Increasing patient safety in veterinary ... - Wiley Online Library

Clinical Practice Review

Journal of Veterinary Emergency and Critical Care 19(1) 2009, pp 66–73 doi:10.1111/j.1476-4431.2009.00387.x

Increasing patient safety in veterinary transfusion medicine: an overview of pretransfusion testing Lynel J. Tocci, DVM, MT(ASCP)SBB and Patty J. Ewing, DVM, MS, DACVP

Abstract Objectives – To review the principles and available technology for pretransfusion testing in veterinary medicine and discuss the indications and importance of test performance before RBC transfusion. Data Sources – Current human and veterinary medical literature: original research articles and scientific reviews. Summary – Indications for RBC transfusion in veterinary medicine include severe anemia or tissue hypoxia resulting from blood loss, decreased erythrocyte production, and hemolyzing conditions such as immunemediated anemia and neonatal isoerythrolysis. Proper blood sample collection, handling, and identification are imperative for high-quality pretransfusion testing. Point-of-care blood typing methods including both typing cards and rapid gel agglutination are readily available for some species. Following blood typing, crossmatching is performed on one or more donor units of appropriate blood type. As an alternative to technically demanding tube crossmatching methods, a point-of-care gel agglutination method has recently become available for use in dogs and cats. Crossmatching reduces the risk of hemolytic transfusion reactions but does not completely eliminate the risk of other types of transfusion reactions in veterinary patients, and for this reason, all transfusion reactions should be appropriately documented and investigated. Conclusion – The administration of blood products is a resource-intensive function of veterinary medicine and optimizing patient safety in transfusion medicine is multifaceted. Adverse reactions can be life threatening. Appropriate donor screening and collection combined with pretransfusion testing decreases the occurrence of incompatible transfusion reactions. (J Vet Emerg Crit Care 2009; 19(1): 66–73) doi: 10.1111/j.1476-4431.2009.00387.x

Keywords: blood typing, crossmatching, gel column agglutination, neonatal isoerythrolysis, transfusion reaction

Introduction RBC transfusions in small and large animal veterinary medicine have become increasingly more common and are an integral part of lifesaving and advanced treatment. Often the indication for a transfusion is in the emergency or surgical setting. Life-threatening anemia from acute hemorrhage, as well as hemolysis due to drugs or toxins, immune-mediated diseases, severe nonregenerative conditions, and neonatal isoerythrolysis (NI), are all situations that may require a transfusion. Advancements in critical care medicine have moved transfusion medicine to the forefront of manFrom the Department of Veterinary Emergency and Specialty Center of New England, Waltham, MA 02454 (Tocci); and the Department of Pathology, Angell Animal Medical Center, Boston, MA 02130 (Ewing). Address correspondence and reprint requests to Dr. Lynel J. Tocci, Department of Veterinary Emergency and Specialty Center of New England, Waltham, MA 02454. Email: [email protected]

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agement of these cases. Today, it is not uncommon to have patients with previous transfusion histories requiring additional transfusions. For this reason, there is a growing need for rapid and reliable point-of-care pretransfusion testing methods in many areas of veterinary medicine. Ideally, blood typing and crossmatching should be performed in all patients requiring a transfusion.1,2 Recent emphasis in veterinary transfusion safety has focused on appropriate donor screening for blood-borne infectious diseases. In 2005, the American College of Veterinary Internal Medicine and the Association of Veterinary Hematology and Transfusion Medicine issued a consensus statement to provide veterinarians with guidelines for canine and feline donor screening.3 This consensus statement represents and should be an attempt to standardize a part of pretransfusion testing; however, the importance of performing pretransfusion recipient blood typing and crossmatching has been & Veterinary Emergency and Critical Care Society 2009

