[Inherited thrombopathia in Simmental cattle]. / Hereditäre Thrombozytopathie beim Simmental Rind.

During the years 2012 to 2014, a total of 5 affected Simmental cattle showing persistent bleeding after minor or unknown trauma, were presented at the Clinic for Ruminants or at the Institute for Genetics of the Vetsuisse-Faculty, University of Berne. The homozygous mutation RASGRP2, initially reported in 2007, was present in all these cases and all available parents were heterozygous carriers thus confirming the recessive mode of inheritance. Three affected animals died as a result of persistent bleeding. One animal was stabilized at the Clinic for Ruminants and was slaughtered one month later. Another case showing persistent bleeding and several hematomas was euthanized after genotyping. A frequency of 10% carriers for the associated mutation was detected in a sample of 145 Simmental sires which were used 2013 for artificial insemination in Switzerland. These bulls are designated as TP carriers and should not be used uncontrolled. Breeding organizations in Switzerland make use of the gene test to select bulls which do not carry the mutation.

Evaluation of coagulation profile in dogs with ACTH-dependent hyperadrenocorticism compared to healthy dogs by rotational thromboelastometry (ROTEM).

Despite their low morbidity, thromboembolic events in hyperadrenocorticism are associated with high mortality. Identifying the main hemostatic abnormalities will improve the prophylactic approach of these canine patients. The aim of this study was to evaluate hemostatic alterations related with ACTH-dependent HAC and its association with hypercoagulable state. For this purpose, 25 dogs diagnosed with ACTH-dependent HAC were compared with 28 healthy dogs as a control group. The hemostatic variables included platelet count, antithrombin, fibrinogen, D-dimer, PT, aPTT, rotational thromboelastometry (ROTEM) and platelet aggregation. Results showed a hypercoagulable state in 32% (8/25) dogs by ROTEM, which had at least 2 of the next features: decreased coagulation time (CT) or clot formation time (CFT) on INTEM (5/25) or EXTEM (4/25); increased maximum clot firmness (MCF) on INTEM (9/25), EXTEM (6/25) and FIBTEM (9/25). These same variables had a significant difference (P≤ 0.05) compared with the control group, as well as the parameters of α-angle and CT. Median fibrinogen levels (310 vs.178 mg/dL), mean platelet aggregation (11.1 vs. 7.9 Ohms), median platelet count (360 vs. 225 ×103/µL) and mean antithrombin activity (140 vs. 119%) were increased in ACTH-dependent HAC dogs compared to control group. PT (7.1 vs. 8.0 seconds) and aPTT (11.6 vs. 15.2 seconds) were also shortened in ACTH-dependent HAC dogs. Our findings confirm the presence of a hypercoagulable tendency in dogs with HAC. Although multifactorial, fibrinogen concentration and MCF FIBTEM showed the relevance of this protein for hypercoagulability in HAC.

Hypercoagulability based on thromboelastography is common in dogs undergoing adrenalectomy.

OBJECTIVE: Thromboelastography (TEG) is a whole blood assay that yields global assessment of hemostasis, as it evaluates clot time, strength, and kinematics of clot formation and lysis. The main objective was to describe preoperative TEG findings in dogs that had an adrenalectomy performed and, secondarily, to describe TEG findings in the dogs with or without hyperadrenocorticism (HAC). ANIMALS: 30 dogs that had preoperative TEG and adrenalectomy performed. METHODS: Medical records between 2018 and 2022 were reviewed. Signalment, diagnostic data, and perioperative treatment were abstracted. RESULTS: 53% (16/30) of the dogs were hypercoagulable, and none were hypocoagulable. Based on histopathology, 6 of 9 dogs with adenocarcinoma were hypercoagulable, 4 of 8 with pheochromocytoma were hypercoagulable, and 6 of 10 with adenoma were hypercoagulable. None of the 3 dogs with other histopathologic diagnoses or combinations of diagnoses (adrenocortical hyperplasia, poorly differentiated sarcoma, and both adrenocortical adenocarcinoma and pheochromocytoma) were hypercoagulable. Of the 14 dogs tested preoperatively for HAC, 4 of 8 HAC dogs were hypercoagulable and 2 of 6 non-HAC dogs were hypercoagulable. CLINICAL RELEVANCE: The present report describes for the first time TEG findings for dogs undergoing adrenalectomy and suggests that the majority of dogs with adrenal neoplasia are hypercoagulable based on TEG results.

