Identification of feline erythrocyte antigen 6 and lack of alloimmunization to feline erythrocyte antigen 4 in cats.

BACKGROUND: New feline erythrocyte antigens (FEAs) have been described based on the presence of naturally occurring alloantibodies (NOAb), but their immunogenicity and clinical relevance are poorly understood. HYPOTHESIS/OBJECTIVES: Describe the immunogenicity of FEA 4 after sensitizing FEA 4-negative cats lacking NOAb and characterize anti-FEA 4 alloantibodies produced, including their rate of appearance, agglutination titer, and immunoglobulin class. ANIMALS: Nineteen healthy type A cats were blood typed for FEAs 1 to 5 to identify suitable donor-recipient pairs for FEA 4 sensitization. METHODS: Four FEA 4-negative cats were transfused with FEA 4-positive red blood cells. Using a gel column technique, posttransfusion samples were screened daily for a week, weekly for a month, and monthly thereafter for anti-FEA 4 alloantibodies. RESULTS: Alloantibodies were not detected in the first 3 recipients despite repeated transfusions (1 and 3 additional transfusions for 2 and 1 recipients, respectively). In the 4th recipient, alloantibodies against its donor red blood cells were detected 21 days postsensitization. However, they were not directed against FEA 4, but rather against a novel FEA not yet described. The alloantibodies, named anti-FEA 6, remained detectable for >4 months after sensitization and were determined to be mostly immunoglobulin M based on sulfhydryl treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Feline erythrocyte antigen 4 does not appear to be immunogenic because repeated sensitization of 4 cats failed to produce detectable anti-FEA 4 alloantibodies. A new immunogenic antigen, named FEA 6, has been discovered, but additional studies are needed to document its clinical importance.

High prevalence of SARS-CoV-2 antibodies and low prevalence of SARS-CoV-2 RNA in cats recently exposed to human cases.

BACKGROUND: The primary objective of this cross-sectional study, conducted in Québec and Bristish Columbia (Canada) between February 2021 and January 2022, was to measure the prevalence of viral RNA in oronasal and rectal swabs and serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) amongst cats living in households with at least one confirmed human case. Secondary objectives included a description of potential risk factors for the presence of SARS-CoV-2 antibodies and an estimation of the association between the presence of viral RNA in swabs as well as SARS-CoV-2 antibodies and clinical signs. Oronasal and rectal swabs and sera were collected from 55 cats from 40 households at most 15 days after a human case confirmation, and at up to two follow-up visits. A RT-qPCR assay and an ELISA were used to detect SARS-CoV-2 RNA in swabs and serum SARS-CoV-2 IgG antibodies, respectively. Prevalence and 95% Bayesian credibility intervals (BCI) were calculated, and associations were evaluated using prevalence ratio and 95% BCI obtained from Bayesian mixed log-binomial models. RESULTS: Nine (0.16; 95% BCI = 0.08-0.28) and 38 (0.69; 95% BCI = 0.56-0.80) cats had at least one positive RT-qPCR and at least one positive serological test result, respectively. No risk factor was associated with the prevalence of SARS-CoV-2 serum antibodies. The prevalence of clinical signs suggestive of COVID-19 in cats, mainly sneezing, was 2.12 (95% BCI = 1.03-3.98) times higher amongst cats with detectable viral RNA compared to those without. CONCLUSIONS: We showed that cats develop antibodies to SARS-CoV-2 when exposed to recent human cases, but detection of viral RNA on swabs is rare, even when sampling occurs soon after confirmation of a human case. Moreover, cats with detectable levels of virus showed clinical signs more often than cats without signs, which can be useful for the management of such cases.

Validation of a cage-side agglutination card for Dal blood typing in dogs.

