Feline Transfusion Medicine: Blood Types and their Clinical Importance

0195-5616/95 $0.00

TRANSFUSION MEDICINE

+ .20

FELINE TRANSFUSION MEDICINE Blood Types and Their Clinical Importance Monika E. Griot-Wenk, Dr med vet, and Urs Giger, PD, Dr med vet, MS, FVH

In today's clinical practice, blood transfusions have become a routine part of the supportive management of critically ill and anemic cats. Although cats still receive transfusions less frequently than do dogs, a great increase in the use of blood transfusions in cats has occurred. At the Veterinary Hospital of the University of Pennsylvania, only 52 blood transfusions were given in 1985 compared with 145 transfusions in 1992. Feline blood donor programs have been developed and techniques for collection of blood from cats have been established. The clinical importance of the feline AB blood group system with the blood types A, B, and AB in feline transfusion medicine has been recognized. Unlike dogs, cats possess naturally occurring antibodies against the other blood types and these alloantibodies are responsible for life-threatening hemolytic transfusion reactions in AB-mismatched blood transfusions. Therefore, blood typing and blood crossmatching procedures are pivotal to ensuring blood compatibility. The purpose of this article is to outline the important features of the feline AB blood group system and its clinical relevance for transfusion medicine and to provide practical guidelines for performing safe and efficacious feline transfusion medicine. This article is an update of earlier reviewsP· 21

From the Department of Clinical Studies, Veterinary Hospital, University of Pennsylvania, Philadelphia, Pennsylvania

VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 25 • NUMBER 6 • NOVEMBER 1995

1305

1306

GRIOT-WENK & GIGER

INDICATIONS FOR BLOOD TRANSFUSIONS

Because feline blood products are a scarce resource and transfusions always impose innate risk, the medical benefits of blood transfusions must be carefully defined in every patient. Anemia is the most common medical indication for transfusion in the cat as illustrated by our survey at the University of Pennsylvania in 1992 (Table 1). In that year a total of 145 blood transfusions were given to 103 feline patients. The majority of the transfusions (74%) were given because of anemia. Only 38 transfusions were administered to nonanemic cats for other reasons (e.g., cats with hepatopathy-induced coagulopathy scheduled to undergo apercutaneous ultrasound-guided liver biopsy) (see Table 1). Cats with acute blood-loss anemia of less than 3 days' duration (n = 10) had a pretransfusion packed cell volume (PCV) of 18.1% and were given a mean of 2.1 blood units (50 mL per unit). In contrast, cats with anemia not related to acute blood loss (reduced hematopoiesis and one case of hemolysis) had a PCV of 12.7% before the transfusion and received a mean of 1.7 blood transfusions. Cats with acute blood loss presumably had insufficient time to adapt to a lower hematocrit and therefore were symptomatic and were transfused earlier than cats with slowly developing anemia caused by inadequate production. Because of the difficulties in preparing blood components from a small whole blood unit, anemic cats are most commonly transfused with · fresh/ stored whole blood rather than blood components (packed red blood cells). Moreover, coagulopathy, thrombocytopenia and thrombopathia, disseminated intravascular coagulopathy, and hypoalbuminemia are observed relatively infrequently in cats compared with dogs. Furthermore, because bleeding cats frequently also are anemic they typically receive fresh whole blood rather than component therapy. In a few veterinary hospitals, however, component therapy has become the preferred treatment in cats. 26 For indications and preparation of blood Table 1. BLOOD TRANSFUSIONS IN CATS AT THE VETERINARY HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA (1992)

Indication

Cats (n)

Transfusions (n)

Mean Transfusion/ Cat (Range)

Anemic cats* Regenerative anemiat Nonregenerative anemia Acute blood loss (:53 d) Reduced hematopoiesis Nonclassified anemia Nonanemic cats

65 19 40 10 30 6 38

107 39 62 21 41 6 38

1.6 2 (1-8) 1.5 (1-4) 2.1 (1-4) 1.4 (1-3) 1.0 ND:j:

*PCV <26% tRegenerative anemia 2=0.4% corrected reticulocytes. :j:ND = not determined.

Mean Pretransfusion PCV% (Range) 12.8 13.3 13.0 18.1 12.1 10.7 NO

(6-20) (4-25) (12-25) (4-20) (5-17)

FELINE TRANSFUSION MEDICINE: BLOOD TYPES AND THEIR IMPORTANCE

1307

components, see Kristensen article on general principles of small animal blood component administration and Purvis article on autotransfusion in the emergency patient? BLOOD TYPES IN CATS

Thus far, only one blood group system, the AB system, has been recognized in cats. 3 • 27 It consists of three blood types: type A, type B, and type AB. Type A is the most common blood type; however, the frequency of type A and Bin Domestic Shorthair cats differs markedly between parts of the United States and worldwide (Table 2). 3 • 21 • 22 The distribution of type A and B among purebred cats also varies markedly (Table 3) 19• 22; however, no geographic variation was observed in the three purebred breeds (Abyssinian, Persian, and Devon Rex cats) studied. 21 Knowledge of the blood type frequency in each breed is important when estimating the risk of AB incompatibility reactions. Based on the type-B frequency, the risk of a transfusion reaction in an untyped British Shorthair cat is 40% when receiving AB-unmatched blood from a common Type-A donor. In contrast, the risk in Siamese cats receiving type A blood is negligible because all Siamese and related breeds have type A blood. The third feline blood type AB, first recognized by Auer and Bell/ occurs very rarely. 23 Blood type AB has been found in Domestic Table 2. BLOOD TYPE FREQUENCY IN DOMESTIC SHORTHAIR AND LONGHAIR CATS IN VARIOUS COUNTRIES Country United States* Northeast North Central/Rocky Mountain Southeast Southwest West coast Australia, Brisbanet Europe:j: Austria England Finland France Germany Italy Netherlands Scotland Switzerland

