form, which in humans is linked to IgA antibodies but unknown in horses. Immunological transfusion reactions are reported as <10% in horses [29, 31]. Plasma can also contain large amounts of sodium, which could lead to clinically significant hypernatremia in small patients (e.g. neonates).
Prevention
Type of plasma
It has been suggested that commercial plasma leads to fewer adverse side effects than home‐made plasma, although this was not supported by a clinical study in a hospital setting [31].
Method of plasma preparation could play a role in incidence of adverse effects. Plasma prepared by gravity or centrifuge sedimentation contains a greater amount of cellular material compared to plasma obtained by plasmapheresis. Therefore, the latter preparation method could potentially lead to a lower incidence of immunological reactions [30]. Plasmapheresis is well tolerated by horses and used for collection of plasma without complications but requires specialized equipment.
Cross‐matching before plasma transfusion would only be able to prevent hemolytic transfusion reactions, which are the result of antibodies in the recipient plasma reacting with the erythrocytes of the donor. This is a very rare occurrence. Cross matching before plasma transfusion is rarely performed.
Using blood products from a “universal donor” negative for Aa and Qa antigen can help prevent severe reactions. While horses have many different blood antigens, only Aa and Qa are responsible for the majority of severe hemolytic reactions.
Plasma from geldings or maiden mares is preferred over stallions and mares with prior pregnancies.
Administration of plasma
Frozen plasma should be thawed at 30–37°C, in a water bath prior to administration to avoid precipitation of proteins which can occur when thawed at a higher temperature, (e.g. in a microwave).
Plasma transfusions should be administered using a blood administration set with a filter to reduce the number of clots transfused. Blood clots travel through the systemic circulation and lead potentially to cardiac side effects or pulmonary artery obstruction resulting in fatal incidents.
The plasma transfusion should be started at a rate of 0.3–0.5 mL/kg/ for the first 10–20 minutes. During this time the horse should be continuously monitored for signs of adverse reactions and a brief physical examination should be performed every 5 minutes. Parameters that should be monitored and should not increase during that time include heart rate, respiratory rate and temperature. The occurrence of respiratory distress, cardiac arrhythmias, urticaria, muscle tremors, salivation and coughing should also be monitored. If no reaction occurs, the plasma can be administered faster.
Other
If multiple plasma transfusions are required within a short period of time, preferably plasma from the same donor should be used.
Heparin (2,000 IU/L) can be added to the thawed plasma to prevent blood clot formation during and after transfusion. The addition of heparin to plasma before transfusion has caused allergic reactions in humans. This has not been proven in foals; however, all foals with adverse effects in one study had received plasma with added heparin [31].
Diagnosis
Complications associated with plasma administration are most commonly recognized within the first 15 minutes of the start of administration, but have been observed up to 48 hours post‐transfusion. Clinical signs of transfusion reactions include urticaria (see Figure 6.4), anaphylaxis, pruritus, edema, tachypnea, tachycardia, pyrexia, colic, changes in mentation, muscle fasciculations, and evidence of hemolysis (hemolytic plasma, hemoglobinuria). Signs of anaphylaxis usually occur after transfusion of a few milliliters of plasma and include colic, diarrhea, laryngeal edema, hypotension, shock, cardiac arrhythmias, cardiac arrest, and loss of consciousness [29, 31].
Figure 6.4 Urticaria due to an immunological reaction after plasma transfusion in a horse.
Treatment
Stop transfusion immediately. Administer non‐steroidal anti‐inflammatory drug (flunixin meglumine 1.1 mg/kg IV) and dexamethasone (0.05–0.1 mg/kg IV). Antihistamines (diphenhydramine 0.5–1 mg/kg IV) can be administered based on human recommendations; however, their benefit has not been proven in horses. In severe cases of anaphylaxis, give epinephrine (0.01–0.02 mL/kg IV). If the reaction was mild an attempt can be made to restart the plasma transfusion at a slower rate. If signs of adverse effects return, the plasma transfusion has to be discontinued and the plasma discarded. If signs recur or signs are severe, use of plasma from a different donor (different lot number in commercial plasma) may be attempted [31].
Expected outcome
Most animals with immunogenic reactions survive with appropriate treatment and discontinuation of the plasma transfusion. Horses that show signs of anaphylaxis are at greatest risk of dying.
Non‐Immunogenic Complications
Bacterial contamination
If plasma is homemade (harvested from plasma donors in‐house) care has to be taken to maintain strict asepsis during the procedure. Plasma should be frozen at –18°C or lower within 8 hours post harvesting and stored for a maximum of 1 year at a minimum of –20°C. Aseptic techniques have to be followed during thawing and administration of both commercial and homemade plasma. Plasma should be placed in an additional plastic bag to prevent contamination
