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Elephant endotheliotropic herpesvirus haemorrhagic disease (EEHV-HD) is widely acknowledged as the most common cause of mortality in young Asian elephants (Elephas maximus) in captivity. The objective of the current study was to perform a blinded, retrospective pathology review of European EEHV-HD fatalities, constituting the largest systematic assessment of EEHV-HD pathology to date. Findings between viral genotypes were compared with the aim to investigate if disseminated intravascular coagulation (DIC) could be substantiated as a significant complicating factor, thereby increasing the understanding of disease pathophysiology. Immunohistochemical staining confirmed endothelial cell (EC) damage and the presence of EC intranuclear inclusion bodies, demonstrating a direct viral cytopathic effect. Microthrombi were observed in 63% of cases in several organs, including lungs, which, together with widespread haemorrhage and thrombocytopenia reported in EEHV-HD case reports, supports the presence of overt DIC as a serious haemostatic complication of active EEHV infection. Death was attributed to widespread vascular damage with multi-organ dysfunction, including severe acute myocardial haemorrhage and subsequent cardiac failure. Systemic inflammation observed in the absence of bacterial infection may be caused by cytokine release syndrome. Findings reinforce the necessity to investigate cytokine responses and haemostatic status during symptomatic and asymptomatic EEHV viraemia, to potentially support the use of anti-inflammatory treatment in conjunction with anti-viral therapy and cardiovascular support.

Objectives: The objective of this study was to determine if inflammatory markers are associated with antithrombin activity in cats., Methods: For a retrospective population of 231 cats admitted to a referral hospital, antithrombin activity was classified as decreased (n = 77), intermediate (n = 97) or in the upper quartile (n = 57). Odds ratios (ORs) were calculated for an association between decreased or upper quartile activity and hypoalbuminemia, hyperfibrinogenemia, band neutrophilia and toxic change. Multiple logistic regression was performed to determine if an association between band neutrophilia and decreased antithrombin activity was independent of decreased hepatic synthesis, consumptive coagulopathy or protein loss., Results: Cats with decreased antithrombin activity were more likely than cats with intermediate-to-upper quartile activity to have band neutrophilia (OR 2.85, P  = 0.0050), hypoalbuminemia (OR 12.1, P <0.0001) or toxic neutrophils (OR 4.47, P <0.0001). Cats with antithrombin activity in the upper quartile were less likely than those with intermediate-to-low activity to have hypoalbuminemia (OR 0.31, P  = 0.0023) or toxic neutrophils (OR 0.44, P  = 0.033). In a regression model that included other mechanisms for decreased antithrombin, band neutrophilia remained associated with decreased antithrombin activity (adjusted OR 2.62, P  = 0.013)., Conclusions and Relevance: Contrary to previous studies suggesting antithrombin is a feline positive acute phase protein, this study demonstrates an association between decreased antithrombin activity and inflammation. Further studies are needed to determine the mechanistic basis of this association.

Objectives: To describe 2 cases of boomslang (Dispholidus typus) envenomation in dogs, with thromboelastographic evaluation performed both pre- and postadministration of monovalent antivenom, and to contrast the clinical application of thromboelastography (TEG) with that of conventional coagulation testing in 1 of these cases for monitoring coagulation status in dogs suffering from such envenomation., Case Series Summary: Two dogs, a Weimeraner and a Dachshund, were referred, on separate occasions, for stabilization and treatment following observed boomslang envenomation. Initial physical examination revealed minor bleeding from the bite wound site in both dogs, along with mild swelling of the surrounding tissue. The Weimeraner also demonstrated bleeding from the gingival margin and had pale mucous membranes at time of presentation. Findings consistent with a diagnosis of disseminated intravascular coagulation (DIC) were noted on conventional coagulation testing. TEG tracings in both dogs revealed a hypocoagulable state preadministration of monovalent antivenom, followed by return to a normocoagulable state immediately postadministration, along with resolution of clinical bleeding. Both dogs were successfully discharged from the hospital, with no adverse reactions, either acute or delayed being noted., New or Unique Information Provided: Boomslang envenomation (hemotoxic snake venom) in dogs is rare, with currently only 3 cases in the literature. Herein, we document a further 2 cases and contrast changes on TEG with that noted on a routine hemostatic testing profile in 1 of these cases, to assess overall coagulation status both pre- and postadministration of antivenom., (© Veterinary Emergency and Critical Care Society 2020.)

Background: Venom-induced consumption coagulopathy (VICC) from tiger snake (Notechis scutatus) envenomation results in a dose-dependent coagulopathy that is detectable on coagulometry. However, individual coagulation factor activities in dogs with tiger snake envenomation have not been determined. This study aimed to characterise VICC and the time course of recovery in tiger snake envenomed dogs and to investigate an association between tiger snake venom (TSV) concentrations and factor activity., Methods: This was a prospective, observational, cohort study. The study cohort was 11 dogs of any age, breed, sex, body weight >10 kg, confirmed serum TSV on ELISA and treated with antivenom. Blood was collected at enrolment before antivenom administration, then at 3, 12 and 24 h after antivenom administration. Tiger snake venom concentrations were detected with a sandwich ELISA. Fibrinogen was measured using a modified Clauss method, and coagulation factors (F) II, V, VII, VIII and X were measured with factor-deficient human plasma using a modified prothrombin (PT) and activated partial thromboplastin (aPTT) method. Linear mixed models, with multiple imputations of censored observations, were used to determine the effect of time and TSV concentration on the coagulation times and factor activity. This cohort was compared to 20 healthy controls., Results: At enrolment, there were severe deficiencies in fibrinogen, FV and FVIII, with predicted recovery by 10.86, 11.75 and 13.14 h after antivenom, respectively. There were modest deficiencies in FX and FII, with predicted recovery by 20.57 and 32.49 h after antivenom, respectively. No changes were detected in FVII. Prothrombin time and aPTT were markedly prolonged with predicted recovery of aPTT by 12.58 h. Higher serum TSV concentrations were associated with greater deficiencies in FII, FV and FVIII, and greater prolongations in coagulation times. The median (range) serum TSV concentration was 57 (6-2295) ng/mL., Conclusions: In tiger snake envenomed dogs, we detected a profound, TSV-concentration-related consumption of select coagulation factors, that rapidly recovered toward normal. These findings allowed further insight into tiger snake VICC in dogs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Microparticle (MP)-associated tissue factor (TF) activity in plasma might play a role in human disseminated intravascular coagulation (DIC). The aim of this study was to compare MP-TF activity between non-DIC and DIC groups. Ten clinically healthy beagles and 26 diseased dogs were enrolled. The proportion of dogs with increased MP-TF activity was significantly higher in the DIC group than the non-DIC group (P=0.014). MP-TF activity in the DIC group was significantly higher than the non-DIC group (P=0.021). MP-TF activity positively correlated with plasma D-dimer concentration (r=0.42, P=0.034). Moreover, MP-TF activity was decreased by the time of recovery in some dogs with DIC. Larger prospective studies are warranted to assess its value as a diagnostic and prognostic biomarker in DIC.

