Krista E. Estell, K. Gary Magdesian
Use of Fresh and Frozen Blood Products in Foals
Disease processes that necessitate transfusion of blood products to the neonatal foal are common in both field and referral hospital practice. A variety of products is available for transfusion, including fresh or frozen plasma, platelet-rich plasma (PRP), fresh whole blood, and packed red blood cells (RBCs). Recognition of disease entities and management of these diseases with the appropriate blood product is important in successful treatment of the neonatal foal.
Plasma Products
Failure of Passive Transfer of Immunity
Failure of transfer of passive immunity (conventionally referred to as failure of passive transfer [FPT]) is one of the most common problems affecting neonatal foals. Immunoglobulins must be passively transferred from mare to foal through colostrum in the first 12 to 24 hours of life. Serum immunoglobulin G (IgG) concentration can be quantified by several means, but the most practical are stallside enzyme-linked immunosorbent assay tests.1 These values are semiquantitative; for example, a value of 800 mg/dL or higher is considered adequate transfer of passive immunity. Values from 400 to 800 mg/dL signify partial FPT, and values less than 400 mg/dL indicate complete FPT. Ideally, IgG concentration is tested in the first 10 to 16 hours of life, a point when enteral administration of colostrum may still effectively raise the serum immunoglobulin concentration. In addition to IgG, colostrum contains IgA, which provides mucosal gastrointestinal immunity, as well as IgM, complement, and growth factors; it also contains lymphocytes and is an important source of calories. On average, foals require 1 to 2 L of high-quality (specific gravity >1.060) colostrum.
Foals with complete or partial FPT that are older than 12 to 16 hours should be treated with intravenous plasma transfusion. Commercial frozen equine plasma for use in managing FPT is a U.S. Department of Agriculture–licensed product. Most of these products’ manufacturers guarantee a minimum concentration of IgG and a freezing life of 2 to 3 years. Plasma should be administered through an aseptically placed 14- or 16-gauge intravenous catheter; the plasma bag is connected to the catheter with a blood or plasma administration set containing an in-line filter. Diazepam, administered at 0.1 to 0.2 mg/kg intravenously, provides adequate chemical restraint necessary for catheterization and administration of plasma in the healthy or active and ambulatory neonate. Septic foals should, and usually can, be catheterized without sedation to avoid further cardiopulmonary depression. The volume of plasma necessary to attain an IgG concentration of greater than 800 mg/dL depends on pretransfusion IgG concentration and clinical status of the foal, as well as the quantity of immunoglobulin contained in the donor plasma. A dose of 20 to 40 mL/kg is often needed in foals with complete FPT. After administration, immunoglobulins equilibrate between the intravascular and extravascular spaces, and as much as 50% leaves the circulation. Foals with sepsis may sequester an even higher proportion of immunoglobulins extravascularly because of increased vascular permeability. Additionally, critically ill foals may catabolize or utilize immunoglobulins during sepsis. Therefore IgG concentrations should be rechecked 12 to 24 hours after plasma has been administered in sick foals to evaluate for temporal loss of IgG.
Plasma should be administered slowly initially, at a rate of 1 drop/second (with a 10-drop/mL administration set; i.e., 6 mL/minute for an average-sized foal) for the first 5 to 10 minutes while the foal is monitored for signs of transfusion reactions. If no signs of reaction are observed, the rate of administration can be increased, and the balance of the first unit or liter can be given as a bolus over 60 minutes provided that volume administration is not contraindicated (such as in a foal with cardiac failure, anuria, or fluid overload). The foal should be monitored for signs of transfusion reactions throughout the duration of plasma administration. Clinical signs of transfusion reactions in foals include fever, tachycardia, tachypnea, colic, muscle fasciculation, facial edema, urticaria, and coughing. The incidence of adverse effects after plasma transfusion in neonatal foals is approximately 10%. Deaths are rare. Development of transfusion reaction necessitates discontinuation or slowing of the rate of plasma administration as a minimum intervention. When clinical signs of reaction do not respond to discontinuation of plasma administration, an antihistamine (diphenhydramine, 0.5 to 1 mg/kg, IM or slowly IV, once) should be given. Foals with anaphylaxis, anaphylactoid, or other severe forms of reaction may need a corticosteroid (dexamethasone, 0.04 mg/kg, IV, once), with or without epinephrine (0.01 to 0.02 mg/kg [0.5 to 1 mL of 1 : 1000 concentration], slowly IV, for a standard-sized foal). Septic or other critically ill foals often need more than 1 L of plasma; the rate of administration of subsequent units should be slower to avoid fluid overload. An initial liter may be given as a bolus, if indicated for volume replacement; after the initial bolus, subsequent units of plasma should be given slowly and may be administered in place of crystalloid fluids at a maintenance rate of 4 to 6 mL/kg per hour (or higher if tolerated), or as intermittent, small boluses (100 to 200 mL given hourly) over 5 to 10 hours.
