ORIGINAL RESEARCH: Thrombin-activatable fibrinolysis inhibitor activity in healthy and diseased dogs

Abstract

Background: In people, increased thrombin-activatable fibrinolysis inhibitor (TAFI) antigen has been associated with increased risk of thrombosis, and decreased TAFI may contribute to bleeding diathesis. TAFI activity in dogs has been described in experimental models, but not in dogs with spontaneous disease. Objective: The aim of this study was to compare TAFI activity in healthy dogs with TAFI activity in dogs with spontaneous disease. Methods: Plasma samples from 20 clinically healthy Beagles and from 35 dogs with various diseases were analyzed using a commercial chromogenic assay that measured TAFI activity relative to activity in standardized pooled human plasma. Results: Median TAFI activity for the 20 Beagles was 46.1% (range 32.2-70.8%) compared with 62.6% (29.1-250%) for the 35 diseased dogs, and 14/35 (40%) had TAFI activities 4 the upper limit for controls. The highest individual activities (4 225%) were in 3 dogs with malignant neoplasms and 1 dog with thrombocytopenia. For data grouped by diagnosis, median TAFI activity was 61.7% for benign neoplasia (n = 5), 64.9% for malignant neoplasia (n = 8), 75.5% for Angiostrongylus vasorum infection (n = 4), 68.8% for bacterial sepsis (n = 7), and 58.7% for miscellaneous diseases (n = 11). Compared with TAFI activity in control dogs, median TAFI activity was significantly increased only in the group of dogs with bacterial sepsis. Conclusion: Bacterial sepsis was associated with significantly increased TAFI activity, and individual dogs with increased TAFI activities were found in all disease groups. The role of TAFI in the pathogenesis of hemostatic disorders in dogs and its value as a prognostic indicator deserve further investigation.

Blood markers of fibrinolysis and endothelial activation in canine babesiosis

“…TAFI is activated by thrombin, the key component of the coagulation system, either free or in complex with TM [41]. In dogs, TAFI activity has been described only in experimental models of thrombosis [42, 43] and in studies in dogs with various spontaneous diseases [44]. Higher TAFI concentrations were found in dogs with complicated babesiosis on day 6 compared to dogs with uncomplicated babesiosis and also compared to dogs with complicated babesiosis at admission.…”

Endogenous fibrinolytic potential in tissue‐plasminogen activator‐modified thromboelastography analysis is significantly decreased in dogs suffering from diseases predisposing to thrombosis

“…Sepsis has previously been associated with reduced activity of endogenous anticoagulants in dogs, suggesting an imbalance of hemostasis with a tendency toward a procoagulant state in affected dogs . For instance, significantly increased thrombin‐activatable fibrinolysis inhibitor (TAFI) activity was determined in dogs with bacterial sepsis …”

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 1—Defining populations at risk

“…Bacterial endocarditis, septic peritonitis, and aspiration pneumonia are commonly identified; however, the direct association between sepsis and thrombosis is complicated by the frequent presence of concurrent disease processes that also potentially affect hemostasis including immune‐mediated disease and neoplasia . Despite this, hemostatic alterations consistent with hypercoagulability have been identified in dogs similar to those seen in people including reduced endogenous anticoagulants (protein C 104 and antithrombin) increased fibrinogen, increased thrombin activatable fibrinolysis inhibitor, thrombomodulin downregulation, and platelet hyperreactivity …”