Number of Cats Typed

Percentage Type A

Percentage Type B

1450 506 534 483 812 1895

99.7 99.6 98.5 97.5 95.3 73.7

0.3 0.4 1.5 2.5 4.7 26.3

101 477 61 350 600 401 103 70 1018

97.0 97.1 100 85.1 94.0 88.8 96.1 97.1 99.6

3.0 2.9 0 14.9 6.0 11.2 3.9 2.9 0.4

*Data from Giger U, Griot-Wenk ME, BOcheler J, et al: Geographical variation of the feline blood type frequencies in the United States. Feline Practice 19:21-27, 1991. tData from Auer L, Bell K: The AB blood group system in cats. Anim Genet 12:287-297, 1981. :j:Data from Giger U, Gorman NT, Hubler M, et al: Frequencies of feline type A and B blood types in Europe. Anim Genet 23(suppl. 1):17-18, 1992.

1308

GRIOT-WENK & GIGER

Table 3. FREQUENCY OF BLOOD TYPE B IN PUREBRED CATS IN THE UNITED STATES Type B Frequency*

No type B cats 1%-1 0% type B cats 11 %-20% type B cats 20%-45% type B cats

Breeds

Siamese and related breeds, Burmese, Tonkinese, Russian Blue Maine Coon, Norwegian Forest Abyssinian, Birman, Persian, Somali, Sphinx, Scottish Fold Exotic and British Shorthair Cats, Cornish and Devon Rex

*Type A frequency is calculated by subtracting the type B frequency from 100%. Data from Giger U, BOcheler J, Patterson DF: Frequency and inheritance of A and B blood types in feline breeds of the United States. J Hered 82:15-20, 1991.

Shorthair cats and in the Abyssinian, Birman, British Shorthair, Norwegian Forest, Persian, Scottish Fold, and Somali breeds (updated from Griot-Wenk and Giger23 ). Similar to humans, the feline blood type antigens are defined by specific carbohydrates attached to membrane lipids and proteins on the surface of red blood cells. Analysis of red blood cell glycolipids reveals that specific neuraminic acids on gangliosides attached to ceramide dihexoside as a backbone correlate with the feline blood group antigens.24 Specifically, N-glycolyl-neuraminic acid determines the A antigen and N-acetyl-neuraminic acid the B antigen. 2· 24 A combination of equal amounts of both neuraminic acids was found in type AB cats, which express both type A and B antigens on the erythrocyte surface. 24 The feline blood group antigens A and B are inherited as a simple autosomal mendelian trait with A being completely dominant over B. 19 In contrast to the situation in humans, however, blood type AB is not the result of codominant inheritance of type A and B. Only specific matings in families with type AB cats result in type AB offspring. 3· 23 Based on extensive pedigree analysis and breeding experiments, we speculate that a third allele at the same gene locus as that of A and B is responsible for the blood type AB. 24 Unlike dogs, cats possess naturally occurring antibodies, known as alloantibodies, against the blood group antigen they lack. 3· 9· 14· 18· 19· 22· 29· 35 These alloantibodies are of great clinical importance because they are responsible for potentially life-threatening incompatibility reactions such as transfusion reactions5· 6 • 17· 18· 35 and neonatal isoerythrolysis. 11• 16 Alloantibodies can be transferred via colostrum up to 16 hours after birth 13 and all type-B kittens (and to a much lesser degree, type-A kittens) develop alloantibodies at a few weeks of age. 9 This immune response is believed to be triggered by common food and bacterial antigens. Thus, cats do not need to be sensitized by a prior blood transfusion or pregnancy to develop alloantibodies, and adverse reactions can occur with the first blood transfusion and in kittens from a primiparous queen. All type-B cats older than 3 months have high titers of anti-A

FELINE TRANSFUSION MEDICINE: BLOOD TYPES AN D THEIR IMPORTANCE

1309

antibodies (greater than 1:32).3• 9 These strong hemagglutinins and hemolysins of type-B cats are mainly of the IgM immunoglobulin class. 9• 28• 34• 35 In contrast to type-B cats, cats with type-A blood have only weak anti-B alloantibodies that consist of equal parts of IgG and IgM immunoglobulins.9 These anti-B antibodies markedly accelerate the destruction of transfused B cells in type-A cats. Because type-AB cats express both antigenic markers, they have no alloantibodies in their plasma. FELINE BLOOD TYPING

Commercial veterinary laboratories and veterinary schools are now routinely blood typing cats and a simple whole blood test has been developed as an in-house practice test (Fig. 1). Our own laboratory has typed more than 10,000 cats over the last 6 years. Furthermore, similar to testing for dog erythrocyte antigen (DEA) 1.1,1 simple typing cards are soon commercially available for cats. Blood typing reagents are blood type

red blood cell agglutination with anti-A serum anti-B reagent

type A

strong

typeB

typeAB

• •

none

none

strong

strong

strong

Figure 1. Feline blood typing using a simple whole blood test. Typing reagents: (1) anti-A serum: serum collected from any type B cat, heated for 30 minutes at 56°C, and stored in small aliquots (e.g. 1 mL) at - 20oc until used; (2) anti-B reagent: Lectin Triticum vulgaris, #L- 9640, Sigma, St. Louis, MO. Stock solution: add 1 mg T. vulgaris to 1 mL 0.9% NaCI = 1 mg/mL, use 64 J.LL of stock solution (1 mg/mL) and 936 J.LL 0.9% NaCI = 64 J.Lg/mL and store in aliquots at -20°C. A small amount of typing reagents may be kept at 4°C for up to 6 weeks. Procedure: (1) collect 0.5 mL of blood into a ethylenediaminetetraacetic acid (EDTA) tube, or capillary tube; (2) place two drops (50J.LL) of anti-A, anti-B reagent onto separate glass slides labeled with anti-A and anti-B, respectively; (3) add to each slide one drop (25 fLL) of whole blood and mix gently with pipette, needle, or capillary tube tip; (4) rock slide gently back and forth and look for hemagglutination after 1 to 5 minutes. Simple feline typing cards will soon become available.