Plasma donor horses should be well vaccinated, healthy, adult horses that have been tested for equine infectious anemia, piroplasmosis, and equine arteritis virus. Recently, a flavivirus has been associated with serum hepatitis (Theiler’s disease) in horses previously administered plasma transfusions; in the future, testing of donors for this virus may also be recommended. Donors to be used for RBC transfusion (whole blood or packed RBCs) optimally are negative for blood group factors Aa and Qa; they should also be screened annually for antierythrocyte antibodies (lysins and agglutinins) against known blood groups. Geldings that have been housed away from donkeys or mules (to avoid sensitization to “donkey factor” RBC antigen and donkey platelet antigens) make ideal donors. In the absence of blood typing, a minor cross-match test between donor plasma and recipient blood cells should be performed, in addition to a major cross-match, whenever red cells are to be transfused. Commercial plasma is tested for antierythrocyte antibodies, but not for antiplatelet antibody.
Sepsis and Disseminated Intravascular Coagulation
Sepsis, often associated with FPT, is the most common cause of morbidity and death in equine neonates. Clinical signs include lethargy, decreased nursing, abnormalities in temperature regulation, mucous membrane petechiae, tachypnea, variable tachycardia, hyperemic to pale mucous membranes, and weak, thready pulses with cool extremities when shock ensues. Plasma has been an important component of therapy for the treatment of sepsis in neonates despite conflicting evidence on its efficacy. Septic and clinically ill foals have lowered innate immune function, manifested by decreased phagocytic function, compared with healthy foals. In addition to providing immunoglobulins, plasma also contains antithrombin, coagulation factors, acute phase proteins, and complement, all of which may be beneficial in treatment for sepsis. Studies have revealed that plasma transfusions enhance immunity and phagocytic activity by increasing opsonic capacity in foals, but research findings as to efficacy of treatment are conflicting.
Fresh frozen plasma contains all clotting factors, including both labile and stable factors. Labile factors include factors V and VIII, whereas the stable factors are II, VII, IX, and X. Fresh frozen plasma is frozen (to −18° C or lower) within 8 hours of collection, without having been refrigerated. Labile factors are stable for up to 1 year with freezing.
Immunoprophylaxis
Hyperimmune plasma has been used for both prophylaxis and treatment of infectious diseases such as Rhodococcus equi, Escherichia coli, Clostridium botulinum, Salmonella spp, West Nile virus, Streptococcus equi subsp equi, and rotavirus infections, in some instances being used in an extralabel fashion. Plasma from donors vaccinated against Clostridium difficile and Clostridium perfringens has also been used empirically and on an extralabel basis as treatment for enteric clostridiosis (associated with C difficile and C perfringens infections). Plasma is considered hyperimmune when harvested from donor horses that have been vaccinated against the agent of concern, and contains quantified levels of antibodies against these agents. The clinical benefits of hyperimmune plasma products have not been well documented; the best studied is in the area of R equi immunoprophylaxis. Although some studies have shown clinical and in vitro benefit from hyperimmune plasma administered prophylactically to prevent R equi infection, others have failed to show a change in morbidity, mortality rate, or severity of disease. This seems to vary depending on the type of plasma administered. Overall, there is a slight advantage in terms of the number of published studies reporting a reduction in the incidence of rhodococcal pneumonia on endemic farms over those not demonstrating benefit; based on these studies and on experience, the authors recommend the use of hyperimmune R equi plasma as part of a pneumonia prevention program on farms with an endemic rhodococcal presence.