Death from sepsis results from progressive organ dysfunction. Early recognition of increased illness severity or deterioration in clinical status enables timely interventions that can improve outcomes. We aimed to define septic shock by consensus and to use the existing literature to identify associated clinical and clinicopathologic abnormalities that would aid rapid identification of the most severely affected patients. We systematically reviewed the available data on sepsis in dogs and cats to identify factors that were predictive of multiple organ dysfunction or mortality. Septic shock was defined as a subset of sepsis with increased mortality, associated with cardiovascular instability and metabolic abnormalities indicative of impaired tissue perfusion despite adequate fluid resuscitation. Clinically, septic shock can manifest as hyperlactatemia, persistent hypotension, and progressive organ dysfunction. For the assessment of prognosis in dogs, we suggest scoring organ dysfunction and illness severity using validated instruments, and measuring objective physiologic parameters, lactate, and ionized calcium, and performing CBCs and serum biochemistry profiles. Where available, serial measurements of protein C and antithrombin activity, and quantitation of acute phase proteins and cytokine concentrations, should be considered. Fewer data were available for cats, and although many similar conclusions were reached as for dogs, only limited recommendations could be made.

Sepsis is the clinical syndrome that results from the host response to severe or widespread infection and is a frequent cause of death in veterinary critical care settings. Rapid diagnosis aids early treatment initiation, and hence, how sepsis is defined and identified clinically has implications for patient outcomes. Recent changes in the definitions of sepsis in human adult and pediatric patients have reduced the alignment of veterinary sepsis definitions with those in human medicine. We defined sepsis in cats and dogs by consensus and systematically reviewed the veterinary evidence to make recommendations for clinical identification of sepsis in small animals. We define sepsis as the life-threatening syndrome associated with a dysregulated host response to infection, resulting in organ dysfunction. We recommend that, in dogs and cats with infection, identification of organ dysfunction is required for the diagnosis of sepsis. We recommend that a formal illness severity assessment be performed using validated, structured scores and that measurements of the requisite physiological and laboratory parameters be undertaken to enable identification of organ dysfunction or score calculation.

OBJECTIVE:To evaluate dogs presenting with hemorrhagic pericardial effusion (PCE) for the presence of hyperfibrinolysis. DESIGN:Prospective observational study. SETTING:Single veterinary teaching hospital. MEASUREMENTS AND MAIN RESULTS:Dogs with PCE had blood samples collected before pericardiocentesis for PCV, total plasma protein and blood lactate concentrations, venous blood gas, and thromboelastography modified with tissue plasminogen activator (tPA-TEG). Fibrinolysis was assessed on tPA-TEG using the percentage of clot lysis at 30 min (LY30) after maximum clot strength (MA). Hyperfibrinolysis was defined as an LY30 of ≥20%. LY30 values were compared with values from a cohort of healthy dogs. Most dogs with PCE (14/16 [87.5%]) were hyperfibrinolytic, whereas no control dogs had hyperfibrinolysis. The median LY30 for dogs with PCE (51.5%, range: 3.0%-77.6%) was significantly higher than that of control dogs (1.3%, range: 0.0%-5.8%; p < 0.001). CONCLUSIONS:Compared with dogs that are healthy, dogs with hemorrhagic PCE are hyperfibrinolytic as assessed by LY30 on tPA-TEG. Given that dogs with hemorrhagic PCE may experience ongoing hemorrhage after pericardiocentesis, further investigation into the use of antifibrinolytic medications in these patients is warranted.

