Thrombin generation test for evaluating hemostatic effects of Brazilian snake venoms

Duarte, Rita Carolina Figueiredo; Rios, Danyelle Romana Alves; Leite, Paula Mendonça; Alves, Luan Carlos Vieira; Magalhães, Henrique P. B.; Ferriani, Maria das Graçãs Carvalho

doi:10.1016/j.toxicon.2019.03.012

Cited by 19 publications

(12 citation statements)

References 19 publications

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“…Activation of these factors by venom leads to generate endogenous thrombin in vitro, even without the addition of TF as a trigger [175]. Thus snakebite-related coagulopathy should be distinct from the usual disseminated intravascular coagulopathy due to a thrombin generation mediated by the TF/VIIa pathway [176].…”

Section: Coagulation Factor Activatorsmentioning

confidence: 99%

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

Larréché

Chippaux

Chevillard

et al. 2021

IJMS

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Toxins from Bothrops venoms targeting hemostasis are responsible for a broad range of clinical and biological syndromes including local and systemic bleeding, incoagulability, thrombotic microangiopathy and macrothrombosis. Beyond hemostais disorders, toxins are also involved in the pathogenesis of edema and in most complications such as hypovolemia, cardiovascular collapse, acute kidney injury, myonecrosis, compartmental syndrome and superinfection. These toxins can be classified as enzymatic proteins (snake venom metalloproteinases, snake venom serine proteases, phospholipases A2 and L-amino acid oxidases) and non-enzymatic proteins (desintegrins and C-type lectin proteins). Bleeding is due to a multifocal toxicity targeting vessels, platelets and coagulation factors. Vessel damage due to the degradation of basement membrane and the subsequent disruption of endothelial cell integrity under hydrostatic pressure and tangential shear stress is primarily responsible for bleeding. Hemorrhage is promoted by thrombocytopenia, platelet hypoaggregation, consumption coagulopathy and fibrin(ogen)olysis. Onset of thrombotic microangiopathy is probably due to the switch of endothelium to a prothrombotic phenotype with overexpression of tissue factor and other pro-aggregating biomarkers in association with activation of platelets and coagulation. Thrombosis involving large-caliber vessels in B. lanceolatus envenomation remains a unique entity, which exact pathophysiology remains poorly understood.

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Section: Coagulation Factor Activatorsmentioning

confidence: 99%

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

Larréché

Chippaux

Chevillard

et al. 2021

IJMS

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“…Such existing classic techniques are not sensitive to all stages of hemostasis, especially to detect hypercoagulable and mild hypocoagulable states, because they only provide evidence about the commencement of the coagulation process (Wolberg, 2007, Lecut et al 2015, Duarte et al 2017. Results obtained from such methods often do not correlate with clinical manifestations (Duarte et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid

et al. 2021

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In Brazil, snakes from the Bothrops genus are responsible for thousands of accidents, and their venoms are mainly composed of proteolytic enzymes. Although the antibothropic serum produced by the Brazilian Institutes is remarkably efficient, more studies are necessary, especially in veterinary medicine. The venom contain enzymes and non-enzymatic proteins that interfere with hemostasis leading to hemorrhage or even thrombosis. Possible treatment associations with known bothropic antivenom were the reason for the development of the present study. The aim of this study was to evaluate hemostasis alterations caused by Bothrops alternatus venom in rabbits followed by treatments with anti-bothropic serum, tranexamic acid and desmopressin. Twenty New Zealand rabbits were distributed into five groups (n=4) that were experimentally envenomed with 150mcg/kg of B. alternatus venom via intramuscular injection and treated as follow: Group 1 (G1) was the positive control and received venom and PBS/BSA; Group 2 (G2) was treated with tranexamic acid; Group 3 (G3) with desmopressin; Group 4 (G4) with tranexamic acid and anti-bothropic serum; and Group 5 (G5) with anti-bothropic serum and desmopressin. Blood samples were collected before venom administration, and one, four, eight and 12 hours after, for Partial activated partial thromboplastin time, Prothrombin Time, Thrombin Time and fibrinogen evaluation. Thrombin generation (TG) test was carried out with a pool of samples from final times (8 and 12h). At the end of 12h, all animals were euthanized and necropsy was conducted. Samples from muscle tissue, heart, lungs and kidney were analyzed. Classic coagulation tests showed no significant differences amongst groups and times. However, TG indicated that the venom causes a hypocoagulability state, which was not reversed by proposed treatments. Histology showed muscle inflammation, hemorrhage and necrosis, as well as hemorrhage in other tissues with no differences amongst groups. B. alternatus envenomation causes hypocoagulability detected by TG assay, but not through classical coagulation tests. The use of tranexamic acid and desmopressin for hemostasis stabilization after inoculation of the venom did not show advantage in coagulation restoration.

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“…204 Interference by α 2 -macroglobulin (α 2 M) is a possible limitation of TGA assays, because the chromogenic substrates cannot distinguish between thrombin and the α 2 M-thrombin complex. 200 One solution is using a metalloproteinase from Mexican west coast rattlesnake (Crotalus basiliscus) venom, proteinase A, to inactivate α 2 M. [205][206][207] TGAs and thromboelastography have been used in research studies on the hemostatic effects of snake venom, [208][209][210] and thromboelastography can be used as a POC assay for management of VICC. [211][212][213]…”

Section: Thrombin Generation Assays and Thromboelastographymentioning

confidence: 99%

“…TGAs and thromboelastography have been used in research studies on the hemostatic effects of snake venom, 208 209 210 and thromboelastography can be used as a POC assay for management of VICC. 211 212 213…”

Section: Thrombin Generation Assays and Thromboelastographymentioning

confidence: 99%

Snake Venoms in Diagnostic Hemostasis and Thrombosis

Moore

2021

Semin Thromb Hemost

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Snake venoms have evolved primarily to immobilize and kill prey, and consequently, they contain some of the most potent natural toxins. Part of that armory is a range of hemotoxic components that affect every area of hemostasis, which we have harnessed to great effect in the study and diagnosis of hemostatic disorders. The most widely used are those that affect coagulation, such as thrombin-like enzymes unaffected by heparin and direct thrombin inhibitors, which can help confirm or dispute their presence in plasma. The liquid gold of coagulation activators is Russell's viper venom, since it contains activators of factor X and factor V. It is used in a range of clotting-based assays, such as assessment of factor X and factor V deficiencies, protein C and protein S deficiencies, activated protein C resistance, and probably the most important test for lupus anticoagulants, the dilute Russell's viper venom time. Activators of prothrombin, such as oscutarin C from Coastal Taipan venom and ecarin from saw-scaled viper venom, are employed in prothrombin activity assays and lupus anticoagulant detection, and ecarin has a valuable role in quantitative assays of direct thrombin inhibitors. Snake venoms affecting primary hemostasis include botrocetin from the jararaca, which can be used to assay von Willebrand factor activity, and convulxin from the cascavel, which can be used to detect deficiency of the platelet collagen receptor, glycoprotein VI. This article takes the reader to every area of the diagnostic hemostasis laboratory to appreciate the myriad applications of snake venoms available in diagnostic practice.

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Thrombin generation test for evaluating hemostatic effects of Brazilian snake venoms

Cited by 19 publications

References 19 publications

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid

Snake Venoms in Diagnostic Hemostasis and Thrombosis

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