Pretransfusion testing in veterinary medicine

discussed but has not been standardized to date. Effective quality assurance reviews of transfusion practices in the clinical setting of veterinary medicine are rarely performed and, to the authors’ knowledge, no published data or recommendations exist. Unlike the 24-hour service provided by clinical laboratories in human hospitals, on-site veterinary clinical laboratories, if available, have specific hours of operation. After hours, veterinarians and nursing staff become responsible for performing pretransfusion testing for their patients. In most other practices, laboratory testing is sent to off-site laboratories making turn around time a limiting factor. In the past, one limitation to the practice of highquality transfusion medicine was the lack of availability of point-of-care pretransfusion tests. Because of this there has been limited performance of compatibility testing in clinical practice despite the necessity. Fortunately, efficient and reliable test methods now exist. Advances in the technology beyond those used in the highly specialized referral center, veterinary hospital, or university are available and veterinarian awareness and use of these tests is imperative to all those practicing transfusion medicine. Adverse, incompatible transfusions can be life threatening. It is beyond the scope of this paper to detail the types of transfusion reactions seen in transfused animals and the reader is referred to other resources for that information.4 This paper will review the principles and available technology for pretransfusion testing before RBC transfusion in veterinary medicine and discuss the indications and importance of test performance in clinical practice regardless of the size of the facility.

tifact of collection or sample handling. It is also an indicator of antibody-induced intravascular RBC lysis. Whenever possible, a hemolyzed sample should be replaced with a new sample. If a hemolyzed sample is used, proper documentation should be made in the patient record. RBCs from the donor are required for a major crossmatch. Most stored RBC units contain integrally attached alliqotted segments to provide donor RBCs needed for the test. Plasma from the donor is required for a minor crossmatch. Most stored units of whole blood contain integrally attached aliquotted segments that can be centrifuged to provide donor plasma needed for the test. If segments are unavailable an EDTA sample from the donor can be used to obtain RBCs and plasma. In most cases testing may be performed hours to days before the need for a transfusion. However, based on recommendations in the human standards there may be situations in veterinary patients that require the sample not be older than 3 days for a crossmatch to be performed.6 This may include all animals with a history of pregnancy, previous transfusion, or both, as these situations may stimulate alloantibody production. Antibody production can occur in as little as 3–4 days from exposure and remain at detectable levels for years. The goal of the age of the sample is to reflect the patient’s current immunologic status. A recent study of 35 previously pregnant dogs investigated the incidence of alloantibodies. All dogs were pregnant 4 weeks to 24 months before sampling. No indication was found that pregnancy stimulated alloantibody production when compared with control dogs; however, 4 of the 35 (11.4%) pregnant dogs and 2 of the 15 (13.3%) control dogs were found to have alloantibodies.a

Samples The first step in pretransfusion testing is proper blood sample collection. In human medicine, errors in sample identification are the most common cause of hemolytic transfusion reactions.5 A correctly labeled sample is equally important in veterinary medicine. Each sample should be labeled with unique identifiers such as the name of the patient and the owner’s last name as well as a medical record number if available. Additionally, the date of collection and species is also recommended to be included on the sample label. Unlabeled or incorrectly labeled samples should not be used for testing. For blood typing, whole blood is collected into an EDTA anticoagulant tube. Blood is collected into a serum separator or clot tube for patients requiring a crossmatch. The sample is centrifuged and serum is used for testing. Good veinipuncture technique should be used to avoid hemolysis. Hemolysis can be an ar-

Blood typing Blood groups are defined by inherited antigens on the surface of the RBC. These genetic markers are species specific and vary in immunogenicity and clinical significance. Regardless of the species, RBC antigens contribute to the recognition of self and can elicit the production of an antibody when introduced into the circulation of an animal whose RBCs lack that antigen. In veterinary medicine, this becomes significant in situations of RBC transfusion and NI.

Canine Blood Types There are 7 internationally recognized canine blood groups categorized under the dog erythrocyte antigen (DEA) system. By convention, the canine blood types are designated using the DEA acronym followed by the numerical designation of the blood group. Commercial

& Veterinary Emergency and Critical Care Society 2009, doi: 10.1111/j.1476-4431.2009.00387.x