Evaluation of clopidogrel, hypercoagulability, and platelet count in dogs undergoing splenectomy for splenic masses.

Dogs that had splenectomy are predisposed to fatal thrombotic conditions, and thrombocytosis is a risk factor for post-splenectomy hypercoagulability. However, in veterinary medicine, there are no specific therapeutic approaches for managing this hypercoagulability. This study aimed to determine the preventive effect of clopidogrel on post-operative hypercoagulability during the first 2 weeks post-splenectomy in dogs with splenic masses. This study included 12 dogs that had splenectomy. Seven dogs received no treatment (group A), and five were treated with clopidogrel (group B). Clopidogrel was loaded at 10 mg/kg on day 2 and continued at 2 mg/kg until day 14. Blood samples were collected on the day of surgery and 2, 7, and 14 days after splenectomy in both groups. In group B, thromboelastography (TEG) was performed on the same days. In group A, there was significant elevation of platelet counts on days 7 (p = 0.007) and 14 (p = 0.001) compared to day 0. In group B, the platelet counts were significantly elevated on day 7 (p = 0.032) but no significant difference was found on day 14 compared to day 0. Platelet counts on day 14 were significantly higher in group A than in group B (p = 0.03). The lower platelet counts were correlated with alterations in TEG parameters, and no significant differences were found in the K and α-angle values at all postoperative assessment points compared to day 0. Our study suggests that clopidogrel may reduce post-operative thrombocytosis and hypercoagulability in dogs that undergo splenectomy for splenic masses.

Refractory shock, hypercoagulability, and multiorgan thrombosis associated with hypertrophic osteodystrophy in a dog.

OBJECTIVE: To describe the clinical findings and case progression in a dog presenting with severe systemic inflammatory response, refractory shock, progressive metabolic acidosis, and respiratory failure that was ultimately diagnosed with hypertrophic osteodystrophy (HOD). CASE SUMMARY: A 4-month-old male intact Mastiff presented with a 24-hour history of lethargy and generalized ostealgia. On examination, the dog was recumbent, febrile, and tachycardic with pain on palpation of the abdomen, right femur, and mandible. Appendicular joint radiographs showed changes consistent with osteochondrosis and ulnar-retained cartilaginous cores, with no overt evidence of HOD. Initial treatment included IV fluid therapy, multimodal analgesia, and broad-spectrum antimicrobials. Vasopressor therapy was initiated following hemodynamic decompensation. Synovial fluid cytological analysis and culture revealed nonseptic suppurative inflammation and no bacterial growth, respectively. Blood and urine cultures also yielded no growth. Viscoelastic testing was consistent with hypercoagulability. The dog initially had a metabolic acidosis with appropriate respiratory compensation that progressed to a mixed metabolic and respiratory acidosis despite aggressive therapies that included antimicrobials, vasopressors, positive inotropes, and corticosteroids. Humane euthanasia was elected approximately 32 hours after admission. Necropsy yielded a diagnosis of HOD. NEW OR UNIQUE INFORMATION PROVIDED: This is the first report detailing the occurrence of refractory shock and hypercoagulability associated with HOD in a dog without evidence of another identified comorbidity. HOD should be considered in any young, large-breed dog with generalized ostealgia and signs of systemic illness, even in the absence of classic radiographic abnormalities. Further investigation of coagulation status in dogs with HOD and a secondary systemic inflammatory response is warranted.

Point-of-care global coagulation assay parameters in normal dogs and dogs with primary immune-mediated hemolytic anemia.