1310

GRIOT-WENK & GIGER

readily available from us (Dr. U. Giger, VHUP, 3900 Delancey Street, Philadelphia, PA 19104-6010). The typing reagent to recognize type-A (and type-AB) cats is serum from type-B cats, which contains alloantibodies that strongly agglutinate type-A (and type-AB) cells. Triticum vulgaris (wheat germ; L-9640, Sigma, St. Louis, MO), a lectin recognizing the B antigen, is used with type-B (and type-AB) cats and has replaced the relatively weak anti-B serum.l 0, 24 The blood type of a cat can be confirmed by determining the patient's alloantibodies, anti-A or anti-B antibodies, a procedure called back-typing. Back-typing is performed similarly to blood typing except that known type-A and type-B red blood cells are tested against the patient's plasma. Cats with type-A blood have weak anti-B alloantibodies and agglutinate only type-B cells, and type-B cats always have strong anti-A alloantibodies and agglutinate type-A cells: Red blood cells from cats with type-AB blood agglutinate with the anti-A and anti-B reagents. In the back-typing procedure, however, serum (or plasma) from typeAB cats does not agglutinate type-A or type-B cells because they have no alloantibodies. BLOOD CROSSMATCHING TEST

Whereas blood typing determines the blood group antigens on the red blood cell surface, blood crossmatching (BCM) tests detect any serum (plasma) incompatibility between donor and recipient, even outside the AB blood group system. Thus, the BCM assay is used to identify any hemolyzing and hemagglutinating antibodies between donor or recipient plasma against recipient or donor red blood cells. The major BCM assay tests for alloantibodies in the recipient's plasma against donor red blood cells, whereas the minor BCM test looks for alloantibodies in the donor plasma against recipient cells. Macroscopic autoagglutination of the patient's blood (a rare event in cats) and severely hemolyzed blood samples preclude the performance of the BCM test. Based on the BCM test results, one might be able to predict the blood type of a cat because of the presence of naturally occurring alloantibodies (excluding the rare blood type AB). The various possible BCM test results are illustrated in Figure 2. A compatible major and minor BCM result indicates the same blood type of the donor and recipient. Because the donor's blood type should be known (donors are usually type A), the recipient's blood type can be inferred. A strong incompatible major and a weak incompatible minor BCM test result indicates that the recipient has type B blood. In contrast, a weak incompatible major with a strong incompatible minor BCM test result implies that the recipient has type A blood and that the donor has type B blood. Other than blood type-related incompatibilities we have seen such incompatibility test results in anemic cats infected with feline leukemia virus (FeLV). Ideally, both blood typing of the recipient and donor as well as

• • •

FELINE TRANSFUSION MEDICINE: BLOOD TYPES AND THEIR IMPORTANCE

compatible BCM tests

incompatible major BCM test

incompatible minor BCM test

recipient and donor same blood type

recipient B, donor A

recipient A, donor B

1311

Figure 2. Feline blood crossmatching (BCM) test with whole blood. Procedure: simplified from regular BCM based on strong feline anti-A alloantibodies. (1 ) Collect 0.5 ml blood (anticoagulated with EDTA) from recipient and all donors (or take one segment from donor blood bag). (2) Separate plasma from red blood cells (RBCs) by centrifugation (1000 x g for 5 minutes) or let sit for 1 to 2 hours on bench. (3) Remove plasma from each sample with a pipette and place into labeled glass or plastic tubes. (4) Prepare for each donor 3 glass slides labeled with major, minor, and recipient control. (5) Place onto each slide 2 drops (50J.LL) of plasma and 1 drop (25J.LL) red blood cells as follows: major BCM test = recipient plasma + donor cells RBCs; minor BCM test = donor plasma + recipient RBCs; recipient control = recipient plasma + recipient RBCs. (6) Mix gently back and forth and examine for hemagglutination after 1 to 5 minutes. Interpretation of major and minor BCM tests: agglutination is a sign of serum incompatibility reaction. Unlike in dogs, the eat's blood type can be inferred based on the BCM test results as the blood type of the donor cat should be known and has typically blood type A (exception rare blood type AB). Note: Recipient control not illustrated, but agglutination of recipient control may be observed in case recipient has immune-mediated hemolysis with autoagglutination interfering with BCM test (rare in cats).

