Kaolin-activated Thromboelastography Research Articles

Diagnosis of canine pulmonary thromboembolism by computed tomography and mathematical modelling using haemostatic and inflammatory variables

There is no evidence-based diagnostic approach for diagnosis of pulmonary thromboembolism (PTE) in dogs. Many dogs with diseases that predispose to thrombosis are hypercoagulable when assessed with thromboelastography (TEG), but no direct link has been established. The aims of this study were: (1) to investigate if diseased dogs with PTE, diagnosed by computed tomography pulmonary angiography (CTPA), had evidence of hypercoagulability by TEG; (2) to characterise haemostatic and inflammatory changes in dogs with PTE; (3) to construct models for prediction of PTE based on combinations of haemostatic and inflammatory variables; and (4) to evaluate the performance of D-dimer measurement for prediction of PTE. Twenty-five dogs were included in this prospective observational study (PTE: n=6; non-PTE: n=19). Clot strength G values did not differ between the PTE and non-PTE groups in tissue factor (TF) or kaolin-activated TEG analyses. Haemostatic and inflammatory variables did not differ between the two groups. Linear discriminant analysis generated a model for prediction of PTE with a sensitivity and specificity of 100% when TF results were used as TEG data, and a model with sensitivity of 83% and specificity of 100% when kaolin results were used as TEG data. Receiver operating characteristic analysis of D-dimer levels showed that a value of >0.3mg/L yielded a sensitivity of 100% and a specificity of 71.4%. In conclusion, the study supports CTPA as method for diagnosing canine PTE, but shows that TEG alone cannot identify dogs with PTE. Models for prediction of PTE were generated, but require further validation.

Operator-based variability of equine thromboelastography.

To determine the extent of intraoperator (between duplicate samples) and interoperator (between different operators) variability in equine thromboelastography (TEG). Kaolin-activated TEG was performed in duplicate by operator-pair A/B or A/C (2 groups of 10 horses) using discrete setups, within 30-45 minutes of vacuum-assisted blood collection. Recorded TEG variables included clot initiation time (R), clot formation time (K), rate of clot formation (α), clot strength (MA), and viscoelastic/shear strength (G). Operators independently determined the clinical coagulation status for each sample. Intra- and interoperator variabilities were reported as coefficients of variation (CV), using descriptive statistics and paired samples t-test or Wilcoxon matched pair signed-rank test (P < 0.05 considered significant). Twenty hospitalized adult horses with no clinical evidence of systemic inflammation. Mean intraoperator CVs ranged from 2.6 to 14% (operator A), 2.8 to 13% (operator B) and 1.2 to 18% (operator C). Both intra- and interoperator variabilities were lowest for MA (1.2-3.2%) and G (2.9-7.3%), and highest for K (13-23%). Mean CVs for all TEG parameters were lower when comparing intra- to interoperator variation. Seventy percent of horses had at least 1 TEG variable (out of 4 replicates) outside the established reference intervals. Assessment of coagulation status was conserved between operators in 9/10 and 8/10 horses for A/B and A/C, respectively, with comparable agreement between operator A/B (к = 0.73) and A/C (к = 0.74). TEG measurements of MA and G are more reproducible than assessment of K, within samples and between operators. The highest test variability was thus observed within the early phase of clot formation.

Effects of hemolysis and lipemia interference on kaolin-activated thromboelastography, and comparison with conventional coagulation tests

