Viscoelastic coagulation monitoring parameters in cats with acute arterial thromboembolism.

BACKGROUND: Hypercoagulability has been documented in cats with cardiac disease. However, hemostatic parameters, including viscoelastic coagulation monitoring (VCM) have not been reported in cats with arterial thromboembolism (ATE). HYPOTHESIS/OBJECTIVES: Compare VCM parameters in cats with acute cardiogenic ATE and in control cats. ANIMALS: Sixteen cats with ATE and 30 control cats. METHODS: Multicenter university-based prospective study. Cardiogenic ATE was diagnosed based on physical examination and by ultrasonographically-diagnosed left atrial enlargement. Viscoelastic coagulation monitor analysis, CBC, serum biochemistry profile and coagulation profile were performed at admission in cats with ATE. Analysis from healthy control cats was performed using blood collected by direct venipuncture. Our objective was comparison of VCM parameters clot time (CT), clot formation time (CFT), alpha angle (Angle), maximum clot formation (MCF), amplitude at 10 and 20 minutes (A10 and A20, respectively) and clot lysis index at 30 and 45 minutes (LI30 and LI45, respectively) between ATE and control cats. RESULTS: Cats with ATE had a decreased angle compared to control cats, with a median (range) of 43° (30-48°) compared to 47° (14-59°; P = .01). The parameters A10, A20 and MCF were decreased in ATE cats compared to control cats with a median (range) of 19 units (8-32) compared to 22 units (6-38), 24.5 units (11-40) compared to 29 units (10-47) and 29.5 units (13-44) compared to 33.5 units (14-53), respectively (P = .01, .01 and .01, respectively). The parameters CT, CFT, LI30 and LI45 were similar between groups (P = .22, .09, .62 and .34, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with cardiogenic ATE cats have VCM parameters consistent with hypocoagulability compared with healthy cats.

Rapid resolution of hyperfibrinolysis in dogs with spontaneous hemoperitoneum following surgical control of hemorrhage.

OBJECTIVE: To estimate the point prevalence and duration of hyperfibrinolysis (HF) in dogs undergoing surgical control of spontaneous hemoperitoneum (SHP). DESIGN: Prospective observational study. SETTING: Single veterinary teaching hospital. ANIMALS: Forty-five client-owned dogs with SHP were screened for HF. Eighteen HF dogs treated surgically were studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Dogs with SHP and evidence of shock admitted for surgical control of hemorrhage were screened for HF. Blood samples were collected for PCV, total plasma protein, platelet count, and thromboelastography with 50 U/mL of tissue plasminogen activator at presentation and every 8 hours postoperatively until 72 hours, discharge, or death. HF was defined as a tissue plasminogen activator-activated thromboelastography lysis percentage measured 30 minutes after maximum amplitude (LY30) of ≥20%. LY30 values were compared to a cohort of samples obtained from healthy dogs (n = 22). The point prevalence of HF in all dogs screened was 40% (18/45 dogs), and the mean LY30 at baseline for HF dogs was 48.9% (±24.2%), which was significantly higher than that of control dogs (4.8% ± 7.1%, P < 0.001) and non-HF dogs (1.9% ± 5.7%, P < 0.001). In HF dogs, there was a significant decrease in LY30 between baseline and 8 hours (P < 0.0001) and between 8 and 16 hours (P = 0.035) but no significant change thereafter. LY30 at 8 hours (4%, range: 0%-23.4%) was not statistically different from control dogs (6.5%, range: 1.2%-32.8%, P = 0.664) suggesting early resolution of HF in this population. Only 2 of 18 dogs were persistently hyperfibrinolytic at 24 hours. Malignancy was diagnosed in 12 of 18 dogs (66.6%), while a benign etiology occurred in 6 of 18 dogs (33.3%). All HF dogs survived to discharge. CONCLUSIONS: HF occurs in some dogs with hypovolemic shock due to hemoperitoneum but resolves rapidly following surgical control of bleeding without antifibrinolytic medications. Routine postoperative use of antifibrinolytics in dogs with hemoperitoneum in dogs undergoing surgical control of bleeding may not be warranted.

