Blood markers of fibrinolysis and endothelial activation in canine babesiosis

Abstract

BackgroundCanine babesiosis is a tick-borne disease caused by hemoprotozoan parasites of the genus Babesia. The disease can be clinically classified into uncomplicated and complicated forms. The aim of this study was to assess the level of endothelial activation and alterations in the fibrinolytic pathway during canine babesiosis.ResultsBlood samples were collected on the day of admission and on the 6th day after treatment with imidocarb propionate, from 30 dogs of various breeds and of both sexes with naturally occurring babesiosis caused by B. canis. In this prospective study, plasminogen activity was assessed using a chromogenic assay, and concentrations of high mobility group box-1 protein (HMGB-1), intercellular adhesive molecule-1 (ICAM-1), vascular adhesive molecule-1 (VCAM-1), soluble urokinase receptor of plasminogen activator (suPAR), thrombin activatable fibrinolysis inhibitor (TAFI), soluble thrombomodulin (TM) and plasminogen activator inhibitor-1 (PAI-1) were determined using a canine specific ELISA. Concentrations of TM, HMGB-1, VCAM-1 and suPAR were increased in dogs with babesiosis at admission compared to healthy dogs. After treatment, concentrations of TM were lower in infected dogs compared to healthy dogs. Dogs with babesiosis also had increased concentrations of TM, ICAM-1 and HMGB-1 and decreased plasminogen and PAI-1 at presentation compared to day 6 after treatment. Dogs with complicated babesiosis had higher concentrations of TM, HMGB1 and TAFI at admission compared to the 6th day.ConclusionsBiomarkers of endothelial activation and fibrinolysis were altered in dogs with babesiosis. Further studies into their usefulness as biomarkers of disease severity or prognosis is warranted.

Canine Babesiosis: Where Do We Stand?

“…Also, research conducted with the amino-terminal portion of C-type natriuretic peptide(NT-pCNP), which is expressed primarily by the vascular endothelium and macrophages in response to several stimuli, confi rmed that NT-pCNP can be considered a good prognostic pro-infl ammatory marker of the outcome in canine babesiosis [158]. Our latest results confi rmed that haemostatic alterations in uncomplicated babesiosis represent a procoagulant state that is mostly reversed during treatment, although biomarkers of endothelial activation and fi brinolysis were also altered in dogs with babesiosis [98,159]. Namely, the concentration of soluble thrombomodulin, high mobility group box-1 protein, vascular adhesive molecule-1, and soluble urokinase receptor of plasminogen activator were increased in dogs with babesiosis at admission while plasminogen and plasminogen activator inhibitor-1 were decreased at presentation compared to day 6 after treatment [159].…”

“…A transient coagulopathy with abnormalities in prothrombin time, activated partial thromboplastin time, fi brinogen, D-dimer and thromboelastography was also found in dogs with uncomplicated B. rossi infections [97]. Fibrinolysis was also affected in complicated B. canis infections, where dogs showed decreased concentrations of fi brinolysis inhibitors, plasminogen activator inhibitor-1 and thrombin-activatable fi brinolysis inhibitor antigen at admission, that lead to increased fi brinolytic activity [98]. In addition to infl uencing haemostatic activity, the proinflammatory state in babesiosis also has an effect on the function of endothelium.…”

Neopterin and Soluble Urokinase Type Plasminogen Activator Receptor as Biomarkers in Dogs with Systemic Inflammatory Response Syndrome

“…suPAR is a marker of fibrinolysis and inflammation that is released from immunologically active cells. suPAR reveals the patho-physiological mechanisms that are active on cell surface (Wittenhagen et al, 2004;Kofoed et al, 2008;Kuleš et al, 2017). In a study comparing dogs with babesiosis and healthy ones, significant increases in suPAR levels were determined and it was stated that it would be useful in the evaluation of the stage of the disease.…”

“…In a study comparing dogs with babesiosis and healthy ones, significant increases in suPAR levels were determined and it was stated that it would be useful in the evaluation of the stage of the disease. It was also reported that increased suPAR concentrations may be a reflection of inflammatory response in dogs with babesiosis (Kuleš et al, 2017). In a study on patients with sepsis in intensive care, it was stated that there is an increase in suPAR level throughout acute inflammation (Kofoed et al, 2008).…”

Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases

“…Recently, Kules and colleagues found that HMGB-1, an endothelial activation marker, was increased in dogs with babesiosis in parallel with elevated soluble urokinase receptor of plasminogen activator (suPAR), suggesting a possible role of HMGB-1 in fibrinolysis [142]. Besides, HMGB-1 has been shown to induce the formation of plasminogen activator inhibitor-1/tissue plasminogen activator (PAI-1/tPA) complexes, suggesting that HMGB-1 might prevent fibrinolysis via increased PAI-tPA complexes in endothelial cells [143].…”