The effects of hemolysis and lipemia on thromboelastography (TEG) analysis have been scarcely evaluated in human samples, and neglected in clinical practice. We aimed to investigate the effects of in vitro mechanical hemolysis and lipemia on TEG analysis and conventional coagulation tests. Twenty-four healthy volunteers were enrolled in the study. Besides the controls, three groups with slight, moderate and severe mechanical hemolysis were constituted according to free hemoglobin (Hb) concentrations of 0.5–1.0, 2.0–6.0 and 7.0–13.0 g/L, respectively; and three groups with mild, moderate and high lipemia were established according to triglyceride concentrations of ∼6.0, ∼12.0, and ∼18.0 mmol/L, respectively. Four TEG parameters, reaction time (R), coagulation time (K), angle (α), and maximum amplitude (MA), were measured alongside conventional plasma tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) by mechanical method, and platelet count by optical method. Results showed that the median R and MA values at moderate and severe hemolysis and K at severe hemolysis exceeded respective reference intervals, and were considered unacceptable. Median values of TEG parameters in lipemic samples were all within reference intervals. Bias values of conventional plasma tests PT, APTT and FIB in hemolyzed or lipemic samples were all lower than the Clinical Laboratory Improvement Amendments (CLIA) allowable limits. Bias values of platelet count at moderate to severe hemolysis and lipemia exceeded the CLIA allowable limits. In conclusion, the detection of TEG was in general more affected by mechanical hemolysis than plasma coagulation tests. Pre-analytical variables should be taken into account when unexpected TEG results are obtained.

Correlation between thromboelastography and traditional coagulation test parameters in hospitalized dogs.

A hospital-based, prospective cross-sectional study was used to compare kaolin-activated thromboelastography (TEG) parameters with traditional coagulation tests in 29 hospitalized dogs. Cases were included if the attending clinician requested coagulation testing. Blood was obtained from each dog and coagulation (prothrombin time, partial thromboplastin time, antithrombin activity, d-dimer concentration, and fibrinogen concentration) and TEG analyses were performed. Hematocrit (Hct) was also measured. Traditional coagulation results were evaluated for correlation with those from kaolin-activated TEG. Spearman’s correlation was used to calculate correlation coefficients. Fibrinogen was positively correlated with maximum amplitude (Pearson r=0.72, P<0.001) and global clot strength (Pearson r=0.72, P<0.001). There was no correlation between any of the remaining coagulation variables, TEG parameters, or Hct. Results of kaolin-activated TEG and traditional coagulation tests are not interchangeable means of monitoring coagulation derangements in this intensive care unit patient population. Determination of a true outcome measure is necessary to establish TEG’s clinical relevance to veterinary medicine.

Reference values for kaolin-activated thromboelastography in volunteers of Anhui Province in China.

The assessment of the coagulation status using thromboelastography (TEG) in Chinese population has less been reported. This study aimed to establish reliable reference values for kaolin-activated TEG in Chinese volunteers. A total of 1681 Chinese adult individuals were recruited for this study. The reference individuals were stratified by gender and age, and the TEG values were measured on the basis of strict quality control. The 95% reference values were determined using nonparametric statistical methods. The sex-related 95% reference values were reaction time (R):4.2-8.7minutes; clotting time (K): 1.2-3.2minutes; alpha angle (α): 47.0-72.3 degree; maximum amplitude (MA): 49.1-70.5mm for males, and R: 3.7-9.0minutes; K: 1.0-3.2minutes; α: 48.4-74.4 degree; MA: 46.8-72.4mm for females. Also, the TEG parameters indicated a relatively more hypercoagulable profile in both female and elder groups. This study established the reference values for kaolin-activated TEG in the target Chinese population, which might provide a reference for both clinical and laboratory studies.

Kaolin-activated thromboelastography and standard coagulation assays in cyanotic and acyanotic infants undergoing complex cardiac surgery: a prospective cohort study.