BACKGROUND: Although 98% of the canine population is Dal-positive, Dal-negative dogs are more common in some breeds such as Doberman Pinschers (42.4%) and Dalmatians (11.7%), and finding compatible blood for these breeds may be challenging, given limited access to Dal blood typing. OBJECTIVES: To validate a cage-side agglutination card for Dal blood typing and determine the lowest packed cell volume (PCV threshold) at which interpretation remains accurate. ANIMALS: One-hundred fifty dogs, including 38 blood donors, 52 Doberman Pinschers, 23 Dalmatians and 37 anemic dogs. Three additional Dal-positive canine blood donors were included to establish the PCV threshold. METHODS: Dal blood typing was performed on blood samples preserved in ethylenediaminetetraacetic acid (EDTA) <48 hours using the cage-side agglutination card and a gel column technique (gold standard). The PCV threshold was determined using plasma-diluted blood samples. All results were read by 2 observers, blinded to each other's interpretation and to the sample's origin. RESULTS: Interobserver agreement was 98% and 100% using the card and gel column assays, respectively. Overall, the sensitivity and specificity of the cards were 86%-87.6% and 96.6%-100%, respectively, depending on the observer. However, 18 samples were mistyped using the agglutination cards (15/18 by both observers): 1 false-positive (Doberman Pinscher), and 17 false-negative samples including 13 anemic dogs (PCV range, 5%-24%; median, 13%). The PCV threshold allowing reliable interpretation was determined to be >20%. CONCLUSIONS AND CLINICAL IMPORTANCE: Dal agglutination cards are reliable as a cage-side test, but results should be interpreted cautiously in severely anemic patients.

Production and characterization of a murine anti-dal monoclonal antibody for blood typing in dogs.

Considering the strong immunogenicity of the Dal antigen, and that > 98% of dogs, including blood donors, are Dal-positive, finding compatible blood for a previously transfused Dal-negative patient may be challenging. This is exacerbated by limited access to typing reagents, which currently rely on polyclonal antibodies (PAb) produced following sensitization of dogs. Therefore, the objective of this study was to produce and characterize an anti-Dal murine monoclonal antibody (MAb). Conventional hybridoma technology was used to produce MAb directed against canine red blood cells (cRBC). Briefly, female BALB/c mice were immunized via repeated intraperitoneal injections of washed Dal-positive cRBC (DEA 1,3,7 negative; DEA 4,5 positive) until serologic titers were sufficient (>1:1000). Following fusion with myeloma cells, 573 hybridoma cell culture supernatants were obtained and screened for MAb of interest using a gel column agglutination technique and known Dal-negative and Dal-positive cRBC. Fifteen supernatants led to cRBC agglutination, but only one had the desired pattern (i.e. anti-Dal). To assess its specificity and sensitivity, Dal blood typing of 62 canine EDTA-blood samples was performed using the anti-Dal MAb and two canine PAb: 45 Dal-positive and 17 Dal-negative were identified with 100% agreement between reagents (kappa =1). The anti-Dal MAb produced was further determined to be an IgG1. Conventional hybridoma technology, aided by a gel column technique, has enabled the production of a murine MAb specific against the canine Dal antigen. This will ensure long-term perennity of Dal blood typing, facilitate clinical management and research, as well as avoid resorting to repeat dog sensitization.

2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics.

OBJECTIVES: To systematically review available evidence and establish guidelines related to the use of thrombolytics for the management of small animals with suspected or confirmed thrombosis. DESIGN: PICO (Population, Intervention, Control, and Outcome) questions were formulated, and worksheets completed as part of a standardized and systematic literature evaluation. The population of interest included dogs and cats (considered separately) and arterial and venous thrombosis. The interventions assessed were the use of thrombolytics, compared to no thrombolytics, with or without anticoagulants or antiplatelet agents. Specific protocols for recombinant tissue plasminogen activator were also evaluated. Outcomes assessed included efficacy and safety. Relevant articles were categorized according to level of evidence, quality, and as to whether they supported, were neutral to, or opposed the PICO questions. Conclusions from the PICO worksheets were used to draft guidelines, which were subsequently refined via Delphi surveys undertaken by the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) working group. RESULTS: Fourteen PICO questions were developed, generating 14 guidelines. The majority of the literature addressing the PICO questions in dogs is experimental studies (level of evidence 3), thus providing insufficient evidence to determine if thrombolysis improves patient-centered outcomes. In cats, literature was more limited and often neutral to the PICO questions, precluding strong evidence-based recommendations for thrombolytic use. Rather, for both species, suggestions are made regarding considerations for when thrombolytic drugs may be considered, the combination of thrombolytics with anticoagulant or antiplatelet drugs, and the choice of thrombolytic agent. CONCLUSIONS: Substantial additional research is needed to address the role of thrombolytics for the treatment of arterial and venous thrombosis in dogs and cats. Clinical trials with patient-centered outcomes will be most valuable for addressing knowledge gaps in the field.

2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 1- Defining populations at risk.