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L.J. Tocci & P.J. Ewing

typing antisera are available for DEA 1.1, 1.2, 3, 4, 5, and 7.7,8 Typing sera for DEA 6 and DEA 8 no longer exist. Both DEA 1.1 and 1.2 are considered significant in transfusion medicine. DEA 1.1 is known to be extremely antigenic and is the DEA antigen routinely determined in both patients and donors. DEA 1.1negative dogs exposed to DEA 1.1 positive RBC will likely become sensitized and produce anti-DEA 1.1 antibody. Anti-DEA 1.1 has been reported to cause an acute hemolytic transfusion reaction in a previously sensitized DEA 1.1 negative dog.9 DEA 3 has a low prevalence in dogs in the United States with a reported percentage of 6% while DEA 4 has a high prevalence with a reported percentage of 98%.4 A serious hemolytic transfusion reaction has been reported to occur in a previously sensitized DEA 4-negative dog from exposure to a DEA 4-positive RBC donor.10 DEA 5 and 7 antigens are present in 23% and 45% of the canine population, respectively, and controversy exists regarding the clinical significance of antibodies directed against these antigens.7,8 Antibodies to DEA 3, 5, and 7 occur in dogs negative for these antigens and delayed RBC survival is suspected to occur if transfused to antigen negative patients.7 Beyond the internationally recognized blood groups, a new antigen referred to as Dal antigen has recently been described.7,11 Blais and colleagues describe a transfusion-induced alloantibody in a Dalmatian that led to the investigation and resulted in the identification of the corresponding antigen. This newly recognized antigen called Dal was found to have no correlation to known DEA antigens. Additionally, the Dal antigen appears to be found in very high frequency in dogs other than Dalmatians. Further studies will be needed to determine the frequency of its occurrence universally and in specific breeds as well as the clinical significance of the anti-Dal antibody.11 Allogenic blood transfusions have the potential to introduce foreign antigens into the recipient. The ideal universal canine blood donor would be negative for the most common antigens other than those of high frequency in the universal population (eg, DEA 4).7 At this time, there is not a consensus as to the universal canine donor. At a minimum, DEA 1.1 typing should be performed on all donors and, time permitting, patients. In the emergent situation DEA 1.1-negative RBCs can be given to patients without a known blood type. Fortunately, without prior sensitization, dogs do not possess naturally occurring antibodies to DEA 1.1 making the first transfusion of DEA 1.1-positive RBCs unlikely to cause an immediate problem in a DEA 1.1-negative dog. Extended blood typing beyond DEA 1.1 would be indicated with incompatible crossmatches or transfusion reactions. 68

Feline Blood Types Until recently, the feline AB blood group system was thought to be limited to 3 blood types: type A, type B, and type AB. Like humans, cats possess naturally occurring antibodies against other blood group antigens that they lack. These alloantibodies are responsible for hemolytic transfusion reactions in mismatched or incompatible blood transfusions and cases of NI.12–15 Feline type A is the predominant type worldwide; however, incidence varies within breed and geographic location.12–14 Additional antigens outside the AB blood group have been suspected based on type-specific incompatible crossmatches. Weinstein and colleagues recently reported a blood-group antigen and clinically relevant alloantibody distinct from the AB blood group system that investigators named Mik. Their findings show that in Mik antigen negative cats, anti-Mik is a naturally occurring alloantibody similar to anti-A and anti-B present in type B and type A cats. The clinical significance of the Mik antibody was discovered following an acute hemolytic transfusion reaction in a renal transplant recipient.16 A universal feline blood donor does not exist. Blood typing should be performed in all patients and donors. At this time, type AB cats are considered universal RBC recipients as these cats do not have anti-A or anti-B alloantibodies. These cats can receive RBC units of type A, type B, or type AB. Importantly, these cats are not universal whole blood or plasma recipients as any antiA or anti-B in a donor unit can cause hemolysis or decreased RBC survival. Regardless of the patient’s blood type, a crossmatch in addition to blood typing is recommended. The findings of Weinstein and colleagues support the recommendations to perform a pretransfusion crossmatch in all feline transfusion cases regardless of blood type and transfusion history.

Equine Blood Types The International Society of Animal Genetics recognizes 7 blood groups in the horse: A, C, D, K, P, Q, and U. Research to date has defined 34 factors distributed within these 7 blood groups. Of the RBC antigens, Aa and Q, are reported to be the most antigenic.17 These antigens are responsible for the majority of cases of equine NI.18 The prevalence of antibodies causing NI is low; 1% in Thoroughbred mares and 2% in Standardbred mares.19 Blood typing of both stallions and mares before breeding or delivery will identify those at risk. Allogenic blood transfusions in horses have the potential to introduce foreign antigens into the recipient. The universal equine blood donor would, therefore, ideally be negative for the most common antigens.