Several studies report the use of thromboelatography (TEG) to monitor coagulation in pediatric cardiac surgery. The aim of this study was to compare baseline and intraoperative TEG, TEG-functional fibrinogen, and standard coagulation assays in children with cyanotic and acyanotic congenital heart disease (CHD) undergoing cardiac surgery. This is a prospective observational study of 63 children aged <24months undergoing cardiac surgery with cardiopulmonary bypass (CPB). Exclusion criteria included preoperative anticoagulant therapy and hepatic failure. We collected blood at anesthesia induction (T1), at lowest temperature after CPB start (T2), and after heparin neutralization (T3). Coagulation was evaluated by TEG (reaction time [R]), k, alpha-angle, maximum amplitude (MA), MA-fibrinogen (MA-fib), and by standard coagulation assays (prothrombin time, activated partial thromboplastin time, fibrinogen level, platelet [PLT] count). Sixty-three patients were enrolled (38 cyanotic and 25 acyanotic). Median age was 4 [IQR 2-6]months and median weight was 5 [IQR 3.7-6.5]kg. Most common surgeries were: ventricular septal defect repair (n=13), Fallot correction (n=11), and arterial switch operation (n=10). Cyanotic and acyanotic children were well matched: R, k, MA, and MA-fib at T1, T2, and T3 were not significantly different between cyanotic and acyanotic children. At T2, significant correlations were showed between MA and PLT count (r=0.4; P=0.0008) and k and plasma fibrinogen level (r=-0.54; P<0.0001). At T3, significant correlations were showed between MA and PLT count (r=0.5; P<0.0001), G and PLT count (r=0.6; P<0.0001), and MA-fib and plasma fibrinogen level (r=0.5; P=0.002). According to our findings, cyanosis does not affect TEG parameters in children with CHD. PLT count and plasma fibrinogen significantly correlated (are significantly associated) with MA and MA-fib respectively, suggesting that use of TEG after protamine administration may be prompted for improved hemostatic monitoring in the perioperative phase.

Defining Haemostatic Safety Zones for the Practice of Sport in Patients with Severe Haemophilia By Thromboelastography

Introduction: Sport may comprise variable physical activity associated bleeding risk(BRisk) in haemophilia. We aimed to determine value of global thromboelastography (TEG) profile for tailoring prophylaxis in patients younger than 18 years old (YO) with severe haemophilia A (SHA) subjected to activities with different BRisk.Methods: Patients with SHA, younger than 18 YO and on prophylaxis at least 12 months before inclusion were invited to participate. Patients signed informed consent before inclusion. Samples before prophylactic dosing were collected. Factor VIII (FVIII) and kaolin-activated TEG profile were determined. Physical activity (PhA) and annual joint bleeding rate (AJBR) were recorded retrospectively. BRisk was categorized following the US-National Haemophilia Foundation guidelines (1= safe; 1.5= safe-moderate risk; 2= moderate risk; 2.5= moderate-dangerous risk; 3= dangerous risk of bleeding).Results: 26 patients, median age (min-max) 10.3 (6.8-14.3) YO were included. Sixty one percent of patients had BRisk= 1.0; 7.7% had BRisk= 2.0 and 2.5; 23,1% had BRisk= 3. In the last 12 months, haemarthrosis were presented in 33% of patients with BRisk=3.0 and 13% in those with BRisk= 1.0. Interesting, patients with BRisk= 2.0 or 2.5 did not present any joint bleeding in the previous year. Median levels of FVIII was 0.5 (0.0-1.9) IU/dl. There were no differences on trough FVIII levels between patients with or without joint bleeds (FVIII= 0.3 [0.0-1.9] and 1.1[0.2-4.4] IU/dl respectively, p=0.515) in the year before. There was no correlation between FVIII trough plasma levels and the AJBR (p=0.416). TEG trough profiles were similar in patients with and without haemarthrosis. However, patients with AJBR=0 presented a clear correlation between trough TEG parameters and BRisk (BRisk vs. k: r=-0,439; p= 0.047 and BRisk vs. alpha angle: r= 0.478; p= 0.025) so that, the higher the exercise-associated BRisk the higher procoagulant state needed to keep a joint-bleeding-free state. This correlation was not found for FVIII.Conclusions: Kaolin-activated TEG assay may help to define safety zones to minimize bleedings in response to PhA in patients < 18 YO with SHA and may guide prophylaxis tailoring depending on BRisk of PhA. DisclosuresNo relevant conflicts of interest to declare.

