Rita M. Hanel

Partnership on Rotational ViscoElastic Test Standardization (PROVETS): Evidence‐based guidelines on rotational viscoelastic assays in veterinary medicine

Objective To systematically examine the evidence relating to the performance of rotational viscoelastic testing in companion animals, to develop assay guidelines, and to identify knowledge gaps. Design Multiple questions were considered within 5 parent domains, specifically system comparability, sample handling, assay activation and test protocol, definitions and data reporting, and nonstandard assays. Standardized, systematic evaluation of the literature was performed. Relevant articles were categorized according to level of evidence and assessed for quality. Consensus was developed regarding conclusions for application of concepts to clinical practice. Setting Academic and referral veterinary medical centers. Results Databases searched included Medline, Commonwealth Agricultural Bureaux abstracts, and Google Scholar. Worksheets were prepared evaluating 28 questions across the 5 domains and generating 84 assay guidelines. Conclusions Evidence-based guidelines for the performance of thromboelastography in companion animals were generated through this process. Some of these guidelines are well supported while others will benefit from additional evidence. Many knowledge gaps were identified and future work should be directed to address these gaps and to objectively evaluate the impact of these guidelines on assay comparability within and between centers.OBJECTIVE To systematically examine the evidence relating to the performance of rotational viscoelastic testing in companion animals, to develop assay guidelines, and to identify knowledge gaps. DESIGN Multiple questions were considered within 5 parent domains, specifically system comparability, sample handling, assay activation and test protocol, definitions and data reporting, and nonstandard assays. Standardized, systematic evaluation of the literature was performed. Relevant articles were categorized according to level of evidence and assessed for quality. Consensus was developed regarding conclusions for application of concepts to clinical practice. SETTING Academic and referral veterinary medical centers. RESULTS Databases searched included Medline, Commonwealth Agricultural Bureaux abstracts, and Google Scholar. Worksheets were prepared evaluating 28 questions across the 5 domains and generating 84 assay guidelines. CONCLUSIONS Evidence-based guidelines for the performance of thromboelastography in companion animals were generated through this process. Some of these guidelines are well supported while others will benefit from additional evidence. Many knowledge gaps were identified and future work should be directed to address these gaps and to objectively evaluate the impact of these guidelines on assay comparability within and between centers.

Systematic evaluation of evidence on veterinary viscoelastic testing part 4: Definitions and data reporting.

Objective To systematically examine evidence surrounding definitions and reporting of data for viscoelastic testing in veterinary medicine. Design Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Setting Academic and referral veterinary medical centers. Results Databases searched included Medline, CAB abstracts, and Google Scholar. Conclusions All 4 standard thromboelastography (TEG) and rotational thromboelastometry (ROTEM) variables should be universally reported, and the reporting of shear elastic modulus in addition to maximum amplitude (MA) is encouraged. There is insufficient evidence to support universal usage of the coagulation index at this time. The K value and clot formation time are the most variable of the 4 parameters, with alpha angle, MA, and maximum clot firmness generally the least variable. Individual studies should report sufficient data on patients and institutional controls to enable definitions of hypo- and hypercoagulability to be evaluated post-hoc, and it is recommended that all studies specifically report how these conditions were defined. In reporting data relating to fibrinolysis, the TEG variables LY30, LY60, CL30, CL60, and the ROTEM variables LI30, LI60, ML, LOT, and LT should be documented. Studies should report sufficient data on patients and controls to enable definitions of hyper- and hypofibrinolysis to be evaluated post-hoc, and we suggest that standard TEG/ROTEM assays may be unable to detect hypofibrinolysis in companion animals. We recommend that every center establish reference intervals, which are specific to either TEG or ROTEM. These reference intervals should be established using veterinary clinical pathology guidelines, standardized protocols, and a minimum of 40 healthy animals. There are currently insufficient data in companion animals to suggest a utility for Vcurve variables beyond that of standard TEG variables.OBJECTIVE To systematically examine evidence surrounding definitions and reporting of data for viscoelastic testing in veterinary medicine. DESIGN Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. SETTING Academic and referral veterinary medical centers. RESULTS Databases searched included Medline, CAB abstracts, and Google Scholar. CONCLUSIONS All 4 standard thromboelastography (TEG) and rotational thromboelastometry (ROTEM) variables should be universally reported, and the reporting of shear elastic modulus in addition to maximum amplitude (MA) is encouraged. There is insufficient evidence to support universal usage of the coagulation index at this time. The K value and clot formation time are the most variable of the 4 parameters, with alpha angle, MA, and maximum clot firmness generally the least variable. Individual studies should report sufficient data on patients and institutional controls to enable definitions of hypo- and hypercoagulability to be evaluated post-hoc, and it is recommended that all studies specifically report how these conditions were defined. In reporting data relating to fibrinolysis, the TEG variables LY30, LY60, CL30, CL60, and the ROTEM variables LI30, LI60, ML, LOT, and LT should be documented. Studies should report sufficient data on patients and controls to enable definitions of hyper- and hypofibrinolysis to be evaluated post-hoc, and we suggest that standard TEG/ROTEM assays may be unable to detect hypofibrinolysis in companion animals. We recommend that every center establish reference intervals, which are specific to either TEG or ROTEM. These reference intervals should be established using veterinary clinical pathology guidelines, standardized protocols, and a minimum of 40 healthy animals. There are currently insufficient data in companion animals to suggest a utility for Vcurve variables beyond that of standard TEG variables.

