Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs.

Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.

Mesenteric thrombus associated with pulmonary, splenic, portal, and caval thrombi in a dog that was presented for an acute abdomen.

A 6-year-old Labrador retriever dog was presented for acute abdominal pain. A tentative diagnosis of mesenteric thrombosis was established antemortem. The dog was treated with supportive care and anti-coagulation but was ultimately euthanized due to disease-related complications. Necropsy examination confirmed an acute mesenteric thrombus along with widespread thromboembolic disease. Potential causes were protein-losing nephropathy, hepatopathy, and/or corticosteroid administration.

Thrombose mésentérique associée à des thromboses pulmonaire, splénique, portale et cavale chez un chien présenté pour un abdomen aigu. Un Labrador de 6 ans est présenté pour abdomen aigu. Un diagnostic de thrombose mésentérique est établi. Malgré le traitement, l'animal est euthanasié. L'autopsie confirme la thrombose de l'artère mésentérique ainsi que d'autres organes intra-abdominaux. Les causes potentielles sont une fuite urinaire de protéines, une atteinte hépatique, et/ou un traitement stéroïdien.(Traduit par les auteurs).

Effects of hematocrit and red blood cell-independent viscosity on canine thromboelastographic tracings.

BACKGROUND: It is well established that hematocrit (Hct) influences whole blood thromboelastography (TEG) tracings. Previous studies showed hypercoagulable TEG tracings in anemic patients despite clinical expectations that anemia often prolongs bleeding. TEG is a viscoelastic assessment of clot kinetics, and Hct is the main determinant of whole blood viscosity. TEG changes in anemia may be an in vitro artifact due to Hct effect on blood viscosity rather than true in vivo changes in hemostasis. The effect of changes in whole blood viscosity on TEG independent of Hct is not well understood. STUDY DESIGN AND METHODS: Twenty-one blood samples from seven dogs were manipulated to produce one of three Hct conditions (45, 20, and 10%). Each was tested in two situations: viscosity adjusted to normal by adding alginate (ALG) or dilution with equal volume of saline (SAL). Both samples were analyzed with TEG simultaneously. RESULTS: Twenty percent Hct plus ALG and 10% Hct plus ALG were significantly more viscous than their SAL counterparts (p=0.0156). Ten percent Hct plus SAL, 20% Hct plus SAL, and 45% Hct plus SAL all had different viscosities (p=0.006). Twenty percent Hct plus SAL and 10% Hct plus SAL had significantly shorter K and higher angle, MA, and G compared to their ALG counterparts as well as 45% Hct plus SAL (p<0.05). CONCLUSIONS: ALG samples with low Hct, normal viscosity showed hypocoagulable tracings, whereas SAL samples with low Hct, low viscosity showed hypercoagulable tracings. TEG variables are influenced by whole blood viscosity altered with ALG, independently of Hct.

Feline Aortic Thromboembolism: Recent advances and future prospects.

PRACTICAL RELEVANCE: Feline aortic thromboembolism (FATE) is commonly encountered in clinical medicine, especially in emergency situations. This often devastating syndrome usually develops secondarily to severe heart disease, and has short- and long-term consequences. CLINICAL FEATURES: The clinical presentation of FATE is consistent with peripheral ischemic neuropathy, usually in both pelvic limbs. Diagnosis is relatively straightforward, but can be assisted with Doppler ultrasound, point-of-care ultrasound or infrared thermal imaging. RECENT ADVANCES AND FUTURE PROSPECTS: Interpretation of survival rates in cats with FATE has been hampered by historically high admission euthanasia, but recent studies suggest a survival rate with supportive care of 30-40%. Moreover, with advances in post-FATE thromboprophylaxis, median survival times of over 1 year are being achieved. Future directions include use of thrombolytic agents and treatment of common FATE sequelae such as acute kidney injury and reperfusion injury. OUTLINE: This article, aimed at small animal veterinarians, including emergency practitioners, reviews key aspects of the clinical presentation, diagnosis and treatment options for FATE, with a view to guiding client and veterinarian decision-making. Three case studies are included to illustrate the practical application of information presented in the review. EVIDENCE BASE: There are limited prospective studies on FATE, although the recent literature reflects a resurgence in clinical research interest in the past few years. Advances in FATE treatment will benefit many cats and it is important that research efforts continue to identify appropriate treatment modalities.

Viscoelastic coagulation monitoring parameters in cats with acute arterial thromboembolism.