Changes in Hematologic and Coagulation Profiles in Rabbits with Right-ventricle Pacing.

The aim of this study was to evaluate changes in hematology and coagulation in rabbits with right-ventricle pacing without medication. Blood was collected from ten non-anesthetized male rabbits from the jugular vein before and one month after pacemaker placement. Total erythrocyte, leukocyte and platelet count, hemoglobin, hematocrit and differential leukocyte count were done on automatic veterinary flow cytometry hematologic analyzer. Prothrombin time, activated partial thromboplastin time, fibrinogen level, D-dimers and kaolin-activated thromboelastography was measured from citrated blood. We found an increase in red blood cell mass and decrease in platelet count, while coagulation tests did not diff er between samplings. Right-ventricle pacing seems to have no influence on hemostasis in rabbits.

Thromboelastography predicts risks of obstetric complication occurrence in (hypo)dysfibrinogenemia patients under non-pregnant state.

Congenital (hypo)dysfibrinogenemia patients may have obstetric complications during their pregnancies. This study aimed to evaluate thromboelastography (TEG) as a potential tool for assessing the tendency for obstetric complications in those patients in a non-pregnant state. A total of 22 female subjects with congenital (hypo)dysfibrinogenemia were recruited. Nine subjects had histories of obstetric complications and the other 13 subjects had at least one uneventful pregnancy without obstetric complications as yet. Detailed clinical investigation and phenotype/genotype detection were carried out, and both kaolin-activated TEG and functional fibrinogen TEG (FF-TEG) were applied in all subjects. Significant differences were identified in all TEG parameters except for R and angle between these two groups (P < 0.05) by covariance analysis. Receiver operating characteristic (ROC) analysis of discrimination between these two groups of patients was performed for TEG parameters. Significantly high odds ratio (OR) of obstetric complications occurrence were demonstrated in K ≥ 3.8 min, maximum amplitude (MA) ≤ 54.2 mm, comprehensive index (CI) ≤ -3 (11.67, 95% CI 1.527-89.121, P < 0.05 in all), and MA-CFF ≤ 12.1 mm (20.00, 95% confidence interval (95% CI) 1.967-203.322, P = 0.002). Moreover, MA-CFF had better prognostic performance, with a corresponding area under the receiver operating curve of 0.923 (range 0.815-1.031, P = 0.001). This study suggests that (hypo)dysfibrinogenemia patients with values outside of the cut-off values of TEG assays under non-pregnant state may have a higher risk of obstetric complications occurring when they are pregnant. No parameters under non-pregnant state in clinical laboratory have ever been reported to be risk factors for obstetric complication occurrence in (hypo)dysfibrinogenemia patients. This study explored such parameters in TEG assays and found that parameters of TEG assays under non-pregnant status might predict the occurrence of obstetric complications, which could provide physicians with important information about whether fibrinogen replacement therapy is required, so as to prevent the occurrence of obstetric complications, especially for patients who are asymptomatic in daily life.

Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel. Results from a prospective, randomised, double-blind, placebo-controlled study.

There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation.

Thromboelastography Values in Hispaniolan Amazon Parrots ( Amazona ventralis ): A Pilot Study.

Thromboelastography (TEG) provides a global assessment of coagulation, including the rate of clot initiation, clot kinetics, achievement of maximum clot strength, and fibrinolysis. Thromboelastography (TEG) is used with increasing frequency in the field of veterinary medicine, although its usefulness in avian species has not been adequately explored. The purpose of this preliminary study was to assess the applicability of TEG in psittacine birds. Kaolin-activated TEG was used to analyze citrated whole blood collected routinely from 8 healthy adult Hispaniolan Amazon parrots ( Amazona ventralis ). The minimum and maximum TEG values obtained included time to clot initiation (2.6-15 minutes), clot formation time (4.3-20.8 minutes), α angle (12.7°-47.9°), maximum amplitude of clot strength (26.3-46.2 mm), and percentage of lysis 30 minutes after achievement of maximum amplitude (0%-5.3%). The TEG values demonstrated comparative hypocoagulability relative to published values in canine and feline species. Differences may be explained by either the in vitro temperature at which TEG is standardly performed or the method of activation used in this study. Although TEG may have significant advantages over traditional coagulation tests, including lack of need for species-specific reagents, further evaluation is required in a variety of avian species and while exploring various TEG methodologies before this technology can be recommended for use in clinical cases.