ObjectiveThe aim of this report is to raise awareness of the risk of oxidant-induced erythrocyte injury, including Heinz body (HB) anemia, in critically ill dogs by describing the condition in five dogs receiving constant rate infusions of propofol.Case summaryThis case series describes five dogs with suspected propofol-induced HB anemia undergoing mechanical ventilation (MV) for lower motor neuron disease. Four of the five dogs were treated for tick paralysis (Ixodes holocyclus) and one was treated for suspected eastern brown snake (Pseudonaja textilis) envenomation. Propofol constant rate infusions were administered as part of total intravenous anesthesia. All five dogs became anemic, and a complete blood count and blood smear interpretation by a specialist clinical pathologist confirmed the presence of oxidative red blood cell injury (eccentrocytosis and HBs). The duration of MV ranged from 76 to 131 h, with HBs identified within 47–96 h of commencing propofol. All five dogs survived to discharge, with one dog requiring a blood transfusion.DiscussionWhile propofol-induced HB anemia is a recognized phenomenon in cats, to the author’s knowledge, this is the first case series detailing multiple occurrences in dogs. Veterinarians should be aware of the risk of propofol-induced oxidative erythrocyte injury in dogs receiving prolonged infusions of propofol, and consider risk mitigation by using propofol as part of multiagent intravenous anesthesia, keeping dose rates as low as possible, and daily monitoring of blood smears and red blood cell indices.

IntroductionProkinetics are used to treat gastrointestinal (GI) dysmotility in critically ill dogs but there have been no published studies characterizing their use. The objective of this multi-institutional retrospective cohort study was to describe the use of the prokinetics erythromycin and metoclopramide in dogs hospitalized in two institutions. We hypothesized that there would be change over time and differences between institutions in the use of erythromycin and metoclopramide.MethodsDogs for inclusion were identified by fee code searches for injectable erythromycin and metoclopramide in the electronic medical record systems of The Animal Hospital at Murdoch University and Western Australian Veterinary Emergency and Specialty Hospital for the years 2018 and 2023. 75 cases from each hospital in each year were selected for inclusion from the search results using a formal randomization procedure to yield a total case number of 300. Data collected for each dog included signalment, diagnosis, reason(s) for starting prokinetics, the injectable prokinetic(s) used, frequency, and doses. Chi square or Fisher’s exact tests were used as appropriate to compare the proportions of dogs receiving metoclopramide alone, erythromycin alone, or both prokinetics in 2018 and 2023, the proportions of dogs receiving metoclopramide or erythromycin as sole prokinetics between the two institutions, and the proportions of dogs receiving a single prokinetic versus dual prokinetics between the two institutions.ResultsPrimary GI diseases accounted for the majority of the diagnoses. The most common reasons for starting a prokinetic were vomiting, an imaging diagnosis of ileus, prophylaxis following abdominal surgery, and regurgitation. Metoclopramide was administered as a sole prokinetic in the majority of dogs, fewer cases received erythromycin alone, or both prokinetics. Use of metoclopramide alone decreased from 2018 to 2023, with more dogs receiving erythromycin alone or both prokinetics in 2023. There were also significant differences in prokinetic use between institutions.DiscussionProspective studies to investigate the effectiveness and safety of metoclopramide and erythromycin as prokinetics in dogs are warranted.