OBJECTIVE: To compare viscoelastic parameters between healthy control dogs and dogs with primary immune-mediated hemolytic anemia (pIMHA) using a new, point-of-care viscoelastic coagulation monitor (VCM).a DESIGN: Retrospective study from 2017 to 2021. SETTING: Three regional private referral centers. ANIMALS: Eighteen client-owned dogs with pIMHA and 33 healthy control dogs. pIMHA dogs were defined based on established criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of dogs with pIMHA and VCM performed at diagnosis from 2017 to 2021 and apparently healthy control dogs voluntarily enrolled in the blood donor program from 2017 to 2018 were reviewed. For the healthy control dogs, consent was obtained to perform VCM in addition to traditional screening. Compared to healthy control dogs, dogs with pIMHA had mean VCM parameters consistent with hypercoagulability, demonstrated by lower mean (SD) clot formation time (108 s [30] vs 233 s [55]; P < 0.0001), higher mean alpha angle (62 degrees [6] vs 52 degrees [6]; P < 0.0001), higher mean maximum clot formation (49 VCM units [11] vs 32 VCM units [5]; P < 0.0001), higher mean amplitude at 10 minutes (40 VCM units [11] vs 19 VCM units [3]; P < 0.0001), and higher mean amplitude at 20 minutes (47 VCM units [11] vs 25 VCM units [4]; P < 0.0001). pIMHA dogs also had significantly higher median (interquartile range) lysis index at 30 minutes (100% [100-100] vs 98% [90-100]; P < 0.0001). When compared to 3 established normal canine reference intervals, dogs with pIMHA had a significantly higher proportion of VCM variables (48%-57%) consistent with hypercoagulability, and a significant percentage of pIMHA dogs (78%-89%) had VCM tracings consistent with hypercoagulability overall, irrespective of the interval utilized for interpretation. CONCLUSIONS: This study demonstrates hypercoagulability in dogs with pIMHA when compared to healthy control dogs using VCM. Prospective evaluation is warranted to further characterize these findings as well as to evaluate their clinical impact.

Hemostatic profiles in dogs with sudden acquired retinal degeneration syndrome.

BACKGROUND: Sudden acquired retinal degeneration syndrome (SARDS) is a common cause of irreversible blindness in dogs. It bears clinical resemblance to hypercortisolism, which can be associated with hypercoagulability. The role of hypercoagulability in dogs with SARDS is unknown. OBJECTIVE: Determine hemostatic profiles in dogs with SARDS. ANIMALS: Prospective pilot study: Dogs with a history of SARDS (n = 12). Prospective case-control study: Dogs with recent onset of SARDS (n = 7) and age-, breed-, and sex-matched controls (n = 7). METHODS: Prospective pilot study: We performed thromboelastography (TEG). Prospective case-control study: Dogs had CBC, serum biochemistry, urinalysis, TEG, fibrinogen concentration, antithrombin activity, D-dimers, thrombin-antithrombin complexes, and optical platelet aggregometry performed. RESULTS: Prospective pilot study: 9/12 dogs with a history of SARDS were hypercoagulable with increased TEG G value and 2/3 had hyperfibrinogenemia. Case-control study: All dogs with SARDS and 5/7 controls were hypercoagulable based on TEG G value. Dogs with SARDS had significantly higher G values (median, 12.7 kdynes/s; range, 11.2-25.4; P = .04) and plasma fibrinogen concentration (median, 463 mg/dL; range, 391-680; P < .001) compared to controls. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypercoagulability was common in both dogs with SARDS and controls, but dogs with SARDS were significantly more hypercoagulable on TEG. The role of hypercoagulability in the pathogenesis of SARDS remains to be determined.

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

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

Circulating hyaluronan as a marker of endothelial glycocalyx damage in dogs with myxomatous mitral valve disease and dogs in a hypercoagulable state.