Prospective multicenter evaluation of coagulation abnormalities in dogs following severe acute trauma

OBJECTIVES To describe coagulation abnormalities in dogs following severe acute trauma and to evaluate the relationship between coagulation, clinical, and laboratory variables, and disease and injury severity, as well as the ability of coagulation variables to predict the presence of body cavity hemorrhage (BCH), necessity of blood product administration, and outcome. DESIGN Prospective, multicenter, observational study. SETTING Two university teaching hospitals. ANIMALS Forty client-owned dogs sustaining severe blunt or penetrating trauma. INTERVENTIONS Blood samples were collected within 12 hours of the traumatic incident for measurement of blood gases, lactate concentration, platelet count, activated clotting time, prothrombin time, activated partial thromboplastin time (aPTT), fibrinogen concentration, antithrombin activity, D-dimer concentration, protein C activity, plasmin inhibition, plasminogen activity, and kaolin-activated thomboelastography. RESULTS Decreased platelet count was a risk factor for the presence of BCH (P = 0.006) and decreased platelet count (P < 0.001), protein C activity (P = 0.001), angle (α) (P = 0.001), maximum amplitude (MA) (P < 0.001), and clot strength (G) (P = 0.002) were risk factors for blood product administration. Nonsurviving dogs were hypocoagulable with prolonged aPTT (P = 0.008), decreased plasmin inhibition (P = 0.033), decreased α (P = 0.021), and decreased MA (P = 0.038) compared to surviving dogs. Multivariate analysis accounting for disease severity showed that prolonged aPTT (P = 0.004, OR = 1.74) was the strongest predictor of nonsurvival. Prolonged aPTT was positively correlated with APPLE-fast score (P < 0.001, r(2) = 0.35), lactate concentration (P < 0.001, r(2) = 0.35), and negative base excess (P = 0.001, r(2) = 0.27). Acute traumatic coagulopathy, as defined by 2 or more abnormal coagulation tests, was diagnosed in 15% of dogs at hospital admission and was more common in dogs with increased disease severity (P = 0.002), decreased systolic blood pressure (P = 0.002), and increased lactate concentration (P = 0.011). CONCLUSIONS In dogs with severe traumatic injuries and hypoperfusion, measurement of thromboelastography and aPTT should be considered to support clinical assessments in predicting the need for blood product administration and nonsurvival.

Hypercoagulability in dogs with protein-losing nephropathy as assessed by thromboelastography.

BACKGROUND Dogs with protein-losing nephropathy (PLN) are at risk of thromboembolic disease, but the mechanism leading to hypercoagulability and the population of dogs at risk are unknown. OBJECTIVES To characterize thromboelastography (TEG) and its association with serum albumin (SALB), UPC, and antithrombin activity in dogs with PLN. ANIMALS Twenty-eight client-owned dogs with PLN (urine protein:creatinine ratio [UPC] > 2.0) and 8 control dogs were prospectively enrolled in this observational study. METHODS TEG parameters, antithrombin activity, serum biochemical profiles, and UPC were measured. TEG analyses were run in duplicate with kaolin activation; reaction time (R), clot formation time (K), α-angle (α), maximal amplitude (MA), and global clot strength (G) were analyzed. RESULTS Dogs with PLN had lower K (P = .004), and higher α (P = .001), MA (P < .001), and G (P < .001) values than controls. No significant correlation between TEG parameters and UPC, SALB, or antithrombin was noted. Twelve PLN dogs (42.8%) were azotemic and 19 (67.8%) were hypoalbuminemic (SALB < 3.0 g/dL); 11 had SALB < 2.5 g/dL. CONCLUSIONS AND CLINICAL IMPORTANCE These results indicate that dogs with PLN have TEG values that demonstrate hypercoagulability compared with a control population but that antithrombin, SALB, or UPC cannot be used in isolation to predict this result. A comprehensive evaluation of the coagulation system in individual patients may be necessary to predict the point at which anti-thrombotic therapy is indicated.