BACKGROUND: Hypercoagulability has been documented in cats with cardiac disease. However, hemostatic parameters, including viscoelastic coagulation monitoring (VCM) have not been reported in cats with arterial thromboembolism (ATE). HYPOTHESIS/OBJECTIVES: Compare VCM parameters in cats with acute cardiogenic ATE and in control cats. ANIMALS: Sixteen cats with ATE and 30 control cats. METHODS: Multicenter university-based prospective study. Cardiogenic ATE was diagnosed based on physical examination and by ultrasonographically-diagnosed left atrial enlargement. Viscoelastic coagulation monitor analysis, CBC, serum biochemistry profile and coagulation profile were performed at admission in cats with ATE. Analysis from healthy control cats was performed using blood collected by direct venipuncture. Our objective was comparison of VCM parameters clot time (CT), clot formation time (CFT), alpha angle (Angle), maximum clot formation (MCF), amplitude at 10 and 20 minutes (A10 and A20, respectively) and clot lysis index at 30 and 45 minutes (LI30 and LI45, respectively) between ATE and control cats. RESULTS: Cats with ATE had a decreased angle compared to control cats, with a median (range) of 43° (30-48°) compared to 47° (14-59°; P = .01). The parameters A10, A20 and MCF were decreased in ATE cats compared to control cats with a median (range) of 19 units (8-32) compared to 22 units (6-38), 24.5 units (11-40) compared to 29 units (10-47) and 29.5 units (13-44) compared to 33.5 units (14-53), respectively (P = .01, .01 and .01, respectively). The parameters CT, CFT, LI30 and LI45 were similar between groups (P = .22, .09, .62 and .34, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with cardiogenic ATE cats have VCM parameters consistent with hypocoagulability compared with healthy cats.

Breaking barriers in trauma research: A narrative review of opportunities to leverage veterinary trauma for accelerated translation to clinical solutions for pets and people.

Trauma is a common cause of morbidity and mortality in humans and companion animals. Recent efforts in procedural development, training, quality systems, data collection, and research have positively impacted patient outcomes; however, significant unmet need still exists. Coordinated efforts by collaborative, translational, multidisciplinary teams to advance trauma care and improve outcomes have the potential to benefit both human and veterinary patient populations. Strategic use of veterinary clinical trials informed by expertise along the research spectrum (i.e., benchtop discovery, applied science and engineering, large laboratory animal models, clinical veterinary studies, and human randomized trials) can lead to increased therapeutic options for animals while accelerating and enhancing translation by providing early data to reduce the cost and the risk of failed human clinical trials. Active topics of collaboration across the translational continuum include advancements in resuscitation (including austere environments), acute traumatic coagulopathy, trauma-induced coagulopathy, traumatic brain injury, systems biology, and trauma immunology. Mechanisms to improve funding and support innovative team science approaches to current problems in trauma care can accelerate needed, sustainable, and impactful progress in the field. This review article summarizes our current understanding of veterinary and human trauma, thereby identifying knowledge gaps and opportunities for collaborative, translational research to improve multispecies outcomes. This translational trauma group of MDs, PhDs, and DVMs posit that a common understanding of injury patterns and resulting cellular dysregulation in humans and companion animals has the potential to accelerate translation of research findings into clinical solutions.

Assessment of microcirculation variables and endothelial glycocalyx using sidestream dark field videomicroscopy in anesthetized dogs undergoing cardiopulmonary bypass.

Introduction: To evaluate microcirculation and endothelial glycocalyx (eGC) variables using sidestream darkfield (SDF) videomicroscopy in canine cardiopulmonary bypass (CPB). Methods: Dogs undergoing CPB for surgical correction of naturally-occurring cardiac disease were prospectively included. Variables collected included patient demographics, underlying cardiac disease, red blood cell flow (Flow), 4-25 µm vessel density (Density), absolute capillary blood volume (CBVabs), relative capillary blood volume (CBVrel) and eGC width assessed by perfused boundary region (PBR). Anesthetized healthy dogs were used as control. Microcirculation and eGC variables were compared at baseline under anesthesia (T0), on CPB prior to cross clamping (T1), after cross clamp removal following surgical correction (T2) and at surgical closure (T3). Results: Twelve dogs were enrolled, including 10 with a complete dataset. Median Flow was 233.9, 79.9, 164.3, and 136.1 µm/s at T0, T1, T2, and T3, respectively, (p = 1.00). Median Density was 173.3, 118.4, 121.0 and 155.4 mm/mm2 at T0, T1, T2, and T3, respectively, (p = 1.00). Median CBVabs decreased over time: 7.4, 6.6, 4.8 and 4.7 103µm3 at T0, T1, T2, and T3, respectively, (p < 0.01). Median CBVrel increased over time: 1.1, 1.5,1.1, and 1.3 103µm3 at T0, T1, T2, and T3, respectively, (p < 0.001). Median PBR increased over time: 1.8, 2.1, 2.4, 2.1 µm at T0, T1, T2, and T3, respectively, (p < 0.001). Compared to control dogs (n = 8), CPB dogs had lower CBVabs at T0. Conclusion: Alterations in eGC thickness and microvascular occur in dogs undergoing CPB for naturally-occurring cardiac disease.

