<i>Bothrops</i> snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy

Oliveira, Sâmella Silva de; Alves, Eliane Campos; Santos, Alessandra dos Santos; Nascimento, Evaldo; Pereira, João Pedro Tavares; Silva, Iran Mendonça da; Sachett, Jacqueline de Almeida Gonçalves; Ibiapina, Hiochelson Najibe dos Santos; Sarraf, Lybia Kássia Santos; Bernal, Jorge Carlos Contreras; Freitas-de-Sousa, Luciana Aparecida; Colombini, Mônica; Marques, Hedylamar Oliveira; Lacerda, Marcus Vinícius Guimarães; Moura-da-Silva, Ana Maria; Fan, Hui Wen; Ferreira, Luíz Carlos de Lima; Martins, Ida Sigueko Sano; Monteiro, Wuelton Marcelo

doi:10.1080/15563650.2019.1634273

Cited by 26 publications

(49 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, B. atrox venom toxins present fibrin(ogen)olytic and thrombolytic activity which also contribute to coagulopathy (41). Among the hemostatic changes observed in patients from B. atrox snakebites, blood incoagulability is accompanied by low plasma levels of fibrinogen and increased levels of fibrin/fibrinogen degradation products, which characterize an intravascular pro-coagulant effect (10,42). Our data show that 76.4% of snakebite patients have hypofibrinogenemia, which is close to values found in a previous study (26).…”

Section: Discussionsupporting

confidence: 89%

“…Among these effects, inflammatory and hemostatic disorders are frequently observed in patients. Envenomation's by viperid snakes often cause local and systemic bleeding (9,10), such as gingivorrhagia, epistaxis, hematemesis, hematuria, bleeding in the uteris, and placenta (in pregnant women) (11,12) and bleeding in the central nervous system (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Correlating Fibrinogen Consumption and Profiles of Inflammatory Molecules in Human Envenomation's by Bothrops atrox in the Brazilian Amazon

et al. 2020

Self Cite

View full text Add to dashboard Cite

Snakebites are considered a major public health problem worldwide. In the Amazon region of Brazil, the snake Bothrops atrox ( B. atrox ) is responsible for 90% of the bites. These bites may cause local and systemic signs from acute inflammatory reaction and hemostatic changes, and present common hemorrhagic disorders. These alterations occur due the action of hemostatically active and immunogenic toxins which are capable of triggering a wide range of hemostatic and inflammatory events. However, the crosstalk between coagulation disorders and inflammatory reaction still has gaps in snakebites. Thus, the goal of this study was to describe the relationship between the consumption of fibrinogen and the profile of inflammatory molecules (chemokines and cytokines) in evenomations by B. atrox snakebites. A prospective study was carried out with individuals who had suffered B. atrox snakebites and presented different levels of fibrinogen consumption (normal fibrinogen [NF] and hypofibrinogenemia [HF]). Seventeen patients with NF and 55 patients with HF were eligible for the study, in addition to 50 healthy controls (CG). The molecules CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-γ, IL-4, and IL-17A were quantified in plasma using the CBA technique at three different times (pre-antivenom therapy [T0], 24 h [T1], and 48 h [T2] after antivenom therapy). The profile of the circulating inflammatory response is different between the groups studied, with HF patients having higher concentrations of CCL-5 and lower IFN-γ. In addition, antivenom therapy seems to have a positive effect, leading to a profile of circulating inflammatory response similar in quantification of T1 and T2 on both groups. Furthermore, these results suggest that a number of interactions of CXCL-8, CXCL-9, CCL-2, IL-6, and IFN-γ in HF patients are directly affected by fibrinogen levels, which may be related to the inflammatory response and coagulation mutual relationship induced by B. atrox venom. The present study is the first report on inflammation-coagulation crosstalk involving snakebite patients and supports the better understanding of envenomation's pathophysiology mechanisms and guides in the search for novel biomarkers and prospective therapies.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Correlating Fibrinogen Consumption and Profiles of Inflammatory Molecules in Human Envenomation's by Bothrops atrox in the Brazilian Amazon

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…A previous study in the Pará State, eastern Brazilian Amazon, has shown that Bothrops envenomations cause decreased levels of fibrinogen and alpha 2-antiplasmin, elevated fibrin/fibrinogen degradation product (FDP), and D-dimer concentrations [18]. Similar results were also reported in a study involving Bothrops snakebite patients in the Amazonas State, western Brazilian Amazon, in which some coagulation components recovered within 48 h after starting antivenom therapy [19]. Despite the clinical similarities of Bothrops envenomations in Brazil, thrombocytopenia is an infrequent event in Bothrops envenomation that occurs in the Amazon (caused mainly by B. atrox) compared to those in the southern region (caused by B. jararaca) [18][19][20].…”