Effects of in vitro hemodilution with crystalloids, colloids, and plasma on canine whole blood coagulation as determined by kaolin-activated thromboelastography.

To investigate the effects of in vitro hemodilution with lactated Ringers solution (LRS), hetastarch (HES), and fresh frozen plasma (FFP) on whole blood coagulation in dogs as assessed by kaolin-activated thromboelastography. In vitro experimental study. University teaching hospital. Six healthy client-owned dogs. Whole blood was collected and diluted in vitro at a 33% and 67% dilution with either LRS, HES, or FFP. Kaolin-activated thromboelastography was performed on each sample as well as a control. Thromboelastographic parameters R (min), alpha (deg), K (min), and MA (mm) were measured and compared to the sample control for each dilution using mixed model methodology. Prolongation in coagulation times were seen at both dilutions with LRS and HES. There was no significant difference in R times at the 33% dilution, but R time was significantly prolonged at the 67% dilution with HES (P = 0.004). MA was significantly decreased for LRS at both dilutions (P = 0.013, P < 0.001) and more profoundly decreased for HES (P < 0.001, P = 0.006). No significant difference in any parameter was found for FFP. In vitro hemodilution of whole blood with both LRS and HES but not FFP resulted in significant effects on coagulation with HES having a more profound effect. In vivo evaluation of changes in coagulation with various resuscitation fluids is warranted and may be clinically relevant.

Thromboelastographic Evaluation of Dogs with Acute Liver Disease.

BackgroundGiven the liver's pivotal role in hemostasis and fibrinolysis, the coagulopathy accompanying hepatic disease is complex.Hypothesis/ObjectivesTo prospectively evaluate kaolin‐activated thromboelastography (TEG) in dogs with acute liver disease (ALD) and compare with plasma‐based coagulation tests.AnimalsTwenty‐one dogs with a diagnosis of ALD based on recent onset of clinical signs accompanied by increases in serum bilirubin concentration and alanine aminotransferase activity.MethodsClinical presentation, CBC, serum biochemistry, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and TEG analysis were evaluated in 21 dogs with a subset also having fibrinogen, antithrombin (AT) activity, protein C (PC) activity, d‐dimers, and von Willebrand's factor (vWF) activity analyzed. A PT >1.5 times the upper limit of normal defined acute liver failure (ALF).ResultsDogs with ALD had mean increases in R, K, LY30, PT, aPTT, and vWF activity, and decreases in angle, maximal amplitude (MA), G, AT activity, and PC activity. The TEG results defined dogs as hypocoagulable (11/21), normocoagulable (8/21), or hypercoagulable (2/21). Increases in LY30 defined 8/21 dogs as hyperfibrinolytic. Hypocoagulable and hyperfibrinolytic dogs had lower fibrinogen and PC activity than dogs without these abnormalities. Overall, ALF dogs had greater increases in K and LY30, and decreases in MA, G, and PC activity than dogs with less severe hepatic impairment. Results for MA and LY30 were positively correlated with serum bilirubin concentration and white blood cell count, and negatively correlated with serum cholesterol concentration.Conclusions and Clinical Importance ALD dogs have a range of coagulation abnormalities that trend toward hypocoagulability and hyperfibrinolysis as functional impairment occurs.

Is some better than none: are TEG and TGA profiles different in severe FVIII-deficient patients with inhibitors?