2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics.

OBJECTIVES: To systematically review available evidence and establish guidelines related to the use of thrombolytics for the management of small animals with suspected or confirmed thrombosis. DESIGN: PICO (Population, Intervention, Control, and Outcome) questions were formulated, and worksheets completed as part of a standardized and systematic literature evaluation. The population of interest included dogs and cats (considered separately) and arterial and venous thrombosis. The interventions assessed were the use of thrombolytics, compared to no thrombolytics, with or without anticoagulants or antiplatelet agents. Specific protocols for recombinant tissue plasminogen activator were also evaluated. Outcomes assessed included efficacy and safety. Relevant articles were categorized according to level of evidence, quality, and as to whether they supported, were neutral to, or opposed the PICO questions. Conclusions from the PICO worksheets were used to draft guidelines, which were subsequently refined via Delphi surveys undertaken by the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) working group. RESULTS: Fourteen PICO questions were developed, generating 14 guidelines. The majority of the literature addressing the PICO questions in dogs is experimental studies (level of evidence 3), thus providing insufficient evidence to determine if thrombolysis improves patient-centered outcomes. In cats, literature was more limited and often neutral to the PICO questions, precluding strong evidence-based recommendations for thrombolytic use. Rather, for both species, suggestions are made regarding considerations for when thrombolytic drugs may be considered, the combination of thrombolytics with anticoagulant or antiplatelet drugs, and the choice of thrombolytic agent. CONCLUSIONS: Substantial additional research is needed to address the role of thrombolytics for the treatment of arterial and venous thrombosis in dogs and cats. Clinical trials with patient-centered outcomes will be most valuable for addressing knowledge gaps in the field.

Early career clinicians euthanize more dogs with nontraumatic hemoabdomen but not gastric dilatation and volvulus than more experienced clinicians.

OBJECTIVE: To determine if clinician experience influenced the euthanasia rate in 2 common surgical emergencies. ANIMALS: 142 dogs with nontraumatic hemoabdomen (NTH) due to suspected ruptured splenic mass and 99 dogs with gastric dilatation-volvulus (GDV) where the owner either elected surgery or euthanasia. PROCEDURES: Medical records were reviewed for dogs that had either NTH or GDV. For each patient, the owner's decision to pursue euthanasia versus surgery was recorded. The primary clinician was categorized as an intern, defined as a clinician with < 12 months experience, or a non-intern, defined as a clinician with more than 12 months experience. The euthanasia rates were compared used a Fisher exact, and the 95% CI was calculated for the risk of euthanasia if the primary clinician was an intern compared with a non-intern. If a difference was identified, subgroups comparing time of day, referral status, age, Hct, total solids, lactate, and heart rate were evaluated using a t test with a Bonferroni correction for the continuous variables and a Fisher exact for categorical variables. RESULTS: For dogs with NTH, the euthanasia rate for cases primarily managed by non-interns (52%) was significantly lower than that of interns (76%; P = .005). The relative risk of euthanasia associated with NTH when the case was treated by an intern was 1.44 with a 95% CI of 1.1229 to 1.8567. For 99 dogs with GDV, the rate of euthanasia was not different between interns and non-interns. CLINICAL RELEVANCE: The euthanasia rate for dogs with NTH may be impacted by the level of experience of the clinician. Support of new clinicians during challenging conversations should be provided.

Thromboelastography in cats with cholestatic liver disease.