Section: Introductionsupporting

confidence: 73%

Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor

Oliveira

Alves

Santos

et al. 2020

Toxins

Self Cite

View full text Add to dashboard Cite

Bleeding is a common hemostatic disorder that occurs in Bothrops envenomations. We evaluated the changes in coagulation, fibrinolysis components, and platelets in Bothrops atrox envenomations with bleeding. This is an observational study with B. atrox snakebite patients (n = 100) treated in Manaus, Brazilian Amazon. Bleeding was recorded on admission and during hospitalization. We found that the platelet count in our patients presented a weak correlation to tissue factor, factor II, and plasminogen. Tissue factor presented weak correlation to factor V, II, D-dimer, plasminogen, alpha 2-antiplasmin, and moderate correlation to fibrinogen and fibrin/fibrinogen degradation product (FDP). Patients with systemic bleeding (n = 20) presented low levels of factor V, II, fibrinogen, plasminogen, and alpha 2-antiplasmin, and high levels of tissue factor and FDP compared to those without bleeding. Patients with only local bleeding (n = 41) and without bleeding showed similar levels of hemostatic factors. Thrombocytopenia was observed mainly in patients with systemic bleeding and increased levels of serum venom. No association was found between venom levels and systemic bleeding, or between venom levels and clinical severity of envenomation. This is the first report that shows the participation of the extrinsic coagulation pathway in the consumption coagulopathy of B. atrox envenomations with systemic bleeding due to tissue factor release.

show abstract

“…It commonly arises in the case of microvascular damage by proteolytic degradation of the basement membrane [ 21 ]. The involved enzymes are PI and P-III snake venom metalloproteinases (examples in the venom of B. atrox are Batroxase [ 22 ], Atroxlysin-Ia [ 23 ] and Batroxrhagin [ 24 ]). Systemic bleeding observed in snakebites was reported in 3.6–15.3% of patients [ 15 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Features and Management of Snakebite Envenoming in French Guiana

Résière

Houcke

Pujo

et al. 2020

Toxins

View full text Add to dashboard Cite

The management of snakebite (SB) envenoming in French Guiana (FG) is based on symptomatic measures and antivenom (AV) administration (Antivipmyn Tri®; Instituto Bioclon—Mexico). Our study aimed to assess clinical manifestations, the efficacy, and safety of Antivipmyn Tri® in the management of SB. Our study is a prospective observational work. It was conducted in the Intensive Care Unit (ICU) of Cayenne General Hospital between January 1st, 2016 and December 31, 2019. We included all patients hospitalized for SB envenoming. Our study contained three groups (without AV, three vials, and six vials Antivipmyn Tri®). During the study period, 133 patients were included. The main clinical symptoms were edema (98.5%), pain (97.7%), systemic hemorrhage (18%), blister (14.3%), and local hemorrhage (14.3%). AV was prescribed for 83 patients (62.3%), and 17 of them (20%) developed early adverse reactions. Biological parameters at admission showed defibrinogenation in 124 cases (93.2%), International Normalized Ratio (INR) > 2 in 104 cases (78.2%), and partial thromboplastin time (PTT) > 1.5 in 74 cases (55.6%). The time from SB to AV was 9:00 (5:22–20:40). The median time from SB to achieve a normal dosage of fibrinogen was 47:00 vs. 25:30, that of Factor II was 24:55 vs. 15:10, that of Factor V was 31:42 vs. 19:42, and that of Factor VIII was 21:30 vs. 10:20 in patients without and with AV, respectively, (p < 0.001 for all factors). Patients receiving Antivipmyn Tri® showed a reduction in the time to return to normal clotting tests, as compared to those who did not. We suggest assessing other antivenoms available in the region to compare their efficacy and safety with Antivipmyn Tri® in FG.

show abstract

Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy

Cited by 26 publications

References 42 publications

Correlating Fibrinogen Consumption and Profiles of Inflammatory Molecules in Human Envenomation's by Bothrops atrox in the Brazilian Amazon

Correlating Fibrinogen Consumption and Profiles of Inflammatory Molecules in Human Envenomation's by Bothrops atrox in the Brazilian Amazon

Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor

Clinical Features and Management of Snakebite Envenoming in French Guiana

Contact Info

Product

Resources

About