Introduction:There is limited published information on iron toxicosis in dogs, and it is unclear if dogs follow the four stages of progression as in humans. The objective of this retrospective case series was to describe the clinical course and treatment of dogs presenting after iron EDTA ingestion. Methods:Cases were retrieved through an electronic medical records search at three veterinary teaching hospitals and three private referral hospitals in Australia. Non-parametric descriptive statistics are reported. Results:61 dogs met the inclusion criteria. The most common iron-containing product ingested was iron EDTA molluscicide (60/61), with only one dog ingesting iron EDTA plant fertilizer. Notably, 20 out of 61 dogs (32.8%) had no clinical signs before presentation. Vomiting without blood was the most common clinical sign (21), followed by lethargy (16), diarrhea without blood (15), ataxia/weakness (12), and signs consistent with abdominal pain (10). Abdominal pain was the most common physical examination finding (21), followed by dehydration (10). Forty dogs underwent some form of gastrointestinal decontamination. The median pre-chelation serum iron concentration was 61.3 μmol/L (Min-Max 9-356, n = 40), while the median post-chelation concentration was 14.7 μmol/L (5.72-44, n = 22). Overall, 10 dogs were managed as outpatients, while 51 dogs were treated as inpatients. Inpatient treatments included desferoxamine (43), gastroprotectants (41), antiemetics and/or prokinetics (36), analgesia (24), and hepatoprotectants (4). The most common protocol for desferoxamine administration was a continuous intravenous infusion at 15 mg/kg/h (n = 27); other dogs received 40 mg/kg intramuscularly (n = 13). Two dogs had an anaphylactic reaction to an inadvertent bolus of desferoxamine, while two had allergic reactions possibly related to desferoxamine. Two dogs developed neutropenia, and one developed acute respiratory distress syndrome, possibly as a result of desferoxamine treatment. Overall, 91.8% of dogs survived to discharge. One dog died during hospitalization, experiencing cardiac arrhythmias, shock, and cardiac arrest despite treatment. When considering the stage of iron toxicoses, 16/61 (26.2%) dogs never developed clinical toxicosis, 44 dogs (72.1%) had evidence of Stage 1 clinical signs, 4 dogs (6.6%) also had evidence of Stage 2 clinical signs, and 19 dogs (31.1%) progressed to Stage 3 clinical signs. No dogs had Stage 4 clinical signs (delayed gastrointestinal stricture). A single case was euthanized for acute hepatic failure upon re-presentation after initial survival to discharge. Conclusion:Iron EDTA toxicosis has a good prognosis in dogs following prompt treatment, but severe organ damage, including hepatic and cardiovascular dysfunction, can occur. Additionally, desferoxamine was well tolerated when administered according to published protocols, but potentially fatal adverse effects can occur.

Introduction:The use of rivaroxaban, an oral direct factor Xa inhibitor, has only been described in a small number of publications in cats. The study objective was to describe the use of rivaroxaban in a large population of hospitalised cats. Methods:Cases were retrospectively identified from June 2017 to July 2024 at seven veterinary specialty hospitals. Any cat prescribed rivaroxaban was eligible for inclusion. Data extracted from the medical records included signalment (age, sex, breed), body weight, reason for commencing rivaroxaban, dose and duration of rivaroxaban, concurrent anticoagulant and antiplatelet therapies, potential rivaroxaban adverse effects, and outcome. Non-parametric descriptive statistics are reported. Results:In total, 66 cats were included. Median rivaroxaban dose was 2.5 mg (Min-Max 1.25-10, Q1-Q3 2.5-5.0), equal to 0.73 mg/kg/day (Min-Max 0.28-1.87, Q1-Q3 0.53-1.0). A total of 36 cats (54.5%) were within the suggested dose range of 0.5-1 mg/kg/day of the Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines, 14 (21.2%) were below, while 16 (24.2%) were above. Median duration of rivaroxaban was 26.5 days (Min-Max 0-442, Q1-Q3 2-60), although followup was variable. The indication for rivaroxaban administration was confirmed thrombosis (48, 72.7%), strong clinical suspicion of thrombosis (6, 9.1%), and prophylaxis (12, 18.2%). Most thrombi were arterial, including aortic thromboembolism affecting both pelvic limbs (25/54 cats with thrombosis, 46.3%), arterial thrombosis affecting a single limb (16, 29.6%), and cardiac chamber thrombus (7, 13%). Cardiac disease was the most common thrombosis risk factor (53/66, 80.3%). Other CURATIVE defined risk factors included immune-mediated haemolytic anaemia in four cats (6.1%) and sepsis in one cat. Other thromboprophylaxis administered included clopidogrel in 58 cats (87.9%), dalteparin in 8 cats (12.1%), and aspirin in 4 cats (6.1%). Potential adverse effects prompting rivaroxaban discontinuation included one case each of vomiting, a cerebrovascular accident, gastrointestinal bleeding, and haemorrhagic pleural effusion. Forty-five cats (68.2%) survived to hospital discharge, 14 (21.2%) were euthanised, two (3%) died, and five (7.6%) were taken home against medical advice. Conclusion:Rivaroxaban was well tolerated in a large population of cats, predominantly prescribed for arterial thrombosis associated with cardiac disease.