Severe factor VIII (FVIII)-deficient patients with and without FVIII inhibitors cannot be distinguished using FVIII levels. The FVIII assay is sensitive to detect factor levels below 1%. While severe FVIII-deficient, non-inhibitor patients have FVIII<1%, they may retain unmeasurable residual factor activity. In contrast, inhibitor patients have a FVIII antibody that presumably fully eliminates FVIII activity. It is unknown whether thromboelastography (TEG) and thrombin generation assay (TGA) can differentiate between patients with FVIII<1% with and without the presence of FVIII inhibitors. The primary objective was to discern whether TEG and TGA could differentiate between severe FVIII-deficient patients with and without the presence of FVIII inhibitors. A secondary objective was to correlate TEG and TGA to annualized bleeding rates. This observational study performed TEG and TGA in healthy volunteers (N=15), severe FVIII-deficient (N=15) and severe FVIII-deficient patients with inhibitors (N=15). Kaolin-activated TEG was better at differentiating reaction time (31.3 vs. 120min respectively, P=0.004) and kinetics time (6.1 vs. 23.1min respectively, P=0.028) between the non-inhibitor and inhibitor patients. TEG activated by tissue factor in plasma-containing corn trypsin inhibitor failed to differentiate groups. The TGA failed to differentiate peak thrombin, endogenous thrombin potential and lag time between groups. There was no correlation between TEG and TGA with annualized bleeding rates. Kaolin-activated TEG, but not TGA, differentiated between severe FVIII-deficient patients with and without inhibitors. These assays did not find a correlation to annualized bleeding rate.

Evaluation of tranexamic acid and ε-aminocaproic acid concentrations required to inhibit fibrinolysis in plasma of dogs and humans.

To determine minimum plasma concentrations of the antifibrinolytic agents tranexamic acid (TEA) and ε-aminocaproic acid (EACA) needed to completely inhibit fibrinolysis in canine and human plasma after induction of hyperfibrinolysis. Pooled citrated plasma from 7 dogs and commercial pooled citrated human plasma. Concentrations of EACA from 0 μg/mL to 500 μg/mL and of TEA from 0 μg/mL to 160 μg/mL were added to pooled citrated canine and human plasma. Hyperfibrinolysis was induced with 1,000 units of tissue plasminogen activator/mL, and kaolin-activated thromboelastography was performed in duplicate. The minimum concentrations required to completely inhibit fibrinolysis 30 minutes after maximum amplitude of the thromboelastography tracing occurred were determined. Minimum plasma concentrations necessary for complete inhibition of fibrinolysis by EACA and TEA in pooled canine plasma were estimated as 511.7 μg/mL (95% confidence interval [CI], 433.2 to 590.3 μg/mL) and 144.7 μg/mL (95% CI, 125.2 to 164.2 μg/mL), respectively. Concentrations of EACA and TEA necessary for complete inhibition of fibrinolysis in pooled human plasma were estimated as 122.0 μg/mL (95% CI, 106.2 to 137.8 μg/mL) and 14.7 μg/mL (95% CI, 13.7 to 15.6 μg/mL), respectively. Results supported the concept that dogs are hyperfibrinolytic, compared with humans. Higher doses of EACA and TEA may be required to fully inhibit fibrinolysis in dogs.

Thromboelastographic evaluation of hemostatic function in dogs treated for crotalid snake envenomation.