The endothelial glycocalyx (eGlx) lines the luminal surface of endothelial cells, maintaining vascular health. Glycocalyx damage is pathophysiologically important in many diseases across species however few studies have investigated its breakdown in naturally occurring disease in dogs. The aims of the study were to investigate eGlx damage in dogs with myxomatous mitral valve disease (MMVD) diagnosed on echocardiography, and dogs in a hypercoagulable state diagnosed using thromboelastography (TEG), by measuring serum hyaluronan concentrations. Serum hyaluronan was quantified in dogs with MMVD (n = 27), hypercoagulability (n = 21), and in healthy controls dogs (n = 18). Serum hyaluronan concentrations were measured using a commercially-available ELISA validated for use in dogs. Hyaluronan concentrations were compared among groups using Kruskal-Wallis tests, and post-hoc with Dunn's tests. Serum hyaluronan concentrations (median [range]) were significantly increased in dogs with MMVD (62.4 [22.8-201] ng/mL; P = 0.031) and hypercoagulability (92.40 [16.9-247.6] ng/mL; P < 0.001) compared to controls (45.7 [8.7-80.2] ng/mL). Measurement of serum hyaluronan concentration offers a clinically applicable marker of eGlx health and suggests the presence of eGlx damage in dogs with MMVD and dogs in a hypercoagulable state.

Thromboelastography in obese horses with insulin dysregulation compared to healthy controls.

BACKGROUND: Both obesity and metabolic syndrome are associated with hypercoagulability in people, increasing the risk of cardiovascular disease and thromboembolic events. Whether hypercoagulability exists in obese, insulin-dysregulated horses is unknown. HYPOTHESIS/OBJECTIVES: To determine if coagulation profiles differ between healthy horses and those with obesity and insulin dysregulation. ANIMALS: Fifteen healthy horses (CON) and 15 obese, insulin-dysregulated horses (OBID). Individuals were university or client owned. METHODS: Case-control study. Obesity was defined as a body condition score (BCS) ≥7.5/9 (modified Henneke scale). Insulin dysregulation status was assessed by an oral sugar test (OST). Kaolin-thromboelastography and traditional coagulation variables were compared between groups. The direction and strength of the association between coagulation variables and BCS and OST results were determined using Spearman's correlation. RESULTS: Thromboelastography variables MA (OBID: 69.5 ± 4.5 mm; CON: 64.8 ± 4.3 mm; P = .007) and G-value (OBID: 11749 ± 2536 dyn/m2 ; CON: 9319 ± 1650 dyn/m2 ; P = .004) were higher in OBID compared to CON. Positive correlations between MA and BCS (R = 0.45, P = .01) and serum insulin (T0 : R = 0.45, P = .01; T60 : R = 0.39, P = .03), and G-value and BCS (R = 0.46, P = .01), and serum insulin (T0 : R = 0.48, P = .007; T60 : R = 0.43, P = .02; T90 : R = 0.38, P = .04) were present. CONCLUSIONS AND CLINICAL IMPORTANCE: Obese, insulin-dysregulated horses are hypercoagulable compared to healthy controls.

Persistent hypercoagulability in dogs envenomated by the European adder (Vipera berus berus).

BACKGROUND: Envenomation by the European adder, Vipera berus berus (Vbb), is a medical emergency. The overall in vivo haemostatic effects of pro- and anticoagulant components in Vbb venom, and the downstream effects of cellular injury and systemic inflammation, are unclear. OBJECTIVES: To longitudinally describe the global coagulation status of dogs after Vbb envenomation and compare to healthy controls. A secondary aim was to investigate differences between dogs treated with and without antivenom. METHODS: Citrated plasma was collected at presentation, 12 hours (h), 24 h, 36 h and 15 days after bite from 28 dogs envenomated by Vbb, and from 28 healthy controls at a single timepoint. Thrombin generation (initiated with and without exogenous phospholipids and tissue factor), thrombin-antithrombin (TAT)-complexes and the procoagulant activity of phosphatidylserine (PS)-expressing extracellular vesicles (EVs), expressed as PS-equivalents, were measured. RESULTS: At presentation the envenomated dogs were hypercoagulable compared to controls, measured as increased thrombin generation, TAT-complexes and PS-equivalents. The hypercoagulability decreased gradually but compared to controls thrombin generation and PS-equivalents were still increased at day 15. The discrepancy in peak thrombin between envenomated dogs and controls was greater when the measurement was phospholipid-dependent, indicating that PS-positive EVs contribute to hypercoagulability. Lag time was shorter in non-antivenom treated dogs, compared to antivenom treated dogs <24 h after envenomation. CONCLUSIONS: Hypercoagulability was measured in dogs up to 15 days after Vbb envenomation. Dogs treated with antivenom may be less hypercoagulable than their non-antivenom treated counterparts. Thrombin generation is a promising diagnostic and monitoring tool for Vbb envenomation.

