Search Results (7)

Background: Consumption coagulopathy and hemorrhagic syndrome are the typical features of Bothrops sp. snake envenoming. In contrast, B. lanceolatus envenoming can induce thrombotic complications. Our aim was to test whether crude B. lanceolatus and B. atrox venoms would display procoagulant activity and induce thrombus formation under flow conditions. Methods and Principal Findings: Fibrin formation in human plasma was observed for B. lanceolatus venom at 250–1000 ng/mL concentrations, which also induced clot formation in purified human fibrinogen, indicating thrombin-like activity. The degradation of fibrinogen confirmed the fibrinogenolytic activity of B. lanceolatus venom. B. lanceolatus venom displayed consistent thrombin-like and kallikrein-like activity increases in plasma conditions. The well-known procoagulant B. atrox venom activated plasmatic coagulation factors in vitro and induced firm thrombus formation under high shear rate conditions. In contrast, B. lanceolatus venom induced the formation of fragile thrombi that could not resist shear stress. Conclusions: Our results suggest that crude B. lanceolatus venom displays amidolytic activity and can activate the coagulation cascade, leading to prothrombin activation. B. lanceolatus venom induces the formation of an unstable thrombus under flow conditions, which can be prevented by the specific monovalent antivenom Bothrofav^®. Full article

Bothrofav, a monospecific antivenom, was introduced in June 1991 and has shown excellent effectiveness against life-threatening and thrombotic complications of Bothrops lanceolatus envenoming. Because of the reoccurrence of cerebral stroke events despite the timely administration of antivenom, new batches of Bothrofav were produced and introduced into clinical use in January 2011. This study’s aim was to evaluate the effectiveness of Bothrofav generations at treating B. lanceolatus envenoming. During the first period of the study (2000–2010), 107 patients were treated with vials of antivenom produced in June 1991, while 282 envenomed patients were treated with vials of antivenom produced in January 2011 in the second study period (2011–2023). Despite timely antivenom administration, thrombotic complications reoccurred after an interval free of thrombotic events, and a timeframe analysis suggested that the clinical efficacy of Bothrofav declined after it reached its 10-year shelf-life. In of the case of an antivenom shortage due to the absence of regular batch production, no adverse effects were identified before the antivenom reached its 10-year shelf-life, which is beyond the accepted shelf-life for a liquid-formulation antivenom. While our study does not support the use of expired antivenom for potent, life-threatening B. lanceolatus envenoming, it can be a scientific message to public entities proving the necessity of new antivenom production for B. lanceolatus envenoming. Full article

Bothrops venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of B. atrox and B. lanceolatus venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav^™, Inoserp^™ South America, Antivipmyn^™ TRI, and PoliVal-ICP^™) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. B. lanceolatus venom was completely dependent on calcium but less dependent on phospholipids than B. atrox venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav^™ was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with B. atrox and thrombosis with B. lanceolatus). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with Bothrops bites. Full article

Consumption coagulopathy and hemorrhagic syndrome exacerbated by blood anticoagulability remain the most important causes of lethality associated with Bothrops snake envenomation. Bothrops venom also engages platelet aggregation on the injured endothelium via von Willebrand factor (vWF) interactions. Besides platelet aggregation, some Bothrops venom toxins may induce qualitative thrombopathy, which has been in part related to the inhibition of vWF activation. We tested whether B. lanceolatus venom impaired vWF to collagen(s) binding (vWF:CB) activity. Experiments were performed with B. lanceolatus crude venom, in the presence or absence of Bothrofav, a monospecific B. lanceolatus antivenom. Venom of B. lanceolatus fully inhibited vWF to collagen type I and III binding, suggesting venom interactions with the vWF A3 domain. In contrast, B. lanceolatus venom increased vWF to collagen type VI binding, suggesting the enhancement of vWF binding to collagen at the vWF A1 domain. Hence, B. lanceolatus venom exhibited contrasting in vitro effects in terms of the adhesive properties of vWF to collagen. On the other hand, the antivenom Bothrofav reversed the inhibitory effects of B. lanceolatus venom on vWF collagen binding activity. In light of the respective distribution of collagen type III and collagen type VI in perivascular connective tissue and the sub-endothelium, a putative association between an increase in vWF:CB activity for collagen type VI and the onset of thrombotic events in human B. lanceolatus envenomation might be considered. Full article

