FeMV is a cathepsin-dependent unique morbillivirus infecting the kidneys of domestic cats.

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 FeMVUS5 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 FeMVUS5 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.

Hydroxyethyl starch 130/0.4 (6%) and succinylated gelatine (4%) interfere with refractometry in dogs with haemorrhagic shock.

OBJECTIVE: To determine if low molecular weight synthetic colloid fluids administered to dogs interfere with refractometric estimates of total plasma protein (TPPr) and urine osmolality (UOsm). STUDY DESIGN: Experimental study. ANIMALS: Eighteen healthy Greyhound dogs. METHODS: Anaesthetized Greyhounds subjected to haemorrhage for 60 minutes were given 80 mL kg-1 of Plasma-Lyte 148 (CRYST), or 20 mL kg-1 of hydroxyethyl starch 130/0.4 (HES) or succinylated gelatine (GELO) (n = 6 per group) intravenously over 20 minutes. Refractometric (TPPr) and biuret total plasma protein (TPPb) were measured before haemorrhage (Baseline), at end of shock (Shock), immediately (T20), then 40 minutes (T60), 100 minutes (T120) and 160 minutes (T180) after fluid administration. Urine specific gravity (USG) and UOsm were measured at all time points except T20. Estimated UOsm (eUOsm) was calculated from USG. Bias and limits of agreement (LOA) for TPPr versus TPPb, and eUOsm versus UOsm were calculated at each time point. RESULTS: For dogs given CRYST and GELO, median TPPr and TPPb decreased in parallel, with a small consistent TPP bias (CRYST range of bias, 0.38-0.67 g dL-1; GELO range of bias, 0.42-0.58 g dL-1). Dogs given HES showed divergence between median TPPr and TPPb after T20, with a peak bias at T20 of 1.62 g dL-1 (LOA 1.29-1.95). Dogs given HES and GELO had markedly increased USG [HES peak median USG at T180 of 1.119 (Q1-Q3 1.103-1.122); GELO peak median USG at T120 of 1.114 (Q1-Q3 1.082-1.119)], with large increases in bias between eUOsm and UOsm [HES peak bias at T60 of 2995 mOsm kg-1 (LOA 2032-3958 mOsm kg-1); GELO peak bias at T120 of 2465 mOsm kg-1 (LOA 940-3990 mOsm kg-1)]. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of HES and GELO to dogs with haemorrhagic shock interferes with refractometric measurements for at least 3 hours after administration.

Evaluation of the sterility of single-dose medications used in a multiple-dose fashion.

Bacterial proliferation was evaluated in single-dose medications used in a multi-dose fashion and when medications were intentionally inoculated with bacteria. Of 5 experimentally punctured medications, 1 of 75 vials (50% dextrose) became contaminated. When intentionally inoculated, hydroxyethyl starch and heparinized saline supported microbial growth. Based on these findings, it is recommended that hydroxyethyl starch and heparinized saline not be used in a multi-dose fashion.

Évaluation de la stérilité des médicaments à dose unique utilisés pour plusieurs doses. On a évalué la prolifération bactérienne dans les médicaments à dose unique utilisés pour plusieurs doses et lorsque les médicaments sont intentionnellement inoculés avec des bactéries. Parmi les cinq médicaments ayant subi une ponction expérimentale, 1 des 75 flacons (50 % dextrose) a été contaminé. Lorsqu'ils étaient inoculés intentionnellement, l'hydroxyéthylcellulose et le soluté physiologique hépariné supportaient la croissance microbienne. En se basant sur ces résultats, il est recommandé que l'hydroxyéthylcellulose et le soluté physiologique hépariné ne soient pas utilisés pour plusieurs doses.(Traduit par Isabelle Vallières).

A pilot comparison of limited versus large fluid volume resuscitation in canine spontaneous hemoperitoneum.