Infrared thermography is a novel tool to assess small intestinal surface temperature in dogs undergoing laparotomy for foreign body obstruction.

OBJECTIVE: To evaluate local temperature differences directly over and adjacent to small intestinal foreign body obstruction (FBO) using infrared thermography (IRT) in dogs. ANIMALS: 49 client-owned dogs were initially enrolled. METHODS: In a prospective, clinical observational study, IRT was utilized to compare median small intestinal (SI) surface temperature differences at the site of FBO and segments oral and aboral before and after surgical resolution from April 24, 2019, to July 19, 2020. These differences were evaluated for correlation with canine acute patient physiologic and laboratory evaluation fast (APPLEfast) scoring, lactate, foreign body material (hard vs soft), and blood pressure. RESULTS: There was not a significant surface temperature difference between SI segments at the site of FBO, oral or aboral. After resolution of obstruction, there was a significant decrease in median temperature directly over the FBO (2.4 °C; IQR, -2.55 to 10.6 °C; P = .0043). A decrease in surface temperature of the oral SI segment was appreciated with FBO due to hard material (-1.7 °C; IQR, -5.2 to 3.4 °C), whereas soft material had an increase in SI surface temperature oral to the FBO (+1.1 °C; IQR, 0.3 to 3.2 °C). This difference did not achieve significance (P = .08; Z = 1.75). No correlation was found between APPLEfast, lactate, or blood pressure and SI segment temperatures. CLINICAL RELEVANCE: IRT may be useful diagnostic modality to identify changes in small intestinal surface temperature relating to FBO. Further evaluation is warranted to determine if IRT may be a clinically useful to evaluate intestinal perfusion.

Thromboelastographic results and hypercoagulability in dogs with surgically treated hepatocellular adenoma and carcinoma: A Veterinary Society of Surgical Oncology prospective study.

BACKGROUND: The most common haemostatic abnormality in dogs with cancer is hypercoagulability. A transient hypercoagulability has been documented in people with hepatocellular carcinoma (HCC) that resolves within weeks following hepatic tumour resection. OBJECTIVE: The objective was to compare the haemostatic status of dogs with liver tumours and healthy control dogs, by comparing coagulation and thromboelastography (TEG) measurements at three time points. METHODS: Liver tumour and healthy control dogs receiving surgery for liver lobectomy and ovariohysterectomy, respectively, were prospectively enrolled. All dogs had blood collected at three time points: pre-operative, 24 h post-operative and ~2 weeks post-operative. Haematological and haemostatic values were compared across time points in each group using repeated measures ANOVA tests. RESULTS: Ten and eight dogs were enrolled for the liver and control groups, respectively. Platelet count was significantly higher in the liver group than the control group at all time points, but within the normal range (pre-operative: 438.7 vs. 300.9 × 109 /L, p = .0078; 24 h post-operative: 416.2 vs. 283.9 × 109 /L, p = .0123; 10-14 days post-operative: 524.6 vs. 317.3 × 109 /L, p = .0072). The measure of the overall coagulant state (G-value) was significantly increased for the liver group compared to the control group at all time points (pre-operative: 15.6 vs. 8.6 d/sc, p = .0003; 24 h post-operative: 18.3 vs. 11.2 d/sc, p = .039; 10-14 days post-operative: 15.1 vs. 9.6 d/sc, p = .015). CONCLUSION: The liver group was hypercoagulable based on elevated G-values at all time points compared to the control group. This hypercoagulability was attributed to the effect of hepatic tumours alone, and not secondary to surgery and anaesthesia.

Comparison of placement characteristics using two intraosseous devices in canine and feline cadavers by novice users.