OBJECTIVES: While thromboelastography (TEG) has helped define a complex state of hemostasis in dogs and humans with hepatobiliary disease, it has not been explored in cats with cholestatic liver disease (CLD). The objective of this study was to describe TEG parameters in cats with CLD and to compare these parameters with conventional plasma-based coagulation tests, white blood cell (WBC) count and biochemical indicators of liver disease grade and severity. METHODS: Eighteen cats with CLD, defined by a serum bilirubin ⩾3 mg/dl and a greater than two-fold increase in serum alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) activity, were prospectively enrolled. All cats received vitamin K1 subcutaneously for 24-36 h prior to acquisition of blood for kaolin-activated TEG analysis, prothrombin time (PT) and activated partial thromboplastin time (aPTT). Patient total solids, packed cell volume, platelet count, WBC count, and serum liver enzymes and bilirubin were extracted from the medical record and correlated with coagulation test results. RESULTS: TEG global clot strength (TEG G) values defined 9/18 (50%), 5/18 (28%) and 4/18 (22%) cats as hypercoagulable, normocoagulable or hypocoagulable, respectively. TEG G was significantly negatively correlated with PT, aPTT and serum ALP activity and positively correlated with total solids. Five cats (5/18, 28%) were hyperfibrinolytic with clot lysis at 60 mins (LY 60) >15.3%. LY 60 was significantly positively correlated with PT. CONCLUSIONS AND RELEVANCE: By TEG analysis, cholestatic cats replete with vitamin K1 display a variety of coagulation profiles. Indications of synthetic failure (prolonged PT and aPTT) were associated with hypocoagulable and hyperfibrinolytic TEG parameters. High disease activity (serum ALP) was associated with a hypocoagulable state.

The Use of Antithrombotics in Critical Illness.

Hypercoagulable tendencies may develop in critically ill dogs and to a less known extent, cats. Although the use of antithrombotics is well-established in critically ill people, the indications and approach are far less well-known in dogs and cats. The goal of this article was to review the relevant CURATIVE guidelines, as well as other sources, and to provide recommendations for critically ill patients with directions for future investigation.

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.

Multicenter investigation of hemostatic dysfunction in 15 dogs with acute pancreatitis.

OBJECTIVE: To characterize hemostatic profiles in dogs with acute pancreatitis. DESIGN: Prospective and observational study. SETTING: Tertiary referral centers. ANIMALS: Fifteen client-owned dogs with acute pancreatitis enrolled between December 1, 2011 and June 1, 2012. MATERIALS AND METHODS: Blood samples were collected on admission for measurement of platelet count, PCV, thromboelastography (TEG), antithrombin, prothrombin time, activated partial thromboplastin time, D-dimer, von Willebrand factor, and fibrinogen values, which were compared to reference intervals derived from healthy dogs. The Wilcoxon rank-sum test was used to test for differences in continuous variables between study subjects and reference intervals. MEASUREMENTS AND MAIN RESULTS: Dogs with acute pancreatitis were globally hypercoagulable using TEG when compared with reference intervals. Dogs with acute pancreatitis had significantly higher D-dimers (1,144 µg/L vs 251 µg/L [6264.5 vs 1374.5 nmol/L]; P = 0.001), fibrinogen (837 vs 232 mg/dL [8.37 vs 2.32 g/L]; P < 0.001), and von Willebrand factor (92.9% vs 65.1%; P = 0.02) as well as significantly lower antithrombin (85.7% vs 120%; P < 0.001) and prothrombin time values (3.8 vs 7.6 sec; P < 0.001) than reference intervals. CONCLUSIONS: Laboratory evidence of hypercoagulability was present in dogs with acute pancreatitis. TEG may be useful in dogs with acute pancreatitis for monitoring response to therapy and guiding therapeutic interventions.

Multicenter in vitro thromboelastography and thromboelastometry standardization.

