Anaphylactoid Reactions

An anaphylactoid reaction is one that, mim­ics anaphylaxis but has no immunologic basis. A common anaphylactoid reaction occurs from accidental intra-arterial injection.¹⁴

Anaphylactoid reactions are most easily dif­ferentiated from true anaphylactic reactions by time of onset of clinical signs. Signs of ana­phylaxis begin 30-60 seconds after injection of the offending agent. In contrast, an intra-ar-terial reaction occurs immediately upon injec­tion (within 5-10 seconds) and is characterized by the phrase, "The horse fell off of the needle." Such reactions are caused by misplaced iv or im injections. Penicillin G and promazine tran-quilizers are often involved in such reactions.

Clinical Signs: Horses given an intracarotid injection begin to hyperventilate, lean back, become wide-eyed and may collapse during the last phase of injection. Some horses become ex­tremely excited and blindly stagger into sur­rounding objects, gallop until the reaction subsides, or become recumbent.

Intravenous injection of some drugs can also cause anaphylactoid reactions, characterized by sweating, hyperventilation and GI signs, without excitation. Antihistamines, tetracy-clines, iodine solutions and vitamin prepara­tions have been associated with such reactions.'⁵

Some drugs cause unpredictable anaphylac­toid reactions when given by the recommended route of administration. Ketamine should only be used in horses after the administration of xylazine has produced sedative effects. Keta­mine used alone has caused hyperexcitability.¹⁶ Acepromazine has caused marked depression and collapse.¹⁶

Treatment: Excited animals should be re­strained physically, if not dangerous for the handler, or placed in an open area to minimize chances of collision with stationary objects. Once the excitement phase is over, the horse should be assessed for the need of iv fluid ther­apy. Epinephrine and corticosteroids may also be beneficial,

Prevention: Proper iv injection technics are essential for prevention of anaphylactoid re­actions from accidental intra-carotid injection. Physical restraint, by an experienced handier, or chemical restraint, using tranquilizers or sedatives given im, should be used to calm frac­tious animals prior to iv injection.

Schwartzman Phenomenon

The Schwartzman phenomenon, a rare re­action in horses, is precipitated by an initial sensitizing dose of endotoxin, followed by va-soconstriction and intravascular coagulation. Use of alpha-stimulators and corticosteroids may predispose to the reaction.¹⁷

Clinical Signs: There are few reports of the Schwartzman phenomenon in the veterinary literature. In a report on 3 affected horses, clin­ical signs included anorexia, anuria, icterus, fever, hematuria and diarrhea.'⁸ Two other af­fected horses had renal enlargement.¹⁹

Pathologic Changes: Bilateral renal necrosis is the hallmark of this reaction (Fig 7).

Treatment: Because of the nature of the le­sion, renal function should be monitored and long-term iv fluid therapy administered. Anti­biotics may be used to treat secondary bacte­rial infections. Corticosteroid use may or may not be beneficial.

Blood-Typing and Transfusion

Intravenous injection of whole blood or plasma increases circulating blood volume and sup-

Fig 7. Cross-section of a kidney with renal cortical ne­crosis.

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plies antibodies, electrolytes, nutrients and blood elements. Blood or plasma transfusion is indicated in serious blood loss from trauma, some types of shock, septicemia, severe GI or respiratory disease, purpura hemorrhagica, se­vere burns and neonatal isoerythrolysis.

Transfusion of whole blood is of limited use in adult horses but is very beneficial in foals. The usefulness of transfusions is limited by several factors; they require a great deal of time to administer properly; whole blood can only be stored for one month; blood loss is a dynamic event that usually necessitates mul­tiple transfusions; and most practitioners are unfamiliar with the transfusion procedure. An example of the limited value of blood transfu­sion in adult horses is the case of an 8-year-old mare that ruptured a uterine artery at partu­rition. The animal became depressed and had a PCV of 25% 9 hours postpartum. The PCV declined to 12% by 20 hours postpartum, at which time 3 L whole blood (PCV 41%) were administered iv. The mare recovered despite the fact that the transfusion raised the PCV only 1%.

In lieu of transfusions, other measures can be taken in the treatment of anemic horses. Stress should be minimized by keeping such horses in a small, quiet stall away from other activity. Tranquilizers should not be used or used in minimal doses when necessary. The PCV should be measured at 12-hour intervals to assess the full extent of the anemia and to determine if splenic contraction has offset the low PCV. Hydration and electrolyte balance should be carefully maintained. Administra­tion of hematinics and vitamin supplements may also be beneficial.

Blood-Typing

The use of blood-typing and cross-matching is recommended to prevent transfusion reac­tions. Blood-typing is also used by several breed registries as a form of identification and verification of parentage, especially when 2 or more stallions are involved. The efficacy of se-rologic and electrophoretic blood-typing tests to determine paternity when 2 stallions are in­volved was 90%.²⁰

Equine blood has been classified into 8 types, including 24 factors.²⁰.²¹ At this writing, only the University of California at Davis has the facilities for equine blood-typing. Because no marker unique to a single breed has been found, blood-typing cannot be used to prove a horse's breed.