BCM are performed before any blood transfusion. If blood typing is not available in a timely fashion, at least a BCM test should be done. Because the main concern is strong anti-A alloantibodies, the BCM test can be performed similarly to blood typing with whole blood, which can be used quickly on an emergency basis (see Fig. 2). This abbreviated BCM test w ould only show whether the patient and donor are AB compatible. Administration of a small amount of blood to test for incompatibility is no longer an acceptable procedure because transfusion reactions are independent of the amount of blood given and therefore as little as 1 mL of AS-incom patible blood can result in a life-threatening acute hemolytic tran sfusion reaction. 5' 6• 18 CHARACTERISTICS OF FELINE BLOOD DONORS

To ensure an adequate and safe blood supply, great care should be taken in donor selection, don or management, and collection of blood . The ideal feline blood donor is a shorth aired , large (5 kg or heavier) but lean, young (2 to 5 years) cat of either gender. Neutering of donors is not required, but may facilitate m an agement. Donor cats must be kept

1312

GRIOT-WENK & GIGER

strictly indoors because of the high risk of viral infections. Cats with a good temperament are preferred because the need for sedation when collecting blood is reduced, thereby diminishing the risk and impact of blood donation. For larger clinics having some donors in-house is convenient, but many facilities operate using staff- or client-owned donor cats. In-house donor cats or on-call cats near the facility are an acceptable source of immediately available fresh whole blood of appropriate blood type. Feline blood, as discussed later, can only be stored for a limited amount of time when using the commonly applied open system for blood collection. Donor cats must be in good health and should not receive any medication. Our in-house cats are examined regularly and blood tests are performed twice yearly including a complete blood count, serum biochemistry profile, urinalysis, and fecal examination for endoparasites. Furthermore, blood donors should be screened twice yearly for viral infections (FeLV, feline immunodeficiency virus, and feline infectious peritonitis (FIP)) and for hemobartonellosis by serology or evaluation of peripheral blood smears, respectively. Regular vaccinations against rhinotracheitis, feline calicivirus, panleukopenia, chlamydia, and rabies are also required, whereas vaccinations against FeL V and FIP are optional. Splenectomy is not recommended for blood donors. Detailed records are kept for each donor cat and should include dates of blood donation, amount of blood drawn, recipients of blood transfusion, and any adverse reactions in addition to general health data. Cats can donate 10 to 12 mL of whole blood per kilogram of body weight, corresponding to a feline unit of 50 to 75 mL of whole blood from a 5- to 6-kg cat, every 21 days. Client-owned donor cats are usually bled no more than every 6 weeks. Cats that donate regularly every 3 weeks should not only be fed a high-performance diet but may also require supplementation with oral ferrous sulfate twice weekly (Feosal, 10 mg/kg) because iron is a limiting element for red blood cell production. Well-maintained donor cats can donate blood for many years. As an alternative to the generally used allogeneic blood transfusions, the use of autologous blood may be considered. Cats scheduled for elective surgeries with expected large blood loss can easily donate 1 to 2 units of blood a few days to 2 weeks before the procedure. The collected blood is then available for autologous transfusion if needed during or after surgery, reducing the risks of allogeneic blood transfusions and circumventing the limited availability of blood. BLOOD TYPES OF FELINE BLOOD DONORS

Because of the presence of naturally occurring alloantibodies, no universal feline blood donors exist and only typed, matched blood can be used for effective and safe transfusions. All blood donors should be typed. Type-A cats must be transfused with crossmatched type-A blood, and type-B cats must receive type-B blood.

FELINE TRANSFUSION MEDICINE: BLOOD TYPES AND THEIR IMPORTANCE

1313

Type-A kittens with anemia resulting from neonatal isoerythrolysis, however, may represent a special circumstance. Type-A kittens born to type-B queens may absorb large amounts of anti-A antibodies via colostrum and may develop signs of neonatal isoerythrolysis in the first few days of life. Neonatal isoerythrolysis is best prevented by avoiding incompatible matings between type-B queens and type-A toms. If an incompatible mating has occurred, however, neonatal isoerythrolysis can still be prevented by not allowing the kittens to receive colostrum (with anti-A alloantibodies) for 16 hours after birth and by foster-nursing the kittens during that timeY During the first 2 days of life, one might give washed type-B cells (free of anti-A antibodies) to kittens in immediate need of blood to avoid any further hemolysis. 16 Thereafter, these type-A kittens should receive type-A blood because all colostral anti-A antibodies in the plasma of type-A kittens will have bound type A cells. Type A is the most common blood type and thus donors should have type-A blood. Ideally, one would also have access to a type-B donor cat. Type-B donors can be located by typing purebred cats; in some parts of the United States and the world even Domestic Shorthair cats commonly have type-B blood. 21 • 22 No commercial feline blood banks are presently available. The Veterinary Hospital of the University of Pennsylvania will ship type-B blood on request on an emergency basis. Ideally, type-AB cats should be transfused with type-AB blood. As type-AB cats are extremely rare, one is not likely to find a type-AB donor. However, as type-AB cats lack alloantibodies to type-A and typeB cells, they can be safely transfused with type-A blood. The small amount of anti-Bin the plasma of the type-A blood transfusion appeared not to have any deleterious effects. 18• 23 BLOOD COLLECTION AND STORAGE

Before collection of blood from a donor cat, a physical examination is performed and the body weight and PCV /hemoglobin (Hb) concentration are obtained. The PCV and Hb concentration must be greater than or equal to 35% and 11 g/ dL, respectively. Good-tempered cats wrapped in a towel may well accept blood collection without sedation; however, many cats must be sedated for blood collection. A combination of ketamine (1 to 2 mg/kg), diazepam (0.1 mg/kg), and atropine (0.01 mg/kg) can be administered intravenously. Other sedatives such as acepromazine cause hypotension and interfere with platelet function and should be avoided. Most of the guidelines for canine· blood collection also apply for cats. The jugular veins are the preferred site of blood collection. The neck must be clipped and aseptically prepared. Blood can be collected with a closed collection system consisting of a 150-mL multipurpose blood donor bag with the appropriate amount of anticoagulant (1 mL per 9 mL of blood) attached to a vacuum chamber (Animal Blood Bank, Dixon, CA). 30 Alternatively, because of the low