ObjectiveTo discuss the definitions of sepsis in human and veterinary medicine.DesignInternational, multicenter position statement on the need for consensus definitions of sepsis in veterinary medicine.SettingVeterinary private practice and university teaching hospitals.AnimalsDogs and cats.InterventionsNone.Measurements and Main ResultsSepsis is a life-threatening condition associated with the body's response to an infection. In human medicine, sepsis has been defined by consensus on 3 occasions, most recently in 2016. In veterinary medicine, there is little uniformity in how sepsis is defined and no consensus on how to identify it clinically. Most publications rely on modified criteria derived from the 1991 and 2001 human consensus definitions. There is a divergence between the human and veterinary descriptions of sepsis and no consensus on how to diagnose the syndrome. This impedes research, hampers the translation of pathophysiology insights to the clinic, and limits our abilities to optimize patient care. It may be time to formally define sepsis in veterinary medicine to help the field move forward. In this narrative review, we present a synopsis of prior attempts to define sepsis in human and veterinary medicine, discuss developments in our understanding, and highlight some criticisms and shortcomings of existing schemes.ConclusionsThis review is intended to serve as the foundation of current efforts to establish a consensus definition for sepsis in small animals and ultimately generate evidence-based criteria for its recognition in veterinary clinical practice.

A 14-y-old, castrated male, diabetic, domestic longhaired cat was presented for investigation of anemia. General examination revealed widespread cutaneous erythematous macules and patches. Hematology and bone marrow aspiration revealed severe regenerative anemia and marked erythroid hyperplasia, respectively. Low numbers of intermediate-to-large, atypical lymphocytes were observed in the blood smear and bone marrow aspirates. Various imaging modalities demonstrated a diffuse pulmonary bronchial pattern, multifocal mural thickening of the urinary bladder, splenomegaly, and mild tri-cavitary effusion. Skin biopsies and cytologic examination of the pleural effusion demonstrated round-cell neoplasia consistent with lymphoma. Autopsy confirmed disseminated T-cell lymphoma, mostly affecting the urinary bladder, stomach, lymph nodes, and interscapular subcutis and muscles. Angiocentrism and nerve infiltration were present. The cutaneous erythematous patches, characterized by perivascular neoplastic lymphocytic infiltrates and angiodestruction, were a manifestation of the disseminated lymphoma in this cat, similar to the lesions reported in humans affected by angioimmunoblastic T-cell lymphoma.

Red blood cell (RBC) transfusion is associated with recipient inflammation and infection, which may be triggered by excessive circulating iron. Iron chelation following transfusion may reduce these risks. The aim of this study was to evaluate the effect of deferoxamine on circulating iron and inflammation biomarkers over time and in vitro growth of Escherichia coli (E. coli) following RBC transfusion in dogs with atraumatic hemorrhage. Anesthetized dogs were subject to atraumatic hemorrhage and transfusion of RBCs, then randomized to receive either deferoxamine or saline placebo of equivalent volume (n = 10 per group) in a blinded fashion. Blood was sampled before hemorrhage and then 2, 4, and 6 h later. Following hemorrhage and RBC transfusion, free iron increased in all dogs over time (both p < 0.001). Inflammation biomarkers interleukin-6 (IL6), CXC motif chemokine-8 (CXCL8), interleukin-10 (IL10), and keratinocyte-derived chemokine (KC) increased in all dogs over time (all p < 0.001). Logarithmic growth of E. coli clones within blood collected 6 h post-transfusion was not different between groups. Only total iron-binding capacity was different between groups over time, being significantly increased in the deferoxamine group at 2 and 4 h post-transfusion (both p < 0.001). In summary, while free iron and inflammation biomarkers increased post-RBC transfusion, deferoxamine administration did not impact circulating free iron, inflammation biomarkers, or in vitro growth of E. coli when compared with placebo.

