Sonoclot® Evaluation of Single‐ and Multiple‐Dose Subcutaneous Unfractionated Heparin Therapy in Healthy Adult Dogs

Abstract

Background: Heparin therapy is difficult to monitor due to variation in animal response. While laboratory measurements of activated partial thromboplasin time (aPTT) and Anti-Xa activity (AXA) accurately describe heparin effect, their availability is limited.Hypothesis: Sonoclot analysis would be as sensitive as AXA and aPTT to monitor effects of unfractionated heparin (UFH) in healthy adult dogs.Animals: Six adult mixed-breed dogs. Methods: A prospective study design was employed. On day 1, baseline samples were collected (CBC, PT, aPTT, and Sonoclot), and UFH (300 U/kg SC) was administered to 6 dogs following an IV loading dose of 50 U/kg. Sonoclot and aPTT were performed hourly for 12 hours. AXA was assayed at hours 3, 6, 9, and 12. UFH (300 U/kg q8 h SC) was administered at 12 hours, and subsequently (q8 h) for 2 additional days. On day 4, a final dose of UFH was administered, and a sampling protocol identical to day 1 was performed.Results: Sonoclot activated clotting time (ACT) and clot rate (CR) correlated with AXA (R = 0.69, R = 0.65, respectively, P < .001), although to a lesser degree than aPTT (R = 0.75, P < .001). Linear regression using ACT and CR as covariates indicated a stronger correlation with AXA (R = 0.73, P < .001). ACT values strongly correlated with aPTT (R = 0.87, P < .001).Conclusions and Clinical Importance: Administration of UFH to healthy dogs results in progressive changes in Sonoclot values. AXA was correlated with a combination of ACT and CR and with aPTT. Sonoclot may play a role in monitoring UFH therapy; however, prospective studies evaluating its utility in clinical cases are warranted.

ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs

“…Anti‐Xa monitoring is not widely available to veterinarians. If an anti‐Xa assay is not available, then it is reasonable to consider the activated clotting time, activated partial thromboplastin time (aPTT), thrombin generation, or viscoelastic tests to monitor anticoagulant treatment . Nomograms for adjustment of UFH treatment using aPTT and thromboelastographic assays have been proposed, but are currently only available in abstract form .…”

“…One further RCT found no difference in survival in dogs treated with rivaroxaban compared with dogs treated with clopidogrel and ultra-low-dose aspirin ( activated clotting time, activated partial thromboplastin time (aPTT), thrombin generation, or viscoelastic tests to monitor anticoagulant treatment. 153,[156][157][158][159][160][161][162][163][164] Nomograms for adjustment of UFH treatment using aPTT and thromboelastographic assays have been proposed, but are currently only available in abstract form. 165,166 The original derivation of UFH aPTT prolongation targets was performed using thrombotic models in dogs.…”

Postoperative Hemostasis Monitoring and Management

“…71 UFH has been studied extensively in veterinary medicine and generally requires 3-times-a-day dose administration, although use as a constant rate infusion has also been described. 72,73 LMWHs are about one-third the molecular weight of UFH and are derived by chemical or enzymatic depolymerization. LMWH has reduced binding to proteins, endothelial cells, and macrophages, and the smaller size renders these molecules unable to inactivate thrombin.…”

Hematologic Disorders

“…UFH has variable pharmacodynamics that are not only dose dependent, but also unpredictable to a certain degree. 81,82 The coagulation effects of a single (250 U kg −1 ) subcutaneous dose of UFH (as monitored by coagulation testing) wane 9-12 h after the dose but with more persistent coagulation effects after prolonged dosing. The maximum anticoagulant effect of a single UFH subcutaneous injection is about 4 h after the injection.…”

“…UFH effect may be monitored by measuring the anti-factor Xa activity in the plasma or may be estimated by evaluating the aPTT, which prolongs with heparin therapy. 81 The anesthetist should assess the coagulation status of patients before anesthesia. In patients receiving heparin therapeutically, coagulation times are expected to be only moderately prolonged (approximately twice normal), and the danger of uncontrollable hemorrhage is not as great as in those patients with profound prolongations of coagulation times.…”