Clinical experience of anti-Xa monitoring in critically ill dogs receiving dalteparin

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

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 4-Refining and monitoring antithrombotic therapies

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

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

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. Hemophilia A is an X-linked recessive bleeding disorder caused by deficiency or dysfunction of FVIII. Although classically inherited in an X-linked familial pattern in both humans and dogs, de novo mutations of the FVIII gene located on the long arm of the X chromosome may also occur, which results in sporadic cases in previously unaffected families.1,2 Clinical severity of hemophilia A in humans, as defined by frequency of bleeding events and transfusion needs, is inversely related to residual FVIII:C,3 but to our knowledge, no such population studies have been reported for dogs. Factor VIII deficiency in humans is classified as mild (FVIII:C, 6% to 20%), moderate (FVIII:C, 2% to 5%), or severe (FVIII:C, < 2%).2–4 Severely affected humans have frequent episodes of spontaneous hemorrhage that require periodic FVIII replacement therapy, which is most often administered as FVIII concentrates and rarely as transfusions of cryoprecipitate, FFP, or fresh whole blood. Recipients of multiple transfusions may develop anti-FVIII antibodies that bind to transfused FVIII, thereby inhibiting coagulant activity; this has been verified in both humans and dogs.5–8 Hemophilia A in dogs is most commonly suspected because of episodes of clinical hemorrhage and is confirmed by identification of a specific deficiency of FVIII:C in the absence of deficiencies of other coagulation factors. Clinical signs in dogs with hemophilia A include subcutaneous hematoma and intermittent bleeding at an injection site, prolonged bleeding at eruption sites of deciduous teeth, hematoma formation or prolonged bleeding after surgery, abnormal bleeding from minor wounds, and lameness attributable to hemarthrosis.9 Although dogs with hepatic synthetic failure and consumptive and dilutional coagulopathies may have markedly low FVIII:C, these patients typically have obvious underlying disease and combined deficiencies of coagulation factors and fibrinogen that differentiate them from dogs with hemophilia A. The long-term management and survival rate of dogs with hemophilia A maintained in a research colony have been described6; however, to the authors’ knowledge, no comparable information is available regarding client-owned pet dogs. The objectives of the study reported here were to describe the long-term outcome for a group of dogs with hemophilia A at clinical practices and to determine the relationship between FVIII:C at diagnosis and severity of clinical signs and 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

Effect of urinary bladder lavage on in-hospital recurrence of urethral obstruction and durations of urinary catheter retention and hospitalization for male cats

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. In male cats, UO is a life-threatening emergency that occurs as a complication of feline lower urinary tract disorders. Although UO in male cats occurs commonly, consensus regarding the most appropriate way to medically manage affected cats is lacking, as is evidence to formulate standardized recommendations.1 Consequently, clinicians are likely to manage affected cats on the basis of procedures with which they are familiar or that are routinely performed at their place of employment. A frustrating complication associated with UO is recurrence of the obstruction, which can develop in the short or long term. Recurrence of UO can lead to prolonged or repeated hospitalization or surgical intervention (eg, perineal urethrostomy), resulting in an increase in morbidity, financial commitment, and risk for euthanasia.2–4 For male cats with UO, most clinicians recommend strategies for decreasing the risk for recurrence, such as dietary changes, pharmacological treatments, and environmental modifications, following initial treatment.1,5,6 Despite those recommendations, recurrence of UO is common, particularly in the short term while affected cats are hospitalized for the initial occurrence. Some clinicians believe that lavaging the urinary bladder with saline (0.9% NaCl) solution at the time the urinary tract is unblocked and a urinary catheter is placed may help to remove or dilute debris, mucous plugs, urinary crystals, bacteria, or blood clots, thereby decreasing the risk for recurrence of the UO. To our knowledge, the efficacy of urinary bladder lavage on in-hospital recurrence of UO in male cats has not been evaluated. The objective of the study reported here was to evaluate the effect of urinary bladder lavage at the time of urinary tract catheterization for treatment of UO in male cats on the in-hospital recurrence rate of the condition and durations of urinary catheter retention and hospitalization. The null hypotheses were that urinary bladder lavage would have no effect on in-hospital UO recurrence, duration of urinary catheter retention, and duration of hospitalization