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Objectives: To systematically review the evidence for therapeutic monitoring of antithrombotic drugs in small animals, develop guidelines regarding antithrombotic monitoring, and identify knowledge gaps in the field. Design: First, a standardized, systematic literature review was conducted to address predefined PICO (Population/Patient, Intervention, Control, Outcome) questions, with categorization of relevant articles according to level of evidence and quality. Preliminary guidelines were developed by PICO worksheet authors and the domain chair. Thereafter, a Delphi‐style survey was used to develop consensus on guidelines regarding therapeutic monitoring of antithrombotics in dogs and cats. Setting: Academic and referral veterinary medical centers. Results: PICO questions regarding the utility of therapeutic monitoring were developed for 6 different antithrombotic drugs or drug classes, including aspirin, clopidogrel, warfarin, unfractionated heparin, the low molecular weight heparins, and rivaroxaban, The majority of the literature pertaining to therapeutic monitoring of antithrombotic drugs was either performed in experimental animal models of disease or involved studies of drug pharmacokinetics and pharmacodynamics in healthy laboratory animals. There was a paucity of high level of evidence studies directly addressing the PICO questions, which limited the strength of recommendations that could be provided. The final guidelines recommend that therapeutic monitoring should be performed when using warfarin or unfractionated heparin in dogs and cats at risk of thrombosis. There is insufficient evidence to make strong recommendations for therapeutic monitoring of aspirin or low molecular weight heparin in dogs and cats at this time. Conclusions: As in other CURATIVE domains, significant knowledge gaps were highlighted, indicating the need for substantial additional research in this field. Ongoing investigation of the role of therapeutic monitoring of antithrombotic therapies will undoubtedly facilitate improved outcomes for dogs and cats at risk of thrombosis. [ABSTRACT FROM AUTHOR]

Objective To evaluate hemostatic changes following experimental acute hemorrhage in dogs using traditional coagulation tests (eg, platelet count, prothrombin time [PT], and activated partial thromboplastin time [aPTT]), kaolin-activated thromboelastography (TEG), and whole blood multiple electrode impedance platelet aggregometry. Design Prospective study. Setting Research laboratory. Animals Five Beagles. Interventions Dogs were anesthetized prior to obtaining blood samples for baseline PCV, total plasma protein (TPP), arterial blood-gas, platelet count, PT, aPTT, TEG, fibrinogen, and aggregometry. Blood was obtained at 4 additional time points, following 20% blood volume loss, 40% blood volume loss, 60 minutes of sustained hypotension, and after autologous blood transfusion. In addition, heart rate and direct arterial blood pressure were measured at each time point. Measurements and Main Results Significant decreases were noted for PCV ( P = 0.048), TPP ( P < 0.0001), and arterial blood pressures ( P < 0.0001) over time. Platelet count did not change significantly ( P = 0.879), but platelet function was decreased following hemorrhage when arachidonic acid ( P = 0.004) and ADP ( P = 0.008) were used as agonists. The TEG variables R ( P = 0.030), MA ( P = 0.043), and G ( P = 0.037) were significantly, albeit mildly, changed following hemorrhage. Significant prolongations in PT ( P < 0.0001) and aPTT ( P = 0.041), and decreases in fibrinogen concentration ( P = 0.002) were also seen. Conclusion Platelet dysfunction occurred following hemorrhage in this model, despite a stable platelet count. Additionally, significant changes associated with hemorrhage were documented in aPTT, fibrinogen, and MA. Platelet function testing in dogs with naturally occurring hemorrhage warrants further investigation. [ABSTRACT FROM AUTHOR]

Objectives To describe a population of critically ill dogs receiving dalteparin monitored with an anti-Xa assay, to assess the potential utility of serial monitoring, and to investigate the association between pre-treatment thromboelastography (TEG) and the ability to achieve targeted anti-Xa activity. Design Descriptive retrospective study. Setting Veterinary teaching hospital. Animals Thirty-eight client-owned dogs receiving dalteparin and monitored with an anti-Xa assay. Interventions None. Measurements and Main Results Medical records were retrospectively reviewed for signalment, underlying disease, clinicopathological data, occurrence of thromboembolic events, complications, and outcome. Thirty-eight dogs receiving dalteparin were monitored with an anti-Xa assay. Diseases included hematological disease, protein-losing disease, neoplastic disease, and septic processes. Pretreatment hypercoagulability was present in 34/35 dogs by assessment of TEG. Five cases of thromboembolism were confirmed prior to starting treatment and 4 cases occurred during hospitalization. Bleeding complications were rare (3/38) and 29/38 dogs survived to discharge. Interpretation of the anti-Xa assay allowed for dose adjustment although reliable achievement of target anti-Xa activity was not demonstrated. Dogs with higher G values on pretreatment TEG were significantly less likely to achieve the target anti-Xa activity (ie, be above or below the target range). Conclusions Dalteparin was well tolerated in a heterogeneous population of dogs. However, dose adjustment in response to anti-Xa activity interpretation inconsistently resulted in subsequent attainment of the target anti-Xa range. Development of guidelines may be warranted to more consistently achieve the target range. Dogs that appear more hypercoagulable on pre-treatment TEG may require closer monitoring and greater dose adjustment to achieve the target anti-Xa range. [ABSTRACT FROM AUTHOR]