Effect of antivenin dose on outcome from crotalid envenomation: 218 dogs (1988–2006)

OBJECTIVE To determine whether the dose of antivenin administered is associated with a difference in survival of crotalid-envenomated dogs. A secondary objective was to determine whether other covariables affect survival. DESIGN Retrospective study (1988-2006). SETTING Private referral center and university small animal teaching hospital. ANIMALS Two hundred and eighteen dogs with evidence of crotalid envenomation and treatment with equine-derived antivenin. INTERVENTIONS Administration of antivenin. MEASUREMENTS AND MAIN RESULTS Patient signalment, physical and clinicopathologic data at time of presentation, treatments, complications of antivenin therapy, length and cost of hospitalization, and outcome were recorded. Confidence intervals were determined for the difference in median number of vials administered and for median dosage for patients that lived versus died. Penalized logistic regression was performed to evaluate the effect of other covariables on survival. The median age of affected dogs was 3 years (range 6 w-12 y) with a median weight of 25.7 kg (range 1.95-86.4 kg). The median number of antivenin vials administered was 1.0 (range 1.0-10.0). Acute and chronic reactions were reported in 7% (16/218) and 0.9% (2/218) of dogs, respectively. Nine of 218 dogs (4.1%) died. The median number of vials administered to the nonsurvivors and survivors were 2.0 (range 1-5 vials) and 1.0 (range 1-10 vials), respectively. The median number of vials received was significantly different in dogs that died versus those that lived (P<0.05). Increased heart rate (P=0.02) and petechiation (P=0.04) were associated with decreased likelihood of survival, while diphenhydramine (P=0.02) and fluoroquinolone (P=0.046) administration was associated with increased likelihood of survival. The median duration of hospitalization was 1.0 day (range 2 h-22 d). The median cost of hospitalization was US

Effects of acepromazine maleate on platelet function assessed by use of adenosine diphosphate activated– and arachidonic acid– activated modified thromboelastography in healthy dogs

1592.00 (range US

Comparison of venous sampling methods for thromboelastography in clinically normal dogs

267.20-US

Effect of intravenous administration of dextrose on coagulation in healthy dogs

6738.00). CONCLUSION The administration of more vials of antivenin is potentially associated with negative outcome; however, a causal relationship has not been established. Controlled, prospective studies are needed to optimize antivenin administration.

Coagulation abnormalities in 5 cats with naturally occurring cytauxzoonosis

OBJECTIVE To evaluate the effect of acepromazine maleate administered IV on platelet function assessed in healthy dogs by use of a modified thromboelastography assay. ANIMALS 6 healthy adult mixed-breed dogs. PROCEDURES Dogs received each of 3 treatments (saline [0.9% NaCl] solution [1 to 2 mL, IV] and acepromazine maleate [0.05 and 0.1 mg/kg, IV]) in a randomized crossover study with a minimum 3-day washout period between treatments. From each dog, blood samples were collected via jugular venipuncture immediately before and 30 and 240 minutes after administration of each treatment. A modified thromboelastography assay, consisting of citrated kaolin-activated (baseline assessment), reptilase-ADP-activated (ADP-activated), and reptilase-arachidonic acid (AA)-activated (AA-activated) thromboelastography, was performed for each sample. Platelet inhibition was evaluated by assessing the percentage change in maximum amplitude for ADP-activated or AA-activated samples, compared with baseline values. Percentage change in maximum amplitude was analyzed by use of Skillings-Mack tests with significance accepted at a family-wise error rate of P < 0.05 by use of Bonferroni corrections for multiple comparisons. RESULTS No significant differences were found in the percentage change of maximum amplitude from baseline for ADP-activated or AA-activated samples among treatments at any time. CONCLUSIONS AND CLINICAL RELEVANCE Platelet function in dogs, as assessed by use of a modified thromboelastography assay, was not inhibited by acepromazine at doses of 0.05 or 0.1 mg/kg, IV. This was in contrast to previous reports in which it was suggested that acepromazine may alter platelet function via inhibition of ADP and AA.

Evaluation of the Lactate Plus monitor for plasma lactate concentration measurement in dogs.

OBJECTIVE To evaluate effects of blood collection method and site on results of thromboelastography in healthy dogs. ANIMALS 8 clinically normal purpose-bred dogs. PROCEDURES Blood was collected from the external jugular vein by syringe aspiration via direct venipuncture with a 20-gauge needle, through a central venous catheter, or into an evacuated tube with a 21-gauge winged needle catheter. Blood was collected from the lateral saphenous vein by syringe aspiration via direct venipuncture with a 20-gauge needle or into an evacuated tube with a 21-gauge winged needle catheter. Kaolin-activated thromboelastographic analyses were performed, and R (reaction time), K (clot formation time), α angle, maximal amplitude, and G (global clot strength) were analyzed. RESULTS No significant differences were observed with regard to sampling site. Sample collection method had no effect on thromboelastographic results for saphenous vein samples. Blood samples collected from the jugular vein by syringe aspiration had a lower R and K and higher α angle than did blood samples collected from the jugular vein by evacuated tube collection. Significant differences were observed between blood samples collected from the jugular vein by syringe aspiration and samples collected from the saphenous vein by evacuated tube collection and between samples collected from the saphenous vein by evacuated tube collection and samples collected from the jugular vein through a central venous catheter. CONCLUSIONS AND CLINICAL RELEVANCE Different sampling methods resulted in small but significant differences in thromboelastographic values. Results justify the use of standardized techniques for research purposes, but all of these sampling methods were acceptable for 1-time clinical use.