Introduction: Intraosseous (IO) catheterization enables rapid access to systemic circulation in critical patients. A battery-powered IO device (BPIO) utilized in veterinary practice is reliable in facilitating IO catheter placement. A new spring-powered IO device (SPIO) has been developed for people but has not been tested in veterinary patients. The goal of our study was to compare placement characteristics and flow rates achieved with the BPIO compared to the SPIO in animals when operated by novice users. Methods: Six veterinary students performed 72 catheterizations in the humeri and tibias of 12 dog and 6 cat cadavers. The user, cadaver, device, and site of placement were randomized. Flow rates were determined by three-minute infusions. Results: In dogs, overall success rates (50% BPIO, 46% SPIO; p = 0.775) and flow rates based on location were similar between devices. Successful placement was faster on average with the BPIO (34.4 s for BPIO and 55.0 s for SPIO, p = 0.0392). However, time to successful placement between devices was not statistically significant based on location (humerus: 34.7 s for BPIO and 43.1 s for SPIO, p = 0.3329; tibia: 33.3 s for BPIO and 132.6 s for SPIO, p = 0.1153). In cats, success rates were similar between devices (16.7% for BPIO and 16.7% for SPIO, p = 1.000), but limited successful placements prevented further analysis. Discussion: This is the first study to examine the use of the SPIO in animals, providing preliminary data for future IO studies and potential applications for training in the clinical setting.

Sidestream dark field imaging and biomarker evaluation reveal minimal significant changes to the microcirculation and glycocalyx in a canine hemorrhagic shock model.

OBJECTIVE: To investigate the effects of hemorrhagic shock and fresh whole blood resuscitation on the microcirculation and endothelial glycocalyx using sidestream dark field (SDF) imaging and plasma biomarkers. ANIMALS: 8 purpose-bred dogs. METHODS: Pressure-targeted hemorrhagic shock was induced in anesthetized dogs. SDF measurement of perfused boundary region and microcirculatory variables (RBC flow, total vessel density, and relative and absolute capillary blood volume), biomarker measurement (heparan sulfate, hyaluronan, VE-cadherin, and syndecan-1), mean arterial blood pressure, and cardiac output measurement were performed before anesthesia (TP0), after induction (TP1), after hemorrhagic shock (TP2), and after 50% retransfusion (TP3) and 100% retransfusion (TP4). RESULTS: At TP1, TP2, TP3, and TP4, mean arterial blood pressure was 74.25 ± 7.17 mm Hg, 49.50 ± 13.74 mm Hg, 63.50 ± 13.29 mm Hg, and 71.38 ± 8.77 mm Hg, and cardiac output was 2.57 ± 1.01 L/min, 0.8 ± 0.36 L/min, 1.81 ± 0.57 L/min, and 2.93 ± 1.22 L/min, respectively. Heparan sulfate, hyaluronan, syndecan-1, and VE-cadherin ranges were 24.80 to 77.72 ng/mL, 5.77 to 105.06 ng/mL, below detection to 1,545.69 pg/mL, and 0 to 2.52 ng/mL, respectively. Perfused boundary region, RBC flow, total vessel density, and relative and absolute capillary blood volume ranges were 1.75 to 2.68 µm, 89.6 to 584.5 µm/s, 51.7 to 1,914.3 mm/m2, 0.94 to 1.53 103 µm3, and 1.50 to 94.30 103 µm3, respectively. Heparan sulfate decreased significantly over time (P = .016). No significant differences were found for microcirculatory variables, perfused boundary regions, or other biomarkers. CLINICAL RELEVANCE: This was the first study to assess microvascular dysfunction and endothelial shedding in a canine hemorrhagic shock model using SDF microscopy (Glycocheck) and plasma biomarkers. Further studies are needed to determine clinical relevance.

Epsilon aminocaproic acid for the prevention of delayed postoperative bleeding in retired racing greyhounds undergoing gonadectomy.

