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.

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.

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.

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.

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.

Satellite teaching hospitals and public-private collaborations in veterinary medical clinical education.

Veterinary teaching hospitals (VTHs) are facing more and greater challenges than at any time in the past. Changes in demand, expanding information, improving technology, an evolving workforce, declining state support, and an increasingly diverse consumer base have combined to render many traditional VTH modes of operation obsolete. In pursuit of continued success in achieving their academic mission, VTHs are exploring new business models, including innovative collaborations with the private sector. This report provides details on existing models for public-private collaboration at several colleges and schools of veterinary medicine, including those at Kansas State University, Purdue University, the University of Florida, and Tufts University. Although each of these institutions' models is unique, several commonalities exist, related to expansion of the case load available for teaching, the potential positive impact on recruitment and retention of clinical faculty, and the potential for easing financial pressures on the associated VTH. These new models represent innovative approaches that work to meet many of the key emerging challenges facing VTHs today.

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.

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.

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.

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.

Biochemical analysis of pericardial fluid and whole blood in dogs with pericardial effusion.

Studies evaluating pericardial fluid analysis in dogs to determine the etiology of pericardial effusions have yielded conflicting results. The purpose of this prospective study was to compare acid-base status, electrolyte concentrations, glucose, and lactate of pericardial fluid to peripheral blood from dogs with pericardial effusion and to compare these variables between dogs with neoplastic and nonneoplastic pericardial effusion. Acid-base status, electrolyte concentrations, glucose, hematocrit, urea nitrogen, and lactate concentrations were evaluated in peripheral blood samples and in pericardial effusion samples of 41 client-owned dogs with pericardial effusion. Common abnormal findings in the peripheral blood of dogs with pericardial effusion included hyperlactatemia (n = 38 [of 41]; 93%), hyponatremia (n = 25/41; 61%), hyperglycemia (n = 13/41; 32%), and hypermagnesemia (n = 13/41; 32%). Bicarbonate, sodium, ionized calcium, glucose, and hematocrit were all significantly lower in the pericardial fluid compared with peripheral blood, whereas lactate, chloride, and PCO2 were significantly higher in the pericardial fluid. When comparing the concentrations of variables in the pericardial fluid of dogs with neoplasia (n = 28) to those without neoplasia (n = 13), pH, bicarbonate, and chloride were significantly lower in dogs with neoplasia, whereas lactate, hematocrit, and urea nitrogen were significantly higher in the pericardial fluid of dogs with neoplasia. The difference between peripheral and pericardial glucose concentrations was significantly larger in dogs with neoplasia than in dogs without neoplasia. Although differences between variables in dogs with neoplastic and nonneoplastic pericardial effusion were documented, clinical relevance is likely limited by the degree of overlap between the 2 groups.

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.

Serum nitrate and nitrite in dogs with spontaneous cardiac disease.

The purpose of this study was to determine whether nitric oxide (NO) concentrations are high in dogs with chronic valvular disease (CVD) and dilated cardiomyopathy (DCM) compared to healthy controls and to determine whether NO concentrations are correlated with type of cardiac disease, disease severity, medical therapy, or serum tumor necrosis factor (TNF) and interleukin-1 (IL-1). Blood was collected from 32 dogs with DCM, from 10 dogs with CVD, and from 10 healthy controls. Indirect determination of NO concentrations was performed by a commercial photoabsorbance assay that uses a Greiss reagent to measure the concentration of nitrite and nitrate (NN), end products of NO metabolism. TNF and IL-1 activities were measured by bioassay. Mean NN concentrations were significantly higher in dogs with heart disease (median, 4.57 microM; range, 0.00-31.05 microM) than in controls (median, 0.00 microM; range, 0.00-6.16 microM; P = .04). NN concentrations in dogs with cardiac disease were not correlated with type or severity of cardiac disease, medication type, or TNF and IL-1 concentrations. NN concentrations were inversely correlated with fractional shortening. The results of this study suggest that metabolites of NO are increased in some dogs with cardiac disease, but these increases appear to be independent of disease severity, TNF and IL-1 concentrations, and type of pharmacologic intervention.

Hemostatic changes in dogs with naturally occurring sepsis.

Sepsis is a frequent source of morbidity and mortality in critically ill patients. The goal of this case control study was to measure hemostatic changes in dogs with naturally occurring sepsis. Blood was collected within 24 hours of admission from 20 dogs that fulfilled the criteria for sepsis. Sepsis was defined as histologic or microbiological confirmation of infection and 2 or more of the following criteria: hypo- or hyperthermia, tachycardia, tachypnea, or leukopenia, leukocytosis, or > 3% bands. Culture and sensitivities were performed on appropriate samples from all septic dogs. Twenty-eight control dogs were enrolled on the basis of normal results of physical examination, CBC, serum biochemistry, and coagulation profile. Plasma samples were analyzed for prothrombin time (PT), partial thromboplastin time (PTT), fibrin(ogen) degradation products (FDP), D-dimer (DD) concentrations, antithrombin (AT) activity, and protein C (PC) activity. Data were compared between groups by chi-square or independent t-tests. PC (P < .001) and AT (P < .001) activities were significantly lower in dogs with sepsis compared to controls. Dogs with sepsis had significantly higher PT (P = .007), PTT (P = .005), D-dimer (P = .005), and FDP (P = .001) compared to controls. Platelet counts were not significantly different between groups. Ten of the 20 septic dogs (50%) died, but no association was identified between any of the measured variables and outcome. These findings are consistent with previous studies in animals with experimentally induced disease and in clinical studies of humans. On the basis of these results, further investigation of the role of AT and PC in canine sepsis is warranted.

Transfusion medicine in veterinary emergency and critical care medicine.

Transfusion medicine is a vital part of veterinary emergency and critical care medicine. The goals of this article are to review blood banking and the transfusion principles surrounding care of the critically ill or injured small animal, to highlight the differences in emergency/critical care transfusions compared with standard transfusion medicine, and to discuss traumatic blood loss and sepsis as unique entities in emergency and critical medicine.