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 of the infusion ports if they are exposed. Transfusion should be completed after 4 hours to avoid bacterial contamination. Plasma provides optimal culture conditions for bacteria and once introduced they can proliferate quickly and cause sepsis in the recipient. Clinical signs, diagnosis and treatment of sepsis are not part of this chapter and the reader is referred to other chapters or references.
Transmission of disease
There are reports that equine infectious anemia virus has been transmitted through contaminated plasma products in Germany and Italy [32]. It is possible that other blood‐borne diseases such as anaplasmosis, piroplasmosis, Dourine (Trypanosoma cruzi) and others could be transferred via plasma transfusion; however, this has not been reported. USDA licensed plasma products are free of infectious diseases. Other products (not licensed by the USDA) are not regulated. If homemade plasma is used, donors should be free of equine infectious anemia and should be tested at least annually, depending on risk of exposure.
Serum Hepatitis
Definition
Acute hepatic necrosis (serum hepatitis, Theiler’s disease, post vaccination hepatitis) is a disease associated with administration of biological products of equine origin. Clinical manifestations of serum hepatitis usually occur with rapid onset 2–3 months (up to 6 months) after administration of a biological product.
Risk factors
Risk factors for developing serum hepatitis after administration of tetanus antitoxin include pregnancy or lactation. It is unknown whether this is also true for serum hepatitis following plasma transfusion [33].
Pathogenesis
Serum hepatitis has been reported after administration of plasma in horses [33]. The plasma was reported to come from the same commercial source but from different batches. The incidence of serum hepatitis following plasma administration was low (<0.4%) in one study, although there is currently a lack of long‐term follow‐up reports after plasma transfusion [33]. However, outbreaks after plasma transfusion have also been reported, with morbidity rates ranging from 1% to 18% [34].
The disease shares many similarities with human post transfusion hepatitis, which was associated with administration of blood products before the detection of the Hepatitis B and C viruses. Based on these observations an infectious agent has been suggested to play a role. Recently three members of the Flaviviridae, close relatives of the human hepaciviruses, have been identified in horses (equine hepacivirus (EHVC), equine Pegivirus, and Theiler’s disease associated virus, TDAV). The later has been associated with an outbreak of equine serum hepatitis [34]. The virus has since been experimentally inoculated into healthy horses of which one developed elevated liver enzymes further strengthening the theory that TDAV might be a causative agent of Theiler’s disease [34]. Equine hepacivirus has also been found in horses with serum hepatitis and has been shown to cause clinical disease in experimentally infected horses [35]. Evidence is mounting that Theiler’s disease is associated with equine hepatotropic viruses potentially transmitted via contaminated blood products.
Prevention
Avoid unnecessary plasma transfusions (see also complications of colloid use).
Diagnosis
Clinical signs include lethargy, anorexia, profound icterus, decreased gastrointestinal tract activity and various nervous system signs due to hepatoencephalopathy and liver failure. Diagnosis is based on a history of administration of plasma or another biological product, elevated liver enzymes, bile acids and bilirubin. Subclinical cases with elevations of liver enzymes but without overt clinical signs have also been reported.
Treatment
There is no specific treatment for Theiler’s disease. Supportive treatment with intravenous fluids and treatment for hepatoencephalopathy can be attempted.
Expected outcome
The mortality rate among symptomatic horses ranges between 50% and 90%.
Circulatory overload
Circulatory overload is unlikely in the adult horse but does occur in foals. For further information, see section on Circulatory Overload earlier in this chapter.
Storage‐associated changes
Clots or introduction of air into the bag may occur during storage. A rare adverse event is venous air embolism [36].
Complications