OBJECTIVE: To evaluate the effects of epsilon aminocaproic acid (EACA) on the prevalence of postoperative bleeding in retired racing Greyhounds (RRG), and to assess its effects on selected thrombelastography (TEG) and fibrinolysis variables. STUDY DESIGN: Double-blinded, prospective, randomized study. METHODS: 100 RRG had elective ovariohysterectomy or orchiectomy and were administered EACA or placebo for 3 days after surgery. TEG variables were analyzed preoperatively and 24, 48, and 72 hours after surgery. RESULTS: Thirty percent (15/50) of RRG in the placebo group had delayed postoperative bleeding starting 36-48 hours after surgery compared with 10% (5/50) in the EACA group (P = .012). On the TEG variables, the slopes for R and K time were significantly different between treatment groups (P <.05); the R and K time decreased over time in the EACA group after surgery whereas they increased in the placebo group. The angle, maximal amplitude (MA), and G slopes were also significantly different between treatment groups (P = .001, .001, and .006, respectively). The angle, MA, and G increased postoperatively over time in the EACA group and decreased in the placebo group. All these changes are supportive of hypercoagulability associated with EACA administration. CONCLUSION: Postoperative administration of EACA significantly decreased the prevalence of postoperative bleeding in RRG undergoing surgery by increasing the clot strength.

Prospective investigation of factors associated with success on the American College of Veterinary Emergency and Critical Care certification examination (2016-2018).

OBJECTIVE: To assess the association of candidate attributes and residency training factors with success on the American College of Veterinary Emergency and Critical Care (ACVECC) board certification examination and to develop multivariable models of first-attempt success. DESIGN: Prospective survey-based study. SETTING: Post-assessment ACVECC examination candidates. ANIMALS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Comprehensive surveys were distributed to ACVECC examination candidates in 2016 to 2018 after completion of their assessments, but prior to publication of examination results. Unique anonymous candidate identification numbers were used to match survey responses to outcome data from the office of the ACVECC Executive Secretary. After curation to retain only the first response from each candidate, there were 97 unique candidate responses available for analysis. Univariate analyses identified multiple factors associated with first-attempt success and multiple differences between academic and private practice residency programs. Multivariable logistic regression modeling suggested that 5 factors were independently associated with first-attempt success on the ACVECC examination, specifically younger age, more weeks of study prior to the examination, training at a facility with more ACVECC Diplomates, training at a facility with more ACVECC residents, and having no requirement to manage both Emergency Room (ER) and Critical Care (CC) cases simultaneously. CONCLUSIONS: Numerous resident and training center factors are associated with success in the ACVECC board certification examination. Residents and training centers might be able to use these data to enhance training, but caution must be exercised because these data are associative only.

Safety profile of repeated infusion of platelet-like nanoparticles in healthy dogs.

OBJECTIVE: To assess the safety and efficacy of the platelet-like nanoparticle (PLN), and to assess its safety in repeated administration. ANIMALS: 6 purpose-bred dogs. PROCEDURES: The PLN was administered IV at 3 different doses using a randomized crossover design. Each dog received a full dose of 8 X 1010 particles/10 kg, half dose, and 10 times the dose, with a 14-day washout period between doses. Biochemical, prothrombin time, partial thromboplastin time, and fibrinogen analyses were performed at baseline and 96 hours postinfusion. A CBC, kaolin-activated thromboelastography, platelet function assay closure time, and buccal mucosal bleeding time were performed at baseline and 1, 6, 24, 48, 72, and 96 hours postinfusion. RESULTS: No significant changes were observed over time in the thromboelastography parameters, closure time, and buccal mucosal bleeding time. After the administration of the half dose, hematocrit levels decreased significantly at 1, 6, 24, 48, and 96 hours, with all values within the reference range. The platelet count was decreased significantly at hours 1, 6, 24, 48, and 72 after administration of the half dose, with values less than the reference range at all hours but hour 72. No significant changes in serum biochemistry, coagulation panel, and fibrinogen were observed for all doses. No adverse events were noted during the first infusion. Three dogs experienced transient sedation and nausea after repeat infusion. CLINICAL RELEVANCE: The PLN resulted in a dilution of hematocrit and platelets, and did not significantly alter hemostasis negatively. The safety of repeated doses should be investigated further in dogs.

Bilateral lysis of aortic saddle thrombus with early tissue plasminogen activator (BLASTT): a prospective, randomized, placebo-controlled study in feline acute aortic thromboembolism.

