Platelet dysfunction during Bothrops jararaca snake envenomation in rabbits

Santoro, Marcelo Larami; Sano-Martins, Ida Sigueko

doi:10.1160/th04-02-0120

Cited by 49 publications

(18 citation statements)

References 68 publications

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“…However, our results do not agree with the traditional assumption that thrombin-like enzymes are the main toxins accounting for defibrinogenation, and indicate that SVMP are crucial enzymes promoting fibrinogen consumption, at least in rabbits [7], [24], mice [38], and rats. However, which class of toxins accounts for most fibrinogen consumption in humans remains to be investigated, but we demonstrate herein that procoagulant enzymes and high TF plasma levels may exert a relevant role in the hemostatic disorder evoked by Bothrops bites, since intravascular thrombin generation, evidenced by raised plasma levels of TAT complex [52], [53], are noticed in patients.…”

Section: Discussioncontrasting

confidence: 99%

“…Blood counts were determined in an automated cell counter BC-2800 Vet (Mindray, China). To obtain plasma samples, blood (4.3 mL) was collected into plastic bottles containing 700 µL of CTAD anticoagulant (75 mM trisodium citrate, 42 mM citric acid, 139 mM dextrose, 15 mM theophylline, 3.7 mM adenosine, 0.2 mM dipyridamole, and 2 µM imipramine) [7] and 50 µL of Bothrops antivenin, and centrifuged at 2500 g for 15 min at 4°C. Serum samples were obtained by maintaining blood (500 µL) without anticoagulant or antivenin at 37°C for 2 h, followed by centrifugation as mentioned above.…”

Section: Methodsmentioning

confidence: 99%

“…Snake venom metalloproteinases (SVMP) and serine proteinases (SVSP), the two main protein families found in BjV with anti-hemostatic activity [6], have been implicated in the hemostatic disorders associated with envenomation [7]. SVMP present in Bothrops venoms belong to a zinc-dependent enzyme family, which contributes to the inflammatory, proteolytic, hemorrhagic and procoagulant (prothrombin and factor X activators) activities in snake venoms [8]–[10].…”

Section: Introductionmentioning

confidence: 99%

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Bothrops jararaca Venom Metalloproteinases Are Essential for Coagulopathy and Increase Plasma Tissue Factor Levels during Envenomation

et al. 2014

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Background/AimsBleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF), resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a) whether TF and protein disulfide isomerase (PDI), an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b) the involvement and significance of snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) to hemostatic disturbances.Methods/Principal FindingsCrude Bothrops jararaca venom (BjV) was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV.ConclusionsSVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in engendering bleeding manifestations in severely-envenomed patients.

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Section: Discussioncontrasting

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bothrops jararaca Venom Metalloproteinases Are Essential for Coagulopathy and Increase Plasma Tissue Factor Levels during Envenomation

et al. 2014

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“…RBC morphology was evaluated manually in blood smears stained with Romanowsky panchromatic stain. Platelet counts were determined manually using a buffered hypotonic solution 45 in a Neubauer hemocytometer. Blood samples were anticoagulated with 3.8% trisodium citrate, as mentioned earlier, to obtain citrated plasma.…”

Section: Blood Samplingmentioning

confidence: 99%

Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis

Senise

Yamashita

Santoro

2015

Exp Biol Med (Maywood)

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To attain fully functional biological activity, vitamin-K dependent coagulation factors (VKDCF) are g-carboxylated prior to secretion from liver. Warfarin impairs the g-carboxylation, and consequently their physiological function. Bothrops jararaca snake venom (BjV) contains several activators of blood coagulation, especially procoagulant enzymes (prothrombin and factor X activators) and thrombin-like enzymes. In order to clarify the relative contribution of prothrombin and factor X activators to the hemostatic disturbances occurring during experimental B. jararaca envenomation, warfarin was used to deplete VKDCF, prior to BjV administration. Male Wistar rats were pretreated with saline (Sal) or warfarin (War) and inoculated subsequently with BjV or saline, thus forming four groups: Sal þ Sal (negative control), Sal þ BjV (positive control), War þ Sal (warfarinization control), and War þ BjV. Three hours after inoculation, prothrombin and factor X levels fell 40% and 50%, respectively; levels of both factors decreased more than 97% in the War þ Sal and War þ BjV groups. Platelet counts dropped 93% and 76% in Sal þ BjV and War þ BjV, respectively, and plasma fibrinogen levels decreased 86% exclusively in Sal þ BjV. After 6 and 24 h, platelet counts and fibrinogen levels increased progressively. A dramatic augmentation in plasma hemoglobin levels and the presence of schizocytes and microcytes in the Sal þ BjV group indicated the development of intravascular hemolysis, which was prevented by warfarin pretreatment. Our findings show that intravascular thrombin generation has the foremost role in the pathogenesis of coagulopathy and intravascular hemolysis, but not in the development of thrombocytopenia, in B. jararaca envenomation in rats; in addition, fibrinogenases (metalloproteinases) may contribute to coagulopathy more than thrombin-like enzymes.