Objective: To evaluate the utility of the chemiluminescent enzyme immunoassay (CLEIA) method for point-of-care (POC) measurement of canine plasma thrombin-antithrombin complex (TAT) concentration., Assessment and Main Results: Plasma TAT concentration was measured in 54 healthy dogs and in 72 dogs with various diseases. A significant correlation was found between TAT concentration measured by CLEIA and that measured by an ELISA that was previously used in dogs. The upper limit of the reference value of TAT concentrations measured by CLEIA was determined to be 0.2 ng/mL based on the TAT concentration in 54 healthy dogs. TAT concentrations exceeded the reference interval in a portion of dogs when a hypercoagulable state may be present., Conclusions: Canine plasma TAT concentrations measured using CLEIA were correlated with that measured using ELISA. Hence, a POC testing instrument may be used for early detection of activation of thrombin generation in emergency and critical care settings., (© Veterinary Emergency and Critical Care Society 2019.)

Coagulopathies in horses are common and potentially life-threatening. In equine field medicine, a portable point-of-care (POC) prothrombin time (PT) testing device could be useful to identify early changes in extrinsic clotting. The CoaguChek-XS (Roche Diagnostics) is a small, portable POC PT analyzer used in human medicine. Our preliminary study assessed the suitability of CoaguChek-XS for testing PT in horses and established the PT reference interval (PT RI) in healthy horses using this instrument. Blood samples collected from 102 healthy and ill horses were analyzed with the CoaguChek-XS and compared to a semi-automated coagulometric analyzer (SACA) as the gold standard. There was a significant positive correlation between the 2 measurement methods ( r = 0.765, p < 0.01), and very good agreement, with 97% of the samples falling within limits of agreement. The mean CoaguChek-XS PT coefficient of variation was 0.8%, indicating high precision. With high precision and good agreement with the coagulometric PT, the CoaguChek-XS should be further validated for PT measurement in horses.

This study compared the haematological, haemostatic and thromboelastometric (TEM) parameters between dogs with and without suspected disseminated intravascular coagulation (DIC). Seventy-six dogs with a medical condition known to predispose to DIC were prospectively included in the study. Thirty-eight dogs (50 per cent) presented with haemorrhagic diatheses. DIC was diagnosed in 32 dogs (42 per cent). Thirty-five dogs (46 per cent) had a normal TEM profile, 25 dogs (33 per cent) had a hypercoagulable profile and 16 dogs (21 per cent) had a hypocoagulable profile. Except for the lysis parameters, all TEM parameters were significantly correlated with the presence of DIC in univariate and multivariate analyses. Mortality rates were significantly higher in dogs with DIC (50 per cent) than in dogs without DIC (27 per cent, P=0.043; OR 2.667, 95 per cent CI 1.049 to 6.701), and mortality rates were significantly higher in dogs with a hypocoagulable profile (69 per cent) than in dogs with a hypercoagulable (24 per cent, P=0.017; OR 4.800, 95 per cent CI 1.241 to 16.220) or a normal profile (31 per cent, P=0.046; OR 3.429; 95 per cent CI 1.006 to 11.470). All TEM parameters were significantly associated with mortality in univariate and multivariate analyses. Thromboelastometry appears to be a valuable tool for the diagnosis and prognosis of dogs with suspected DIC, especially those with a hypocoagulable profile that was associated with increased risk of death and increased risk of haemorrhagic diatheses., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Disseminated intravascular coagulation (DIC) is a complex, dynamic and hemostatic disorder which develops secondarily to a disease characterized with an imbalance in the pro-coagulant and anti-coagulant components of hemostasis. The aim of the study is to evaluate hemostatic dysfunc- tion and the DIC syndrome in cattle with displaced abomasum (DA), with using the hematologic analyses and an extensive coagulation profile in the 96 hour-period including before and after surgery. The animal material of the study consisted of 12 dairy cows diagnosed with displaced abomasum (9 LDA and 3 RDA without volvulus) in the 2-4 week period after parturation and with no other post-partum disease. In dairy cows diagnosed with DA, hematological, coagulomet- ric (PT, APTT, Fibrinogen) and coagulation factor analyses [D-Dimer, TAT (thrombin-anti- thrombin complex), ATIII (antithrombin III), PAI-1 (plazminogen activator inhibitor-1] were performed in blood samples obtained before the operation as well as 30 minutes, 60 minutes and 2, 5, 10, 24, 48, 72 and 96 hours after the operation. In the DA cases, abnormalities were found in 6 of the 8 coagulation parameters. In the LDA and RDA groups, prolonged PT (sec), PT (INR) and APTT, hypofibrinogenemia, an increase in serum D-Dimer concentration at 72 and 96 hours after the operation and an increase in serum ATIII concentrations before and 30, 60 minutes and 2, 5, 72 and 96 hours after the operation was found (p⟨0.05). Hemostatic dysfunction and the risk of DIC developing in DA cases and continuing in the post-operative period was determined., (Copyright© by the Polish Academy of Sciences.)

Objective: The clinical diagnosis of disseminated intravascular coagulation (DIC) in dogs is challenging. It was hypothesized that dogs with laboratory abnormalities consistent with overt DIC have increased mortality and hence survival could be used to evaluate the performance of DIC scoring systems. Four DIC scoring systems were compared in clinically ill dogs: The International Society of Thrombosis and Haemostasis (ISTH) score; a previously published veterinary DIC score; a system using in-house reference intervals (RIs) for coagulation assays; and the published veterinary DIC score modified by use of in-house RI values., Design: Retrospective cohort study., Setting: University teaching hospital., Animals: Eight hundred four client-owned dogs with underlying disorders associated with DIC., Interventions: None., Measurements and Main Results: Medical records were reviewed to identify dogs for which a coagulation panel consisting of coagulation times, D-dimer concentration, antithrombin activity, fibrinogen concentration, and platelet count had been analyzed. Four methods for overt DIC scoring were then applied, and the ability of these scores to predict mortality was evaluated. Use of institution RIs for diagnosis of overt DIC provided the most accurate prognostic assessment. A score based on abnormalities in 3 of 6 parameters to identify overt DIC was 72.7% sensitive and 80.9% specific for mortality and was accurate in 78.4% of cases. The mortality rate of dogs diagnosed with overt DIC via this method was 62.5%, compared to 12.9% in the dogs not in overt DIC, a relative risk of nonsurvival of 4.84 (95% confidence interval 3.80-6.16)., Conclusions: In dogs at-risk for DIC, an in-house RI scoring system accurately predicted mortality. With further prospective validation, this system holds promise as a diagnostic tool for consistent characterization of overt DIC in clinical studies and clinical practice., (© Veterinary Emergency and Critical Care Society 2018.)