Although blood from random donors may be safely used for a single transfusion, subsequent transfusion of incompatible blood may result in severe reactions. Antibodies against incom­patible blood are produced within several days of the initial transfusion. Cross-matching of the blood of the recipient with that of potential donors should always be performed before ad­ministration of blood to foals with neonatal iso­erythrolysis. Cross-matching is also recom­mended before giving blood, especially repeat­edly, to a mare that may be used for breeding because introduction of antigens not contained in the mare's RBC may increase the chances of birth of a foal with neonatal isoerythrolysis. Antibodies can also develop in mares that have received vaccines of equine origin.

If it is impossible to cross-match blood prior to transfusion, it may be safer to use animals of a different breed or bloodline as donors. Al­though minor incompatibilities (donor's serum agglutinates recipient's cells) are less likely to be serious than major incompatibilities, there is less chance of their occurring if the following animals are not used as donors: horses that have received transfusions with blood that was not cross-matched or was known to contain an­tigens not found in its RBC, mares that have produced foals with neonatal isoerythrolysis, and horses that have received vaccines of equine origin.

Healthy, mature horses from the same farm or area should be chosen as donors. If possible, an animal that has recovered completely from the disease, if an infectious disease is being treated, should be used because beneficial an­tibodies may have developed during the ill­ness. The prospective donor should be examined and the mucous membranes inspected for nor­mal color. Preference should be given to donors with high hematocrit and hemoglobin levels.

Cross-Matching Technic; A cross-matching technic, using an agglutination test and a he-molytic test, has been described elsewhere.²⁰ The following cross-matching test is more re­liable than macroscopic plate or tube tests be­cause weak agglutinations, which cannot be recognized macroscopically, often occur. Blood samples are collected from the recipient and several prospective donors. The clots are al­lowed to separate or a centrifuge is used to sep­arate them from the serum. The serum is removed from each sample and put into labeled tubes. A suspension of RBC is made from the blood of each animal by resuspending cells from the clot in 2-3 ml saline, which is easily

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Fig 8. Strong agglutination on the microscopic tube agglutination test.

done by transferring the cells with an applica­tor stick. The cell suspension should be of such concentration that it looks like thin tomato juice. One drop of the cell suspension and 2 drops of serum are added to a test tube for each test: donor cells plus recipient serum (major test) and donor serum plus recipient cells (mi­nor test). The tubes are incubated for 5-8 min­utes in a 37-F water bath or for 30 minutes at room temperature and are then centrifuged at about 1000 rpm for 1 minute. To resuspend the cells the tubes are jarred sharply by hitting the hand containing the tubes against a solid ob­ject. Strong agglutination can be detected ma-croscopically. The contents of the tubes are then placed on a slide and examined microscop­ically at 100X magnification. Coverslips are not used. If there is doubt that agglutination has occurred, the slide should be tipped from side to side for a few minutes. If agglutination is occurring, it becomes stronger; if not, any clumps not due to agglutination will break up. Figures 8-10 show strong agglutination, weak agglutination, and a negative test.

The major and minor tests were negative in just less than half of randomly selected ani­mals in one study.²² Both tests should be nega­tive before blood is administered. Reactions occurring on the minor test are less serious be­cause the serum of the donor, which contains the antibodies, is diluted in the entire blood volume of the recipient, and less agglutination and hemolysis are likely to occur than if the donor's cells are agglutinated by the recipient's serum (major reaction). If a more suitable do­nor is not available, blood that is positive only in the minor test may be used. A phenomenon known as autoagglutination occurs rarely, especially in animals that are anemic or have a viral infection. When it occurs, the recipient cells are agglutinated by their own serum in vitro. In these cases, the prospective donor's cells usually show some agglutination in the minor test because autoaggiutinins in the recipient's serum agglutinate them.

Fig 9. Weak agglutination on the microscopic tube ag­glutination test.

Blood Transfusion

The usual way to collect blood for transfu­sion is to distend the jugular vein and intro­duce a 12-ga or 10-ga needle into the vein. A gallon of blood can be collected in 6-10 minutes with a 10-ga needle. Equipment used to collect blood should be autoclaved prior to collection of blood and aseptic technic used during collec­tion to minimize bacterial contamination. An­tibiotics (1 g streptomycin and 1 million IU procaine penicillin G/gallon blood) should be added to prevent bacterial growth in blood to be stored for several weeks.

Blood is collected in 1- or 2-gallon containers for use in mature horses and in 500-ml contain­ers for foals. Heparin (4 units/ml blood) or so­dium citrate (0.1 ml 0.4% solution/ml blood) should be added to the container to prevent co­agulation of blood.²³ A 4% solution of sodium citrate can be made by adding 500 ml sterile water to 20 g sodium citrate in a bottle. To make a final dilution of 0.4%, 400 ml of this solution are put into each gallon container and 50 ml into each 500-ml container.