OBJECTIVE: To establish and compare the repeatability and reproducibility of activated thromboelastography (TEG) and thromboelastometry (ROTEM) assays. DESIGN: Multicenter in vitro test standardization. SETTING: Veterinary academic centers. ANIMALS: Test samples were obtained from normal, healthy dogs. Sixty identical 5 mL aliquots of canine platelet-rich plasma collected by apheresis, frozen in 6% dimethyl sulfoxide, were tested initially. Sixty identical 6 mL aliquots of canine fresh frozen plasma with admixed cryoprecipitate were subsequently evaluated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Frozen study samples, quality controls, reagents, and consumables were distributed to participating centers (7 TEG and 3 ROTEM). TEG centers analyzed study samples with kaolin and tissue factor activated assays; ROTEM centers ran proprietary ellagic acid activated and tissue factor activated assays. All machines underwent quality control prior to sample analysis. Within- and between-center coefficients of variation (CVs) were calculated and compared using Mann-Whitney tests and calculation of intraclass correlation coefficients. Within and between centers, individual parameters for both TEG and ROTEM assays were comparable. Both within-center and between-center CVs varied markedly (0.7-120.5% and 1.4-116.5%, respectively) with assay type, instrument, and parameter. CVs for equivalent parameters were not significantly different between the 2 platforms. Intraclass correlation coefficients suggested moderate agreement between centers. In general, individual parameter CVs for platelet-rich plasma samples were lower in TEG centers, while CVs for canine fresh frozen plasma with admixed cryoprecipitate samples were lower in ROTEM centers. CONCLUSIONS: More variation within and between centers was identified than anticipated, but some parameters such as alpha angle were repeatable and reproducible. Sample types for future multicenter standardization efforts will require further optimization and may need to be adapted separately to each platform. Individual centers using viscoelastic tests for evaluation and management of clinical patients should take steps to minimize preanalytical and analytical sources of variation.

Evaluation of thromboelastography in bitches with pyometra.

We investigated the effect of pyometra on kaolin-activated thromboelastography (TEG). Eighteen client-owned dogs with pyometra and 8 healthy spayed dogs were recruited. TEG parameters and packed cell volume were determined. Results from spayed females and from intact females with pyometra were compared using a Student t-test and Wilcoxon rank sum test. Bitches with pyometra were hypercoagulable compared to spayed bitches as evidenced by elevated maximum amplitude, G, and alpha angle. There were no significant group differences in R time, K time, or clot lysis at 30 or 60 min. Dogs with pyometra should be anticipated to have hypercoagulable TEG variables, and this should be addressed when planning surgical and medical therapy.

Adult-onset, chronic, cyclic thrombocytopenia in a Rhesus macaque (Macaca mulatta) after dengue virus vaccination and viral challenge.

An 8-year-old, male Rhesus macaque (Macaca mulatta), previously used for dengue virus (DENV) vaccine research with viral challenge, was presented with adult-onset, chronic, cyclic thrombocytopenia. Platelet number, morphology, and function were evaluated by automated hematology, peripheral blood smears, electron microscopy, flow cytometry, and impedance aggregometry. Bone marrow was evaluated by cytology. Both serum anti-dengue nonstructural protein 1 (NS1) antibodies and anti-platelet antibodies were detected by ELISA. Platelet characterization showed a lack of aggregation to all agonists (ADP, ASP, and collagen), increased activation with increased expression of surface marker (HLA-ABC), and an absence of surface receptor GPIX during clinical episodes of petechiae and ecchymoses, even in the presence of normal platelet counts. Bone marrow aspirates identified potential mild megakaryocytic hypoplasia. All platelet functions and morphologic attributes were within normal limits during clinically normal phases. Presence of anti-dengue NS1 serum antibodies confirmed a positive DENV titer 8 years postvaccination. Based on the history and clinical findings, a primary differential diagnosis for this chronic, cyclic platelet pathology was autoimmune platelet destruction with potential bone marrow involvement.

The use of rivaroxaban for the treatment of thrombotic complications in four dogs.