Table 1: Laboratories performing equine blood-typing serology Hematology Laboratory Veterinary Medical Teaching Hospital University of California Davis Equine Parentage Testing and Research Laboratory University of Kentucky

Currently, a universal equine donor would be one that is negative for Aa and Qa. A Quarter Horse or Standardbred would most likely be negative for these factors.17 Figure 1: Example of canine and feline blood-typing card.

Blood Typing Methods The principle of all veterinary blood typing methods is a visible hemagglutination reaction between patient RBC surface antigens and known reagent monoclonal or polyclonal antisera. In human medicine tube, slide, microwell, and gel column methods are used. Serologic methods in veterinary transfusion medicine are similar to human technologies where tube, card, and gel column methods exist. The International Society of Animal Genetics is responsible for the standardization of bloodtyping reagents and blood-type nomenclature for small and large animals worldwide. Unfortunately, the availability of blood-typing reagents is limited in veterinary transfusion medicine and extended typing antisera are not widely available. Blood typing in large animals is limited to specialized laboratories (Table 1), and to date, no commercially available blood-typing reagents for in-house testing exist for horses. Commercially available point-of-care testing is available for cats and dogs (Table 2). Typing cardsb for canines and felines became available in the 1990s. These cards have a lyophilized reagent on the cards that is reconstituted with a diluent before performing the test. The cards contain a patient/donor test area as well as controls (Figure 1). For the dog, DEA 1.1 typing is available and for the cat, types A, B, and AB can be determined. The test is standardized and adaptable to

either the clinical laboratory or a point-of-care situation. False positives have been reported with the canine cards and weak reactions have been reported with the feline AB blood type.c,20,21 Until recently, typing cards were the only reasonable option for point-of-care testing in general practice. A novel gel column agglutination testd is now available for both canine and feline blood typing, which offers an alternative method (Figures 2 and 3). Instead of test cards, the gel column agglutination test utilizes microtubes that contain reagent as well as gel particles that act as a sieve. The principle of this test is a visible hemagglutination reaction where unagglutinated cells pass through the gel and pellet at the bottom of the microtube, while large agglutinates remain suspended in the gel. This test offers some advantages over the card method. In most cases, the result is visually easier to interpret. Additionally, the gel fixes the agglutination reaction so that it can be viewed for a longer time and allows multiple people to review the results. A photocopy of the results can be made and put in the patient’s medical record. Centrifugation is strictly controlled with a specially designed centrifuge. The centrifuge may be cost prohibitive for smaller facilities. In 2005, comparison studies of canine and feline blood-typing methods were published.20,21 In these

Table 2: Canine and feline blood typing tests

Manufacturer

Test

2008 approximate cost (USD)

DiaMedn DiaMedn RapidVet-H DMS Laboratories Inc RapidVet-H DMS Laboratories Inc

Canine gel typing cards Feline gel typing cards Canine typing cards Feline typing cards

$257.58/box $171.72/box $330.00/box $250.00/box

n

of of of of

12 12 15 15

cards cards cards cards

3 3 1 1

patient patient patient patient

tests/card tests/card test/card test/card

DiaMed Workstation includes centrifuge, specimen racks, pipettes, tips for pipettes, and diluent dispensers. $1885.00.


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Figure 2: Example of gel card for canine blood typing.

limited comparative studies, good correlation between the typing cards and the gel test was observed for DEA 1.1 typing in dogs and type A and type B cats. To date, no published data exist in the veterinary literature that include comparison of labor costs or cost per test of the gel versus the card test. Based on the authors’ personal experience where both testing methods are used, the gel method is less time consuming and the total cost incurred is less per test without including the start-up costs of purchasing the equipment (diluent dispensers, pipette, special centrifuge).

Antibody Screen In human blood-banking laboratories, the antibodyscreening test is used to detect the presence of unexpected RBC antibodies in the serum of a patient requiring a transfusion. This screening test detects clinically significant antibodies that could cause an immediate or delayed transfusion reaction. The patient’s serum is tested against RBCs of known phenotypes and can be performed in 3 phases (immediate, 371C incubation, and antiglobulin). The antibody-screening test will detect 99.9% of atypical antibodies. When an unexpected antibody is detected, its specificity can be de-

Figure 3: Example of gel card for feline blood typing.

