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.

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

Background: Coagulopathies in horses with gastrointestinal disease are frequently identified and associated with morbidity and fatality.



Objective: Determine if thrombelastography (TEG) identifies abnormalities associated with lesion type, presence of systemic inflammatory response syndrome (SIRS), morbidity, and fatality more consistently than traditional coagulation testing.



Animals: One-hundred and one horses examined for gastrointestinal disease and 20 healthy horses.



Methods: TEG, tissue factor (TF)-TEG, and traditional coagulation panels parameters and percentages of horses with coagulopathies were compared for lesion type, presence of SIRS, complications, and survival.



Results: Changes in individual parameters and increased incidence of coagulopathies were associated with fatality (R, P= .007; k-value [K], P= .004; clot lysis [CL]30, P= .037; CL60, P= .050; angle [Ang], P= .0003; maximum amplitude [MA], P= .006; lysis [Ly]30, P= .042; Ly60, P= .027; CI, P= .0004; ≥ 2 TEG coagulopathies, P= .013; ≥ 3 TEG coagulopathies, P= .038; TF-R, P= .037; TF-K, P= .004; TF-CL30, P < .0001; TF-CL60, P < .0001; TF-Ang, P= .005; TF-Ly30, P= .0002; TF-Ly60, P < .0001; TF-CI, P= .043; ≥ 1 TF-TEG coagulopathies, P= .003; ≥ 2 TF-TEG coagulopathies, P= .0004; prothrombin tme [PT], P < .0001; activated partial throboplastin time [aPTT], P= .021), inflammatory lesions (MA, P= .013; TF-CL30, P= .033; TF-CL60, P= .010; TF-Ly60, P= .011; ≥ 1 TF-TEG coagulopathy, P= .036; ≥ 2 TF-TEG coagulopathy, P= .0007; PT, P= .0005; fibrinogen, P= .019), SIRS (MA, P= .004; TF-CL30, P= .019; TF-CL60, P= .013; TF-Ly30, P= .020; TF-Ly60, P= .010; PT, P < .0001; aPTT, P= .032; disseminated intravascular coagulation, P= .005), and complications (ileus: aPTT, P= .020; diarrhea: TF-CL30, P= .040; TF-Ly30, P= .041; thrombophlebitis: ≥ 1 TF-TEG coagulopathy, P= .018; laminitis: MA, P= .004; CL60, P= .045; CI, P= .036; TF-MA, P= .019; TF-TEG CI, P= .019). Abnormalities in TEG and TF-TEG parameters were indicative of hypocoagulation and hypofibrinolysis.



Conclusions and Clinical Importance: TEG identifies changes in coagulation and fibrinolysis associated with lesion type, SIRS, morbidity, and fatality in horses with gastrointestinal disease.

/pdf/thrombelastography-in-horses-with-acute-gastrointestinal-4epjzgzmw3.pdf

Thrombelastography in horses with acute gastrointestinal disease.

Objective

To examine systematically the evidence on sample acquisition and handling for the thrombo elastography (TEG) and rotational thromboelastometry (ROTEM) viscoelastic point of care instruments and to identify knowledge gaps.



Design

Six questions were considered, addressing sampling site, collection system, anticoagulant, collection procedure, and sample storage. Standardized, systematic evaluation of the literature was performed. Relevant articles were categorized according to level of evidence (LOE). Consensus was developed regarding conclusions for application of concepts to clinical practice.



Setting

Academic and referral veterinary medical centers.



Results

PubMed and CAB abstracts were searched. Eighteen papers were initially chosen; 5 of these papers applied to > 1 domain question. Three papers were used to address 2 questions each, and 2 papers were used to address 3 questions each. Most papers were judged LOE 3 (Good or Fair). Two of 5 papers were judged to be the same LOE each time they were used; 2 papers were judged to be LOE 3, Fair for 1 question and 3, Good for a second question; 1 paper used to address 3 questions was judged LOE 3, Good twice and 3, Fair once. Fourteen additional papers were evaluated post hoc during manuscript preparation.