Case Description-A 3-year-old 19-kg (42-lb) spayed female mixed-breed dog was referred after being hit by a car. Injuries included pneumothorax, hemothorax, pulmonary contusions, a full-thickness axillary skin wound, and a grade I transverse fracture of the midshaft of the right humerus. Following patient stabilization, open reduction and internal fixation of the fracture were performed. The dog had weight-bearing lameness at the time of discharge. Eight days after fracture repair, the dog was reevaluated for acute onset of signs of pain and non-weight-bearing lameness in the right forelimb. Clinical Findings-Physical examination findings in the right fore limb (knuckling and coolness, with absent digital pulses) were suggestive of a thrombus. Ultrasonography confirmed a right brachial artery thrombus with minimal blood flow to the affected limb. Treatment and Outcome-Unfractionated heparin was administered via continuous IV infusion for the first 36 hours of hospitalization. Clopidogrel administration was also started at this time . During hospitalization, rapid clinical improvement occurred, and the dog was discharged 48 hours after admission. The transition to outpatient therapy was achieved by discontinuation of the unfractionated heparin infusion at 36 hours and beginning SC administration of dalteparin . Outpatient treatment with dalteparin and clopidogrel was continued. Repeated physical examination and ultrasonography 5 weeks later revealed resolution of the thrombus and normal blood flow to the limb. Anticoagulant administration was discontinued at that time. Clinical Relevance-Thrombosis should be suspected in any dog with signs of acute pain after severe trauma or fracture repa ir, with or without concurrent lameness, that do not resolve with appropriate treatment. Restoration of blood flow to the affected limb after initiation of unfractionated heparin and clopidogrel administration followed by outpatient treatment with dalteparin and clopidogrel was achieved in this case. [ABSTRACT FROM AUTHOR]

Objective-To evaluate whole blood hemostasis by means of thromboelastography in dogs with primary immune-mediated hemolytic anemia (IMHA) to determine whether these dogs had evidence of hypercoagulability prior to the administration of immunosuppressant medications, blood transfusion products, or anticoagulant agents. Design-Evaluation study. Animals-il client-owned dogs admitted to a teaching hospital for management of primary IMHA and 20 clinically normal dogs. Procedures-Citrated whole blood samples were obtained from all dogs for performance of kaolin-activated thromboelastography. Citrated plasma was harvested from blood samples of dogs with IMHA for plasma-based coagulation testing, including activated partial thromboplastin time, prothrombin time, D-dimer concentration, fibrinogen concentration, and antithrombin activity. Results-Compared with control dogs, dogs with primary IMHA had evidence of hypercoagulability as indicated by a significantly lower median (range) clot formation time (0.8 seconds 10.8 to 2.0 seconds] vs 1.9 seconds 11.3 to 3.8 seconds]), higher median angle (76.1° [59.2° to 84.6°] vs 64.0° [45.4° to 71.0°]), higher median maximum amplitude (75.9 mm [66.3 to 86.3 mm] vs 55.7 mm [49.9 to 63.6 mm]), and higher median clot strength (15,000 dyne/cm2 [9,900 to 31,400 dyne/cm2] vs 6,100 dyne/cm2 [4,900 to 8,700 dyne/cm2]). Conclusions and Clinical Relevance-Dogs with primary IMHA had hypercoagulability as demonstrated by thromboelastography at the time of initial diagnosis and prior to treatment. Such hypercoagulability may be a precursor to clinically evident thrombosis as a complication of the disease process. [ABSTRACT FROM AUTHOR]

To characterize the clinical course of disease and identify prognostic indicators for immune-mediated thrombocytopenia in dogs. Design-Retrospective cohort study. Animals-73 dogs treated for immune-mediated thrombocytopenia at the Foster Hospital for Small Animals at the Tufts Cummings School of Veterinary Medicine and the Tufts Veterinary Emergency Treatment and Specialties Hospital. Procedures-Medical records from the period of January 2002 through June 2008 were reviewed to identify dogs with a diagnosis of immune-mediated thrombocytopenia. Data collected included signalment, clinical signs, results of initial diagnostic tests, treatment, complications, and survival duration. Results-Dog ages ranged from 5 months to 15 years (median, 8.1 years). Cocker Spaniels were overrepresented, compared with their distribution in the entire hospital population during the same period. Sixty-one of the 73 (84%) dogs survived to discharges. Seven (11%) of those dogs were lost to follow-up. Five of the remaining 54 (9%) dogs had a relapse of the disease. The presence of melena or high BUN concentration at admission to the hospital was significantly correlated with a decreased probability of survival. Conclusions and Clinical Relevance-Immune-mediated thrombocytopenia is a serious yet treatable disease, which may have a lower rate of recurrence than previously reported. The presence of melena or high BUN concentration in the study suggested a poor prognosis for affected dogs. [ABSTRACT FROM AUTHOR]