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termined by testing the patient’s serum against a panel of reagent RBCs of known antigen composition. Once the specificity of the antibody is identified, antigen negative blood can be obtained for transfusion. The antibody screen is the pretransfusion test that is most important in human transfusion medicine. An antibody screen is currently not commercially available or a routine test used in small animal veterinary transfusion medicine. It has been utilized in specialized research settings to determine the specificity of antibodies.a,11 A variation of the antibody screen is available to evaluate mare serum for the presence of anti-RBC antibodies 30 days before foaling.17 Serum from the mare is tested against several different RBCs of known phenotypes that represent the major blood groups. This test is utilized to identify in advance at risk mares and foals in order to prevent NI.

Crossmatch The major crossmatch is the serological test designed to determine compatibility between the donor RBCs and the recipient (patient). The test is designed to help prevent incompatible RBC transfusions that could lead to immune-mediated hemolytic transfusion reactions. The test end point, like blood typing and antibody screening, is a visible hemagglutination reaction. Donor RBCs are incubated with recipient serum and observed for visible agglutination. If an agglutination reaction is demonstrated, an incompatibility exists and the donor RBCs should not be used for the transfusion. In this situation, the recipient has either a naturally occurring antibody or an induced alloantibody directed against an antigen present on the donor RBCs. If no agglutination is noted, the crossmatch is considered compatible and RBCs acceptable for transfusion. The minor crossmatch is the serological test designed to determine compatibility between the donor plasma and the recipient (patient). The transfusion of plasma containing RBC products (whole blood) has the potential to cause destruction of patient RBCs if the donor has an alloantibody. This test can therefore be helpful in determining potential transfusion problems. This should be considered in animals receiving whole blood transfusions. It is important to note that a compatible major crossmatch, minor crossmatch, or both does not guarantee normal RBC survival and does not completely eliminate the risk of the transfusion. Delayed transfusion reactions are caused by production of RBC antibody shortly after a transfusion of the corresponding antigen. Unfortunately, before the transfusion these antibodies are present in low titers and not detected by the cross-



match. Additionally, crossmatching does not prevent leukocyte, and protein reactions. A retrospective review of equine transfusions by Hurcombe et al supports this principle.22 Adverse reactions varying from urticarial to anaphylactic shock were reported in 7 of the 44 (16%) equine transfusions. In 2 of the 7 cases, adverse urticarial reactions occurred despite compatibility of both the major and minor crossmatch.22

Crossmatching Methods In human medicine, the crossmatch was first described in 1907 and has been modified multiple times. Major milestones in its evolution include multiple rapid techniques, from test tube to gel, as well as multiple types of enhancement media such as high protein, enzymes, and antiglobulin. If a slide or tube technique is used, the experience of the person performing the test is of high importance. Slide or tube agglutination reactions should be evaluated by a medical technologist or other appropriately trained individual to assure accurate interpretation. In small and large animal veterinary medicine, the saline agglutination or the indirect antiglobulin tube crossmatch is used. If performed correctly, these tube techniques should identify potential transfusion incompatibilities. However, the test can be time consuming and cumbersome and is most often reserved for the clinical laboratory setting. An alternative method, gel agglutination is currently available in veterinary practice for canine and feline crossmatching. The test is less time consuming, standardized, and does not require a medical technologist for interpretation. Additionally, reactions are stable and can be reviewed by multiple people at a later time. To date, there have been no published veterinary studies comparing crossmatching via tube assay to the gel agglutination method. However, the Dal antigen investigators utilized a gel technology in conjunction with a standard tube technology for crossmatching and reported agreement of both methods.11 In human medicine the gel test is comparable to the tube assay for both the indirect and direct antiglobulin tests.23–26 There are currently 2 commercially available gel tests for canine and feline crossmatching: one manufactured by DiaMed and one manufactured by DMS Laboratoriese,f (Figure 4). In equine transfusion medicine, there are 2 additional assays used that are based on the crossmatch methodology.17 These tests are designed to detect alloantibodies in the mare’s serum directed against the foal’s RBCs. The first test is a hemolytic assay that is available from veterinary laboratories experienced in equine serology (Table 1). In this test, serum from the mare is incubated with RBCs of the foal in the presence of complement. If an antigen-antibody reaction takes place, complement

Figure 4: Example of gel crossmatching tubes.

activation occurs, and subsequent lysis/hemolysis develops. This is considered a positive test result. The second test is the jaundice foal agglutination (JFA) test. The JFA test does not utilize complement. The test is based on serial dilution (1:2 to 1:128) of maternal serum or colostrum with a 5% suspension of the foal’s RBCs. If agglutination is present, the mare has antibodies directed against the foal’s RBCs (positive test). Positive results in either assay indicate incompatibility between the mare and foal, in which case, colostrum from the mare should not be given to the foal.17 The hemolytic assay is technically difficult to perform, which precludes its use as a rapid assay for the solo equine practitioner or small practice. However, the JFA has the advantage of being adapted for use as a point-ofcare test.

