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

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          Abstract

          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.

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          Interpretation of the Correlation Coefficient: A Basic Review

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            Snakebites as cause of deaths in the Western Brazilian Amazon: Why and who dies? Deaths from snakebites in the Amazon.

            Snake envenoming represents a major burden for public health worldwide. In the Amazon, the official number of cases and deaths detected is probably underestimated because of the difficulty riverine and indigenous populations have reaching health centers in order to receive medical assistance. Thus, integrated analysis of health information systems must be used in order to improve adequate health policies. The aim of this work is to describe a series of deaths and identify risk factors for lethality from snakebites in the state of Amazonas, Brazil. All deaths from snakebites reported to the Brazilian Notifiable Diseases Surveillance System (SINAN) and to the Mortality Information System (SIM; ICD10-10th revision, X.29), from 2007 to 2015, were included. Variables were assessed by blocks with distal (ecological variables), intermediate (demographics) and proximal (clinical variables) components to identify predictors of case fatality. A total of 127 deaths from snakebites were recorded, with 58 pairs found through linkage of the SINAN and SIM databases (45.7%), 37 (29.1%) deaths found only in SINAN and 32 (25.2%) found only in the SIM. Deaths occurred mostly in males (95 cases; 74.8%) living in rural areas (78.6%). The most affected age group was the ≥61 years old (36 cases; 28.4%). Snakebites were presumably due to Bothrops snakes in 68.5% of the cases and Lachesis in 29.5% based on clinico-epidemiological diagnosis. A proportion of 26.2% of the cases received treatment over 24 h after the bite ocurred. On admission, cases were mostly classified as severe (65.6%). Overall, 28 patients (22.0%). Deceased without any medical assistance Antivenom was given to 53.5%. In the multivariate analysis, a distance from Manaus >300 km [OR = 3.40 (95%CI = 1.99-5.79); (p < 0.001)]; age ≥61 years [OR = 4.31 (95%CI = 1.22-15.21); (p = 0.023)] and Indigenous status [OR = 5.47 (95%CI = 2.37-12.66); (p < 0.001)] were independently associated with case fatality from snakebites. Severe snakebites [OR = 16.24 (95%CI = 4.37-60.39); (p < 0.001)] and a lack of antivenom administration [OR = 4.21 (95%CI = 1.30-13.19); (p = 0.014)] were also independently associated with case fatality. Respiratory failure/dyspnea, systemic bleeding, sepsis and shock were recorded only among fatal cases. In conclusion, i) death from snakebites was underreported in the mortality surveillance system; ii) older age groups living in remote municipalities and indigenous peoples were the population groups most prone to death; iii) lack or underdosage of antivenom resulted in higher case fatality and iv) systemic bleeding, circulatory shock, sepsis and acute respiratory failure were strongly associated to fatal outcome.
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              Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens

              A. Clauss (1957)
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                29 August 2020
                September 2020
                : 12
                : 9
                : 554
                Affiliations
                [1 ]Carlos Borborema Clinical Research Institute, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, Manaus 69040-000, Brazil; oliveira.samella@ 123456gmail.com (S.S.O.); anealves.enf@ 123456gmail.com (E.C.A.); alessandrasantos910@ 123456gmail.com (A.S.S.); elyfreitas46@ 123456gmail.com (E.F.N.); pedro02.tavares@ 123456gmail.com (J.P.T.P.); iramend3@ 123456gmail.com (I.M.S.); jac.sachett@ 123456gmail.com (J.A.G.S.); lybsarraff@ 123456gmail.com (L.K.S.S.); marcuslacerda.br@ 123456gmail.com (M.V.G.L.); ana.moura@ 123456butantan.gov.br (A.M.M.-d.-S.); ferreira.luiz@ 123456gmail.com (L.C.L.F.)
                [2 ]School of Health Sciences, Amazonas State University, Manaus 69065-001, Brazil
                [3 ]Immunopathology Laboratory, Butantan Institute, São Paulo 05503-900, Brazil; luciana.sousa@ 123456butantan.gov.br (L.A.F.-d.-S.); monica.colombini@ 123456butantan.gov.br (M.C.)
                [4 ]Hemostasis Laboratory, Amazonas State Hematology and Haemotherapy Hospital Foundation, Manaus 69050-001, Brazil; hedyomarques@ 123456gmail.com
                [5 ]Institute of Biological Sciences, Federal University of Amazonas, Manaus 69070-000, Brazil; marcosartim@ 123456hotmail.com
                [6 ]Pathophysiology Laboratory, Butantan Institute, São Paulo 05503-900, Brazil
                Author notes
                [* ]Correspondence: ida.sano@ 123456butantan.gov.br (I.S.S.-M.); wueltonmm@ 123456gmail.com (W.M.M.); Tel.: +55-112-627-9743 (I.S.S.-M.); +55-922-127-3555 (W.M.M.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-4426-0731
                https://orcid.org/0000-0003-1787-6634
                https://orcid.org/0000-0002-0848-1940
                Article
                toxins-12-00554
                10.3390/toxins12090554
                7551922
                32872404
                7a377595-e1b3-421f-91a3-9ecdbaf9f2f8
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 July 2020
                : 13 August 2020
                Categories
                Article

                Molecular medicine
                bothrops atrox envenomation,coagulation factors,systemic bleeding,thrombocytopenia,tissue factor

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