OBJECTIVES: To expand the number of conditions and interventions explored for their associations with thrombosis in the veterinary literature and to provide the basis for prescribing recommendations. DESIGN: A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. The revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated in this iteration included heartworm disease (dogs and cats), immune-mediated hemolytic anemia (cats), protein-losing nephropathy (cats), protein-losing enteropathy (dogs and cats), sepsis (cats), hyperadrenocorticism (cats), liver disease (dogs), congenital portosystemic shunts (dogs and cats) and the following interventions: IV catheters (dogs and cats), arterial catheters (dogs and cats), vascular access ports (dogs and cats), extracorporeal circuits (dogs and cats) and transvenous pacemakers (dogs and cats). RESULTS: Of the diseases evaluated in this iteration, a high risk for thrombosis was defined as heartworm disease or protein-losing enteropathy. Low risk for thrombosis was defined as dogs with liver disease, cats with immune-mediated hemolytic anemia, protein-losing nephropathy, sepsis, or hyperadrenocorticism. CONCLUSIONS: Associations with thrombosis are outlined for various conditions and interventions and provide the basis for management recommendations. Numerous knowledge gaps were identified that represent opportunities for future studies.

Characterization of post-transfusion anti-FEA 1 alloantibodies in transfusion-naive FEA 1-negative cats.

OBJECTIVES: The aim of this study was to characterize anti-feline erythrocyte antigen (FEA) 1 alloantibodies following sensitization of FEA 1-negative cats, including their rate of appearance, agglutination titer over time and immunoglobulin class. A secondary aim was to obtain polyclonal anti-FEA 1 alloantibodies to increase the availability of FEA 1 blood typing. We also describe a case study documenting an acute hemolytic transfusion reaction in a transfusion-naive FEA 1-negative feline patient that received FEA 1-positive blood. METHODS: In this prospective clinical study, 35 cats with blood group type A underwent extensive blood typing for FEA 1-5. Two cats were identified as FEA 1-negative; these cats were transfused uneventfully with 50 ml of FEA 1-positive, but otherwise compatible, packed red blood cells. Post-transfusion blood samples were collected routinely as long as anti-FEA 1 alloantibodies were detected. Appearance of anti-FEA 1 alloantibodies was detected using a gel column crossmatch method. RESULTS: Anti-FEA 1 alloantibodies were detected as early as 5 days post-transfusion and remained detectable for over 400 days in one cat. Agglutination titers in both cats were relatively weak (1:1 to 1:8). The main immunoglobulin class was IgM. CONCLUSIONS AND RELEVANCE: Transfusion of FEA 1-negative, transfusion-naive cats with FEA 1-positive blood results in production of post-transfusion anti-FEA 1 alloantibodies as early as 5 days post-transfusion. Our results confirm the potential immunogenicity of FEA 1 and support crossmatching prior to a blood transfusion, even in transfusion-naive cats. Further studies are needed to better document the clinical importance of these post-transfusion antibodies, as well as to facilitate routine blood typing for the FEA 1 antigen in cats.

Risk of transmittable blood-borne pathogens in blood units from blood donor dogs in Canada.

BACKGROUND: Canine blood donors can be infected by various vector-borne or other pathogens that could be an important cause of morbidity and death in transfusion recipients. HYPOTHESIS/OBJECTIVES: To estimate and predict positivity to transmittable blood-borne pathogens in blood units collected from blood donor dogs in Canada. ANIMALS: Six thousand one hundred and fifty blood units from 1914 active blood donors registered to the Canadian Animal Blood Bank (CABB) between March 2010 and December 2016. METHODS: A registry-based retrospective study. Blood units were screened by SNAP 4Dx/4Dx Plus and PCR panel tests. Information on blood donors and test results were extracted from multiple databases and collated. Logistic regressions were used to predict blood unit positivity. RESULTS: Of 1779 blood units, 0.56% were antibody-positive for Anaplasma phagocytophilum/platys and 0% for Ehrlichia canis/ewingii. After exclusion of antibody-positive units to Anaplasma spp., 1.1% of 6140 blood units were PCR-positive to Anaplasma phagocytophilum, Bartonella spp., Brucella canis, "Candidatus Mycoplasma haematoparvum," Mycoplasma haemocanis, or a combination of these pathogens. Babesia spp., Ehrlichia spp., and Leishmania spp. were not detected. Units from the first blood collection from a dog had higher odds of testing PCR-positive (P < .001) for at least 1 pathogen than units from subsequent collections. CONCLUSIONS AND CLINICAL IMPORTANCE: Although our study indicates a low probability of detecting blood-borne pathogen in blood units collected by this Canadian blood bank, the presence of positive units highlights the importance of the preemptive identification and screening of blood units from healthy blood donors for safe blood banking, especially in first-time donors.