OBJECTIVE: To describe the clinical use of rivaroxaban in the treatment of 4 dogs with vascular thrombosis, 2 with pulmonary thromboembolism and 2 with systemic thrombosis. CASE SERIES SUMMARY: This report describes the use of a direct factor Xa anticoagulant newly approved in human patients for the treatment or prevention of arterial or venous thrombosis. The use of this medication in a clinical setting for canine patients with thromboembolism has not been described before. Two patients were treated with rivaroxaban for pulmonary thromboembolism. Decreases in thrombus size were seen in both patients, but one patient suffered acute respiratory distress and was euthanized while the other continued to do well at the time of this writing. The other 2 patients were treated for systemic thrombosis. Decreases in thrombus size were also noted. One patient later suffered hematochezia of unknown cause, and the other continued to do well at the time of this writing. NEW OR UNIQUE INFORMATION PROVIDED: This is the first published report of the use of a new oral direct factor Xa anticoagulant in dogs in a clinical setting for the treatment of both pulmonary and systemic thrombosis. In this case series, we share our limited experience in the use of this new medication, our strategy in determining appropriate dosages, and our monitoring protocol.

The impact of schistosomes and schistosomiasis on murine blood coagulation and fibrinolysis as determined by thromboelastography (TEG).

Schistosomes are parasitic platyhelminths that currently infect over 200 million people and cause the chronic debilitating disease schistosomiasis. While these large intravascular parasites can disturb blood flow, surprisingly they do not appear to provoke thrombus formation around them in vivo. In order to determine if the worms can alter their local environment to impede coagulation, we incubated adult worms (50 pairs) in murine blood (500 µl) for 1 h at 37 °C and, using thromboelastography (TEG), we compared the coagulation profile of the blood with control blood that never contained worms. Substantial differences were apparent between the two profiles. Blood that had been exposed to schistosomes clotted more slowly and yielded relatively poor, though stable, thrombi; all TEG measures of blood coagulation (R, K, α-angle, MA, G and TMA) differed significantly between conditions. No fibrinolysis (as determined by LY30 and LY60 values) was detected in either case. The observed TEG profile suggests that the worms are acting as local anti-coagulants. Blood recovered from schistosome-infected mice, however, does not behave in this way. At an early time point post infection (4-weeks), the TEG profile of infected murine blood is essentially the same as that of control blood. However at a later time point (7-weeks) infected murine blood clots significantly faster than control blood but these clots also break down faster. The R, K, α-angle, and TMA measures of coagulation are all significantly different between the control versus infected mice as are the LY30 and LY60 values. This profile is indicative of a hypercoagulable state with fibrinolysis and is akin to that seen in human patients with advanced schistosomiasis.

Assessment of the relationships among coagulopathy, hyperfibrinolysis, plasma lactate, and protein C in dogs with spontaneous hemoperitoneum.

OBJECTIVE: To relate coagulation and fibrinolysis derangements to shock severity as reflected by plasma lactate concentrations in dogs with spontaneous hemoperitoneum (SHP) and determine the impact on transfusions. DESIGN: Prospective, observational, case-control study. SETTING: Three veterinary teaching hospitals. ANIMALS: Twenty-eight client-owned dogs with SHP and 28 breed- and age-matched control dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples for platelet counts, coagulation, and anticoagulant assays (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, and protein C, thromboelastography [TEG]), fibrinolysis testing (d-dimer and TEG lysis parameters with and without the addition of 50 U/mL of tissue plasminogen activator [TEG LY30 measured with the addition of 50 U/mL of tPA to the blood sample, LY3050 and TEG LY60 measured with the addition of 50 U/mL of tPA to the blood sample, LY6050 ; LY30 and LY60]), and plasma lactate as an indicator of severity of shock were collected from SHP dogs at the time of diagnosis. SHP dogs were hypocoagulable (prolonged prothrombin time and activated partial thromboplastin time, decreased TEG maximum amplitude) and hyperfibrinolytic (increased LY3050 and TEG LY6050 ) compared to controls. The severity of hypocoagulability was related to protein C activity, while the severity of hyperfibrinolysis was related to plasma lactate concentration. Among the 18 dogs discharged from the hospital, LY3050 was significantly associated with the dose of fresh frozen plasma administered, but none of the parameters were associated with the dose of red blood cells administered. CONCLUSIONS: Dogs with SHP have evidence of hypocoagulability, protein C deficiency, and hyperfibrinolysis. Parameters of hyperfibrinolysis were related to plasma lactate concentrations and volume of plasma transfused during hospitalization. These derangements resemble those found in people with acute coagulopathy of trauma and shock, and activation of protein C may be a common feature to both syndromes.