Reference interval for thrombin-antithrombin complex (TAT) level was determined using an in-house TAT measurement device, and its validity for diagnosis of disseminated intravascular coagulation (DIC) was evaluated in dogs. One hundred and two clinically healthy dogs and 247 diseased dogs with conditions that potentially caused DIC were recruited in the study. Six diagnostic testing for DIC were evaluated in diseased dogs and the diseased dogs were categorized into five groups depending on abnormal findings. TAT was measured in all study animals and between-group differences were evaluated. TAT level was positively associated with severity of DIC. There were no significant differences in TAT levels among clinically healthy dogs, diseased dogs without any abnormal finding and diseased dogs with one abnormal finding in the DIC diagnostic testing. TAT levels in groups with two or more abnormal findings were significantly higher than clinically healthy dogs. Reference interval of TAT level for clinically healthy dogs was ≤ 0.25 ng/ml. Validity of using TAT for early detection of DIC was evaluated. In-house TAT measurement was suggested to be a clinically relevant and useful tool for early detection of canine DIC., Competing Interests: The affiliation of Saitama Animal Medical Center, Iruma-shi does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Prepatent Otostrongylus arteritis results in hemorrhagic diathesis in free-ranging Northern elephant seals (Mirounga angustirostris) attributed to aberrant larval migration of the lungworm, Otostrongylus circumlitus. Clinical signs are often nonspecific, including lethargy, anorexia, and blepharospasm, but can progress to spontaneous frank hemorrhage and death within 72 hours of onset. Previously published case reports describe coagulopathy with prolonged PT and APTT, normal to elevated platelet counts, normal antithrombin concentrations, and low concentrations of fibrinogen degradation products. Disseminated intravascular coagulation was proposed as the cause of hemorrhage, but is inconsistent with some of the reported clinicopathologic changes., Objective: The purpose of this study was to compare plasmatic coagulation and fibrinolysis in healthy and Otostrongylus-affected elephant seals, in order to identify potential therapy. We hypothesized that hyperfibrinolysis contributed to hemorrhage in these cases., Methods: Citrated plasma samples were collected from 3- to 4-month-old Northern elephant seals in a wildlife rehabilitation hospital. The sampled population included 25 healthy, prerelease seals and 32 clinically ill seals diagnosed with presumptive Otostrongylus arteritis. Twenty-one of the included seals had Otostrongylus infestation confirmed at necropsy. Standard coagulation tests and plasma thromboelastography were performed for a complete assessment of coagulation and fibrinolysis., Results: Northern elephant seals with definitive Otostrongylus infestation were hypocoagulable and hypofibrinolytic compared to healthy controls., Conclusions: Results were most consistent with disseminated intravascular coagulation. Treatment with antifibrinolytic drugs to control hemorrhage may be unrewarding; alternative therapies such as plasma transfusions or coagulation factor concentrates should be investigated., (© 2017 American Society for Veterinary Clinical Pathology.)

Objective: To investigate hemostatic analyte abnormalities and their association with mortality in dogs with naturally occurring heatstroke., Design: Prospective observational study., Setting: University teaching hospital., Animals: Thirty client-owned dogs with naturally occurring heatstroke., Interventions: None., Measurements and Main Results: Citrated and EDTA blood samples were collected at presentation and at 4, 12, 24, 36, and 48 hours postpresentation (PP). Hemostatic tests performed included platelet count, prothrombin and activated partial thromboplastin times (PT and aPTT, respectively), antithrombin activity (ATA), total protein C activity (tPCA), fibrinogen, and D-dimer concentrations. The overall survival rate was 60% (18/30 dogs). Older age, higher heart rate and rectal temperature at presentation, and time from onset of clinical signs to presentation were significantly associated with mortality. Hemostatic analytes at presentation were not associated with mortality. Prolonged PT and aPTT at 12-24 hours PP, lower tPCA at 12 hours PP, and hypofibrinogenemia at 24 hours PP were significantly (P < 0.05) associated with mortality. Increased D-dimer concentration and low ATA were common at all time points, but were not associated with mortality. The frequency of disseminated intravascular coagulation (DIC) increased in nonsurvivors throughout hospitalization, but the development of DIC was not associated with mortality. The number of abnormal coagulation disturbances during the first 24 hours was significantly higher in nonsurvivors (P = 0.04)., Conclusions: Hemostatic derangements are common in dogs with naturally occurring heatstroke. Alterations in PT, aPTT, tPCA, and fibrinogen concentrations appear to be associated with the outcome at 12-24 hours PP, exemplifying the need for serial measurement of multiple laboratory hemostatic tests during hospitalization, even when within reference interval on presentation. The development of DIC, as defined in this cohort, was not associated with mortality; however, nonsurvivors had significantly more coagulation abnormalities during the first 24 hours PP., (© Veterinary Emergency and Critical Care Society 2017.)

Disseminated intravascular coagulopathy (DIC) is an acquired disorder of hemostasis resulting in activation of the coagulation and fibrinolytic pathways. It is reported secondarily to multiple disease processes and can be associated with increased mortality. Previous research at Tampa's Lowry Park Zoo (LPZ) demonstrated that Florida manatees ( Trichechus manatus latirostris) with cold stress syndrome (CSS) demonstrated thromboembolic disease. The object of this retrospective study was to establish the presence and clinical relevance of DIC in Florida manatees admitted to LPZ for rehabilitation from 07 March 2010 to 15 August 2015. A coagulation panel, including prothrombin time, partial thromboplastin time, platelet count, fibrinogen level, and D-dimer level was used to diagnose DIC. There were 100 cases identified in the study period: 35 trauma, 43 CSS, 17 secondary to harmful algae blooms (HAB), and five miscellaneous. Manatees with CSS had the highest incidence of DIC with 24 of 43 cases (56%) affected, followed by trauma with 18 of 35 cases (52%) affected. None of the manatees with HAB were found to have DIC. Manatees that developed DIC during rehabilitation or when DIC progressed did not survive. Due to the clinical implications of DIC, identifying its presence and recognizing its severity could improve clinical outcomes by enabling more intensive treatment protocols.

The purpose of this study was to determine the diagnostic importance of coagulation parameters in cattle with natural theileriosis. Nine Holstein cross-breed cattle with theileriosis as infected group and 6 healthy Holstein cattle as control group were used in the present study. Mean fibrinogen level, thrombin time (TT), activated partial thromboplastin time (aPTT) and prothrombin time (PT) were not statistically different when control and infected groups compared, except for the D-dimer concentration. Quantitative D-dimer concentrations were determined by immune-turbidimetric assay. D-dimer values increased significantly (p<0.05) in infected group (631.55 ± 74.41 μg/L) compared to control group (370.00 ± 59.94 μg/L). D-dimer sensitivity and specificity were also determined at cut-off concentrations (372 μg/L). Sensitivity and specificity of D-dimer values were determined to be 88.89% and 83.33%, respectively. D-dimer is thought to be important indicator in the evaluation of the prognosis in theileriosis cases. Analysis of D-dimer values before and after treatment in controlled case studies were suggested in future studies to enlighten the issue.

