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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ftdoajarticles:oai:doaj.org/article:19e7e53c3d6b49728785982860419355 2023-05-15T15:13:00+02:00 Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom. 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 2021-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009715 https://doaj.org/article/19e7e53c3d6b49728785982860419355 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009715 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009715 https://doaj.org/article/19e7e53c3d6b49728785982860419355 PLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009715 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009715 2022-12-31T15:16:59Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 9 e0009715 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
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. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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 in Journal/Newspaper |
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://doi.org/10.1371/journal.pntd.0009715 https://doaj.org/article/19e7e53c3d6b49728785982860419355 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009715 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009715 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009715 https://doaj.org/article/19e7e53c3d6b49728785982860419355 |
op_doi |
https://doi.org/10.1371/journal.pntd.0009715 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
9 |
container_start_page |
e0009715 |
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1766343597396852736 |