Platelet activation in a population of critically ill dogs as measured with whole blood flow cytometry and thromboelastography.

OBJECTIVE: To determine whether critically ill dogs had increased platelet activation and whether the proportion of activated platelets correlated with severity of illness. ANIMALS: 82 dogs in the intensive care unit of a veterinary teaching hospital and 24 healthy control dogs. PROCEDURES: Flow cytometry with monoclonal mouse anti-human CD61 and CD62 antibodies in resting and ADP-treated samples and kaolin-activated thromboelastography were used to compare platelet activation in blood samples of critically ill and control dogs. Serum antithrombin, von Willebrand factor, fibrinogen, and activated protein C concentrations; prothrombin time (PT); and activated partial thromboplastin time (aPTT) were measured. Revised survival prediction index, acute patient physiology and laboratory evaluation, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome scores were used to estimate severity of illness. Severity of illness scores and platelet activation measurements were compared with survival time and duration and cost of hospitalization. RESULTS: Critically ill and control dogs had no differences in platelet activation for non-ADP-treated samples measured. Critically ill dogs had significantly increased platelet activation in response to 2, 6, and 10 µM ADP. Critically ill dogs had significantly increased maximum amplitude, α angle, and global clot strength and significantly decreased clot formation time. Critically ill dogs had significantly increased fibrinogen concentration, PT, and aPTT and significantly decreased antithrombin concentration. Survivors and nonsurvivors had similar flow cytometry and thromboelastography values. Three dogs developed macrothrombosis. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, critically ill dogs had hyperreactive platelets, which may have contributed to a high incidence of hypercoagulability in this patient population.

Clinical outcome after diagnosis of hemophilia A in dogs.

OBJECTIVE: To evaluate the clinical course of dogs with hemophilia A (factor VIII deficiency) and to determine whether factor VIII coagulant activity (FVIII:C) was associated with severity of clinical signs and outcome. DESIGN: Survey study. SAMPLE: Respondent information for 39 client-owned dogs with FVIII deficiency. PROCEDURES: Information was obtained via a survey distributed to the American College of Veterinary Internal Medicine and American College of Veterinary Emergency and Critical Care email list serves and to the Veterinary Information Network community to identify dogs with hemophilia A (FVIII:C ≤ 20%). Severity of FVIII deficiency was classified as mild (FVIII:C, 6% to 20%), moderate (FVIII:C, 2% to 5%), or severe (FVIII:C, < 2%). RESULTS: Data for 39 dogs (38 males and 1 female) were compiled. Mixed-breed dogs, German Shepherd Dogs, and Labrador Retrievers were most commonly affected. In most (34/39) dogs, disease was diagnosed at < 1 year of age. Bleeding associated with teething, minor trauma, vaccination, and elective surgical procedures most commonly prompted FVIII:C testing. Affected dogs had similar signs of spontaneous hemorrhage regardless of the magnitude of FVIII deficiency. Four dogs were euthanized without treatment at the time of diagnosis. Thirty dogs received ≥ 1 blood transfusion; FVIII:C did not appear to influence transfusion requirements. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with hemophilia A have variations in clinical course of the disease and may have a good long-term prognosis. Residual FVIII:C may not be useful for predicting severity of clinical signs, transfusion needs, or long-term prognosis.

An ex vivo evaluation of efficacy of refrigerated canine plasma.