Lymphoma is a cancer arising from B or T lymphocytes that are central immune system ‎components. It is one of the three most common cancers encountered in the canine; ‎lymphoma affects middle-aged to older dogs and usually stems from lymphatic tissues, ‎such as lymph nodes, lymphoid tissue, or spleen. Despite the advance in the management of ‎canine lymphoma, a better understanding of the subtype and tumor aggressiveness is still ‎crucial for improved clinical diagnosis to differentiate malignancy from hyperplastic ‎conditions and to improve decision-making around treating and what treatment type to use. ‎This study aimed to evaluate a potential novel biomarker related to iron metabolism, ‎embryonic haemoglobin (HBE), for early diagnosis. Archived samples in combination with ‎prospective samples collected from dogs with and without lymphoma were used in this ‎study for the retrospective analyses of this tumor based on the same biomarker amplified by ‎real-time quantitative polymerase chain reaction. The HBE mRNA was aberrantly expressed ‎in canine B and T cell lymphoma compared to the normal lymph node tissue and ‎hyperplastic lymph nodes. In conclusion, this study identified a novel potential biomarker for improving lymphoma ‎diagnosis and treatment in dogs. Further studies with larger sample sizes are needed to ‎confirm the suitability of this biomarker for canine lymphoma diagnosis.

Introduction: Alteration in endothelial function during sepsis is thought to play a key role in the progression of organ failure. We herein compared plasma concentrations of endothelial activation biomarkers vascular endothelial growth factor (VEGF), hyaluronan (HA), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF), as well as inflammatory mediator concentrations (IL-6, IL-8, IL-10, C-reactive protein and monocyte chemoattractant protein-1) in dogs with sepsis to healthy dogs. Methods: This study was a multicenter observational clinical trial conducted at two university teaching hospitals from February 2016 until July 2017. The study included 18 client-owned dogs hospitalized with sepsis and at least one distant organ dysfunction, as well as 20 healthy dogs. Plasma biomarker concentrations were measured using ELISA. Severity of illness in dogs with sepsis was calculated using the 5-variable acute physiologic and laboratory evaluation (APPLE(FAST)) score. Biomarker concentrations were compared between septic and healthy dogs using linear models. Results: Septic peritonitis was the most frequent source of sepsis (11/18; 61%), followed by pneumonia (4/18; 22%). Ten dogs (56%) had only 1 organ dysfunction, whereas 3 dogs (17%) had 2, 3 (17%) had 3, 1 (6%) had 4 and 1 (6%) had 5 organ dysfunctions. The median APPLE(FAST) score in the septic dogs was 28.5 (Q1-Q3, 24-31). Mean plasma concentrations of all endothelial and inflammatory biomarkers, except vWF, were higher in the sepsis cohort than in controls. The mean endothelial biomarker concentrations in the septic cohort ranged from similar to 2.7-fold higher for HA (difference in means; 118.2 ng/mL, 95% credible limit; 44.5-221.7) to similar to 150-fold for VEGF (difference in means; 76.6 pg./mL, 95% credible limit; 33.0-143.4), compared to the healthy cohort. Fifteen dogs with sepsis (83%) died; 7 (46%) were euthanized and 8 (53%) died during hospitalization. Conclusion: Dogs with naturally occurring sepsis and organ dysfunction had higher mean concentrations of biomarkers of endothelial activation and inflammation compared to healthy dogs, broadening our understanding of the pathophysiology of sepsis secondary to endothelial dysfunction.