Identification of hypercoagulability in dogs with primary immune-mediated hemolytic anemia by means of thromboelastography.

OBJECTIVE: To evaluate whole blood hemostasis by means of thromboelastography in dogs with primary immune-mediated hemolytic anemia (IMHA) to determine whether these dogs had evidence of hypercoagulability prior to the administration of immunosuppressant medications, blood transfusion products, or anticoagulant agents. DESIGN: Evaluation study. ANIMALS: 11 client-owned dogs admitted to a teaching hospital for management of primary IMHA and 20 clinically normal dogs. PROCEDURES: Citrated whole blood samples were obtained from all dogs for performance of kaolin-activated thromboelastography. Citrated plasma was harvested from blood samples of dogs with IMHA for plasma-based coagulation testing, including activated partial thromboplastin time, prothrombin time, D-dimer concentration, fibrinogen concentration, and antithrombin activity. RESULTS: Compared with control dogs, dogs with primary IMHA had evidence of hypercoagulability as indicated by a significantly lower median (range) clot formation time (0.8 seconds [0.8 to 2.0 seconds] vs 1.9 seconds [1.3 to 3.8 seconds]), higher median angle (76.1° [59.2° to 84.6°] vs 64.0° [45.4° to 71.0°]), higher median maximum amplitude (75.9 mm [66.3 to 86.3 mm] vs 55.7 mm [49.9 to 63.6 mm]), and higher median clot strength (15,000 dyne/cm(2) [9,900 to 31,400 dyne/cm(2)] vs 6,100 dyne/cm(2) [4,900 to 8,700 dyne/cm(2)]). CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with primary IMHA had hypercoagulability as demonstrated by thromboelastography at the time of initial diagnosis and prior to treatment. Such hypercoagulability may be a precursor to clinically evident thrombosis as a complication of the disease process.

Hypercoagulability in dogs with chronic enteropathy and association with serum albumin concentration.

BACKGROUND: Dogs with protein-losing enteropathy (PLE) are at risk of developing a hypercoagulable state, but the prevalence of hypercoagulability in dogs with chronic enteropathies (CE) and normal serum albumin concentration is unknown. HYPOTHESIS: Dogs with CE are predisposed to a hypercoagulable state as assessed by thromboelastography (TEG) independent of serum albumin concentration. METHODS: Dogs with chronic gastrointestinal signs from suspected inflammatory CE between 2017 and 2019 were included. Thirty-eight were evaluated; every dog had a CBC, serum biochemistry panel, and abdominal imaging performed. The Canine Inflammatory Bowel Disease Activity Index (CIBDAI) was calculated. Thromboelastography was performed at presentation, and reaction time (R), kinetic time (K), α-angle, maximal amplitude (MA), and global clot strength (G) were recorded. Dogs were considered hypercoagulable if the G value was ≥25% above the reference interval. RESULTS: Seventeen of 38 (44.7%; 95% confidence interval [CI], 28.6-61.7%) dogs with CE were hypercoagulable. The G value did not differ between the 19 dogs with normal (≥28 g/L) serum albumin concentrations (9.05 kdyn/cm2 ; 95% CI, 7.26-10.84; SD 3.71) and 19 dogs with hypoalbuminemia (11.3 kdyn/cm2 ; 95% CI, 9.04-13.6, SD; 4.7; P = .11). The G value was negatively correlated with hematocrit, serum albumin concentration, and duration of signs and positively correlated with age. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with CE and normal serum albumin concentration can be hypercoagulable as measured by TEG.

Thrombin Generation Assay and Hemostatic Profile for Elucidating Hypercoagulability in Endogenous Canine Hyperadrenocorticism.