1314

GRIOT-WENK & GIGER

blood flow, one might use a 19/21-gauge butterfly catheter (Abbott Laboratories, North Chicago, IL) or 20-gauge needle attached to a threeway stopcock and sterile 10- to 30-mL syringes containing the anticoagulant. Collecting the blood with separate, single syringes requires the transfer of blood from the syringes into a 150-mL transfer pack unit (Baxter Healthcare, Corp., Fenwal Division, Deerfield, IL). This is considered an open system with the potential hazard of bacterial contamination. While collecting the blood, the collection bag or the syringes should be gently inverted to mix the blood with the anticoagulant and thereby prevent clot formation. After collection the anticoagulated blood can be allowed to flow back into the tubing to create segments for blood crossmatching. Sealing of the blood units is best achieved with heat sealers (Baxter Healthcare, Corp.) or clamping with hand sealer clips (Baxter Healthcare, Corp.). The blood units should be labeled with date of collection, donor name, blood type, amount of blood, and type of anticoagulant used. Feline blood should be anticoagulated with sterile citrate (3.8%) with or without preservatives such as phosphate, adenine, and dextrose for storage. Citrate-phosphate-dextrose-adenine (CPDA-1), citrate-phosphate-dextrose (CPO), and acid-citrate-dextrose (ACD) can be obtained from human blood bags or by a separate order and are typically mixed at least in a ratio of 1 mL of anticoagulant to 9 mL of blood. Blood collected aseptically using the closed system in CPDA-1 bags can be stored at 1oc to 6°C up to 5 weeks as long as the blood bags are turned twice weekly,S which improves red blood cell viability. The function and viability of feline red blood cells depend mainly on the ability to generate ATP through anaerobic glycolysis. The release of oxygen is, unlike in dogs, independent of 2,3-diphosphoglyceride. 25 If CPO or ACD is used, blood should only be stored for 3 or 4 weeks, respectively. 31 Blood collected with the syringe method (open system) is not intended for long-term storage. Similar to sodium citrate, heparin also contains no preservatives. However, heparin causes platelet aggregation and inhibits coagulation factors in addition to having no preservative effect and is therefore not recommended as an anticoagulant. RISKS OF DONATING BLOOD

Even under optimal circumstances a small risk remains for the donor cat of an adverse reaction to blood collection. Fatalities attributed to blood donation have been observed only rarely. In human blood donors, deaths after blood donation are generally attributed to underlying, concurrent illnesses33; thus, each donor cat must be examined carefully and only healthy, large cats should be used. Complications with blood donations may include any adverse reactions to sedation during blood collection such as induction of hepatic lipidosis and liver failure or hypovolemic shock. Therefore, donors must be observed during and up to 4 hours after the donation, particularly for signs of hypovolemia

FELINE TRANSFUSION MEDICINE: BLOOD TYPES AND THEIR IMPORTANCE

1315

(tachycardia, cold extremities, weakness, depression, and collapse). Because of the possible complication of hypovolemia and shock, some clinicians routinely replace some of the blood volume with intravenous crystalloid solution (two to three times the volume of the collected blood). Repeated venipunctures may induce thromboembolic complications. ADMINISTRATION OF BLOOD TO CATS

Refrigerated blood may be gently prewarmed to temperatures between 22°C and 37°C immediately before the transfusion. Blood units can be warmed either by keeping the unit at room temperature for 30 to 60 minutes or by placing the unit in a water bath not to exceed 37°C for 30 minutes. Some warming of blood can also be achieved by placing the tubing of the blood administration set through a warm water bath (37°C or less). Warming with a microwave oven is not recommended because of the risk of hemolysis. Pretreatment with antihistamines or corticosteroids or both is unnecessary and has not been proven to avert or ameliorate transfusion reactions in cats or any other species. All blood samples for diagnostic purposes should be drawn before the transfusion if permitted by the patient's condition. The preferred route of administration is via an indwelling intravenous (16- to 22-gauge needle) catheter. In kittens or animals with no accessible veins, the intraosseous route may be chosen because nearly all the transfused cells will be circulating in the vasculature within 5 minutes. 32 The intraperitoneal route is not recommended. Any blood or its components must be given through a commercially available blood administration set with an in-line 170-J.Lm filter (Baxter Healthcare, Corp.) to remove any clots or cell debris. For cats, the use of a pediatric blood filter with reduced dead space (Hemo-Nate Filter, Gesco International, San Antonio, TX) may be preferred over the long regular administration tubing. Sterility must be maintained when connecting a blood unit to the infusion set and the tubing to the catheter. The rate of transfusion depends on the underlying condition of the patient. For instance, a cat with hemorrhagic shock can be given a transfusion as quickly as possible, whereas a cat with cardiac failure may not tolerate a transfusion rate of more than 1 mL/kg/h. A normal rate is 10 mL/kg/h and the transfusion should be completed within 4 hours (American Blood Bank Association guidelines) to avoid bacterial contamination and functional loss of blood elements. Most cats also tolerate intermittent bolus injections of blood from a syringe attached to a pediatric blood filter (Hemo-Nate Filter). While being transfused the patient should be off food to prevent vomiting because transfusions may induce nausea. To avoid hemolysis or hemagglutination, no other kind of fluid or fluid with medications (except for physiologic saline) should be given through the same venous access.

