Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.

Patients bitten by snakes consistently manifest a bleeding tendency, in which thrombocytopenia, consumption coagulopathy, mucous bleeding, and, more rarely, thrombotic microangiopathy, are observed. Von Willebrand factor (VWF) is required for primary hemostasis, and some venom proteins, such as botr...

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Autores principales:	Camila Martos Thomazini, Ana Teresa Azevedo Sachetto, Cynthia Zaccanini de Albuquerque, Vânia Gomes de Moura Mattaraia, Ana Karina de Oliveira, Solange Maria de Toledo Serrano, Ivo Lebrun, Katia Cristina Barbaro, Marcelo Larami Santoro
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/19e7e53c3d6b49728785982860419355
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spelling	oai:doaj.org-article:19e7e53c3d6b497287859828604193552021-12-02T20:24:11ZInvolvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.1935-27271935-273510.1371/journal.pntd.0009715https://doaj.org/article/19e7e53c3d6b497287859828604193552021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009715https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Patients bitten by snakes consistently manifest a bleeding tendency, in which thrombocytopenia, consumption coagulopathy, mucous bleeding, and, more rarely, thrombotic microangiopathy, are observed. Von Willebrand factor (VWF) is required for primary hemostasis, and some venom proteins, such as botrocetin (a C-type lectin-like protein) and snake venom metalloproteinases (SVMP), disturb the normal interaction between platelets and VWF, possibly contributing to snakebite-induced bleedings. To understand the relationship among plasma VWF, platelets, botrocetin and SVMP from Bothrops jararaca snake venom (BjV) in the development of thrombocytopenia, we used (a) Wistar rats injected s.c. with BjV preincubated with anti-botrocetin antibodies (ABA) and/or Na2-EDTA (a SVMP inhibitor), and (b) VWF knockout mice (Vwf-/-) injected with BjV. Under all conditions, BjV induced a rapid and intense thrombocytopenia. In rats, BjV alone reduced the levels of VWF:Ag, VWF:CB, high molecular weight multimers of VWF, ADAMTS13 activity, and factor VIII. Moreover, VWF:Ag levels in rats that received BjV preincubated with Na2-EDTA and/or ABA tended to recover faster. In mice, BjV caused thrombocytopenia in both Vwf-/- and C57BL/6 (background control) strains, and VWF:Ag levels tended to decrease in C57BL/6, demonstrating that thrombocytopenia was independent of the presence of plasma VWF. These findings showed that botrocetin present in BjV failed to affect the extent or the time course of thrombocytopenia induced by envenomation, but it contributed to decrease the levels and function of plasma VWF. Thus, VWF alterations during B. jararaca envenomation are an ancillary event, and not the main mechanism leading to decreased platelet counts.Camila Martos ThomaziniAna Teresa Azevedo SachettoCynthia Zaccanini de AlbuquerqueVânia Gomes de Moura MattaraiaAna Karina de OliveiraSolange Maria de Toledo SerranoIvo LebrunKatia Cristina BarbaroMarcelo Larami SantoroPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009715 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Camila Martos Thomazini Ana Teresa Azevedo Sachetto Cynthia Zaccanini de Albuquerque Vânia Gomes de Moura Mattaraia Ana Karina de Oliveira Solange Maria de Toledo Serrano Ivo Lebrun Katia Cristina Barbaro Marcelo Larami Santoro Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.
description	Patients bitten by snakes consistently manifest a bleeding tendency, in which thrombocytopenia, consumption coagulopathy, mucous bleeding, and, more rarely, thrombotic microangiopathy, are observed. Von Willebrand factor (VWF) is required for primary hemostasis, and some venom proteins, such as botrocetin (a C-type lectin-like protein) and snake venom metalloproteinases (SVMP), disturb the normal interaction between platelets and VWF, possibly contributing to snakebite-induced bleedings. To understand the relationship among plasma VWF, platelets, botrocetin and SVMP from Bothrops jararaca snake venom (BjV) in the development of thrombocytopenia, we used (a) Wistar rats injected s.c. with BjV preincubated with anti-botrocetin antibodies (ABA) and/or Na2-EDTA (a SVMP inhibitor), and (b) VWF knockout mice (Vwf-/-) injected with BjV. Under all conditions, BjV induced a rapid and intense thrombocytopenia. In rats, BjV alone reduced the levels of VWF:Ag, VWF:CB, high molecular weight multimers of VWF, ADAMTS13 activity, and factor VIII. Moreover, VWF:Ag levels in rats that received BjV preincubated with Na2-EDTA and/or ABA tended to recover faster. In mice, BjV caused thrombocytopenia in both Vwf-/- and C57BL/6 (background control) strains, and VWF:Ag levels tended to decrease in C57BL/6, demonstrating that thrombocytopenia was independent of the presence of plasma VWF. These findings showed that botrocetin present in BjV failed to affect the extent or the time course of thrombocytopenia induced by envenomation, but it contributed to decrease the levels and function of plasma VWF. Thus, VWF alterations during B. jararaca envenomation are an ancillary event, and not the main mechanism leading to decreased platelet counts.
format	article
author	Camila Martos Thomazini Ana Teresa Azevedo Sachetto Cynthia Zaccanini de Albuquerque Vânia Gomes de Moura Mattaraia Ana Karina de Oliveira Solange Maria de Toledo Serrano Ivo Lebrun Katia Cristina Barbaro Marcelo Larami Santoro
author_facet	Camila Martos Thomazini Ana Teresa Azevedo Sachetto Cynthia Zaccanini de Albuquerque Vânia Gomes de Moura Mattaraia Ana Karina de Oliveira Solange Maria de Toledo Serrano Ivo Lebrun Katia Cristina Barbaro Marcelo Larami Santoro
author_sort	Camila Martos Thomazini
title	Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.
title_short	Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.
title_full	Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.
title_fullStr	Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.
title_full_unstemmed	Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.
title_sort	involvement of von willebrand factor and botrocetin in the thrombocytopenia induced by bothrops jararaca snake venom.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/19e7e53c3d6b49728785982860419355
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Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.

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