Background: Leptospirosis in dogs is occasionally associated with a hemorrhagic syndrome, the pathophysiology of which is not fully understood., Hypothesis/objectives: To characterize hematologic, hemostatic, and thromboelastometric abnormalities in dogs with leptospirosis and to study their association with hemorrhagic diatheses and outcomes., Animals: Thirty-five client-owned dogs., Methods: A prospective observational single cohort study was conducted. Results from the CBC, coagulation tests (prothrombin, activated partial thromboplastin and thrombin times, fibrinogen, fibrin(ogen) degradation products, and D-dimer concentrations), rotational thromboelastometry (TEM), signalment, hemorrhagic diatheses, occurrence of disseminated intravascular coagulation (DIC) at admission, and survival to discharge were recorded., Results: The most common hematologic and hemostatic abnormalities were anemia (30/35), thrombocytopenia (21/35), and hyperfibrinogenemia (15/35). Eight dogs were diagnosed with DIC. A normal TEM profile was found in 14 dogs, a hypercoagulable profile in 14 dogs, and a hypocoagulable profile in 7 dogs. The 8 dogs with hemorrhagic diatheses at admission had significantly decreased platelet counts (P = .037) and increased D-dimer concentrations (P = .015) compared with other dogs. Dogs with a hypocoagulable profile exhibited more hemorrhagic diatheses compared with the dogs that had normal and hypercoagulable profiles (P = .049). The mortality rate was lower in dogs with a hypercoagulable profile than in those with a hypocoagulable profile (21% vs 57%; P = .043). Disseminated intravascular coagulation was not a significant prognostic factor., Conclusions and Clinical Importance: Thromboelastometric parameters were altered in dogs with both hypercoagulable and hypocoagulable profiles. A hypocoagulable profile was significantly correlated with hemorrhagic diathesis and higher mortality rate., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

A 3-year-old Standardbred gelding with a history of pyrexia, persistent hemorrhage from the oral cavity, and a large, soft swelling at the junction of the caudal aspect of the mandibular rami and proximal neck was evaluated. The horse had neutropenia and anemia, with atypical granulated cells in a blood smear. Additional tests confirmed acute myeloid leukemia with basophilic differentiation, which has been reported in humans, cats, dogs, and cattle but not horses.

Xylitol is a five-carbon sugar alcohol produced from natural resources frequently used as a sugar substitute for humans. We report the development and successful treatment of acute hepatic failure and coagulopathy in a dog after xylitol ingestion. A 9-year-old 4.95 kg (10.9 lb) neutered male Chihuahua was evaluated at a veterinary clinic for vomiting after ingesting 224 g (45 g/kg, 20.5 g/lb) of granulated xylitol. Hypoglycemia developed within 1-2 h, elevated liver values, suggesting the development of acute hepatic failure, within 12 h and coagulopathy less than 24 h after ingestion. Treatment included maropitant, intravenous dextrose, phytonadione, metronidazole, and fresh frozen plasma. N-acetylcysteine (NAC) and S-adensoyl-L-methionine (SAMe) provided hepatic detoxification and support. The dog survived and liver values returned to normal within 1 month post ingestion. No adverse effects to hepatic function have been identified 2 years after acute xylitol toxicity. This paper is one of the few reports of successful management of a dog with hypoglycemia, hepatic failure, and coagulopathy caused by xylitol toxicity. To date, this is the highest published xylitol dose survived by a dog, as well as the only reported case that documents laboratory changes throughout the course of toxicity and includes normal hepatic indices for 7 months following xylitol toxicity. The rapidly expanding use of xylitol in a variety of products intended for human consumption has led to a rise in xylitol toxicity cases reported in dogs, and clinicians should be aware that more dogs may potentially be exposed and develop similar manifestations.

Background: Disseminated intravascular coagulation (DIC) is frequent in horses with severe gastrointestinal disorders. Postmortem studies have found fibrin microthrombi in tissues of these horses, but studies relating these histopathological findings with antemortem hemostatic data are lacking., Hypothesis: Antemortem classification of coagulopathy is related to the presence and severity of fibrin deposits observed postmortem in horses with severe gastrointestinal disorders., Animals: Antemortem hemostatic profile data and postmortem tissue samples (kidney, lung, liver) from 48 horses with colic., Methods: Tissue samples were stained with phosphotungstic acid hematoxylin and immunohistochemical methods for histological examination. A fibrin score (grades 0-4) was assigned for each technique, tissue and horse, as well as the presence or absence of DIC at postmortem examination. D-dimer concentration, prothrombin time (PT), activated partial thromboplastin time (aPTT), and antithrombin (AT) activity, as well as the clinicopathological evidence of coagulopathy, were determined from plasma samples collected 0-24 hours before death or euthanasia. Histologic and clinicopathologic data from the same horses were compared retrospectively., Results: No association was found between antemortem classification of coagulopathy and postmortem diagnosis of DIC based on tissue fibrin deposition. None of the hemostatic parameters was significantly different between horses with or without postmortem diagnosis of DIC. There was no association between horses with fibrin in tissues or different cut-offs for D-dimer concentration and postmortem evidence of DIC., Conclusions and Clinical Importance: Abnormalities of the routine clotting profile, including D-dimer concentration, were not useful in predicting histologic evidence of DIC at necropsy in horses with severe gastrointestinal disorders., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: To characterize hemostasis and determine if disseminated intravascular coagulation (DIC) is present in cats with cytauxzoonosis., Design: Cross-sectional study., Setting: University teaching hospital., Animals: Five client-owned cats with cytologic and PCR-confirmed cytauxzoonosis., Interventions: None., Measurements and Main Results: Admission samples were collected for hemostasis testing including platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, antithrombin (AT), d-dimer, protein C, plasminogen, antiplasmin, factors VII, VIII, IX, X, and XI, von Willebrand factor, and thromboelastography. Results were compiled for combined criteria used to define DIC, and all 5 cats satisfied criteria using a previously described modified scoring system for DIC in cats. The abnormalities found in all 5 cats included thrombocytopenia, low protein C activity, and prolonged prothrombin time; however, none of the cats had low AT activity. None of the cats had clinical signs of hemorrhage despite thrombocytopenia, coagulation factor deficiency (5/5 cats), and thromboelastographic evidence of hypocoagulability (2/5 cats). Three of 5 cats survived to hospital discharge. The nonsurvivors had disseminated cytauxzoonosis with schizont-laden macrophages in vessels of various organs., Conclusions: This is the first report that comprehensively describes the hemostastic status of cats with naturally occurring infection with Cytauxzoon felis. All 5 cats had laboratory evidence of overt DIC. Unlike human and canine models of sepsis-induced DIC, AT deficiency was not found in this series of cats. Further research is warranted to investigate therapeutic strategies targeting thrombotic DIC to improve survival in cats with cytauxzoonosis., (© Veterinary Emergency and Critical Care Society 2015.)

Sepsis is associated with substantial morbidity and mortality in dogs. Alterations in hemostasis by systemic inflammation play an important role in the pathophysiology of sepsis. To evaluate the functional hemostatic changes in sepsis, we evaluated coagulation profiles and flow cytometric measurement of P-selectin (CD62P) expression on platelets, as well as platelet-leukocyte aggregation from a lipopolysaccharide (LPS)-induced endotoxemia model in dogs (n = 7). A sublethal dose of LPS [1 mg/kg body weight (BW)] induced thrombocytopenia and increased activated partial thromboplastin time (aPTT), prothrombin time (PT), and D-dimer concentrations. Flow cytometry analysis showed a significant increase in P-selectin expression on platelets between 1 and 24 h of a total 48 h of the experiment. In addition, platelet-leukocyte aggregation was significantly increased in the early stage of endotoxemia (at 1 and < 6 h for platelet-monocyte aggregation and at 3 h for platelet-neutrophil aggregation). Our results suggest that CD62P expression on platelets and platelet-leukocyte aggregation, as measured by flow cytometry, can be useful biomarkers of disseminated intravascular coagulation (DIC) in canine sepsis. These functional changes contribute to our understanding of the pathophysiology of hemostasis in endotoxemia.