OBJECTIVES: The aim of this study was to investigate the impact of tissue plasminogen activator (TPA) on the treatment of feline aortic thromboembolism (FATE). METHODS: Cats diagnosed with FATE involving ⩾2 limbs were enrolled in a prospective, multicenter, double-blinded, randomized, placebo-controlled study within 6 h of an event. Diagnosis was made by clinical findings and one confirmatory criterion. Cats received placebo or TPA (1 mg/kg/h with the first 10% by bolus). All cats received pain control and thromboprophylaxis. The primary outcome was a change from baseline in a published limb score at 48 h. Secondary outcomes included 48 h survival, survival to discharge and complication proportions. Statistical analyses included pattern-mixture models, logistic regression and Fisher's exact, Student's t- and Mann-Whitney-Wilcoxon tests. RESULTS: Based on a power analysis, 40 cats were enrolled; however, only 20 survived to 48 h (TPA, n = 12; placebo, n = 8 [P = 0.34]). There was a statistically significant improvement in limb scores compared with baseline for both groups (P <0.001). Limb score at 48 h was 1 point lower (better) in the TPA group (P = 0.19). Thrombolysis had no statistically significant effect on 48 h survival (P = 0.22). Lower affected limb lactate was associated with better 48 h survival (odds ratio 1.53, 95% confidence interval 1.08-2.17; P = 0.02). The survival to discharge rates were 45% (TPA) and 30% (placebo; P = 0.51). Complications in the TPA and placebo groups included acute kidney injury (22% and 19%, respectively; P = 1.00) and/or reperfusion injuries (33% and 19%, respectively; P = 0.45). CONCLUSIONS AND RELEVANCE: Survival and complication rates of acute FATE were not different with or without thrombolysis. High in-hospital mortality decreased the statistical power to detect a statistically significant difference between treatments with regard to our primary outcome.

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.

Clinical features and outcome of septic shock in dogs: 37 Cases (2008-2015).

OBJECTIVES: To describe patient characteristics of dogs with septic shock, investigate markers of disease severity, and assess treatment impact on outcome. DESIGN: Retrospective study. SETTING: Single center, university veterinary teaching intensive care unit. ANIMALS: Thirty-seven dogs with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean number of organ dysfunction was 3.24 ± 1.0, and included cardiovascular (100%), respiratory (73%), hematologic (68%), renal (49%), and hepatic (32%) dysfunction. The gastrointestinal tract was the most common source of sepsis. Mean blood pressure prior to resuscitation was 50 ± 8 mm Hg. All dogs were given IV fluids before vasopressor therapy with a mean rate of 12.1 ± 11.0 mL/kg/h. All dogs were given antimicrobials, administered within a mean of 4.3 ± 5.7 hours after diagnosis. Dopamine or norepinephrine was administered IV, respectively in 51.3% and 37.8% of dogs, with a mean duration of hypotension of 2.6 ± 3.0 hours. Mortality rate was 81.1%. Survivors were more likely to have a feeding tube (P = 0.007) and to have gastrointestinal sepsis (P = 0.012), and less likely to have respiratory dysfunction (P < 0.001). APPLEFull scores (P = 0.014) and time to antimicrobial therapy (P = 0.047) were identified as predictors of mortality. Treatment bundles consisting of 7 interventions that may improve outcomes in people with septic shock were evaluated. Survivors received 4.1 ± 1.3 interventions, whereas nonsurvivors received 2.4 ± 1.4 (P = 0.003). CONCLUSIONS: Septic shock in dogs confers a guarded prognosis. Early antimicrobial therapy and the utilization of treatment bundles may increase survivability in dogs with septic shock. More research is warranted to investigate the impact of specific interventions on survival.

Retrospective evaluation of the use of hydrocortisone for treatment of suspected critical illness-related corticosteroid insufficiency (CIRCI) in dogs with septic shock (2010-2017): 47 cases.

