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

2022 Update of the consensus on the rational use of antithrombotics and thrombolytics in Veterinary Critical Care (CURATIVE) Domain 1‐ Defining populations at risk

Objectives To expand the number of conditions and interventions explored for their associations with thrombosis in the veterinary literature and to provide the basis for prescribing recommendations. Design A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. The revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated in this iteration included heartworm disease (dogs and cats), immune-mediated hemolytic anemia (cats), protein-losing nephropathy (cats), protein-losing enteropathy (dogs and cats), sepsis (cats), hyperadrenocorticism (cats), liver disease (dogs), congenital portosystemic shunts (dogs and cats) and the following interventions: IV catheters (dogs and cats), arterial catheters (dogs and cats), vascular access ports (dogs and cats), extracorporeal circuits (dogs and cats) and transvenous pacemakers (dogs and cats). Results Of the diseases evaluated in this iteration, a high risk for thrombosis was defined as heartworm disease or protein-losing enteropathy. Low risk for thrombosis was defined as dogs with liver disease, cats with immune-mediated hemolytic anemia, protein-losing nephropathy, sepsis, or hyperadrenocorticism. Conclusions Associations with thrombosis are outlined for various conditions and interventions and provide the basis for management recommendations. Numerous knowledge gaps were identified that represent opportunities for future studies

Intravenous fluid administration and the coagulation system

Intravenous fluid administration in veterinary patients can alter coagulation function by several mechanisms. Both crystalloid and colloid fluids cause hemodilution, reducing platelet count and plasma coagulation protein concentrations. Hemodilution is associated with a hypercoagulable effect at low dilutions and a hypocoagulable effect at higher dilutions. Composition of crystalloid fluids likely has a minor effect, primarily dependent on fluid ion composition. Hypertonic crystalloids may also cause hypocoagulability. Colloids, both synthetic and natural, can cause hypocoagulability by several mechanisms beyond the effects of hemodilution. These include impaired platelet function, decreased plasma coagulation factor activity, impaired fibrin formation and crosslinking, and accelerated fibrinolysis. The vast majority of the veterinary literature investigates the hypocoagulable effects of hydroxyethyl starch–containing fluids using in vitro, experimental, and clinical studies. However, results are inconsistent, likely due to the varying doses and physicochemical properties of the specific fluid products across studies. In addition, some evidence exists for hypocoagulable effects of gelatin and albumin solutions. There is also evidence that these colloids increase the risk of clinical bleeding in people. Limitations of the veterinary evidence for the hypocoagulable effects of colloid fluids include a predominance of in vitro studies and in vivo studies using healthy subjects, which exclude the interaction of the effects of illness. Therefore, clinical relevance of these effects, especially for low-molecular-weight hydroxyethyl starch, is unknown. Firm recommendations about the most appropriate fluid to use in clinical scenarios cannot be made, although it is prudent to limit the dose of synthetic colloid in at-risk patients. Clinicians should closely monitor relevant coagulation assays and for evidence of hemorrhage in at-risk patients receiving any type of fluid therapy, especially in large volumes

Safe and effective anticoagulation in small animals - Is that too much to ask? Long-awaited first steps

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