ObjectivesTo compare the hemostatic characteristics of cold-stored whole blood (CSWB) from non-greyhound dogs (NGD) and greyhound dogs (GD) over 42 days of storage, notably, platelet closure time (PCT) (NGD only), manual platelet count (PLT) (GD only), ellagic acid (INTEM) and tissue factor activated (EXTEM) rotational thromboelastometry, prothrombin (PT) and activated partial thromboplastin time (aPTT), fibrinogen concentration (FIB), and the activities of factors (F) FII, FV, FVII, FVIII, FIX, FX, FXIII antigen (FXIII:Ag), and von Willebrand factor antigen (vWF:Ag).DesignWhole blood from 10 NGD and 10 GD, was refrigerated in CPD blood bags at 4°C for 42 days. Blood was analyzed before refrigeration (day 0) and at day 1 (d1), 3, 5, 7, 10, 14, 17, 21, 24, 28, 31, 35, 38, and 42. Multivariate linear mixed effects models were created to evaluate coagulation parameters over time and compare NGD and GD. Data are summarized as estimated marginal means with 95% confidence intervals. Significance was set at P < 0.05.ResultsThe PCT for all NGD CSWB was above the device limit by d7. The PLT for GD CSWB did not change during storage. The mean alpha-angle for INTEM and EXTEM decreased to <50% of baseline at d38 and d31 for NGD, and d31 and d17 for GD CSWB. The mean maximum clot firmness (MCF) for INTEM and EXTEM reduced to <50% of baseline at d42 and d28 for both GD and NGD. PT and aPTT for NGD and GD increased over time. For NGD CSWB, the mean FVIII and vWF:Ag activities decreased to <50% of baseline at d7 and d28, respectively, and FIB reached 0.982 g/dL by d24. For GD CSWB, FVIII, FXIII:Ag and FV activities decreased to <50% of baseline by d3, d38, and d38, respectively, and FIB was 0.982 g/dL at baseline. Alpha-angle and MCF for both INTEM and EXTEM, and activities for FII, FV, FIX, FXIII:Ag were significantly lower, and vWF:Ag was significantly higher overall in GD CSWB compared with NGD. A significant difference in the pattern of change over time was detected between NGD and GD in EXTEM alpha-angle, INTEM and EXTEM MCF, FII, and FVIII activities.ConclusionsThe in vitro viscoelastic parameters of GD and NGD CSWB declines over 42 days, but numerous hemostatic parameters (INTEM and EXTEM alpha-angle and MCF, activity of FII, FV, FV, FVII, FIX, FX, FXIII:Ag, vWF:Ag, and FIB) remain within 50% of baseline for more than 14 days. CSWB from GD compared to NGD has reduced hemostatic activity overall, but a similar pattern of decline for most parameters over time.

Thawed plasma (TP) refers to defrosted fresh frozen plasma stored refrigerated. TP is used in human medicine for the rapid provision of coagulation factors and resuscitation of haemorrhagic shock, but its use in dogs is poorly described. The objectives of this historical case series were to describe the reasons for TP transfusion, treatment outcomes, and adverse events associated with canine TP transfusions in a veterinary teaching hospital. We hypothesised that TP would be used most commonly for the treatment of haemorrhage secondary to anticoagulant rodenticide intoxication and trauma. Blood bank plasma transfusion logs were searched to identify dogs that received at least one unit of TP between December 2015 and June 2021. Briefly, 166 dogs received a total of 262 units of TP. Anticoagulant rodenticide intoxication (37/166, 22.3%) was the most common reason for transfusion, followed by traumatic haemorrhage (23, 13.9%) and spontaneous haemoperitoneum (22, 13.2%). The majority of dogs received one unit of TP (111/166, 67.1%) and pRBCs were commonly simultaneously transfused with TP (65, 39.2%). Severe prolongations of prothrombin time and activated partial thromboplastin time were reduced following TP transfusions. Allergic reactions were the most common transfusion reaction (19/166, 11.4%). Most dogs survived to discharge (101/166, 60.8%).

Feline morbillivirus (FeMV) is a recently discovered pathogen of domestic cats and has been classified as a morbillivirus in the Paramyxovirus family. We determined the complete sequence of FeMV US5 directly from an FeMV-positive urine sample without virus isolation or cell passage. Sequence analysis of the viral genome revealed potential divergence from characteristics of archetypal morbilliviruses. First, the virus lacks the canonical polybasic furin cleavage signal in the fusion (F) glycoprotein. Second, conserved amino acids in the hemagglutinin (H) glycoprotein used by all other morbilliviruses for binding and/or fusion activation with the cellular receptor CD150 (signaling lymphocyte activation molecule [SLAM]/F1) are absent. We show that, despite this sequence divergence, FeMV H glycoprotein uses feline CD150 as a receptor and cannot use human CD150. We demonstrate that the protease responsible for cleaving the FeMV F glycoprotein is a cathepsin, making FeMV a unique morbillivirus and more similar to the closely related zoonotic Nipah and Hendra viruses. We developed a reverse genetics system for FeMV US5 and generated recombinant viruses expressing Venus fluorescent protein from an additional transcription unit located either between the phospho-protein ( P ) and matrix ( M ) genes or the H and large ( L ) genes of the genome. We used these recombinant FeMVs to establish a natural infection and demonstrate that FeMV causes an acute morbillivirus-like disease in the cat. Virus was shed in the urine and detectable in the kidneys at later time points. This opens the door for long-term studies to address the postulated role of this morbillivirus in the development of chronic kidney disease.