1316

GRIOT-WENK & GIGER

Even when administering only blood-typed and crossmatched blood, transfusions should be started slowly at a rate of 1 to 3 mL over the first 5 minutes while the recipient is evaluated for any adverse reaction. The patient should also be monitored carefully throughout and after the transfusion, which is best achieved by obtaining baseline values of vital signs (temperature, heart rate, and respiratory rate), PCV, and total solids (TS) before the transfusion. These parameters can then be assessed during and after the transfusion; PCV and TS should be determined at least before and 1 and 24 hours after completion of the blood transfusion. The volume of blood to be administered depends on the degree of anemia, clinical status, and size of the animal. The following formula can be used as a guideline: volume of whole blood (mL) = PCV increase desired(%) X body weight (kg) X 2 Assuming a mean PCV of 37% of the donor blood, administering 3 mL of whole blood per kilogram body weight typically increases the PCV by approximately 1%. Thus, a feline unit of whole blood (50 mL) would raise the PCV of a cat weighing 5 kg by about 5%. If appropriately collected and stored, the transfused AB-matched erythrocytes are expected to have a normal lifespan of approximately 70 days. 18 Patients need not be transfused with the aim of restoring a normal PCV. Typically, a PCV of more than 20% will stabilize a sick cat and safely allow anesthesia and surgical procedures.

ADVERSE REACTIONS TO BLOOD TRANSFUSIONS

Blood transfusions are a safe and effective form of supportive therapy as long as appropriate blood banking techniques are used. Acute hemolytic transfusion reactions resulting from AB-mismatched blood transfusions can be life threatening; however, nearly all such reactions can be avoided by administering only blood-typed and crossmatched feline blood that was properly collected, stored, and administered. Other transfusion reactions include pyrexia, vomiting, and urticaria, which most commonly cause mild and transient signs. In animals with hepatic or cardiac failure, hypocalcemia and circulatory overload may also be observed. Most adverse reactions occur during or shortly after a transfusion. The earlier the signs occur the more serious the complications. In a recent retrospective survey 12 adverse reactions occurred among 246 transfusions; most were transient mild reactions, but one death also occurred. 26 At the earliest suspicious sign of an adverse reaction the transfusion should be interrupted immediately and the cause of the sign should be identified by reviewing the compatibility and quality of the blood. Manifestations of the underlying disease process or drug reaction

FELINE TRANSFUSION MEDICINE: BLOOD TYPES AND THEIR IMPORTANCE

1317

must also be considered as the cause. The most common adverse reactions are outlined below according to clinical signs. Pyrexia

A rise in body temperature of more than 1oc during or within 4 hours of a transfusion is defined as an adverse reaction, and transfusionrelated pyrexia may well be the most common transfusion reaction. It may be caused by an acute hemolytic reaction or bacterial contamination of a unit of blood, but is, as in humans, probably caused mainly by antibodies of the recipient against donor leukocytes, platelets, and/ or plasma proteins. Unfortunately, these latter antibodies are not detected by blood typing or crossmatching and these reactions therefore are difficult to avoid. If pyrexia is associated with hemolysis it may be the result of blood-type incompatibility and chemical, bacterial, and physical lysis. Units with discolored plasma should be discarded. Diagnosis and management of hemolytic transfusion reactions are discussed below. Pyrexia caused by bacterial contamination requires immediate treatment for septic shock. If hemolysis and sepsis have been ruled out, the transfusion may be slowly continued. Fortunately, nonhemolytic, noninfectious pyrexia is usually of transient nature and further intervention with antipyretics is rarely necessary. Close monitoring of the patient is warranted, however, and blood from a different compatible donor should be used if additional transfusions are needed in the future. Vomiting

Vomiting occurs commonly during or after a transfusion and can be related to feeding an animal immediately before, during, or after a transfusion. It may also be observed with rapid administration of blood (greater than or equal to 10 mL/kg/h). If vomiting is the only clinical sign observed and a hemolytic transfusion reaction has been ruled out, the transfusion may be restarted at a slower rate after 10 to 15 minutes. Hemolysis

The most serious transfusion reaction is hemolysis resulting from immediate destruction of donor erythrocytes by the presence of naturally occurring alloantibodies during or shortly after the transfusion. Acute hemolytic transfusion reactions have recently been studied experimentally5· 6• 18 and have also been observed clinically.4• 6• 16• 17• 34• 35 Hemolysis caused by AB-mismatched transfusions is particularly severe in type-B cats receiving type-A blood. In cases of AB-matched transfusions, transfused red blood cells have a half-life of about 35 days. 18 In AS-mismatched transfusions,

1318

GRIOT-WENK & GIGER

however, transfused red blood cells are rapidly destroyed. In particular, the half-life of the transfused type-A red blood cells in type-B cats is only minutes to a few hours because of the high titer of anti-A alloantibodies in type-B cats leading to massive intravascular hemolysis of all transfused type-A cells (Fig. 3). 18 Type-B cats receiving type-A blood exhibit marked clinical signs as a result of massive release of vasoactive and inflammatory compounds because of complement activation, resulting in hypotension and increased vagotonus. During the initial clinical phase the cat may be depressed, recumbent, or bradycardic, show apnea or hypopnea, exhibit cardiac arrhythmia and seizures, or may vocalize, defecate, urinate, or salivate (phase I). 5• 18 Some cats may die during this phase of acute hemolytic reaction. The subsequent recovery phase, which may last for hours, is characterized by tachypnea and tachycardia as a response to phase I. Signs of hemolysis such as hemoglobinemia and hemoglobinuria may become evident.4· 5• 18 These severe systemic signs are independent of the amount of blood given; as little as 1 mL of AB-incompatible blood is sufficient to cause life-threatening signs. 5 • 18 Hemoglobinemia and hemoglobinuria, the hallmark signs of intravascular hemolysis, will only become apparent, however, when larger amounts of AB-incompatible blood are administered. In contrast, type-B erythrocytes transfused into type-A cats have a mean half-life of approximately 2 days because the weak titer of anti-B antibodies causes predominantly extravascular hemolysis without complement activation (see Fig. 3). 18 Therefore, the observed clinical signs in type-A cats receiving type-B blood are generally much milder than those of type-B cats. The transfusions are not efficacious, however, as a rapid drop in PCV to pretransfusion levels occurs within days. Because of the low frequency of type-B cats and the general availability of blood type-A donors, this reaction occurs very rarely clinically and has only been documented experimentally. 5• 18 Upon the first signs of an acute hemolytic transfusion reaction the transfusion is immediately interrupted. Records should be reviewed to identify any clerical errors regarding donor-patient compatibility. Blood typing may have to be repeated and crossmatching should be performed with blood of the unit and other typed donors. The blood bag should be examined for in vitro lysis of erythrocytes by centrifuging a capillary tube. Supportive therapy is provided depending on the severity of clinical signs. Venous access must be ensured and perfusion with adequate fluids maintained. Corticosteroids are unlikely to have any effect on pre-existing antibodies and therefore their use in an acute hemolytic transfusion reaction is questionable unless used as part of shock therapy. Other supportive therapy can include supplementation with oxygen, antihistamines, and epinephrine. In addition to pre-existing alloantibodies, erythrocyte antigens outside of the AB blood group system may potentially induce an immune response and cause delayed hemolytic transfusion reactions (transfused red blood cells are removed 1 to 3 weeks after their administration