Objective--To determine reference values for kaolin-activated thromboelastography in echocardiographically normal cats. Animals--30 healthy cats without evidence of cardiomyopathy on echocardiographic examination. Procedures--All cats underwent echocardiographic examination, the findings of which were reviewed by a board-certified cardiologist. Cats that struggled (n = 10) received mild sedation with butorphanol and midazolam IM to permit phlebotomy without interruption in jugular venous blood flow. Blood samples were collected for analysis of thromboelastography variables, PCV, total solids concentration, platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin concentration. Results--All 4 thromboelastography variables had < 5% mean intra-assay variability. Mean values were as follows: reaction time, 4.3 minutes; clotting time, 1.6 minutes; α angle, 66.5°; and maximum amplitude, 56.4 mm. Compared with nonsedated cats, cats that required sedation had a significantly shorter clotting time and greater α angle, whereas reaction time and maximum amplitude were not significantly different. Conclusions and Clinical Relevance--Kaolin-activated thromboelastography was a reliable test with unremarkable intra-assay variability in echocardiographically normal cats. Sedation may affect certain thromboelastography variables, but the effect is unlikely to be clinically important. It remains unknown whether subclinical cardiomyopathy has a significant effect on thromboelastography variables in cats. [ABSTRACT FROM AUTHOR]

Background Thromboembolism has recently been described as a complication following treatment for idiopathic thrombocytopenic purpura ( ITP). This pilot study was undertaken to determine whether dogs suffering from ITP experience hypercoagulability during treatment and recovery. Study design Thromboelastograms ( TEG) were performed on dogs with ITP within 24 hours of admission to the hospital, the first day the platelet count exceeded 40 × 109/L (Day 1), and on Days 4, 7, and 14. Key findings All dogs had hypocoagulable TEG tracings on initial admission to the hospital, but developed TEG tracings suggestive of hypercoagulability during the study period as indicated by increased maximum amplitude. Significance Dogs with ITP developed changes on TEG consistent with hypercoagulability during the study period. Many factors are likely to contribute to these changes. The clinical risk of thrombosis in these patients is unknown. [ABSTRACT FROM AUTHOR]

Objectives—To evaluate the use of human albumin in critically ill dogs. Design—Retrospective case series. Animals—73 client-owned hospitalized dogs. Procedures—Medical records of dogs that received human albumin were reviewed to assess effects of the use of human albumin on serum albumin concentration, colloid osmotic pressure, and total protein concentration; determine the relationships between these variables and outcome; and assess its safety. Data for signalment, diagnoses, physiologic variables, dosage, amount of crystalloid fluid administered prior to human albumin administration, complications, and outcome were reviewed. Additionally, pre- and postadministration values for serum albumin, colloid osmotic pressure, and total protein were recorded. Results—Administration of human albumin resulted in significant changes in serum albumin, colloid osmotic pressure, and total protein. The serum albumin, total protein, degree of improvement in serum albumin, colloid osmotic pressure, and dosage of human albumin were significantly greater in survivors. Seventeen of 73 (23%) dogs had at least 1 complication that could be potentially associated with the administration of human albumin that occurred during or immediately following administration of human albumin. Three of 73 (4%) dogs had severe delayed complications. Conclusions and Clinical Relevance—Administration of human albumin significantly increased serum albumin, and total protein concentrations and colloid osmotic pressure, especially in survivors. Because of the high mortality rate of the study population and other confounding factors, it was uncertain whether complications were associated with the underlying disease or with human albumin administration. Acute and delayed complications may have been under-recognized. [ABSTRACT FROM AUTHOR]