RHDV (rabbit haemorrhagic disease virus) is an etiologic factor of RHD (rabbit haemorrhagic disease), which is highly morbid and mortal viral infection of an adult European rabbit. Although three decades have passed since the first outbreak of rabbit haemorrhagic disease, the pathogenesis of RHD has still not been fully elucidated. It is known that RHDV replicates in the liver within the first hours following infection, causing necrotic and apoptotic cell death of hepatocytes. Anatomopathological changes are also observed in other organs of infected rabbits, i.e. lungs, spleen, kidneys, heart, as well as central nerve system. These changes leading to animals death are predominantly caused by systemic hemorrhagic diathesis with disseminated intravascular coagulation (DIC), appearing most likely as a consequence of liver cell loss through RHDV-induced apoptosis. In this paper, we presented previously described changes in biochemical and coagulation factors in RHDV infection.

Vipera palaestinae is responsible for most envenomations in humans and domestic animal in Israel. Its venom has pro- and anticoagulant properties. Protein C is a major natural anticoagulant, preventing excess clotting and thrombosis. This study investigated protein C activity and its prognostic value, as well as several other hemostatic analytes in dogs (Canis familiaris) accidently envenomed by V. palaestinae. Protein C activity was compared between envenomed dogs and 33 healthy control dogs. Mean protein C was lower in dogs envenomed by V. palaestinae compared to controls (12.9% vs. 22.9%, respectively; P < 0.01). It was positively correlated with antithrombin activity (r = 0.3, P = 0.04), but not with other hemostatic analytes. The overall mortality rate was 13%, and at presentation no significant protein C activity difference was noted between survivors and non-survivors. A receiver operator characteristics analysis of protein C activity as a predictor of mortality had an area under the curve of 0.7 (95% confidence interval 0.52-0.87). A protein C cutoff point of 8% corresponded to sensitivity and specificity of 70% and 57%, respectively. Dogs diagnosed with consumptive coagulopathy (14%) tended to have lower protein C activity compared to others; however, their mortality did differ from that of other dogs. This is the first study assessing protein C activity in V. palaestinae victims. Decreased protein C activity in such dogs may play a role in formation of thrombosis and hemostatic derangement as well as inflammation in V. palaestinae envenomations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The cross-reactivity of the anti-human D-dimer antibody 1C9-6F10 to the canine D-dimer was evaluated by western blotting using purified canine fibrinogen, fibrin degradation products (XDPs) and plasma from a dog with suspected disseminated intravascular coagulation (DIC). The antibody cross-reacted with canine XDPs and plasma from the dog with suspected DIC. A latex agglutination assay using 1C9-6F10 measured the canine XDPs in dogs. In conclusion, the antibody 1C9-6F10 cross-reacted to the canine D-fragment with high specificity, but lower affinity compared with the human D-dimer. The latex agglutination assay using the 1C9-6F10 antibody was used to measure canine plasma D-dimer concentrations.

An EDTA-anticoagulated blood sample collected from a 1.5-year-old, intact male, English Bulldog was submitted for a CBC. The CBC data and blood smear evaluation revealed borderline high hematocrit (54%, reference interval 37-55%), inappropriate rubricytosis, moderate leukopenia due to both mature neutropenia and lymphopenia, and mild thrombocytopenia. Numerous leukocytes showed evidence of karyolysis, pyknosis, and karyorhexis, and apoptotic bodies were frequent in the background. Many neutrophils had botryoid nuclei characterized by increased numbers of nuclear segments radially arranged with spoke-like, delicate chromatin filaments connecting the segments centrally. The finding of botryoid nuclei and inappropriate rubricytosis was indicative of severe hyperthermia, such as heatstroke. The dog had been exercised a long time during conditions of high temperature and humidity until he collapsed. The dog was diagnosed with severe heatstroke, hypovolemic shock, disseminated intravascular coagulation, and multiorgan dysfunction syndrome. Despite aggressive treatment, the patient died of cardiopulmonary arrest. Botryoid nuclei are frequent in people with heatstroke. In the authors' experience, botryoid nuclei are seen commonly in dogs with heatstroke, but they have never been reported in veterinary medicine. The presence of petechiation with only mild thrombocytopenia and inappropriate rubricytosis also is suggestive of heatstroke and manifests ongoing life-threatening vascular derangement., (© 2013 American Society for Veterinary Clinical Pathology.)

The inflammatory response to infection can activate the coagulation system via complex interactions. If uncontrolled, this may lead to a consumptive coagulopathy, a major risk factor for a poor clinical outcome. This prospective observational study was conducted to determine whether consumptive coagulopathy in dogs with Babesia rossi infection is related to mortality. Seventy-two client-owned dogs diagnosed with canine babesiosis were included. Diagnosis was confirmed by polymerase chain reaction and reverse line blot and dogs co-infected with Babesia vogeli or Ehrlichia canis were excluded. Blood samples were collected at admission. Coagulation factor-, antithrombin (AT)-, and protein C (PC)-activity, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer concentrations were measured. The mortality rate was 18% (13/72 dogs) and the median activities of all the coagulation factors were significantly lower in the non-survivors compared to the survivors. Median PT and aPTT were significantly longer in the non-survivors compared to the survivors. Median AT activity was not significantly different but median PC activity was significantly decreased in the non-survivors. Median D-dimer concentrations were significantly higher in non-survivors compared to survivors. This study showed that dogs that died from B. rossi infection had a more severe consumptive coagulopathy compared to survivors, characterized by procoagulant activation, inhibitor consumption, and increased fibrinolytic activity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Classical swine fever (CSF) is a multi-systemic disease that can be accompanied by severe haemorrhagic lesions. The underlying pathogenetic mechanisms are still far from being understood, though disseminated intravascular coagulation (DIC) was discussed as a major factor. In the presented study, the direct thrombin inhibitor hirudin was used in an attempt to elucidate the role of the coagulation system in the pathogenesis of CSF-induced haemorrhagic lesions. Two groups of piglets (n=5) were infected with highly virulent CSF virus (CSFV) strain CSF0634. One group underwent daily treatment with hirudin, the other served as untreated challenge infection control. Assessment of clinical signs using a clinical score system, coagulation tests, and blood counts were performed daily. Both groups developed acute-lethal CSF with haemorrhagic lesions. Although changes in the coagulation system were seen in the late stages of CSFV infection, our results strongly suggest that DIC does not present the crucial event in the pathogenesis of haemorrhagic lesions., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Resistance to respiratory disease in cattle requires host defense mechanisms that protect against pathogens which have evolved sophisticated strategies to evade them, including an altered function of pulmonary macrophages (MΦs) or the induction of inflammatory responses that cause lung injury and sepsis. The aim of this study was to clarify the mechanisms responsible for vascular changes occurring in the lungs of calves infected with bovine viral diarrhea virus (BVDV) and challenged later with bovine herpesvirus type 1 (BHV-1), evaluating the role of MΦs in the development of pathological lesions in this organ. For this purpose, pulmonary lesions were compared between co-infected calves and healthy animals inoculated only with BHV-1 through immunohistochemical (MAC387, TNFα, IL-1α, iNOS, COX-2 and Factor-VIII) and ultrastructural studies. Both groups of calves presented important vascular alterations produced by fibrin microthrombi and platelet aggregations within the blood vessels. These findings were earlier and more severe in the co-infected group, indicating that the concomitance of BVDV and BHV-1 in the lungs disrupts the pulmonary homeostasis by facilitating the establishment of an inflammatory and procoagulant environment modulated by inflammatory mediators released by pulmonary MΦs. In this regard, the co-infected calves, in spite of presenting a greater number of IMΦs than single-infected group, show a significant decrease in iNOS expression coinciding with the presence of more coagulation lesions. Moreover, animals pre-inoculated with BVDV displayed an alteration in the response of pro-inflammatory cytokines (TNFα and IL-1), which play a key role in activating the immune response, as well as in the local cell-mediated response.