FELINE TRANSFUSION MEDICINE: BLOOD TYPES AND THEIR IMPORTANCE

100 90

- ~ .

80

-

(ij

70 -

2:

60 -

Q)

50

.2: ::1 Vl

Ol

m

c: ~

Q)

Q.

40

-

30

~

"" "" '

I

0

.

0

recipient A, donor B

-

I

I

I

10

20

30

"" "" I

I

40

50

days

100 90 I80

1-

(ij

70

1-

2:

60 I-

.2: ::1 Vl Q)

Ol

~ ~ Q)

Q.

50 40 I30 I20 I10 0

:'-.

. . • .. .

""

""

.. l

10

-

"

I'

60

I

70

-

recipient B, donor A

-

-

" "',

1-

I

-

-- recipient B, donor B

.....

.

0

-

recipient A, donor A

20 f10 f-

1319

I

I

I

20

30

40

-

"" I

50

-

"

I '

60

I

70

days Figure 3. Erythrocyte survival curves of allogeneically matched and mismatched transfusions in type A and type B cats. The mean half-life of type B erythrocytes given to type A cats (mismatched) was only 2.1 days. Matched type B erythrocytes transfused to a type B cat had a mean half-life of 34.4 days, whereas mismatched (recipient B, donor A) erythrocytes had a mean half-life of only 1.3 hours.

1320

GRIOT-WENK & GIGER

because of newly formed alloantibodies.) However, delayed transfusion reactions have not been clinically documented in cats. Hemolysis can also be caused by the administration of hypotonic solutions through the same catheter as the blood, the overheating or freezing of the blood bags, sepsis, or drug reactions. Electrolyte Disturbances

Hypocalcemia may rarely be caused by large amounts of the anticoagulant citrate, which chelates calcium. Because citrate is rapidly metabolized by the liver, citrate toxicity is probably problematic only in patients with liver failure (e.g., due to hepatic lipidosis), in the case of rapid and massive blood transfusion (one blood volume or more), or if the anticoagulant-to-blood ratio was inappropriate. Hypocalcemia is suspected if trembling, tachycardia, or seizures are observed, and calcium gluconate may be given slowly intravenously with continuous monitoring of the electrocardiogram. Ideally, the ionized calcium level is determined before calcium supplementation to document the hypocalcemia. Circulatory Overload

Blood is a colloid and its components therefore have the potential to cause circulatory overload and signs of pulmonary edema such as dyspnea and coughing. Volume overload is mainly a problem in cats with cardiac dysfunction or chronic anemia and in cats given fluids simultaneously with blood. Therefore, transfusions in cats with heart disease or heart failure must be given slowly at a rate not exceeding 1 to 2 mL/kg/h. To reduce the volume, the use of packed red blood cells may be considered if only red blood cells are needed. Management of vascular overload includes immediate withdrawal of the transfusion; treatment with furosemide and oxygen support may be warranted. Urticaria

Allergic reactions caused by transfused allergens unrelated to ABmismatched transfusions that interact with IgE and activate mast cells are rare in cats. Urticaria, pruritus, generalized erythema, and anxiety may occur, in which case the transfusion must be interrupted. Depending on the severity of signs, corticosteroids, antihistamines, ephedrine, and/ or oxygen support may be required. Miscellaneous Reactions

Transmission of infectious diseases is always a potential hazard in transfusion medicine. In particular, the transmission of retroviruses, FIP

FELINE TRANSFUSION MEDICINE: BLOOD TYPES AND THEIR IMPORTANCE

1321

virus, and rickettsia is of major importance in cats and may only be detected years later. The risk of transmission of infections via blood transfusions cannot be completely eradicated but can be significantly reduced by using only healthy, vaccinated, screened, and most importantly, indoor cats.

CONCLUSION

Comprehension of the feline AB blood group system and the naturally occurring alloantibodies is pivotal to prevent life-threatening transfusion reactions. Blood should only be obtained from healthy donor cats using proper blood banking techniques. To grant safe and efficacious blood transfusions, blood compatibility must be ensured by performing blood typing or blood crossmatching or both. Moreover, these guidelines are simple and can easily be followed in any small animal practice. Transfusion reactions therefore can be avoided and many ill cats can be saved.