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“…Bothrops jararaca (B. jararaca) é uma espécie predominantemente noturna e terrestre (Sazima, 1988) e encontra-se em diversos ambientes: florestas tropicais, semitropicais, campos abertos e cerrados (SAZIMA, 1992 SANO-MARTINS et al, 1997;SANTORO;SANO-MARTINS, 2004;VARANDA;GIANNINI, 1999).…”

Section: Bothrops Jararacaunclassified

Análise do transcriptoma do fígado da serpente Bothrops jararaca utilizando expressed sequences tags (ESTs).

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amo, meu porto seguro. Aos meus pais Antônia Maria da Silva Gomes e José Geraldo Gomes, que sempre acreditaram em mim, e sempre fizeram o melhor pela minha educação.Às minhas irmãs Cristiane Maria Gomes e Thais Maria Gomes, minhas companheiras de sempre.Sem vocês nada disso seria possível. E claro ao meu cachorro Theo por sua alegria toda vez que chego em casa." "In memoriam de Faustemira das GraçasCruz Alves Pereira que rezou por mim e me deu força para continuar em meu caminho." AGRADECIMENTOSGostaria de agradecer a todos que direta ou indiretamente tenham contribuído para o término do mestrado e especialmente para a conclusão deste trabalho, que é apenas o início de um longo caminho a ser percorrido, a começar pela minha orientadora Dra. Anita Mitico Tanaka-Azevedo pelos seus ensinamentos, por ter confiado a mim este trabalho e por ter me aceito no seu grupo de trabalho com quem tive a oportunidade de aprender muito, e foi muito importante para o meu crescimento profissional.À Professora Dra. Aparecida Sadae Tanaka, minha co-orientadora, que me acompanhou durante toda a realização deste trabalho, por seu exemplo de profissionalismo, seriedade à pesquisa, e por sempre me fazer enxergar mais longe.Ao amigo Dr. Diego de Souza Buarque que me acompanhou durante todas as fases deste trabalho, obrigada por sua ajuda e companhia em todos os momentos, "inclusive quando escapamos do raio". Obrigada pela paciência.Aos amigos Tatiane Sanches Soares e Felipe Araújo de Oliveira, meus parceiros de todos os momentos, "meu triângulo", obrigada por poder sempre contar com vocês e por vocês sempre me aguentarem durante meus momentos, sou privilegiada por poder contar com vocês! A todos os companheiros do laboratório do Infar e do Instituto Butantan que me ajudaram de diferentes maneiras durante a realização deste trabalho, Gabriela Catalano, Lucyla Tiemi "que sempre tem uma bala para mim", Patrícia Andrade, Thyago Cardoso "por me fazer sempre rir", Stephen Lu, Karla Oliveira, Ricardo Torquato e Karen de Morais Zani. À Dra Kathleen Fernandes Grego do Laboratório de Herpetologia do InstitutoButantan, pela ajuda na coleta do fígado das serpentes B. jararaca. À Professora Glória por sua colaboração e orientação na parte de bioinformática.Aos funcionários do Infar, em especial à técnica Jucilene Barbosa da Silva, pelo sequenciamento e por sua amizade.Às minhas amigas, Andréa Carvalho e Fernanda Soma por sempre me entenderem e me apoiarem durante todas as fases deste trabalho, que sempre estiveram presentes, mesmo à distância quando eu precisava, e sempre me fizeram companhia, à nossas tardes na Starbucks, aos filmes e, claro, aos shows que sempre fizeram parte dessas nossas histórias. Valeu meninas! À minha eterna amiga Tais Costa de Oliveira, que mesmo eu estando longe, e não muito presente, ainda é minha amiga, que mesmo me achando "louca" ainda assim consegue me entender. Porque amizade é assim! Aos meus amigos do Laboratório de Genética do Instituto Butantan, Dra. Sueli "Sesso", Fernando e Prof. Dr. Carlos Marandová, que não est...

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Platelet dysfunction during Bothrops jararaca snake envenomation in rabbits

Cited by 49 publications

References 68 publications

Bothrops jararaca Venom Metalloproteinases Are Essential for Coagulopathy and Increase Plasma Tissue Factor Levels during Envenomation

Bothrops jararaca Venom Metalloproteinases Are Essential for Coagulopathy and Increase Plasma Tissue Factor Levels during Envenomation

Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis

Análise do transcriptoma do fígado da serpente Bothrops jararaca utilizando expressed sequences tags (ESTs).

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