Background: Disseminated intravascular coagulation (DIC) is an acquired disorder characterized by the activation of intravascular coagulation and excessive fibrin formation. It always occurs in association with other clinical conditions, including parasitic diseases. DIC has been described as a unusual complication in human and canine visceral leishmaniasis., Case Presentation: DIC was found in a seven-year-old male mongrel dog naturally infected by Leishmania (Leishmania) chagasi. Haemostasis parameters demonstrated changes in primary and secondary haemostasis and fibrinolysis., Conclusion: DIC is a unusual condition described in canine visceral leishmaniasis and it seems to be associated with several immunological and pathological mechanisms involved in the disease.

A 2-year-old female spayed Epagneul-Breton dog was presented with ecchymoses, but an undisturbed general condition. Clinical examination additionally revealed petechia and a haematoma. Travel history included Italy and Denmark. Laboratory abnormalities were moderate thrombocytopenia, prolonged PT, aPTT and TT, and elevated d-dimers. Initial therapy consisted of plasma transfusions, fluids, doxycycline and famotidine administration. Babesiosis, ehrlichiosis, leishmaniosis, dirofilariosis or anaplasmosis could not be confirmed. Abdominal ultrasound was unremarkable, while thoracic radiographs showed a bronchointerstitial pattern. Faecal samples collected over 3 days were positive for Angiostrongylus vasorum after examination using the Baermann lungworm test. The A. vasorum infection was successfully treated with fenbendazole, whereupon thrombocytopenia and prolonged coagulation times were resolved. In regions of low prevalence, an infection with A. vasorum should also be considered as a differential diagnosis in dogs with coagulation abnormalities. Respiratory signs can be absent with this disease. The patient may have acquired the infection abroad or in Germany.

Background: Inflammation is a major cause of disseminated intravascular coagulation (DIC) in dogs, but underlying mechanisms for its initiation are unknown. We hypothesized that pro-inflammatory cytokines, interleukin (IL)-6 and IL-8, induce tissue factor (TF) expression on canine monocyte surfaces, which may contribute to DIC initiation., Objectives: The objectives of this study were to determine if (1) IL-6 and IL-8 would induce TF activity on canine monocytes, (2) fetal bovine serum or autologous plasma was required for IL-6- or IL-8-induced TF responses in canine monocytes, and (3) these pro-inflammatory cytokines would enhance TF activity on canine monocytes in response to low concentrations of lipopolysaccharide (LPS)., Methods: Canine monocytes were isolated from EDTA-anticoagulated blood as peripheral blood mononuclear cells (PBMC) by double-density gradient centrifugation and adhesion to plastic. Adherent cells were stimulated for 4 hours with recombinant canine (rc)-IL-6 or rc-IL-8 (10-5000 pg/mL) with or without 10% heat-inactivated (HI) fetal bovine serum, untreated autologous canine plasma (ACP), or HI-ACP. Lipopolysaccharide (100 ng/mL) served as a positive control. Cells were also costimulated with either cytokine (100 pg/mL) or low concentrations of LPS (0.1 and 1 ng/mL). Monocytes immunopurified from PBMC with anti-CD14 antibodies were also stimulated with both cytokines (100 and 5000 pg/mL). TF activity on cell surfaces was measured by a 2-stage amidolytic assay, based on activated factor X generation., Results: Neither rc-IL-6 nor rc-IL-8 consistently stimulated TF procoagulant activity in canine PBMC or purified monocytes after 4 hours. Serum, plasma, or low concentrations of LPS did not enhance the TF response to these cytokines., Conclusions: IL-6 or IL-8 at evaluated concentrations may not play major roles in coagulation activation by induction of TF expression on monocytes in dogs with inflammation., (© 2012 American Society for Veterinary Clinical Pathology.)

An eight-year-old entire female boxer was presented with a two-week history of anorexia and lethargy and two-day history of unilateral left epistaxis. Clinical findings and laboratory test results suggested disseminated intravascular coagulation. On blood smear evaluation, occasional large epithelioid-like unclassified cells were detected. Occasionally these cells were organised in small clusters. Bone marrow examination revealed a marked infiltration by a malignant population of the same epithelioid-like cells. The dog was euthanased because of the guarded prognosis. Following histology and immunohistochemistry, a widespread undifferentiated carcinoma of unknown primary origin was diagnosed. To the authors' knowledge, this is the first case of carcinoma cell leukaemia reported in a dog. Carcinoma cell leukaemia is a rare oncological condition previously described in humans, characterised by non-haematopoietic neoplastic cells in peripheral blood., (© 2012 British Small Animal Veterinary Association.)

A 7-year-old female Leonberger dog was referred to the National Veterinary School of Lyon Teaching Hospital with a 2-day history of anorexia and bleeding. A mammary mass had been removed 7 months earlier, but histologic examination was not performed. On physical examination, the dog was depressed and had pale mucous membranes and numerous petechiae and hematomas. Significant laboratory findings were moderate thrombocytopenia, prolonged prothrombin, activated partial thromboplastin, and thrombin times, hypofibrinogenemia, and increased concentration of fibrin(ogen) degradation products. A peripheral blood smear, buffy coat preparation, and bone marrow aspirate contained low numbers of large atypical cells that had moderate nuclear:cytoplasmic ratios, oval nuclei with multiple prominent nuclei, and basophilic cytoplasm with villous projections. A small nodule was found in the left inguinal mammary gland, and a fine-needle aspirate contained cells similar to those in blood and bone marrow. In samples of blood, bone marrow, and the mammary mass, the neoplastic cells were immunoreactive for cytokeratin. The diagnosis was mammary carcinoma with secondary disseminated intravascular coagulation (DIC) and disseminated tumor cells in bone marrow and circulating tumor cells in blood; this diagnosis was not confirmed by histopathologic examination. Owing to clinical deterioration and the poor prognosis, the dog was euthanized and a necropsy was not performed. This is the first report of a canine mammary carcinoma with circulating tumor cells and secondary DIC., (© 2012 American Society for Veterinary Clinical Pathology.)

