Fig 1.
(a) Clotting time (CT) and maximal clot firmness (MCF) assessed by ROTEM in non-treated rat whole blood in presence of 0.9% NaCl (negative control, grey box-plot), r ex-tem (positive control, yellow box-plot), and B. atrox (blue box-plots) or B. lanceolatus venom (red box-plots) added at various concentrations (n = 4); (b) Curves representing the CT and the MCF as a function of the dose of B. atrox (red line) or B. lanceolatus (blue line) venom. Grey dotted area represents the value of negative control. Results are presented as mean ± SD (n = 4).
Fig 2.
ROTEM clotting time (CT, a), ROTEM maximal clot firmness (MCF, b), platelet count (c), and plasma fibrinogen concentration (d) measured at H3, H6, and H24 after 0.9% NaCl (white boxplots), B. atrox (blue boxplots) or B. lanceolatus venom (red boxplots) injection in the rat. Results are presented as mean ± SD (n = 6 rats per group). *p < 0.05, **p < 0.01, ***p < 0.001 as compared to controls.
Fig 3.
Lag time (a), time to peak (b), peak height (c), and endogen thrombin potential (ETP, d) assessed using thrombin generation assay (TGA) at H3, H6, and H24 after 0.9% NaCl (white boxplots), B. atrox (blue boxplots) or B. lanceolatus venom (red boxplots) injection in rats. Results are presented as mean ± SD (n = 6 rats per group). *p < 0.05, **p < 0.01, ***p < 0.001 as compared to controls.
Fig 4.
Lag time (a), time to peak (b), start tail (c), and peak height (d) assessed using fibrinography at H3, H6, and H24 after 0.9% NaCl (white boxplots), B. atrox (blue boxplots) or B. lanceolatus venom (red boxplots) injection in rats. Results are presented as mean ± SD (n = 6 rats per group). *p < 0.05, **p < 0.01 as compared to controls.
Fig 5.
von Willebrand factor (VWF) antigen (a), ADAMTS13 activity (b), soluble E-selectin (c), and soluble intercellular adhesion molecule-1 (ICAM-1, d) measured at H3, H6, and H24 after 0.9% NaCl (white boxplots), B. atrox (blue boxplots) or B. lanceolatus venom (red boxplots) injection in rats. Results are presented as mean ± SD (n = 6 rats per group). *p < 0.05, **p < 0.01 as compared to controls.
Fig 6.
Plasma interleukin-1beta (IL-1β, a), interleukin-6 (IL-6, b) tumor necrosis factor-alpha (TNFα, c), plasminogen activator inhibitor-1 (PAI-1, d), and monocyte chemoattractant protein-1 (MCP-1, e) measured at H3, H6, and H24 after 0.9% NaCl (white boxplots), B. atrox (blue boxplots) or B. lanceolatus venom (red box-plots) injection in rats. Results are presented as mean ± SD (n = 6 rats per group). *p < 0.05, **p < 0.01, ***p < 0.001 as compared to controls.
Fig 7.
Hypothesized mechanisms of Bothrops venom-induced effects on hemostasis. The consumption of platelets and fibrinogen directly by the venom action and indirectly by coagulation factor activation induces a hypocoagulable state promoting bleeding. In contrast, proinflammatory cytokine (IL-6 and TNF-α) and chemokine production (MCP-1) increase tissue factor and factor XIII-A expression on monocytes, fibrinogen hepatocyte synthesis and release by activated platelets, and plasminogen activator inhibitor type I (PAI-1) production, which deactivates tissue plasminogen activator (tPA) and leads to plasmin decrease and fibrinolysis shutdown, inducing hypercoagulability and prothrombotic risk. Created with BioRender.com.