Indications for Pretransfusion Testing A wide variety of blood types exist in domestic animals and new antigens are being discovered with increasing frequency. Pretransfusion compatibility testing is designed to help ensure that the RBC transfusion will be effective while minimizing the risk of adverse reactions (immediate or delayed RBC destruction). The process should include medical record and history review of the patient before testing. The goals of these investigations include: (1) confirm previous blood type, if applicable, (2) determine if the recipient has ever been pregnant, (3) review prior transfusion history, and (4) document current drug therapy. Pretransfusion testing should then proceed to blood typing of the donor and the recipient followed by crossmatching of the donor RBCs with recipient serum by a reliable technique that can detect serological incompatibility. Standards in hu-


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Table 3: Recommended protocol before RBC administration 1. Obtain patient blood sample and label with patient first and last name, species, and date of collection 2. Check patient history for previous blood type and transfusion history 3. Perform blood type on patient sample 4. Select one or more donor units and verify blood type compatibility 5. Perform crossmatch 6. Label donor unit with recipient/patient identification

man medicine require the confirmation of patient’s blood type on each new sample received for test performance as well as verification of the donor unit blood type. To date, this has not been a requirement in veterinary medicine and may be cost prohibitive. Regardless, it is the responsibility of the veterinarian to have procedures in place to ensure optimal safety in blood transfusions. A recommended protocol before RBC administration is presented in Table 3. Blood samples with severe hemolysis, rouleaux, or agglutination are technically more challenging to blood type and crossmatch. In patients with autoantibodies, autoagglutination causes erroneous results in blood typing. Often these antibodies are cold reacting and require that blood samples are maintained at a warm temperature after collection and RBCs washed in warm saline before testing to prevent interference. If rouleaux is causing the spontaneous agglutination, washing the RBCs in saline will correct this by removing the proteins. It is the authors’ opinion that these specimens are best evaluated by the experienced medical technologist or other suitably trained individual.

Emergent or Routine RBC Transfusion for Anemia Emergent transfusion refers to the urgent need for RBC administration for patient survival (eg, massive hemorrhage). In such cases, delay in transfusion in order to perform pretransfusion testing may jeopardize the patient’s life. Fortunately, dogs and horses do not have clinically significant preformed naturally occurring antibodies against the RBC antigens most often implicated in immediate hemolytic transfusion reactions (eg, DEA 1.1, Aa), making the first RBC transfusion a low risk for incompatibility, but a high risk for sensitization. In cats, most fatal transfusion reactions are caused by incompatibilities in type B cats receiving type A RBCs. However, as the Mik antigen reminds us, there may be more blood types in cats than are fully characterized. When blood is urgently needed, the veterinarian must weigh the risk of uncrossmatched RBCs against the risk of delaying the transfusion. In the urgent setting, for dogs, DEA 1.1-negative blood should be given if available. In horses, Aa and Qa negative blood should be given. In both species subsequent transfusions should be cross72

matched. In contrast, crossmatching is always recommended for feline patients.

NI NI is an important hemolytic disease of the newborn foal and a major cause of fading kitten syndrome.27,28 NI is caused by a fetal-maternal blood group incompatibility resulting in destruction of fetal RBC by maternal alloantibody. In mares, this maternal alloantibody is produced in response to foreign antigens on the fetal RBC inherited from the sire. Mares are exposed to fetal RBCs from transplacental hemorrhage during gestation or parturition and alloantibody is produced in response. Sensitization could also be a result of a previous blood transfusion. In contrast, type B queens have naturally occurring anti-A antibodies so prior pregnancy or transfusion is not a requirement for antibody formation. In both species, maternal antibody is passively transferred to the foal or kitten through the colostrum, and hemolysis and resultant anemia occurs within hours to days after birth. NI foals are usually born from a second or subsequent pregnancy but in rare circumstances the first foal can be affected. Feline NI develops in type A or AB kittens born to type B queens. Foals and kittens severely affected by NI may require RBC transfusions. Donor RBC must be negative for the antigens causing the hemolysis. Suitable donors can be identified by performing a crossmatch. In the foal with NI, the optimal donor is the mare. It is important that only the RBCs be transfused as maternal alloantibody is present in the mare’s plasma as well as colostrum. NI kittens should receive type A RBCs. The tom is not an acceptable donor.