Identification of 5 novel feline erythrocyte antigens based on the presence of naturally occurring alloantibodies.

BACKGROUND: Since the discovery of the Mik antigen, several studies have described blood incompatibilities unrelated to the AB system in cats. OBJECTIVE: To estimate the prevalence of cats with non-AB incompatibilities associated with naturally occurring alloantibodies (NOAb), and to begin mapping the corresponding feline erythrocyte antigens (FEA). ANIMALS: Two hundred and fifty-eight type A cats. METHODS: Prospectively, cats were evaluated for the presence of NOAb by crossmatching in groups of 4-6 cats. When NOAb were detected in a cat, its plasma was used as reagent to assess for the presence of the corresponding FEA in all cats included thereafter, and agreement observed between results of this extensive blood typing was evaluated. RESULTS: The chance of detecting incompatibilities by randomly crossmatching 2 cats was 3.9%, which resulted in at least 7% of type A cats having NOAb. Blood typing and agreement analyses performed with 7 newly detected NOAb allowed the identification of 5 presumably distinct FEA. Feline erythrocyte antigens 1 and 5 were most frequent with prevalence of 84% and 96%, respectively. Only FEA 1-negative status was associated with a higher risk of presenting NOAb; with 16.7% of 42 FEA 1-negative cats having NOAb compared to 5.1% of 216 FEA 1-positive cats. CONCLUSIONS AND CLINICAL IMPORTANCE: This study represents a first step of FEA identification outside the AB system. Because of its prevalence and association with NOAb, FEA 1 might correspond to the Mik antigen.

Prevalence of Dal blood type and dog erythrocyte antigens (DEA) 1, 4, and 7 in canine blood donors in Italy and Spain.

BACKGROUND: The aim of this study was to determine the prevalence of Dal, and DEA 1, 4, 7 blood types, in a population of canine blood donors from Italy and Spain. Three hundred and twenty blood donor dogs receiving an annual health evaluation were included in the study. DEA 1 blood type was determined using an immunochromatographic strip technique while Dal, DEA 4 and 7 blood types were determined with polyclonal antisera using agglutination on gel columns. RESULTS: Out of 320 dogs blood typed 7 (2 Cane Corso and 5 Doberman Pinschers) (2.2%) were Dal negative; 137 (42.8%) were positive for DEA 1; 320 (100%) were positive for DEA 4 and 43 (13.4%) were positive for DEA 7. CONCLUSION: This study showed a similar prevalence of DEA 1, 7 and 4 to that reported in previous studies in the same, and in different, geographic areas, and provides new data on the prevalence of the Dal blood group in Italy and Spain. There was no significant difference (P = 0.8409) between prevalence of Dal negative blood types found in our population (2.2%) and the prevalence reported in a canine blood donor population from the USA (2.5%). Our study identified Dal negative dogs in a previously tested breed i.e. Doberman Pinschers, but also the Cane Corso breed was found to have Dal negative dogs.

Comparison of a closed system and an open system for blood collection in feline donors.

OBJECTIVES: This research aimed to evaluate the performance of a closed blood collection system and to compare it with an open system in terms of feasibility, tolerability by the donor, quality of blood collected and bacterial contamination. METHODS: Eight feline blood donors were prospectively and randomly subjected to both collection methods. Heart rate (HR), respiratory rate (RR) and blood pressure (BP) were evaluated before sedation, after sedation and after blood collection. The duration of the donation, the formation of a hematoma, and the degree of hemolysis and packed cell volume (PCV) of each blood unit were evaluated. Aliquot samples were aseptically collected from each unit and tested for bacterial contamination by culture and PCR on days 0, 14 and 28 of storage. RESULTS: There was no significant difference between collection methods for HR and RR at any time point. Before sedation, the mean systolic BP was significantly higher with the closed system (closed 169 mmHg, open 137 mmHg; P = 0.003). The average duration of collection was significantly shorter with the closed system (closed 3 mins 10 s, open 8 mins; P = 0.035); however, the prevalence of a successful blood collection with a single venipuncture and hematoma formation were not significantly different between systems. The mean unit PCV was significantly higher with the open system (closed 31%, open 34%; P = 0.026). On bacterial culture, 15/16 units were negative at all time points (closed 7; open 8). Using PCR, 5/16 units were positive for Ralstonia species for at least one time point (closed 3; open 2). CONCLUSIONS AND RELEVANCE: Our designed closed system appears to be well adapted to feline blood collection and was well tolerated by the donors, performing similarly to an open system, and could represent a valuable clinical device for the development of a feline blood bank, namely feline blood storage.