Treatment for hemorrhagic shock secondary to a spontaneous hemoperitoneum includes restoration of IV volume and surgical control of hemorrhage. This study was designed to determine if limited fluid volume resuscitation (LFVR) with hypertonic saline (HS) and hyperoncotic fluids (hydroxyethylstarch [HES]) results in more rapid cardiovascular stabilization in dogs with spontaneous hemoperitoneum versus conventional resuscitation (CR) with large volume resuscitation. Eighteen client-owned dogs presenting in hemorrhagic shock with a spontaneous hemoperitoneum were enrolled. Dogs were randomized to be fluid resuscitated with up to 90 mL/kg of an isotonic crystalloid (CR group) or up to 8 mL/kg of 7.2% Na chloride (i.e., HS) combined with up to 10 mL/kg of 6% HES. Measurements of vital signs, lactate, packed cell volume (PCV), total solids (TS), and blood pressure were made at standard time points. The primary end point was time to stabilization of hemodynamic parameters (measured in min). Dogs in the LFVR group achieved hemodynamic stabilization significantly faster (20 min; range, 10-25 min) than those in the CR group (35 min; range, 15-50 min; P = .027). Future studies are warranted to further investigate potential benefits associated with LFVR in dogs with spontaneous hemoperitoneum.

Defining sepsis in small animals.

OBJECTIVE: To discuss the definitions of sepsis in human and veterinary medicine. DESIGN: International, multicenter position statement on the need for consensus definitions of sepsis in veterinary medicine. SETTING: Veterinary private practice and university teaching hospitals. ANIMALS: Dogs and cats. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis 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. CONCLUSIONS: This 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.

Clinical Use of Canine Thawed Refrigerated Plasma: A Historical Case Series.

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%).

Disseminated T-cell lymphoma with non-epitheliotropic cutaneous involvement in a cat with erythematous patches and regenerative anemia.

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.

The hemostatic profile of cold-stored whole blood from non-greyhound and greyhound dogs over 42 days.

Objectives: To 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). Design: Whole 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. Results: The 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. Conclusions: The 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.

Biomarkers of endothelial activation and inflammation in dogs with organ dysfunction secondary to sepsis.

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 (APPLEFAST) 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 APPLEFAST 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 ~2.7-fold higher for HA (difference in means; 118.2 ng/mL, 95% credible limit; 44.5-221.7) 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.

Effect of Deferoxamine on Post-Transfusion Iron, Inflammation, and In Vitro Microbial Growth in a Canine Hemorrhagic Shock Model: A Randomized Controlled Blinded Pilot Study.

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.

Retrospective evaluation of the utility of blood cultures in dogs (2009-2018): 45 cases.

BACKGROUND: There is no consensus on obtaining blood cultures routinely in companion animals with suspected sepsis, and there is a paucity of evidence concerning their utility. The objectives of this retrospective study were to determine the yield of positive blood cultures from hospitalized dogs, the prevalence of resistant bacteria, and the frequency and nature of changes to antimicrobial therapy once the culture result became available. KEY FINDINGS: Forty-five dogs had a blood culture submitted over a 10-year period, of which 9(20%) yielded positive growth and 36 (80%) yielded no bacterial growth. The most frequent reasons for submission of blood culture were pyrexia of unknown origin (n = 14), suspected soft tissue infection (7), and suspected discospondylitis (7). The most frequent final diagnoses were soft tissue infection (n = 11), discospondylitis (7), and unknown (6). No significant difference was found between the culture-positive versus culture-negative groups with regard to the most frequent reasons for blood culture (P = 0.55), final diagnoses (P = 0.80), survival until the blood culture result (P = 0.37), or whether the infection was hospital- or community-acquired (P = 0.99). There were significantly more immunosuppressed dogs in the culture-positive group (P = 0.02). Resistance to one or more antimicrobials was documented in all dogs with susceptibility reported. In the culture-positive dogs, 63% had antimicrobial de-escalation and none had escalation, whereas 19% of the culture-negative dogs had de-escalation and 7% had escalation. CONCLUSION: Blood cultures were submitted infrequently, but the proportion of resistance was higher than expected and supports the use of blood cultures in cases of suspected infection resulting in bacteremia.

