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 Associated with Administration of Colloid Therapy
A colloid is a large (high molecular weight, MW) hydrophilic molecule. Colloids do not freely permeate the capillary membrane and remain in the vasculature bed where they are responsible for plasma colloid oncotic (COP) pressure. Proteins, particularly albumin, are natural colloids. Hydroxyethylstarch (HES) is the parent name of a group of synthetic colloids. Other synthetic colloids include gelatins and dextrans, which are not widely used and have been mostly replaced by HES. There are different types (generations) of HES solutions available. They differ in concentration, MW, and molar substitution ratio and pattern of the hydroxyethyl molecules (C2/C6 ratio).
Definition
Volume overload
Coagulopathies
Acute kidney injury
Pro‐inflammatory cytokine release
Allergic reactions. Allergic reactions are very rare as the HES molecule is similar in structure to glycogen. The side effects of HES are due to the cumulative effects of therapy over several days, rather than a single 24‐hour dose. In human medicine there is currently not enough evidence to support a consistent difference between HES generations with regard to morbidity, mortality, hemorrhage and acute kidney injury.
Risk factors
The MW and pattern of substitution determines the pharmacokinetics and pharmacodynamics of the colloid but is also responsible for the severity of side effects [37]. Currently, hetastarch, hexastarch, pentastarch and tetrastarch preparations are available on the market.
Pathogenesis
In human medicine delayed onset pruritus, due to cutaneous deposition of HES in the dendritic cells of the skin (Langerhans cells), is reported in up to 54% of patients and is refractory to treatment. Clinical pruritus occurs usually several weeks after HES administration and may persist for 12–24 months. Side effects include acute renal injury with underlying mechanisms being unclear. Osmotic nephrosis, altered oncotic forces in the glomerulus, lead to a change in glomerular filtration rates and a decrease in reno‐protective albumin have been discussed as a potential cause [38–40]. Some studies have suggested that certain HES generations are associated with a higher risk for renal injury; however, a meta‐analysis of these studies in humans showed insufficient evidence to support this [41]. Human clinical trials and meta‐analysis have shown that the need for receiving renal replacement therapy