Canine hyperadrenocorticism is a common endocrine disorder caused by chronic secretion of glucocorticoid, often associated with hypercoagulability and secondary thrombosis. The thrombin generation assay (TGA) evaluates hemostasis globally by measuring endogenous thrombin potential. We aimed to determine whether TGA is suitable for assessing hypercoagulability in dogs with endogenous hyperadrenocorticism (HAC), and to correlate TGA with coagulation markers including fibrinogen, antithrombin (AT), D-dimer, prothrombin time (PT) and activated partial thromboplastin time (aPTT), and with routine laboratory tests for elucidating prothrombotic mechanisms and evaluating their utility as hypercoagulability screening tests. Thrombin generation performed with high activator concentration showed significantly higher endogenous thrombin potential (ETP) (P = .0239) and peak thrombin (P = .0281) in Cushing patients. Fibrinogen (P = <.0001) and AT (P = .0444) activities were significantly higher in the HAC group, while those of PT (P = .0046) and aPTT (P = .0002) were lower. Basal cortisol levels correlated positively with fibrinogen (r = 0.4503; P = .0355) and negatively with AT activity (r = -0.4580; P = .0280). Fibrinogen and hematocrit values were inversely correlated (r = -0.4853; P = .0076). Our study confirmed the presence of higher thrombin generation in dogs with HAC. However, TGA performed with lower activator concentrations was unsuitable for detecting hypercoagulability. Higher AT and fibrinogen levels and lower aPTT activity were identified in dogs with HAC relative to controls suggesting a potential role for the combined use of these assays when assessing hypercoagulability in canine hyperadrenocorticism.

Presence of nucleosomes in plasma and increased thrombin generation in dogs with acute and chronic gastroenteropathies.

Neutrophil extracellular traps (NETs) which contain nucleosomes protect the host by eliminating extracellular pathogens. However, any inflammatory stimuli can activate NETs and eventually lead to an immune overreaction leading to autoimmune diseases and thrombosis. Acute/chronic gastroenteropathies(aGE/cGE) are prevalent in dogs, and are associated with a strong inflammatory component. The aim of this study was to investigate if dogs with aGE and cGE have increased concentrations of nucleosomes indicative of NETs formation, and whether increased concentrations of nucleosomes are associated with hypercoagulability determined by increased thrombin generation. Twenty-six dogs were enrolled. The dogs were healthy (n = 11), or presented with aGE(n = 7) or cGE(n = 8). Minimum database including CRP, APTT, PT and fibrinogen, was obtained from all dogs. Citrated plasma was batched and used for subsequent analyses. Nucleosome concentration was analysed using a Cell-Death Detection ELISA-kit and thrombin generation by a calibrated automated thrombogram assay. No statistical differences in nucleosome concentrations were present between the groups. Although a numerically increased concentration of nucleosomes where seen in dogs with aGE(median;range) (0.019 AU;0.003-0.088) and cGE(0.023 AU;0.011-0.256) compared to controls(0.007 AU;0.003-0.042). One dog with GI-lymphoma demonstrated a markedly increased concentration of nucleosomes (0.256 AU). Dogs with aGE showed increased thrombin generation by increased peak (p = 0.03) and endogenous thrombin potential (p = 0.03); and increased CRP (p = 0.001), fibrinogen (p = 0.0002) and prolonged APTT (p = 0.03) compared to controls. This proof of concept study demonstrates that dogs with aGE and cGE have presence of nucleosomes with marked increase in one dog with GI-lymphoma. Nucleosomes might be linked to haemostatic alterations in dogs with inflammatory and neoplastic diseases.

Association between hypercoagulability and decreased survival in horses with ischemic or inflammatory gastrointestinal disease.