To characterize the overall hemostatic changes in dogs envenomated by crotaline snakes via kaolin-activated thromboelastography (TEG), and to determine any prognostic/monitoring value from a TEG tracing on presentation, as well as during treatment with antivenom therapy. Prospective observational, cohort study. University teaching hospital and primary emergency hospital. Thirty-eight dogs envenomated by crotaline snakes. TEG tracings were evaluated on presentation to the hospital (pre) as well as immediately following (post) and 12 hours (12 h post) after antivenom treatment, if administered. At presentation, data were available for 38 dogs envenomated by crotaline snakes. Twenty dogs were in Group 1 (Antivenin [Crotalidae] Polyvalent antivenom), 12 dogs were in Group 2 (Antivipmyn antivenom), and 6 dogs in Group 3 that were not treated with antivenom. The average number of vials administered to group 1 and 2 were equal at 2.2. On presentation, based on a G value < TEG reference range, 15/38 (39%) of the dogs had hypocoagulable TEG tracings. There was a significant increase in G and MA value from the pre and 12 hour post measurement (P = 0.0001 and 0.0003, respectively), as well as from the post to 12 hour post measurement (P = 0.003 and, 0.014, respectively). During the study, 5 of 38 dogs died (13%) and of the dogs that died, 4/5 (80%) had angle and MA equal to zero on presentation. A decreased G and MA were significantly associated with mortality (P = 0.02 and 0.04, respectively). A hypocoagulable TEG tracing, particularly a decreased G value and MA, is associated with an increased mortality in crotaline snake envenomation. G and MA also demonstrate a significant increase over treatment time.

Comparison of computed tomography pulmonary angiography and point‐of‐care tests for pulmonary thromboembolism diagnosis in dogs

ObjectivesTo evaluate the feasibility of CT pulmonary angiography for identification of naturally occurring pulmonary thromboembolism in dogs using predefined diagnostic criteria and to assess the ability of echocardiography, cardiac troponins, D-dimers and kaolin-activated thromboelastography to predict the presence of pulmonary thromboembolism in dogs.MethodsTwelve dogs with immune-mediated haemolytic anaemia and evidence of respiratory distress were prospectively evaluated. Dogs were sedated immediately before CT pulmonary angiography using intravenous butorphanol. Spiral CT pulmonary angiography was performed with a 16 detector-row CT scanner using a pressure injector to infuse contrast media through peripheral intravenous catheters. Pulmonary thromboembolism was diagnosed using predefined criteria. Contemporaneous tests included echocardiography, arterial blood gas analysis, kaolin-activated thromboelastography, D-dimers and cardiac troponins.ResultsBased on predefined criteria, four dogs were classified as pulmonary thromboembolism positive, three dogs were suspected to have pulmonary thromboembolism and the remaining five dogs had negative scans. The four dogs identified with pulmonary thromboembolism all had discrete filling defects in main or lobar pulmonary arteries. None of the contemporaneous tests was discriminant for pulmonary thromboembolism diagnosis, although the small sample size was limiting.Clinical SignificanceCT pulmonary angiography can be successfully performed in dogs under sedation, even in at-risk patients with respiratory distress and can both confirm and rule out pulmonary thromboembolism in dogs.

Cigarette Smoking and Antiplatelet Effects of Aspirin Monotherapy Versus Clopidogrel Monotherapy in Patients with Atherosclerotic Disease: Results of a Prospective Pharmacodynamic Study

Smokers have a greater relative benefit of clopidogrel therapy compared with nonsmokers, likely attributed to its enhanced pharmacodynamic (PD) effects. However, to date, all PD studies have been conducted in patients on dual antiplatelet therapy with aspirin and clopidogrel, and it is unknown whether clopidogrel monotherapy can offer more effective antithrombotic effects compared with aspirin alone among smoking patients. Sixty aspirin-treated (81mg/day) patients with vascular disease, classified as nonsmokers, light smokers, and heavy smokers according to cotinine serum levels, were enrolled. Patients were switched to clopidogrel (75mg/day) monotherapy for 7-10days. PD assessments were performed before and after switch by multiple electrode aggregometry (MEA) and kaolin-activated thromboelastography (TEG). Complete PD data were obtained in 57 patients (nonsmokers, n = 27; light smokers, n = 13; heavy smokers, n = 17). On treatment platelet reactivity following MEA, adenosine diphosphate (ADP) + prostaglandin E1 (PGE1) and thrombin receptor-activating peptide (TRAP) stimuli were significantly lower among heavy smokers following switch to clopidogrel. A significant inverse effect was observed with MEA arachidonic acid (ASPI), while neutral findings were shown with MEA collagen (COLL) stimulus. Thrombin and fibrin activity assessed by clot generation parameters were all nonsignificantly different but showed trends towards enhanced antithrombotic activity with clopidogrel among heavy smokers. In heavy smokers with vascular disease manifestations, clopidogrel is associated with enhanced platelet inhibitory effects, affecting purinergic and non-purinergic pathways, compared with aspirin as measured by MEA. Moreover, among smokers, clopidogrel offers trends towards enhanced effects on parameters of clot generation measured by TEG.