Disseminated intravascular coagulation (DIC) spans a continuum in which clinical signs can range from a prothrombotic to a hemorrhagic phenotype, with some patients suffering from both concurrently. DIC is always caused by an underlying condition, with most cases linked to systemic inflammation or infection. Numerous factors contribute to the development of DIC, including aberrations in endothelial function, and altered levels of endogenous procoagulant, anticoagulant, and fibrinolytic factors. Excessive thrombin generation, or failure to localize thrombin production, is the unifying theme throughout this broad condition. DIC can be described as overt or nonovert, each with varying degrees of severity. The ability to concisely define and diagnose such a broad condition has proven challenging, especially in veterinary medicine, where interspecies differences result in phenotypic variability. In most patients, DIC is recognized when a patient experiences noteworthy hematologic changes, such as a drop in circulating platelet count in concert with a 20% to 30% prolongation in the activated partial thromboplastin time. Similar to diagnosing, proven benefits of any particular therapy are difficult to identify. Despite these difficulties, therapy can be optimized with an understanding of the underlying pathology(ies). With appropriate care and a committed owner/veterinary team, patients with DIC can have a favorable outcome., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The aim of this study was to examine the coagulation profile in peste des petits ruminant (PPR) in kids. Five kids from a group of 150 animals (72 goats and 78 kids) were brought to the Veterinary Medical Teaching Hospital from a farm in Burdur province (Turkey) with nasal and ocular discharges and diarrhea. Fifteen goats and 41 kids had died due to diarrhea and three kids were presented to the Department of Pathology for diagnosis. Blood samples were taken from 12 ill animals (infected group) for haematological and biochemical analysis. In addition, five healthy kids were examined from another healthy flock (control group). Leukocyte and lymphocyte numbers of infected group showed significant declinations in comparison to control group (≤0.001). Haemorrhages in all organs of digestive system and small haemorrhagic areas in liver were caused to decrease in erythrocyte and haematocrit values (p ≤ 0.001) in infected group. Concentrations of blood urea nitrogen (BUN) (p ≤ 0.01) and creatinine (p ≤ 0.001) in infected group were significantly higher than control group. Compared to control group, significant increases were determined in serum concentrations of alkaline phosphatase (ALP) (p ≤ 0.01), aspartate aminotransferase (AST) (p ≤ 0.001) and alanine aminotransferase (ALT) (p ≤ 0.001) in the infected group. No significant differences were observed between the infected and control groups for serum gamma glutamyl-transferase (GGT) concentration value. In our study, thrombocytopenia (p ≤ 0.001) together with prolonged activated partial thromboplastin time (APTT; p ≤ 0.01) and prothrombin time (PT; p ≤ 0.001) may show that disseminated intravascular coagulopathy which can occur in kids with PPR.

A high mortality occurs in dogs with idiopathic immune-mediated haemolytic anaemia (IMHA) during the first 2 weeks after the diagnosis. The aim of this study was to investigate the inflammatory response and coagulation abnormalities in dogs with IMHA in relation to the prognosis and to establish the contribution of whole blood tissue factor (TF) and IL-8 gene expressions. Gene expressions in dogs with IMHA were compared to healthy dogs, dogs with DIC, dogs with sepsis, and in two groups of dogs that underwent intensive care treatment but had no evidence for either DIC or sepsis. The whole blood TF and IL-8 expressions were up regulated in all non-IMHA groups. Similarly, the TF expression in IMHA dogs was high, but the intravascular IL-8 expression was not increased. The dogs with IMHA had a pronounced inflammatory response that included a high WBC, left shift and monocytosis in comparison to the other disease groups. Coagulation factor activities in IMHA dogs were decreased fitting consumptive coagulopathy and the acute phase proteins FVIII and fibrinogen were increased. The platelet parameters suggested platelet activation and high platelet turnover in IMHA dogs. The model that best explained mortality contained monocytosis, increased activated partial thromboplastin time and elevated creatinine. Whole blood TF gene expression is up regulated and may contribute to consumptive coagulopathy in dogs with IMHA. Increased TF expression by activated platelets is an alternative explanation and should be investigated., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The objective of this study is to report the use of thromboelastography as a diagnostic tool for the hyperfibrinolytic phase of disseminated intravascular coagulopathy in a dog with metastatic haemangiosarcoma. We established a cytological (i.e. fine needle aspirate) and histopathological (i.e. excisional surgical biopsy) diagnosis of haemangiosarcoma in a 10-year-old male castrated Bichon Frise with multiple dark purple dermoepidermal nodules on the ventral abdomen and medial stifle areas, multiple small pulmonary nodules and a solitary liver mass. The dog was treated with chemotherapy (AC protocol). Forty-nine days after completion of four treatment cycles, the dog was presented for recheck. Complete blood count revealed anaemia and mild thrombocytopenia. Chemistry profile showed no significant abnormalities. Analysis of haemostasis consisted of prolonged clotting times (prothrombin time, activated partial thromboplastin time), mild hypofibrinogenaemia and increased D-dimers. A presumptive diagnosis of disseminated intravascular coagulopathy was made. A re-calcified thromboelastography was simultaneously done to confirm the coagulopathy. Thromboelastographic tracings correlated with the plasma-based test results showing hypocoagulability (prolonged clotting times and prolonged thromboelastography clot kinetics; weaker clot with decreased fibrinogen levels, platelet count and lower thromboelastography tracing amplitude) and hyperfibrinolysis (increased D-dimers and increased D-dimers and increased thromboelastography lysis parameters). Based on these results, the dog was considered to be in the hyperfibrinolytic phase of disseminated intravascular coagulopathy. Results of the conventional haemostasis tests supported those obtained on thromboelastography. Humane euthanasia was performed because of poor prognosis and progressive disease, making further follow-up unavailable. As demonstrated in this case report, thromboelastography was found to be a helpful diagnostic tool for the diagnosis and monitoring of the hyperfibrinolytic phases of disseminated intravascular coagulopathy., (© 2011 British Small Animal Veterinary Association.)

Critically ill small animals are at risk for developing coagulation abnormalities. The processes of inflammation and coagulation are intertwined, and severe inflammation can lead to disturbances of coagulation. Severe coagulation dysfunction is associated with increased morbidity and mortality. Pathophysiology, diagnosis, and treatment of coagulation dysfunction are discussed. Defects in coagulation in small animal patients are complex and a consensus on diagnosis and treatment has yet to be reached., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The percentage of emergency patients with respiratory problems treated at veterinary emergency and critical care facilities is poorly defined. Regardless of whether an animal has a primary lung disease or develops a secondary lung disease during hospitalization, acute respiratory distress syndrome (ARDS) is a common sequela to the failing lung. ARDS is a frequent sequela to sepsis, systemic inflammatory response (SIRS), and disseminated intravascular coagulation and is frequently the pulmonary manifestation of multiple organ dysfunction syndrome (MODS). ARDS, acute lung injury, SIRS, sepsis, and MODS are serious syndromes with grave consequences. Understanding the pathophysiology and consequences of these syndromes is imperative to early recognition., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This article provides an overview of the complex relationship between inflammation and coagulation and a review of routinely available laboratory and point-of-care tests for the detection of inflammation and coagulopathies. In the management of cases requiring ongoing laboratory and clinical evaluation, examination of these two major pathologic processes may assist with diagnosis and improve outcome. Early identification of a pathologic inflammatory process may allow prevention of its progression to syndromes carrying a poorer prognosis, such as disseminated intravascular coagulation and multiple organ dysfunction syndrome.

We measured the plasma D-dimer (DD) concentration in 205 dogs. Simultaneously, fibrinogen/fibrin degradation products (FDPs) concentration, platelet (PLT) count, prothrombin time (PT), activated partial thromboplastin time (APTT), and plasma concentrations of fibrinogen (Fib) were measured in the same dogs. From these results, we were able to divide the animals into four groups: control (healthy dogs, n=18), pre-disseminated intravascular coagulation (preDIC) (n=20), disseminated intravascular coagulation (DIC) (n=21), and other (n=146). Significant differences in plasma DD concentration were found among the four groups: control, 0.45 ± 0.46 µg/ml (reference range, 0-1.37); preDIC, 5.0 ± 4.8 µg/ml; DIC, 16.3 ± 12.2 µg/ml; and other, 1.5 ± 2.7 µg/ml. A weak positive correlation (r=0.62) was found between FDPs and DD concentrations in the DIC group. As a DIC diagnostic test, the PLT/APTT/FDPs/DD combination had the highest accuracy of 100%, with a sensitivity of 73% and a specificity of 97%. We propose the use of FDPs and DD concentrations as part of the DIC diagnostic test panel, with DD and FDPs to provide accurate diagnosis.