Snakebite envenoming is a life threatening neglected tropical disease that represents a considerable public health concern in the tropics. Viperid snakes of the genus Bothrops are among those of greatest medical importance in Latin America, and they frequently cause severe systemic haemotoxicity and local tissue destructive effects in human victims. Although snakebite antivenoms can be effective therapeutics, their efficacy is undermined by venom toxin variation among snake species. In this study we investigated the extent of paraspecific venom cross-reactivity exhibited by three distinct anti-Bothrops antivenoms (Soro antibotrópico-crotálico, BothroFav and PoliVal-ICP) against seven different Bothrops pit viper venoms from across Latin America. We applied a range of in vitro assays to assess the immunological binding and recognition of venom toxins by the antivenoms and their inhibitory activities against specific venom functionalities. Our findings demonstrated that, despite some variations, the monovalent antivenom BothroFav and the polyvalent antivenoms Soro antibotrópico-crotálico and PoliVap-ICP exhibited extensive immunological recognition of the distinct toxins found in the different Bothrops venoms, with Soro antibotrópico-crotálico generally outperformed by the other two products. In vitro functional assays revealed outcomes largely consistent with the immunological binding data, with PoliVap-ICP and BothroFav exhibiting the greatest inhibitory potencies against procoagulant and fibrinogen-depleting venom activities, though Soro antibotrópico-crotálico exhibited potent inhibition of venom metalloproteinase activities. Overall, our findings demonstrate broad levels of antivenom paraspecificity, with in vitro immunological binding and functional inhibition often highly comparable between venoms used to manufacture the antivenoms and those from related species, even in the case of the monovalent antivenom BothroFav. Our findings suggest that the current clinical utility of these antivenoms could possibly be expanded to other parts of Latin America that currently suffer from a lack of specific snakebite therapies. Full article

The toxin composition of snake venoms and, thus, their functional activity, can vary between and within species. Intraspecific venom variation across a species’ geographic range is a major concern for antivenom treatment of envenomations, particularly for countries like French Guiana that lack a locally produced antivenom. Bothrops asper and Bothrops atrox are the most medically significant species of snakes in Latin America, both producing a variety of clinical manifestations, including systemic bleeding. These pathophysiological actions are due to the activation by the venom of the blood clotting factors Factor X and prothrombin, thereby causing severe consumptive coagulopathy. Both species are extremely wide-ranging, and previous studies have shown their venoms to exhibit regional venom variation. In this study, we investigate the differential coagulotoxic effects on human plasma of six venoms (four B. asper and two B. atrox samples) from different geographic locations, spanning from Mexico to Peru. We assessed how the venom variation of these venom samples affects neutralisation by five regionally available antivenoms: Antivipmyn, Antivipmyn-Tri, PoliVal-ICP, Bothrofav, and Soro Antibotrópico (SAB). The results revealed both inter- and intraspecific variations in the clotting activity of the venoms. These variations in turn resulted in significant variation in antivenom efficacy against the coagulotoxic effects of these venoms. Due to variations in the venoms used in the antivenom production process, antivenoms differed in their species-specific or geographical neutralisation capacity. Some antivenoms (PoliVal-ICP, Bothrofav, and SAB) showed species-specific patterns of neutralisation, while another antivenom (Antivipmyn) showed geographic-specific patterns of neutralisation. This study adds to current knowledge of Bothrops venoms and also illustrates the importance of considering evolutionary biology when developing antivenoms. Therefore, these results have tangible, real-world implications by aiding evidence-based design of antivenoms for treatment of the envenomed patient. We stress that these in vitro studies must be backed by future in vivo studies and clinical trials before therapeutic guidelines are issued regarding specific antivenom use in a clinical setting. Full article

Approximately 20–30 declared snakebite cases occurin Martinique each year. Bothrops lanceolatus, a member of the Crotalidae family, is considered to be the only involved snake. B. lanceolatus, commonly named “Fer-de-Lance”, is endemic and only found on this Caribbean island. Envenomation local features include the presence of fang marks, swelling, pain, bleeding from punctures, and ecchymosis. Severe envenomation is associated with multiple systemic thromboses appearing within 48 h of the bite and resulting in cerebral, myocardial or pulmonary infarctions. Diagnosis requires first of all identification of the snake. Coagulation tests are helpful to identify thrombocytopenia or disseminated intravascular coagulation. A clinical score based on 4 grades is helpful to assess envonimation severity. A specific monovalent equine anti-venom (Bothrofav^®, Sanofi-Pasteur, France) to neutralize B. lanceolatus venom is available. Its early administration within 6h from the biting in case of progressive local injures, general signs or coagulation disturbances is effective to prevent severe thrombosis and coagulopathy. Its tolerance is considered to be good. Despite an increasing incidence of bites, no deaths have been recently attributed to B. lanceolatus in Martinique, probably due to the currently recommended strategy of early antivenom administration when required. Full article