Conclusions Optimizing patient safety in transfusion medicine is multifaceted. It involves not only using high-quality RBC components, but also assuring the integrity of the transfusion process from donor collection through posttransfusion evaluation. This facet of human medicine is highly regulated by governmental (eg, Federal Drug Administration) and professional healthcare organizations (eg, Joint Commission of Accreditation of Healthcare Organizations, American Association of Blood Banks, and American College of Pathologists). Similar stringency does not currently exist in veterinary medicine, however, advances are being made. A worthwhile future consideration is for the American College of Veterinary Internal Medicine, Association of Veterinary Hematology and Transfusion Medicine, the American College of Veterinary Emergency Critical Care, and the



American Society for Veterinary Clinical Pathology to issue a consensus statement with recommendations for pretransfusion testing. The purpose of blood typing and crossmatching is to prevent incompatible RBC transfusions that could lead to immune-mediated transfusion reactions. These types of reactions can be life threatening. Anemic and hemorrhaging patients often require additional oxygen carrying capacity and RBC transfusions are one of the few treatments that adequately restore tissue oxygenation. The indication for RBC transfusion is a controversial topic in both human and veterinary medicine, and the decision of whether or not to transfuse is ultimately made by the attending doctor based on his/her clinical evaluation of the condition of the patient. Given this, the transfusion needs to be as safe as possible. As veterinary transfusion medicine continues to advance, mandatory performance of pretransfusion testing will improve patient safety. Furthermore, adverse reactions, when they occur should be documented and investigated. Today, point-of-care pretransfusion testing is readily available for dogs and cats and the crossmatch is becoming the most important pretransfusion test in small and large animal medicine. Emphasis is moving toward technologies that are sensitive, specific, streamlined, and easy to perform. If transfusions are being given, pretransfusion testing is no longer reserved for specialized veterinary care centers. It should be the standard of care before all RBC transfusions.

Footnotes a

b

c

d

e f

Blais MC, Rozanski EA, Hale AS, et al. Incidence of serum alloantibody in dogs with a known history of pregnancy (abstr) In: Proceedings of the American College of Veterinary Internal Medicine; 2007: Seattle, USA. Rapid Vet-H (canine and feline tying cards), DMS Laboratories Inc, Flemington, NJ. DiaMed-ID (canine and feline typing gel), DiaMed, Cressier sur Morat, Switzerland. Moritz A, Widmann T, Hale AS. Comparison of current typing techniques for evaluation of dog erythrocyte antigen 1.1 (abstr). In: Proceedings of the American College of Veterinary Internal Medicine; 1998: San Diego, USA. DiaMed-ID (crossmatch gel), DiaMed. Rapid Vet-H (companion animal crossmatch gel), DMS Laboratories, Inc.

References 1. Giger U, Jackson KV, Weinstein NM, et al. Feline blood typing and crossmatching to ensure blood compatibility: how to avoid hemolytic transfusion reactions and neonatal isoerythrolysis. In: Proceedings of the American College of Veterinary Internal Medicine; Seattle, USA, 2007. 2. Lanevschi A, Wardrop KJ. Principles of transfusion medicine in small animals. Can Vet J 2001; 42:447–454. 3. Wardrop KJ, Reine N, Birkenheuer A, et al. Canine and feline blood donor screening for infectious disease. J Vet Intern Med 2005; 19:135–142.