New findings associated with presumptive systemic lupus erythematosus in a kitten.

CASE SUMMARY: An 8-month-old neutered male domestic shorthair kitten was examined for anorexia, lethargy and palatine ulcers. Systemic lupus erythematosus (SLE) was suspected based on a positive antinuclear antibody (ANA) titer and six manifestations of autoimmunity: fever, paronychia, oral ulcers, proteinuria, thrombocytopenia and leukopenia. Mastocytemia was observed on the blood smear. Although the clinical presentation of this case meets the classification criteria for SLE in humans, tick-borne disease and histopathology evaluation of the oral and cutaneous lesions would have been necessary to support a definite diagnosis of SLE. Baseline ANA titration was performed in two laboratories with conflicting results, which may reflect substrate differences used for the titration, but a false-positive result cannot be excluded. The cat received prednisolone and all clinical and laboratory abnormalities resolved after two months of treatment. Subsequent ANA titers remained positive and were not correlated to the patient's clinical progression. RELEVANCE AND NOVEL INFORMATION: This report describes new findings associated with a presumptive diagnosis of SLE in a kitten, highlighting that SLE may not be ruled out even in young cats and may be associated with mastocytemia. ANA titration is part of the initial diagnostic work-up of SLE but is a non-specific test and discrepancies can be observed between laboratories. The titration of more specific antibodies such as those used in humans would be helpful to diagnose SLE. ANA titration may not correlate with clinical activity of SLE; hence, the interest of an ANA titer follow-up to establish disease control warrants further investigation.

Modified stall-side crossmatch for transfusions in horses.

BACKGROUND: After-hours or out-of-clinic crossmatches are often limited by the lack of access to specialized material and technical expertise. HYPOTHESIS/OBJECTIVES: The goal was to adapt a stall-side crossmatch test for pretransfusion evaluation in horses. ANIMALS: Twelve healthy mares (plasma and blood donors, teaching mares). METHODS: In a prospective study, blood from 12 mares was used to compare the results of 132 crossmatches performed with a rapid gel assay to crossmatches performed with a microgel column assay, and with predicted compatibilities based on blood types and detection of antibodies at a reference laboratory (microplate assay). The rapid gel assay protocol for dogs was adapted to decrease the formation of rouleaux that initially precluded equine erythrocytes migration through the gel. RESULTS: There was a good agreement between the rapid gel assay and the microgel assay as well as with the predicted compatibilities (κ > .6 for both). Agreement was higher between the microgel assay and the predicted compatibilities (κ = .8). The rapid gel assay failed to detect 6 predicted Aa incompatibilities (agglutinins-related), 3 of which were also not detected with the microgel assay. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on these results, the modified rapid gel assay could be useful in settings when access to the microgel assay is not available. Discrepancies between both gel techniques and predicted compatibilities were most often low-grade agglutination, which warrants further investigation to assess their clinical importance.

Clinical application of the American College of Veterinary Emergency and Critical Care (ACVECC) Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines to small animal cases.

OBJECTIVE: To illustrate the application of the Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines to the management of dogs and cats at risk of developing thrombosis using a case-based approach. ETIOLOGY: Dogs and cats become at risk of developing thrombosis from a wide range of conditions. These conditions often involve a specific insult followed by an inflammatory response and when combined with other contributing factors (eg, hypercoagulability, vascular endothelial injury, hemodynamic changes) create favorable conditions for thrombosis. DIAGNOSIS: Development of thrombosis in small animals remains challenging to demonstrate. Compatible clinical signs, the presence of known risk factors, and supporting diagnostic tests may be highly suggestive of the development of thrombosis. THERAPY: Therapeutic recommendations in accordance with the CURATIVE guidelines for dogs and cats are described in specific case vignettes presented. Discussion is centered on antithrombotic drug choices and dosing protocols, as outlined in Domains 2 and 3 of the CURATIVE guidelines. Where appropriate, guidelines related to therapeutic monitoring (Domain 4) and discontinuation of antithrombotics (Domain 5) were included. PROGNOSIS: In small animals at risk of developing thrombosis, overall prognosis may be improved by following consensus-based recommendations on the use of antithrombotics as outlined in the CURATIVE guidelines. Whether such interventions have any impact on outcome requires further investigation.

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 3-Defining antithrombotic protocols.