OBJECTIVES: To determine thawing times of fresh frozen plasma (FFP), and to evaluate the activity of hemostatic proteins (coagulation factors V, VII, VIII, IX, X, and fibrinogen), clotting times (prothrombin time and activated partial thromboplastin time), and sterility of canine plasma stored refrigerated. DESIGN: Prospective laboratory-based study. SETTING: Veterinary teaching hospital blood bank. INTERVENTIONS: Phase 1: Six units of canine FFP were retrieved from the blood bank and thawed individually in a warm water bath. Time for thaw was recorded in minutes and reported as mean ± SD. Phase 2: One unit of fresh whole blood was collected from 9 dogs and processed routinely. Resulting plasma was divided into 2 aliquots, 1 stored as refrigerated plasma (RP) and 1 as frozen plasma. Samples from the RP were taken at 0, 1, 5, 7, and 14 days and from the FFP at days 0 and 14 for determination of clotting factor activity (V, VII, VIII, IX, and X and fibrinogen) and clotting times. Coagulation factors and clotting times were analyzed using a mixed effects linear model for ANOVA, comparing changes over time as well as differences between groups. For all comparisons, a P value of <0.05 was considered significant. Batch bacterial aerobic and anaerobic cultures of the RP samples were submitted on days 7 and 14 and from the frozen plasma on day 14. MEASUREMENTS AND MAIN RESULTS: Time to thaw for FFP units was 34.7 ± 1.38 minutes. Refrigerated storage resulted in significant decreases in the activity of all clotting factors and a subsequent prolongation in clotting times. However, no values were outside of the reference interval. All bacterial cultures yielded no growth. CONCLUSIONS: Refrigerated storage results in only minor loss of coagulation factor activity in canine plasma. The use of RP, therefore, may be a viable option in high-volume veterinary hospitals for rapid correction of coagulopathy in critical care patients.

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.

Hypoperfusion and acute traumatic coagulopathy in severely traumatized canine patients.

OBJECTIVE: To determine the incidence of acute traumatic coagulopathy in dogs suffering severe trauma and to investigate the association of markers of hypoperfusion with coagulation abnormalities. DESIGN: A prospective observational study performed June, 2009 to February, 2011. SETTING: A university teaching hospital. ANIMALS: Thirty client-owned dogs weighing >5 kilograms that were presented to the Tuft's Cummings School of Veterinary Medicine following severe trauma as defined by an animal trauma triage score (ATT) ≥5 and having received no resuscitation with IV fluids or blood products prior to blood sampling. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Prior to resuscitation, data obtained at the time of admission to the emergency service included HCT, platelet count, lactate concentration, pH, base excess, thromboelastrogram (TEG), prothrombin time, activated partial thromboplastin time, fibrinogen level, and protein C activity. Rectal temperature and ATT were recorded for all dogs. Neither HCT nor platelet count was significantly decreased in any of the dogs. Based on G values as measured by TEG, 10/30 dogs (33%) showed evidence of hypercoagulability. Hypocoagulability as determined by prothrombin time, activated partial thromboplastin time, or TEG was not shown in any of the 30 dogs. CONCLUSION: Dogs with severe trauma may experience hypercoagulability that is unrelated to fluid resuscitation or transfusion therapy. Future studies are warranted to better characterize coagulation changes in dogs with severe trauma, particularly in relationship to fluid therapies and/or hemorrhage.

Diseases associated with thrombosis.

Coagulation abnormalities are commonly encountered in critical illness. Traditionally, clinically relevant coagulation disorders have consisted mostly of bleeding associated with advanced stages of disseminated intravascular coagulation or toxin ingestion. However, advances in critical care have highlighted hypercoagulability as a clinically relevant state that must be recognized and treated to optimize the chances of a positive outcome. Retrospective studies of dogs with confirmed thrombosis in varying locations have identified populations most likely to experience hypercoagulable states. Diseases most frequently complicated by thrombosis include immune-mediated disease, neoplasia, systemic inflammation and sepsis, cardiac disease, protein-losing states, and infectious diseases. In this report, the existing retrospective studies will be discussed along with a review of specific disease processes that predispose to a hypercoagulable state. Studies targeting those populations most at risk for thrombotic complications are necessary for better understanding the need for prophylactic anticoagulant therapy.