4. Hohenhaus AE, Rentko V. Blood transfusions and blood substitutes, In: Di Bartola SP. ed. Fluid Therapy in Small Animal Practice, 3rd ed. St. Louis, MO: Saunders; 2006, pp. 574–581. 5. Shulman IA, Downes KA, Sazama K, et al. Pretransfusion compatibility testing for red blood cell administration. Curr Opin Hematol 2001; 8:397–404. 6. Silva MA, ed. Standards for Blood Banks and Transfusion Services, 24th ed. Bethesda, MD: AABB; 2006. 7. Hale AS. Canine blood groups and their importance in veterinary medicine. Vet Clin North Am 1995; 25:1323–1333. 8. Hohenhaus AE. Importance of blood groups and blood group antibodies in companion animal. Transfus Med Rev 2004; 18: 117–126. 9. Giger U, Gelens CJ, Callan MB, et al. An acute transfusion reaction caused by dog erythrocyte antigen 1.1 incompatibility in a previously sensitized dog. J Am Vet Med Assoc 1995; 206:1358–1362. 10. Melzer KJ, Wardrop KJ, Hale AS, et al. A hemolytic transfusion reaction due to DEA 4 alloantibodies in a dog. J Vet Intern Med 2003; 17:931–933. 11. Blais MC, Berman L, Oakley DA, et al. Canine Dal blood type: a red cell antigen lacking in some Dalmatians. J Vet Intern Med 2007; 21:281–286. 12. Auer L, Bell K. The AB blood group system of cats. Anim Blood Groups Biochem Genet 1981; 12:287–297. 13. Giger U, Bucheler J, Patterson DF. Frequency and inheritance of A and B blood types in feline breeds in the United States. J Hered 1991; 82:15–20. 14. Giger U, Kilrain CG, Filippich LJ, et al. Frequencies of feline blood groups in the United States. J Am Vet Med Assoc 1989; 195:1230– 1232. 15. Knottenbelt CM, Addie DD, Day MJ, et al. Determination of the prevalence of feline blood types in the UK. J Small Anim Pract 1999; 40:115–118. 16. Weinstein NM, Blais MC, Harris K, et al. A newly recognized blood group in domestic shorthair cats: the mik red cell antigen. J Vet Intern Med 2007; 21:287–292. 17. Whiting JL, David JB. Neonatal isoerythrolysis. Compend Contin Educ Pract Vet 2000; 10:968–975. 18. Barker RN. Neonatal isoerythrolysis, In: Feldmen BF, Zinkl JG, Jain NC. eds. Schalm’s Veterinary Hematology, 5th ed. Baltimore: Lippincott Williams & Wilkins; 2000, pp. 175–176. 19. Polkes AC.. Neonatal isoerythrolysis: overview, management strategies and long-term outcome. In: Proceedings of the American College of Veterinary Internal Medicine, Charlotte, NC; 2003. 20. Giger U, Stieger K, Palos H. Comparison of various canine bloodtyping methods. Am J Vet Res 2005; 66:1386–1392. 21. Stieger K, Palos H, Giger U. Comparison of various blood-typing methods for the feline AB blood group system. Am J Vet Res 2005; 66:1393–1399. 22. Hurcombe SD, Mudge MC, Hinchcliff KW. Clinical and clinicopathologic variables in adult horses receiving blood transfusions: 31 cases (1999–2005). J Am Vet Med Assoc 2007; 2:267–274. 23. Bromilow IM, Eggington JA, Owen GA, et al. Red cell antibody screening and identification: a comparison of two column technology methods. Br J Biomed Sci 1993; 50:329–333. 24. Pinkerton PH, Ward J, Couvadia AS. An evaluation of a gel technique for antibody screening compared with a conventional tube method. Transfus Med 1993; 3:201–205. 25. Nathalang O, Chuansumrit A, Prayoonwiwat W, et al. Comparison between the conventional tube technique and the gel technique in direct antiglobulin tests. Vox Sang 1997; 72:169–171. 26. Novaretti MCZ, Jens E, Pagliarini T, et al. Comparison of conventional tube test technique and gel microcolumn assay for direct antiglobulin test: a large study. J Clin Lab Anal 2004; 18:255–258. 27. Gordon AA. Neonatal isoerythrolysis, In: Feldmen BF, Zinkl JG, Jain NC. eds. Schalm’s Veterinary Hematology, 5th ed. Baltimore: Lippincott Williams & Wilkins, 772 pp. 28. Bowling AT. Neonatal isoerythrolysis, In: Feldmen BF, Zinkl JG, Jain NC. eds. Schalm’s Veterinary Hematology, 5th ed. Baltimore: Lippincott Williams & Wilkins, 776 pp.


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