OBJECTIVE: To evaluate characteristics of septic shock patients treated with hydrocortisone (HC) due to suspicion of critical illness-related corticosteroid insufficiency (CIRCI) as compared to septic shock patients without suspicion of CIRCI. DESIGN: Retrospective study between February 2010 and October 2017. SETTING: University teaching hospital ICU. ANIMALS: Data were collected for 47 dogs with septic shock. Twenty-one dogs were treated with HC (HC-treated) due to suspicion of CIRCI. Twenty-six dogs did not receive HC (non-HC-treated). INTERVENTIONS: HC was administered either as an intermittent IV bolus or as a constant rate infusion (CRI) to those patients with suspected CIRCI. MEASUREMENTS AND MAIN RESULTS: Significantly higher baseline APPLEfull scores and predicted mortality were detected in the HC-treated patients compared to non-HC-treated patients (0.87 vs 0.44 for predicted mortality, P = 0.039). Patients in the HC-treated group were on more vasopressors and cardiotonics than those in the non-HC-treated group (2.5 vs 1.5, P <0 .001). All patients initially responded to vasopressor administration, with average time to resolution of hypotension being 90 minutes for the HC-treated group compared to 60 minutes for the non-HC-treated group (P = 0.640). However, HC-treated patients took significantly longer to have a sustained resolution (a systolic blood pressure > 90 mm Hg or a mean blood pressure > 65 mm Hg for at least 4 h) of their hypotension after starting vasopressors, as compared to their non-HC-treated counterparts (8.5 vs 4 h, P = 0.001). Three (14.3%) HC-treated patients survived to discharge compared to 9 (34.6%) non-HC-treated patients, but this was not statistically significant. CONCLUSIONS: HC-treated patients had a higher baseline risk of mortality than non-HC-treated patients. There was no significant difference in survival between the HC-treated and non-HC-treated septic shock patients. Further studies are needed to evaluate the use of HC in patients with suspected CIRCI.

Resuscitation Patterns and Massive Transfusion for the Critical Bleeding Dog-A Multicentric Retrospective Study of 69 Cases (2007-2013).

Objective: To describe resuscitation patterns of critically bleeding dogs, including those receiving massive transfusion (MT). Design: Retrospective study from three universities (2007-2013). Animals: Critically bleeding dogs, defined as dogs who received ≥ 25 ml/kg of blood products for treatment of hemorrhagic shock caused by blood loss. Measurements and Main Results: Sixty-nine dogs were included. Sources of critical bleeding were trauma (26.1%), intra/perioperative surgical period (26.1%), miscellaneous (24.6%), and spontaneous hemoabdomen (23.1%). Median (range) age was 7 years (0.5-18). Median body weight was 20 kg (2.6-57). Median pre-transfusion hematocrit, total protein, systolic blood pressure, and lactate were 25% (10-63), 4.1 g/dl (2-7.1), 80 mm Hg (20-181), and 6.4 mmol/L (1.1-18.2), respectively. Median blood product volume administered was 44 ml/kg (25-137.4). Median plasma to red blood cell ratio was 0.8 (0-4), and median non-blood product resuscitation fluid to blood product ratio was 0.5 (0-3.6). MT was given to 47.8% of dogs. Survival rate was 40.6%. The estimated odds of survival were higher by a factor of 1.8 (95% CI: 1.174, 3.094) for a dog with 1 g/dl higher total protein above reference interval and were lower by a factor of 0.6 (95% CI: 0.340, 0.915) per 100% prolongation of partial thromboplastin time above the reference interval. No predictors of MT were identified. Conclusions: Critical bleeding in dogs was associated with a wide range of resuscitation patterns and carries a guarded to poor prognosis.

Effect of packed red blood cell transfusion on thromboelastographic tracings in dogs with naturally occurring anemia.

OBJECTIVE: To assess the effect of packed RBC (pRBC) transfusion on thromboelastographic (TEG) tracings in dogs with naturally occurring anemia. ANIMALS: 22 clinically anemic dogs that received a pRBC transfusion. PROCEDURES: For each dog, a blood sample was collected before and within 3 hours after completion of the pRBC transfusion for a CBC, nonactivated TEG analysis, and measurement of blood viscosity. Wilcoxon signed rank tests were used to compare CBC, viscosity, and TEG variables between pretransfusion and posttransfusion blood samples. Multivariable linear regression was used to assess the effects of pretransfusion-posttransfusion changes in Hct, WBC count, and platelet count on changes in TEG variables. RESULTS: Median posttransfusion Hct (21%; range, 13% to 34%) was significantly greater than the median pretransfusion Hct (12.5%; range, 7% to 29%). Packed RBC transfusion was associated with a median increase in Hct of 6.2% (range, 1.2% to 13%). Maximum amplitude significantly decreased from 74.9 to 73.8 mm and clot strength significantly decreased from 14,906 to 14,119 dynes/s after pRBC transfusion. Blood viscosity significantly increased, whereas platelet and WBC counts significantly decreased after transfusion. Multivariable linear regression revealed that pretransfusion-posttransfusion changes in Hct, WBC count, and platelet count were not associated with changes in TEG variables. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that pRBC transfusion had only small effects on the TEG tracings of hemodynamically stable dogs. Therefore, large changes in TEG tracings following pRBC transfusion are unlikely to be the result of the transfusion and should be investigated further.