BACKGROUND: Coagulopathies are common in horses with ischemic or inflammatory gastrointestinal (GI) disturbances. There is indirect evidence suggesting that early stages of these diseases are characterized by hypercoagulability (HC). HYPOTHESIS/OBJECTIVES: HC, assessed via thromboelastography (TEG), is common in horses with ischemic or inflammatory GI diseases. The degree of HC is correlated with nonsurvival and thrombotic complications. ANIMALS: Thirty client-owned horses with ischemic or inflammatory GI disease, 30 client-owned horses with nonischemic or inflammatory GI disease, and 30 healthy horses (control group). METHODS: Prospective, observational clinical study. TEG profiles of 30 horses with ischemic or inflammatory GI disease were obtained on admission and 48 hours after admission, and these were compared with profiles from 30 horses with nonischemic or inflammatory GI disease and 30 healthy controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin activity (AT), and D-Dimer concentrations were also determined in horses with GI disease. RESULTS: Horses with ischemic or inflammatory GI disease had shorter R times compared with healthy horses (14.8±8.3 versus 22.8±12 minute; P=.011). However, changes were subtle and TEG profiles did not resembled those obtained from animals or humans presumed to be hypercoagulable. Although conventional coagulation testing supported the presence of HC (decreased AT and increased D-Dimer concentrations), TEG and coagulation abnormalities were rarely found in the same horses and the methods were not statistically related. CONCLUSIONS AND CLINICAL IMPORTANCE: There is evidence of HC in horses with GI disease but techniques for diagnoses require refinement.

Postoperative thrombocytosis and thromboelastographic evidence of hypercoagulability in dogs undergoing splenectomy for splenic masses.

OBJECTIVE: To determine the frequency and severity of thrombocytosis and thromboelastographic evidence of hypercoagulability during the first 2 weeks after splenectomy in dogs with splenic masses and to investigate relationships between platelet counts and thromboelastography values. ANIMALS: 34 dogs undergoing splenectomy for splenic masses. PROCEDURES: Blood samples for platelet counts and thromboelastography were obtained at induction of anesthesia (day 0) prior to splenectomy and on days 2, 7, and 14. RESULTS: Mean platelet counts were 167.9 × 103/µL, 260.4 × 103 µ/L, 715.9 × 103/µL, and 582.2 × 103/µL on days 0, 2, 7, and 14, respectively, and were significantly higher at all postoperative assessment points than on day 0. Thrombocytosis was observed in 3% (1/34), 6% (2/33), 81% (21/26), and 69% (18/26) of dogs on days 0, 2, 7, and 14. Platelet counts > 1,000 × 103/µL were observed in 1 dog on day 2 and in 5 dogs on day 7. One or more thromboelastography values suggestive of hypercoagulability were observed in 45% (15/33), 84% (26/31), 89% (24/27), and 84% (21/25) of dogs on days 0, 2, 7, and 14. At each assessment point, higher platelet counts were correlated with thromboelastography values suggestive of hypercoagulability. CONCLUSIONS AND CLINICAL RELEVANCE: Marked thrombocytosis and thromboelastography values suggestive of hypercoagulability were common during the first 2 weeks after splenectomy for the dogs of this study. If present, hypercoagulability could increase the risk for development of postsplenectomy thrombotic conditions such as portal system thrombosis and pulmonary thromboembolism.

Staphylococcus epidermidis sepsis induces hypercoagulability in preterm pigs.

Gram positive bacteria are a cause of sepsis in human preterm infants, and associates with high mortality and hemostatic dysfunction. It is unknown whether bovine colostrum may protect against sepsis and prevent hemostatic dysfunction. The current study was part of an overall sepsis study investigating Staphylococcus epidermidis (SE) induced sepsis in premature pigs including investigation of the effect of feeding bovine colostrum. The specific hypothesis of this study was that the hemostatic response would be hypercoagulable in septic pigs compared to non-infected controls, and that feeding bovine colostrum would increase the hypercoagulant response. Thromboelastography, activated partial thromboplastin time, prothrombin time and fibrinogen concentration were characterized in SE infected pigs, SE infected pigs fed bovine colostrum, and uninfected controls. All pigs were followed for 24 h. In addition, the same parameters were evaluated in a group of premature pigs and a group of full born pigs all followed for 11 days. SE septic premature pigs were characterized by increased clot strength and decreased fibrinolysis, significantly low platelet count and high fibrinogen concentration. Feeding bovine colostrum did not affect the hemostatic response. Compared to full born pigs, preterm newborn pigs demonstrated reduced clot strength, prolonged prothrombin time and low fibrinogen concentration. In all pigs, the fibrinogen concentration increased 11 days post-partum. To conclude, SE induced sepsis in premature pigs resulted in hypercoagulability. Bovine colostrum did not mitigate the hemostatic response. A hypocoagulable hemostatic response was present in healthy preterm pigs compared to full born pigs, similar to previous reports in infants.