Objective: To illustrate the application of the Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines to the management of dogs and cats at risk of developing thrombosis using a case‐based approach. Etiology: Dogs and cats become at risk of developing thrombosis from a wide range of conditions. These conditions often involve a specific insult followed by an inflammatory response and when combined with other contributing factors (eg, hypercoagulability, vascular endothelial injury, hemodynamic changes) create favorable conditions for thrombosis. Diagnosis: Development of thrombosis in small animals remains challenging to demonstrate. Compatible clinical signs, the presence of known risk factors, and supporting diagnostic tests may be highly suggestive of the development of thrombosis. Therapy: Therapeutic recommendations in accordance with the CURATIVE guidelines for dogs and cats are described in specific case vignettes presented. Discussion is centered on antithrombotic drug choices and dosing protocols, as outlined in Domains 2 and 3 of the CURATIVE guidelines. Where appropriate, guidelines related to therapeutic monitoring (Domain 4) and discontinuation of antithrombotics (Domain 5) were included. Prognosis: In small animals at risk of developing thrombosis, overall prognosis may be improved by following consensus‐based recommendations on the use of antithrombotics as outlined in the CURATIVE guidelines. Whether such interventions have any impact on outcome requires further investigation. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the effect of urinary bladder lavage on in-hospital recurrence of urethral obstruction (UO) and durations of urinary catheter retention and hospitalization for male cats. DESIGN Randomized controlled clinical trial. ANIMALS 137 male cats with UO. PROCEDURES Following random allocation, cats either did (flush group; n = 69) or did not (no-flush group; 68) undergo urinary bladder lavage with saline (0.9% NaCl) solution after alleviation of the obstruction and placement of a urethral catheter. Signalment, prior history of UO, presence of crystalluria, difficulty of urinary tract catheterization, in-hospital UO recurrence rate, and durations of urinary catheter retention and hospitalization were compared between the flush and no-flush groups. RESULTS Baseline characteristics did not differ significantly between the 2 treatment groups. The in-hospital UO recurrence rate (9/69 [13%]) and median durations of urinary catheter retention (37 hours; range, 3 to 172 hours) and hospitalization (3 days; range, 0.5 to 12 days) for the flush group did not differ significantly from the in-hospital UO recurrence rate (13/68 [19%]) and median durations of urinary catheter retention (36 hours; range, 1 to 117 hours) and hospitalization (3 days; range, 1 to 9 days) for the no-flush group. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, for male cats with UO, urinary bladder lavage at the time of urethral catheterization had no significant effect on in-hospital recurrence rate of the condition, duration of urinary catheter retention, or duration of hospitalization; however, additional studies are necessary to validate or refute these findings. [ABSTRACT FROM AUTHOR]

Objectives: To systematically review available evidence and establish guidelines related to the risk of developing thrombosis and the management of small animals with antithrombotics. Design: Standardized, systematic evaluation of the literature (identified by searching Medline via PubMed and CAB abstracts) was carried out in 5 domains (Defining populations at risk; Defining rational therapeutic use; Defining evidence‐based protocols; Refining and monitoring antithrombotic therapies; and Discontinuing antithrombotic therapies). Evidence evaluation was carried out using Population, Intervention, Comparison, Outcome generated within each domain questions to address specific aims. This was followed by categorization of relevant articles according to level of evidence and quality (Good, Fair, or Poor). Synthesis of these data led to the development of a series of statements. Consensus on the final guidelines was achieved via Delphi‐style surveys. Draft recommendations were presented at 2 international veterinary conferences and made available for community assessment, review, and comment prior to final revisions and publication. Settings: Academic and referral veterinary medical centers. Results: Over 500 studies were reviewed in detail. Worksheets from all 5 domains generated 59 statements with 83 guideline recommendations that were refined during 3 rounds of Delphi surveys. A high degree of consensus was reached across all guideline recommendations. Conclusions: Overall, systematic evidence evaluations yielded more than 80 recommendations for the treatment of small animals with or at risk of developing thrombosis. Numerous significant knowledge gaps were highlighted by the evidence reviews undertaken, indicating the need for substantial additional research in this field. [ABSTRACT FROM AUTHOR]

Objective– To determine the utility of human intravenous immunoglobulin (hIVIG) for the initial treatment of canine immune-mediated hemolytic anemia (IMHA). Design– Blinded, randomized, clinical trial. Setting– Veterinary teaching hospital. Animals– Twenty-eight, client-owned dogs with primary IMHA. Interventions– At enrollment, after diagnosis of IMHA, dogs were randomly assigned to receive either hIVIG or placebo, in a blinded fashion. For the next 14 days, all dogs received glucocorticoids as the sole immunosuppressant agent. All dogs received low-molecular-weight heparin as an anticoagulant. D-dimer concentrations were evaluated at the beginning and end of the study protocol to monitor for thromboembolic complications. Measurements and Main Results– Twenty-five of 28 dogs (89%) were discharged from the hospital. Thirteen of those received hIVIG and 12 received placebo. Twenty-four dogs (86%) were alive 14 days after enrollment, and of these 13 received hIVIG and 11 received placebo. D-dimer concentrations were elevated in 86% of all dogs at the time of diagnosis. Conclusions– For initial treatment of dogs with IMHA, the addition of hIVIG to corticosteroid treatment did not improve initial response, nor did it shorten hospitalization. [ABSTRACT FROM AUTHOR]