References 1. Andrews GA, Chavey PS, Smith JE: Production, characterization, and applications of a murine monocldnal antibody to dog erythrocyte antigen 1.1. J Am Vet Med Assoc 201:1549-1552, 1992 2. Andrews GA, Chavey PS, Smith JE, Rich L: N-glycolylneuraminic acid and N-acetylneuraminic acid define feline blood group A and B antigens. Blood 79:2485-2491, 1992 3. Auer L, Bell K: The AB blood group system in cats. Anim Genet 12:287-297, 1981 4. Auer L, Bell K: Feline blood transfusion reactions. In Kirk RW (ed): Current Veterinary Therapy IX. Philadelphia, WB Saunders, 1986, pp 515-521 5. Auer L, Bell K: Transfusion reactions in cats due to AB blood group incompatibility. Res Vet Sci 35:145-152, 1983 6. Auer L, Bell K, Coates S: Blood transfusion reactions in the cat. JAm Vet Med Assoc 180:729-730, 1982 7. Authement JM, Wolfsheimer KJ, Catchings S: Canine blood component therapy: Product preparation, storage, and administration. JAm Anim Hosp Assoc 23:483-493, 1987 8. Bticheler J, Cotter SM: Red cell biotinylation as a non-radioactive method of erythrocyte labelling. J Vet Intern Med 8:169, 1994 9. Bticheler J, Giger U: Alloantibodies against A and B blood types in cats. Vet Immunol Immunopathol 38:283-295, 1993 10. Butler M, Andrews GA, Smith JE: Reactivity of lectins with feline erythrocytes. Comparative Haematology International 1:217-219, 1991 11. Cain GR, Suzuki Y: Presumptive neonatal isoerythrolysis in cats. JAm Vet Med Assoc 187:46-48, 1985 12. Callan MB, Giger U: Transfusion medicine. In August JR (ed): Consultations in Feline Internal Medicine. Philadelphia, WB Saunders, 1994, pp 525-532 13. Casal ML, Giger U, Jezyk PF: Transfer of colostral antibodies from the queen to the kitten. J Vet Intern Med 8:171, 1994 14. Eyquem A, Podliachouk L, Milot P: Blood groups in chimpanzees, horses, sheep, pigs and other mammals. Ann NY Acad Sci 97:320-328, 1962 15. Giger U: Feline transfusion medicine. In Hohenhaus AE (ed): Problems in Veterinary Medicine, vol 4. Philadelphia, JB Lippincott, 1992, pp 600-611

1322

GRIOT-WENK & GIGER

16. Giger U: The feline AB blood group system and incompatibility reactions. In Kirk RW (ed): Current Veterinary Therapy XI. Philadelphia, WB Saunders, 1992, pp 470-474 17. Giger U, Akol KG: Acute hemolytic transfusion reaction in an Abyssinian cat with blood type B. J Vet Intern Med 4:315-316, 1990 18. Giger U, Bucheler J: Transfusion of type-A and type-B blood to cats. JAm Vet Med Assoc 198:411-418, 1991 19. Giger U, Bucheler J, Patterson OF: Frequency and inheritance of A and B blood types in feline breeds of the United States. J Hered 82:15-20, 1991 20. Giger U, Gorman NT, Hubler M, et al: Frequencies of feline type A and B blood types in Europe. Anim Genet 23(suppl. 1):17-18, 1992 21. Giger U, Griot-Wenk ME, Bucheler J, et al: Geographical variation of the feline blood type frequencies in the United States. Feline Practice 19:21-27, 1991 22. Giger U, Kilrain CG, Filippich LJ, et al: Frequencies of feline blood groups in the United States. JAm Vet Med Assoc 195:1230-1232, 1989 23. Griot-Wenk M, Giger U: Cats with type AB blood in the United States. J Vet Intern Med 5:139, 1991 24. Griot-Wenk M, Pahlsson P, Chisholm-Chait A, et al: Biochemical characterization of the feline AB blood group system. Anim Genet 24:401-407, 1993 25. Harvey JW: Erythrocyte metabolism. In Kaneko JJ (ed): Biochemistry of Domestic Animals, 4th ed. San Diego, Academic Press, 1989, pp 185-234 26. Henson MS, Kristensen AT, Armstrong PJ, Parrow J: Feline blood component therapy: Retrospective study of 246 transfusions. J Vet Intern Med 8:169, 1994 27. Holmes R: The occurrence of blood groups in cats. J Exp Biol 30:350-357, 1953 28. Ikemoto S, Sakuria Y, Fukui M: Individual difference within the cat blood group detected by isoagglutinin. Japanese Journal of Veterinary Science 43:433-434, 1981 29. Ingebringsten R: The influence of isoagglutinins on the final results of homoplastic transplantation of arteries. J Exp Med 16:169-177, 1912 30. Kaufman PM: Management of the feline blood donor. In Hohenhaus AE (ed): Problems in Veterinary Medicine, vol 4. Philadelphia, JB Lippincott, 1992, pp 555-564 31. Marion RS, Smith JE: Posttransfusion viability of feline erythrocytes stored in acidcitrate-dextrose solution. JAm Vet Med Assoc 183:1459-1460, 1983 32. Otto CM, Crowe DT: Intraosseous resuscitation techniques and applications. In Kirk RW (ed): Current Veterinary Therapy XI. Philadelphia, WB Saunders, 1992, pp 107-112 33. Sazama K: Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion 30:583-590, 1990 34. Wilkerson MJ, Meyers KM, Wardrop KJ: Anti-A isoagglutinins in two blood type B cats are IgG and IgM. Veterinary Clinical Pathology 20:10-14, 1991 35. Wilkerson MJ, Wardrop KJ, Giger U, Meyers KM: Two cat colonies with A and B blood types and a clinical transfusion reaction. Feline Practice 19:22-26, 1991

Address reprint requests to Urs Giger, PO, Dr med vet, MS, FVH, Department of Clinical Studies Veterinary Hospital University of Pennsylvania 3900 Delancey Street Philadelphia, PA 19104-6010