Effect of leukoreduction on inflammation in critically ill dogs receiving red blood cell transfusions: A randomized blinded controlled clinical trial.

BACKGROUND: Prestorage leukoreduction of red blood cell (RBC) bags prevents accumulation of pro-inflammatory mediators and experimentally attenuates post-transfusion inflammation in healthy dogs. However, the effect of leukoreduction on post-transfusion inflammation in critically ill dogs is unclear. HYPOTHESIS: Dogs transfused with leukoreduced (LR) RBC will have lower concentrations of leukocytes, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (CRP) within 24 hours of post-transfusion compared to dogs transfused with nonleukoreduced (NLR) RBC. ANIMALS: Sixty-one RBC-transfused dogs (LR = 34, NLR = 27). METHODS: Randomized, blinded, controlled preliminary clinical trial. Blood bag processing was randomized to create identically appearing LR and NLR bags. Group allocation occurred with transfusion of the oldest compatible RBC bag. Blood samples were collected pretransfusion and at 8 and 24 hours post-transfusion for leukocyte count, IL-6, IL-8, MCP-1, and CRP. Data were analyzed on an intention-to-treat basis using linear mixed effects models. Significance was set at P < .05. RESULTS: No significant differences were found between groups in concentrations of leukocytes (P = .93), IL-6 (P = .99), IL-8 (P = .75), MCP-1 (P = .69), or CRP (P = .18) over time. Eleven LR dogs (32%) and 4 NLR dogs (15%) were euthanized in the hospital (P = .14). No natural deaths occurred. CONCLUSIONS AND CLINICAL IMPORTANCE: No differences in inflammation biomarker concentrations were detected over time between dogs transfused with LR or NLR RBC, but heterogeneity likely hampered the ability to detect a difference with this sample size. The novel randomization and enrollment protocol was successfully implemented across 2 participating institutions and will be easily scaled up for a future multicenter clinical trial.

Biomarkers of Coagulation and Inflammation in Dogs after Randomized Administration of 6% Hydroxyethyl Starch 130/0.4 or Hartmann's Solution.

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.

Stability of ex vivo coagulation factor activity in never-frozen and thawed refrigerated canine plasma stored for 42 days.

OBJECTIVE: The primary objective of this study was to document coagulation factor activity in canine "NEVER-FROZEN" and "THAWED" refrigerated plasma for the purposes of defining recommended expiration dates. We hypothesized that NEVER-FROZEN and THAWED refrigerated plasma would maintain >50% activity of coagulation factors V (FV), VII (FVII), VIII (FVIII), IX (FIX), X (FX), and von Willebrand factor antigen (vWF) and a concentration of fibrinogen above the lower bound of the reference interval (>0.982 g/L) for greater than 14 days but less than 42 days. DESIGN: Prospective laboratory-based study. SETTING: University teaching hospital blood bank. ANIMALS: Ten canine plasma units derived from healthy client-owned blood donors. INTERVENTIONS: Serial sampling (days 0, 1, 3, 5, 7, 10, 14, 17, 21, 24, 28, 32, 35, 39, 42) from NEVER-FROZEN and THAWED refrigerated canine plasma units was conducted for measurement of activities of FV, FVII, FVIII, FIX, FX, vWF, and fibrinogen concentrations using the ACL TOP 300. Plasma was defined as "suitable for transfusion" at a given time point if the entire 95% confidence interval for each factor was above 50% activity and above a fibrinogen concentration of 0.982 g/L. MEASUREMENTS AND MAIN RESULTS: The lower bounds of the FVIII and vWF confidence intervals were above 50% up to and including day 32 for NEVER-FROZEN refrigerated plasma and day 28 for THAWED refrigerated plasma. Confidence intervals for FV, FVII, FIX, and FX remained above 50% activity at all time points. The lower bound of the fibrinogen concentration was <0.982 g/L on day 39 for NEVER-FROZEN refrigerated plasma and on day 35 for THAWED refrigerated plasma. CONCLUSIONS: Refrigerated canine plasma from these 10 dogs retained coagulation factor activity above the limit that we defined as suitable for transfusion for up to 32 days when NEVER-FROZEN and 28 days when THAWED. Further studies should evaluate the clinical outcomes and effects on coagulation factor activity of dogs receiving refrigerated plasma transfusions.