ObjectivesTo compare concentrations of biomarkers of; allergy [mast cell tryptase (MCT) and histamine], inflammation [interleukin (IL)-6,-10, and−18, CXCL8, CCL2, keratinocyte chemoattractant (KC), C-reactive protein (CRP)], endothelial glycocalyx shedding (hyaluronan), coagulation [prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and von Willebrand Factor antigen, protein C (PC) and antithrombin (AT) activity], and hepatopathy [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin] between dogs with anaphylaxis after suspected insect exposure, dogs with critical illness, and healthy dogs.DesignThis was a single center prospective clinical observational comparative biomarker study that included 25 dogs with anaphylaxis (evidence of insect exposure, acute dermatological signs, and other organ involvement), 30 dogs with other critical illness, and 20 healthy dogs. Differences across groups in biomarker concentrations were tested using one-way ANOVA or Kruskal-Wallis test, with significant P values (<0.05) reported for pairwise differences detected by post-hoc tests. Logistic regression models were used to calculate the area under the receiver operator characteristic curve (AUROC) for discrimination between anaphylaxis and non-anaphylactic illness.ResultsHistamine concentration was significantly higher in the anaphylaxis group than the healthy (P < 0.001) and critically ill groups (P < 0.001), whereas no differences in MCT were detected amongst groups. Biomarker concentrations that were increased relative to healthy dogs in both the anaphylaxis and critically ill groups included IL-10 (P < 0.001 and P = 0.007, respectively), CCL2 (P = 0.007 and P < 0.001, respectively) and AST (both P < 0.001), whereas only the critically ill group had significantly increased CRP (P < 0.001), IL-6 (P < 0.001), KC (P < 0.001), ALP (P < 0.001), and fibrinogen (P = 0.016) concentrations, compared to the healthy group. Only dogs with anaphylaxis had significantly higher hyaluronan (P = 0.021) and ALT (P = 0.021) concentrations, and lower PC (P = 0.030) and AT (P = 0.032) activities, compared to healthy dogs. Both CRP and histamine concentration showed good discrimination between anaphylaxis and other critical illness, with an AUROC of 0.96 (95% CI 0.91–1) and 0.81 (95% CI 0.69–0.93), respectively.ConclusionsThis preliminary study in dogs with anaphylaxis after suspected insect exposure, found evidence of an early innate immune response, glycocalyx shedding and anticoagulant consumption. Both CRP and histamine showed potential clinical utility for differentiation between anaphylaxis and other critical illness.

Abstract 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.

Synthetic colloid fluids containing hydroxyethyl starch (HES) have been associated with impairment of coagulation in dogs. It is unknown if HES causes coagulation impairment in dogs with naturally occurring critical illness. This study used banked plasma samples from a blinded, randomized clinical trial comparing HES and balanced isotonic crystalloid for bolus fluid therapy in 39 critically ill dogs. Blood was collected prior to fluid administration and 6, 12, and 24 h thereafter. Coagulation biomarkers measured at each time point included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, and the activities of coagulation factors V, VII, VIII, IX, and X, von Willebrand factor antigen, antithrombin, and protein C. Given the links between coagulation and inflammation, cytokine concentrations were also measured, including interleukins 6, 8, 10, and 18, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. Data were analyzed with linear mixed effects models. No significant treatment-by-time interactions were found for any biomarker, indicating that the pattern of change over time was not modified by treatment. Examining the main effect of time showed significant changes in several coagulation biomarkers and keratinocyte-derived chemokines. This study could not detect evidence of coagulation impairment with HES.