A method of collecting blood in 2-gallon poly­propylene bottles has been described.²³ A rub­ber cork, pierced by 2 pieces of glass tubing, occludes the mouth of the sterile container. One piece of glass tubing leads to a 1-way suc­ tion bulb to create a vacuum for rapid collec-

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tion, and the other piece of glass tubing is con­nected to the iv collection tubing. Most healthy, mature horses can donate 1-2 gallons of blood without difficulty.

Although it is possible to administer too much blood, more often too little is given too late in the course of the disease. The smallest effective dose in a mature horse is 1 gallon (4 L) and 2 gallons are almost always indicated. The blood volume of a horse is about 9% of the body weight. If it is given slowly, up to 20% of the blood volume can be given safely at one time to an animal that has not lost blood by hemorrhage. Most veterinarians prefer to give no more than this at one time. Additional blood can be given at 12-hour intervals as indicated. Larger volumes can be given in cases of blood loss. Twenty percent of the blood volume in a 1000-pound horse is approximately 21/2 gal­lons. A 100-lb foal usually can be given 2 pints of blood if there has been no blood loss.

In transfusions of foals with neonatal iso-erythrolysis, up to 10 pints of blood may be given; however, during the transfusion, blood must be withdrawn from the foal, either simul­taneously or intermittently, and discarded. It is best to start transfusing before withdrawing blood from the foal and eventually to adminis­ter 2-3 pints more blood than is withdrawn and discarded. If more than 20% of the blood vol­ume of an animal is given rapidly (for example, following hemorrhage), calcium gluconate should be administered slowly through a dif­ferent needle because the citrate will bind free Ca in the animal's blood.

Blood should be strained before it is admin­istered. A filter-type transfusion apparatus can be used or, if one is not available, sterile gauze can be placed over the mouth of the bottle be­fore the iv outfit is placed on it. An iv set with a tubing-type air vent should be used to pre­vent air entering when gauze is used as a strainer on the bottle top. Blood also can be strained by placing a metal screen or gauze uver a funnel and pouring the blood through it into another vessel. Clotting on the screen can be prevented by first wetting it with sodium citrate soluJtfbn.

Blod te replace reduced blod volume; eg, following hemorrhage, can be given rapidly. Rapid injection or administration of large doses of blood is especially dangerous, however, in animals with pulmonary or cardiovascular disease and in other debilitated animals. It is well to auscultate the heart and lungs (for pul­monary edema) and check the pulse (estimate 'relative blood pressure) periodically tranfusing these animals. In mature there usually is no untoward effect due t of transfusion if a 14-ga needle is used bottle of blood is suspended not more feet above the injection site. In foals, needle limits the flow satisfactorily if pi is not used and the container is suspend more than a foot above the injection sit recommended rate of injection of blood is minute.²²

Fig 10. Negative reaction on the microscopic t-glutination test. Note the normal, orderly sta'

RBC in rouleaux formation as compared with clumping in Figs 8 and 9.

Plasma Transfusion

Administration of plasma may have use than whole blood transfusions in practice. In acute diarrhea and conditu volving endotoxic shock, as well as afi dominal surgery, the PCV may rise wh plasma protein level falls. Such condif fer a poor prognosis and may be indicat administration of plasma.²⁴ Plasma is ; ministered to foals with failure of transfer of maternal antibodies.^{23 25} An tage of plasma over whole blood is that little risk of transfusion reaction with of plasma.Because plasma can be stored frozen eral years, samples from donor horses submittet to the University of Californ ogy laoboratory for evaluation for hem and agglutinins prior t o collection o amounts. Technics for collection of bio separation of plasma have been describe It is important to remember that any RS remain in the plasma can precipitate ; reactions ir in recipients , Therefore, the

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Fig 11. Development of urticaria after infusion of 1 pt of blood.

tion of RBC from plasma should be accom­plished by centrifugation rather than by gravity. Collaboration with laboratory personnel in lo­cal human medical facilities or blood banks is useful in that regard.

Transfusion Reactions

Although the first blood transfusion of in­compatible blood seldom causes severe illness or death because the level of normally occur­ring antibodies usually is low, cross-matching should be done if possible. If the transfusion history is unknown or vague, it is not wise to transfuse blood without cross-matching. Any hemolysis due to incompatibility causes stress because of the loss of RBC, and because the spleen, liver and reticuloendothelial system must dispose of lysed blood cells and hemoglo­bin. Lower nephron nephrosis occurs if hemol­ysis is extensive.

Reactions to blood or plasma transfusions are similar to other immunologic reactions. The first sign of a ransfusion reaction is uneasiness. The animal may flex each of the hindlegs in turn, yawn several times, and hold its head down. Breathing may become shallow and rapid, or the animal may hold its breath. In a severe reaction, the horse defecates, uri­nates and may fall. Hemorrhage may occur fol lowing such reactions. Sweating, colic and urticaria may also occur (Fig 11).

Neonatal Isoerythrolysis

Neonatal isoerythrolysis is discussed in de­tail in Chapter 9.