OBJECTIVES: To systematically examine the evidence for use of a specific protocol (dose, frequency, route) of selected antithrombotic drugs, in comparisons to no therapy or to other antithrombotic therapies, to reduce the risk of complications or improve outcomes in dogs and cats at risk for thrombosis. DESIGN: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence (LOE) and quality (Good, Fair, or Poor), and development of consensus on conclusions via a Delphi-style survey for application of the concepts to clinical practice. SETTINGS: Academic and referral veterinary medical centers. RESULTS: Databases searched included Medline via PubMed and CAB abstracts. Eight different antithrombotic drugs were investigated using a standardized Patient, Intervention, Comparison, Outcome (PICO) question format both for dogs and cats, including aspirin, clopidogrel, warfarin, unfractionated heparin (UFH), dalteparin, enoxaparin, fondaparinux, and rivaroxaban, generating a total of 16 worksheets. Most studies identified were experimental controlled laboratory studies in companion animals (LOE 3) with only four randomized controlled clinical trials in companion animals (LOE 1). CONCLUSIONS: Overall, evidence-based recommendations concerning specific protocols could not be formulated for most antithrombotic drugs evaluated, either because of the wide range of dosage reported (eg, aspirin in dogs) or the lack of evidence in the current literature. However, clopidogrel administration in dogs and cats at risk of arterial thrombosis, notably in cats at risk of cardiogenic thromboembolism, is supported by the literature, and specific protocols were recommended. Comparably, aspirin should not be used as a sole antithrombotic in cats with cardiomyopathy. Using the available safety profile information contained in the literature, the panel reached consensus on suggested dosage schemes for most antithrombotics. Significant knowledge gaps were highlighted, which will hopefully drive novel research.

American College of Veterinary Emergency and Critical Care (ACVECC) Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines: Small animal.

OBJECTIVES: To systematically review available evidence and establish guidelines related to the risk of developing thrombosis and the management of small animals with antithrombotics. DESIGN: Standardized, systematic evaluation of the literature (identified by searching Medline via PubMed and CAB abstracts) was carried out in 5 domains (Defining populations at risk; Defining rational therapeutic use; Defining evidence-based protocols; Refining and monitoring antithrombotic therapies; and Discontinuing antithrombotic therapies). Evidence evaluation was carried out using Population, Intervention, Comparison, Outcome generated within each domain questions to address specific aims. This was followed by categorization of relevant articles according to level of evidence and quality (Good, Fair, or Poor). Synthesis of these data led to the development of a series of statements. Consensus on the final guidelines was achieved via Delphi-style surveys. Draft recommendations were presented at 2 international veterinary conferences and made available for community assessment, review, and comment prior to final revisions and publication. SETTINGS: Academic and referral veterinary medical centers. RESULTS: Over 500 studies were reviewed in detail. Worksheets from all 5 domains generated 59 statements with 83 guideline recommendations that were refined during 3 rounds of Delphi surveys. A high degree of consensus was reached across all guideline recommendations. CONCLUSIONS: Overall, systematic evidence evaluations yielded more than 80 recommendations for the treatment of small animals with or at risk of developing thrombosis. Numerous significant knowledge gaps were highlighted by the evidence reviews undertaken, indicating the need for substantial additional research in this field.

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 1-Defining populations at risk.

OBJECTIVES: Thrombosis is a well-recognized phenomenon in dogs and cats with a significant impact on morbidity and mortality. Despite growing awareness of thrombosis and increased use of antithrombotic therapy, there is little information in the veterinary literature to guide the use of anticoagulant and antiplatelet medications. The goal of Domain 1 was to explore the association between disease and thrombosis in a number of conditions identified as potential risk factors in the current veterinary literature, to provide the basis for prescribing recommendations. DESIGN: A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. Revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated included immune-mediated hemolytic anemia, protein-losing nephropathy, pancreatitis, glucocorticoid therapy, hyperadrenocorticism, neoplasia, sepsis, cerebrovascular disease, and cardiac disease. SETTINGS: Academic and referral veterinary medical centers. RESULTS: Of the diseases evaluated, a high risk for thrombosis was defined as dogs with immune-mediated hemolytic anemia or protein-losing nephropathy, cats with cardiomyopathy and associated risk factors, or dogs/cats with >1 disease or risk factor for thrombosis. Low or moderate risk for thrombosis was defined as dogs or cats with a single risk factor or disease, or dogs or cats with known risk factor conditions that are likely to resolve in days to weeks following treatment. CONCLUSIONS: Documented disease associations with thrombosis provide the basis for recommendations on prescribing provided in subsequent domains. Numerous knowledge gaps were identified that represent opportunities for future study.