Conclusions

Jugular venipuncture is recommended, but samples from IV catheters can be used. Consistent technique is important for serial sampling, and standardized sampling protocols are recommended for individual centers performing TEG/ROTEM. There is insufficient evidence to recommend use of a specific blood collection system, although use of evacuated blood tubes and 21-Ga or larger needles is suggested. Use of 3.2% buffered sodium citrate in a strict 1:9 ratio of citrate to blood is suggested. Suggested tube draw order is discard/serum, followed by citrate, EDTA, and then heparin. Samples should be held at room temperature for 30 minutes prior to analysis.

Systematic evaluation of evidence on veterinary viscoelastic testing part 2: Sample acquisition and handling

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.

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

Objective – To review the current in vivo and in vitro tests of platelet function (PF) currently available and applicable to companion animals. Data Sources – Scientific reviews, case reports, original clinical and laboratory research publications, and recent veterinary research conference proceedings. Human Data Synthesis – Disorders of primary hemostasis are very common in human medicine. These include inbornerrorsofPFandgranulestoragecontents,primarydiseasemechanismsthatalterPF,disorderssecondary to surgical interventions, and the effects of anticoagulant medications. Knowledge of PF disorders and the optimal method for assessment must be known to understand the mechanism and to monitor the process or drug therapy. Veterinary Data Synthesis– Interest in the study and treatment of primary coagulopathies in clinical veterinary patients has resulted in a surge of recent publications and scientific research presentations. A translational approach that uses laboratory and point-of-care tools to uncover the pathophysiologic mechanisms in the patient with defects in primary hemostasis allows the clinician to plan the diagnosis and treatment more effectively. Summary – Primary hemostatic disorders are being more commonly recognized in clinical veterinary practice. Thediagnosis of plateletdysfunction may be obtained via point-of-care analyzers that use relativelysmall blood samples and have a quick turnaround time. Recent investigations may lead to a better understanding of the pathophysiology of PF disorders and potentially the optimization, or discovery, of novel treatments. Conclusions – The assessment of PF can be completed through in vivo and in vitro point-of-care techniques as well as by submission of blood samples to more specialized platelet biology laboratories. The information obtained including the physical examination and clinical manifestations of a hemostatic disorder, as well as the benefits of each testing modality, must be known prior to the diagnostic investigation of a patient with a coagulopathy.

Assessment of platelet function

Objectives – To evaluate the use of citrated recalcified (nonactivated) thromboelastography (TEG) in healthy horses and horses with colitis and suspected coagulopathies. Design – Prospective, observational study conducted between October 2007 and June 2009. Setting – Veterinary Teaching Hospital. Animals – Forty-five healthy adult horses and 12 sick adult horses with colitis and prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT). Interventions – None. Measurements and Main Results – Whole blood was collected on admission. Coagulation profile (PT, aPTT, platelet count, and fibrinogen concentration) and citrated recalcified whole blood TEG analysis (R-time [R], Ktime [K], angle [a], maximum amplitude [MA], G value [G], lysis at 60min [LY60]) were evaluated. Mean values (SD) for TEG parameters in healthy horses were: R 510.4 (3.1) minutes; K 53.5 (1.2) minutes; a 546.3 (11.0)1 ;M A555.6 (5.1)mm; G 56,429 (1,341)dyn/cm 2 , and LY60 55.1 (2.4)%. Mean coefficients of variation for intra-assay/interindividual variability in healthy horses were: R 54.7%/30.7%, K 54.8%/35.3%, a 54.4%/23.8%, MA 51.4%/9.3%, G 53.4%/20.8%, and LY60 513.1%/47.7%, respectively. Horses with colitis and prolonged PT and/or aPTT had longer mean values for R (Po0.001) and K (Po0.001), narrower mean a (Po0.001), decreased mean MA (P 50.001), and smaller mean G (P 50.02); changes consistent with hypocoagulability. Conclusions – Citrated recalcified (nonactivated) TEG demonstrated changes consistent with hypocoagulability in horses with colitis that had preidentified coagulation abnormalities. This technique has high interindividual variability and low intra-assay variability. TEG may be useful for detecting hypocoagulable states in horses with colitis and suspected coagulopathies.

Paulo Vilar-Saavedra

Papers

Thromboelastography in healthy horses and horses with inflammatory gastrointestinal disorders and suspected coagulopathies.