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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 <jats:italic>Bothrops jararaca<\/jats:italic> 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 Na<jats:sub>2<\/jats:sub>-EDTA (a SVMP inhibitor), and (b) VWF knockout mice (<jats:italic>Vwf<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup>) 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 Na<jats:sub>2<\/jats:sub>-EDTA and\/or ABA tended to recover faster. In mice, BjV caused thrombocytopenia in both <jats:italic>Vwf<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> 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 <jats:italic>B<\/jats:italic>. <jats:italic>jararaca<\/jats:italic> envenomation are an ancillary event, and not the main mechanism leading to decreased platelet counts.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009715","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T17:44:14Z","timestamp":1630691054000},"page":"e0009715","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom"],"prefix":"10.1371","volume":"15","author":[{"given":"Camila Martos","family":"Thomazini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-1209","authenticated-orcid":true,"given":"Ana Teresa 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