Comparison of components of biological variation between 3 equine thromboelastography assays

There is a paucity of information about the analytical performance of thromboelastography (TEG) in horses, specifically concerning components of variation among different analytical methods. Such data may be obtained by nested analysis of repetitive standardized sampling of healthy individuals. The objectives were (1) to assess the relative susceptibility to sources of preanalytical variation in a highly standardized setting, (2) to directly compare and evaluate the observed analytical variation, and (3) to assess the applicability of population-based reference intervals. Blood was collected once from 20 healthy adult horses and weekly for 5 consecutive weeks from 8 healthy adult horses. TEG analyses were performed on citrated whole blood using nonactivated TEG and 2 TEG assays with human recombinant tissue factor (TF) or kaolin as activators. There were significant differences between nonactivated and activated assays for all measured parameters (P < .05). The intraindividual variation was significantly higher with the nonactivated assay compared with TF- and kaolin-activated protocols. Analytical variation was generally low and comparable for all 3 assays. Nonactivated TEG showed the highest degree of within-subject variation, TF-activated TEG (TF-TEG) intermediate and kaolin-activated TEG (K-TEG) the lowest degree of within-subject variation. Nonactivated TEG is more sensitive to preanalytical variation than both TF-TEG and K-TEG. Analytical variation was low and comparable for all assays, but not all parameters reached objective analytical goals. The results further indicate that population-based reference intervals can be readily applied to TF-TEG, but not to nonactivated or K-TEG, where critical difference may provide a better interpretation criterion.

Thromboelastographic Evaluation of Dogs with Congenital Portosystemic Shunts

On plasma-based assays, dogs with congenital portosystemic shunts (CPSS) have changes in serum concentrations of both pro- and anticoagulant proteins, but how these abnormalities affect whole blood coagulation assays (eg, thromboelastography) are unknown. To conduct kaolin-activated thromboelastography (TEG) analysis in dogs with CPSS and to compare TEG coagulation status with clinical presentation, routine serum biochemistry, and plasma-based coagulation tests. Twenty-one client-owned dogs with CPSS confirmed by ultrasound examination or nuclear scintigraphy. In a prospective study, signalment, clinical presentation, TEG analysis, CBC, serum biochemistry, and hemostatic tests (platelet count, prothrombin time [PT], activated partial thromboplastin time [aPTT], quantitative fibrinogen, antithrombin [AT] activity, protein C [PC] activity, d-dimers, and factor VIII activity) were analyzed in dogs with CPSS. Dogs with CPSS had significantly shorter K values and increased angle, maximum amplitude (MA), and G values compared with the reference population. On plasma-based coagulation testing, dogs with CPSS had significantly prolonged PT, lower platelet counts, lower AT and PC activities, and increased d-dimers and factor VIII activity. Evaluation of G value defined 9/21 dogs with CPSS as hypercoagulable. These dogs were more likely to have hepatic encephalopathy (HE) than CPSS dogs that had normal coagulation. TEG analysis detected hemostatic abnormalities consistent with a hypercoagulable state in some dogs with CPSS. The presence of a hypercoagulable state was 40 times more likely in dogs with symptomatic HE.