Allergy, inflammation, hepatopathy and coagulation biomarkers in dogs with suspected anaphylaxis due to insect envenomation.

Objectives: To 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. Design: This 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. Results: Histamine 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. Conclusions: This 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.

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.

Lack of association between feline AB blood groups and retroviral status: a multicenter, multicountry study.

OBJECTIVES: The relationship between blood group antigens and disease has been studied in humans. Blood types have been associated with both decreased and increased rates of various infections. In addition, blood group expression has been shown to vary with some cancers and gastrointestinal diseases. The objective of this study was to explore whether there is a relationship between blood type and retroviral infections in cats. METHODS: Case records from a veterinary research laboratory, veterinary teaching hospitals and veterinary blood banks were retrospectively searched for cats where both blood type and retroviral status (feline leukemia [FeLV], feline immunodeficiency virus [FIV] or both) were listed (part 1). In addition, a sample of 33 cats with confirmed FIV infection was genotyped to determine blood groups (part 2). RESULTS: In part 1, 709 cats were identified, 119 of which were positive for retroviral infection. Among all cases, 621 were type A (87.6%), 68 were type B (9.6%) and 20 were type AB (2.8%). There was no relationship between overall retroviral status (positive/negative) and blood type (P = 0.43), between FeLV status and blood type (P = 0.86) or between FIV status and blood type (P = 0.94). There was no difference in the distribution of blood types between cats that were healthy and typed as possible blood donors vs sick cats that were typed prior to a possible transfusion (P = 0.13). In part 2, of the 33 FIV-infected cats, all blood group genotypes were identified, although this test did not discriminate type A from type AB. CONCLUSIONS AND RELEVANCE: No relationship was identified between feline retroviral status and blood type in this study. The relationship between blood type and other disease states requires further study in veterinary patients.

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 and immunologic assessment of sepsis and the systemic inflammatory response syndrome in cats.

OBJECTIVE: To compare clinical findings and inflammatory mediator production among cats with sepsis, cats with noninfectious systemic inflammatory response syndrome (SIRS), and healthy cats. DESIGN: Case-control study. ANIMALS: Cats with sepsis (n = 16) or SIRS (19) and 8 healthy control cats. PROCEDURES: Clinical variables were recorded for each cat, and plasma tumor necrosis factor (TNF) and interleukin (IL)-1ß activities and IL-6 and CXC chemokine ligand (CXCL)-8 concentrations were determined at initial evaluation. RESULTS: Clinicopathologic abnormalities associated with sepsis in cats included a high band neutrophil percentage, eosinopenia, hyponatremia, hypochloremia, hypoalbuminemia, hypocalcemia, and hyperbilirubinemia. When the sepsis and SIRS groups were compared, the only significant differences in the CBC and plasma biochemical findings were band neutrophil percentage and albumin concentration. Cats with sepsis had significantly greater plasma TNF activity than did healthy cats and were more likely to have detectable concentrations of IL-6 than were cats with SIRS or healthy cats. Plasma IL-1ß activity did not differ among groups, and CXCL-8 was not detectable in most (32/43) cats. Mortality rate was not significantly greater for cats with sepsis (7/16) than for cats with SIRS (5/19). Plasma IL-1ß activity and IL-6 and chloride concentrations were the only variables correlated with nonsurvival in the sepsis group. CONCLUSIONS AND CLINICAL RELEVANCE: Cats with sepsis may have various clinicopathologic abnormalities but are more likely to have a high band neutrophil percentage and hypoalbuminemia than cats with noninfectious SIRS. Plasma interleukin-1ß activity and plasma IL-6 and chloride concentrations may be useful prognostic biomarkers for septic cats.