Hypercoagulability in cats with cardiomyopathy.

BACKGROUND: Arterial thromboembolism (ATE) is a common complication of feline cardiomyopathy; however, the pathogenesis of ATE is unknown. HYPOTHESIS: Systemic activation of the coagulation cascade (hypercoagulability) and endothelial injury promote ATE in cardiomyopathic cats. ANIMALS: Healthy cats (n = 30) and 3 groups of cardiomyopathic cats: Group (1) left atrial enlargement only (LAE [n = 11]), ie, left atrial to aortic ratio >1.4; Group (2) LAE with spontaneous echocardiographic contrast, atrial thrombi or both (SEC-T [n = 16]); and Group (3) acute ATE with LAE (n = 16). METHODS: Hypercoagulability was defined by 2 or more laboratory abnormalities reflecting coagulation factor excess (high fibrinogen concentration or Factor VIII coagulant activity), inhibitor deficiency (low antithrombin activity), or thrombin generation (high thrombin-antithrombin complex [TAT] and d-dimer concentrations). High von Willebrand factor antigen concentration (vWF : Ag) was considered a marker of endothelial injury. Data were analyzed using nonparametric statistics. RESULTS: The 3 groups of cats with cardiac disease had higher median fibrinogen concentrations than did the healthy cats. Criteria of hypercoagulability were found exclusively in cats with SEC-T (50%) and ATE (56%). Hypercoagulability was not associated with left atrial size or congestive heart failure (CHF). ATE cats had significantly higher median vWF : Ag concentration than did the other groups. CONCLUSION AND CLINICAL IMPORTANCE: Systemic hypercoagulability is evident in many cardiomyopathic cats, often without concurrent CHF or overt ATE. Hypercoagulabilty may represent a risk factor for ATE. High vWF : Ag in ATE cats was attributed to downstream endothelial injury from the occlusive thrombus.

The influence of inflammation and hematocrit on clot strength in canine thromboelastographic hypercoagulability.

OBJECTIVE: To investigate parameters causing canine thromboelastographic hypercoagulability and to investigate whether thromboelastography (TEG) with Cytochalasin D (Cyt D) added is related to parameters of platelet activity. DESIGN: Prospective observational study on hemostatic and inflammatory parameters. Data were collected between November 2012 and July 2013. SETTING: University teaching hospital. ANIMALS: Twenty-eight dogs suffering from diseases predisposing to thrombosis and 19 clinically healthy dogs. Diseased dogs were enrolled if they fulfilled inclusion criteria regarding age, size, informed client consent, and obtained a diagnosis of a disease that has been associated with thrombosis or hypercoagulability. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Parameters of coagulation and anticoagulation, fibrinolysis, and antifibrinolysis, platelet activity, inflammation, platelet count, and hematocrit were measured using CBC, TEG, platelet aggregation on multiplate, platelet activity on flow cytometry, and hemostatic and inflammatory markers on plasma and serum analyses. ANOVA and multilinear regression analyses indicated that especially hematocrit and the inflammatory parameters C-reactive protein and interleukin-8 showed best association with overall clot strength in diseased dogs with hypercoagulable TEG tracings. Ratios presumed to reflect platelet contribution to the TEG tracing obtained in TEG analyses with Cyt D were related especially with hematocrit and P-selectin expression of platelets measured after γ-Thrombin activation on flow cytometry. CONCLUSION: Overall clot strength in TEG analyses of the hypercoagulable dogs included in the present study appears to be primarily associated with inflammation as well as hematocrit. Furthermore, the ratio between standard TEG analyses and TEG analyses with Cyt D may reflect some degree of platelet activity.