A template for a scoring system for disseminated intravascular coagulation (DIC) in humans has been proposed by the International Society on Thrombosis and Haemostasis (ISTH). The objective of this study was to develop and validate a similar objective scoring system based on generally available coagulation tests for the diagnosis of DIC in dogs. To develop the scoring system, 100 dogs consecutively admitted to an intensive care unit (ICU) with diseases predisposing for DIC were enrolled prospectively (group A). The validation involved 50 dogs consecutively diagnosed with diseases predisposing for DIC, admitted to a different ICU (group B). Citrated blood samples were collected daily during hospitalisation and diagnosis of DIC was based on the expert evaluation of an extended coagulation panel. A multiple logistic regression model was developed in group A for DIC diagnosis. The integrity and diagnostic accuracy of the model was subsequently evaluated in a separate prospective study at a different ICU (group B) and was carried out according to The Standards for Reporting of Diagnostic Accuracy (STARD) criteria. Thirty-seven dogs were excluded from group A and four from group B due to missing data. Based on expert opinion, 23/63 dogs (37%) had DIC. The final multiple logistic regression model was based on activated partial thromboplastin time, prothrombin time, D-Dimer and fibrinogen. The model had a diagnostic sensitivity and specificity of 90.9% and 90.0%, respectively. The diagnostic accuracy of the model was sustained by prospective evaluation in group B (sensitivity 83.3%, specificity 77.3%). Based on commonly used, plasma-based coagulation assays, it was possible to design an objective diagnostic scoring system for canine DIC with a high sensitivity and specificity., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The venomous viper Vipera palaestinae (Vp) is responsible for most envenomations in humans and animals in Israel. Its venom contains proteases, haemorrhagins, L-amino acid oxidase and phospholipase A2 but its effects on haemostasis have yet to be characterised. This prospective study aimed to characterise haemostatic abnormalities in Vp-envenomed dogs from presentation to discharge or death, and their association with mortality. Samples from 39 Vp-envenomed dogs were collected periodically and examined for haematology, prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin activity (ATA), fibrinogen level and D-dimer concentration. All dogs presented with severe local signs and most (79%) had systemic signs. Six dogs (15%) died. Haemostatic abnormalities were present in 37/39 dogs. Increased D-dimer concentrations were detected in 28/31 dogs. Disseminated intravascular coagulation was diagnosed in 10 dogs and in all non-survivors. Platelet and leucocyte counts at presentation, maximum PT and aPTT, and minimum ATA during hospitalisation were significantly different between survivors and non-survivors and were good predictors of the outcome. The results show that hypercoagulability, consumption and derangement of haemostasis are common in Vp-envenomed dogs and are associated with mortality. Haemostasis should be closely monitored in such dogs., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Background: Canine primary immune-mediated hemolytic anemia (IMHA) is associated with a high-mortality rate. C-reactive protein (CRP) is the most important acute-phase protein in dogs and may have value as a marker of prognosis or response to treatment in IMHA., Objective: The objectives of this study were to evaluate serum CRP concentration in dogs with primary IMHA at presentation and during treatment, to assess potential differences based on survival time, and to compare CRP with other laboratory parameters of inflammation and prognosis., Methods: Inclusion criteria for primary IMHA were anemia (PCV<0.30 L/L), a positive Coombs' test or persistent autoagglutination of erythrocytes, and the exclusion of underlying diseases by other diagnostic tests. Dogs were divided into 2 groups based on survival: dogs that were still alive 14 days after start of treatment (group 1) and dogs that died or were euthanized before day 14 (group 2). Serum CRP concentration, a CBC, and a biochemistry profile were performed on days 0, 3, 8, and 14. Serum CRP also was determined in 25 clinically healthy dogs., Results: CRP concentration in the 25 clinically healthy dogs ranged from 0-8.9 microg/mL (median 2.2 microg/mL). Thirty dogs were diagnosed with primary IMHA, 24 in group 1 and 6 in group 2. On day 0, CRP concentration in dogs in both groups (median 224 microg/mL) was increased above the reference interval. In group 1 dogs, median CRP concentration was 242 microg/mL on day 0, 69 microg/mL on day 3, 35 microg/mL on day 8, and 2 microg/mL on day 14. In group 2 dogs, median CRP concentration was 194 microg/mL on day 0, 119 microg/mL on day 3, and 41 microg/mL on day 8; only 1 dog in group 2 survived to day 8. There was a significant correlation between CRP and total WBC concentrations on days 0 and 3 (r=-.598, P=.003)., Conclusions: Serum CRP concentration was markedly increased in dogs with primary IMHA. CRP concentration did not differ based on patient survival, but might be a marker for long-term monitoring of these patients.

The systemic inflammatory response syndrome (SIRS) is a clinicopathological manifestation of overexuberant acute-phase inflammation caused by infectious or noninfectious etiologies. The systemic release of pro-inflammatory cytokines, chemokines, and lipid and vasoactive mediators induces endothelial damage and microvascular thrombosis, potentially culminating in disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and multiple organ dysfunction (MOD) or failure (MOF). We present five cases in the pig-tailed macaque and olive baboon where SIRS resulted in MOF, ARDS, DIC, and the Waterhouse-Friderichsen syndrome; each with gross and histological elements manifested as edema, deposition of fibrin, hemorrhage, and thrombosis. In the described cases, SIRS was the end-common pathway for multiple risk factors that parallel those documented in humans: major surgery, obstetric complications, and infection. The diagnosis of SIRS should be considered when evaluating nonhuman primate (NHP) cases of MOF manifesting with histological evidence of vascular leakage. Experimental manipulation of NHP models may be complicated by SIRS and accompanying rapid clinical decompensation. Such adverse events may compromise toxicological studies and should be avoided when possible.

The objective of this prospective study was to measure concentrations of D-dimers in 48 cats with various diseases and in 20 healthy cats to evaluate the sensitivity and specificity for D-dimers to diagnose disseminated intravascular coagulation (DIC). The cats were classified as having DIC if an underlying disease and at least three of the following criteria were present: thrombocytopenia, prolonged activated partial thromboplastin time, prothrombin time or thrombin time, schistocytes and/or a reduced antithrombin activity. D-dimer concentrations were measured using a semi-quantitative latex agglutination (LA) test (Accuclot D-Dimer, Sigma Diagnostics). The D-dimer test was positive for 8/12 cats with DIC and for 16/36 sick cats without DIC. D-dimers were negative for all healthy control cats. The comparison of the sick cats with DIC and those without DIC revealed a specificity and sensitivity of the D-dimer test of 56% and 67%; a comparison of the results for healthy cats and cats with DIC revealed a specificity and sensitivity of 100% and 67%, respectively. The D-dimer LA test is only of limited value for the diagnosis of DIC in cats.