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Thromb Haemost 2005; 94(01): 123-131
DOI: 10.1160/TH05-02-0112
Platelets and Blood Cells
Schattauer GmbH

Thrombocytopenia and platelet hypoaggregation induced by Bothrops asper snake venom

Toxins involved and their contribution to metalloproteinase-induced pulmonary hemorrhage
Alexandra Rucavado
1   Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica
,
Mónica Soto
1   Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica
,
Teresa Escalante
1   Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica
,
Gilbert D. Loría
1   Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica
2   Departamento de Microbiología e Inmunología, Facultad de Microbiología, Universidad de Costa Rica, Costa Rica
,
Raghuvir Arni
3   Department of Physics, IBILCE/UNESP, Sao José de Rio Preto, Brazil
,
José María Gutiérrez
1   Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica
› Author AffiliationsFinancial support: This study was supported by Vicerrectoría de Investigación, Universidad de Costa Rica (projects 741-A2–036 and 741-A4–061) and the International Foundation for Science (project F-2707–3).
Further Information

Publication History

Received 15 February 2005

Accepted after revision 04 April 2005

Publication Date:
05 December 2017 (online)

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Summary

Thrombocytopenia and platelet dysfunction occur in patients bitten by Bothrops sp snakes in Latin America. An experimental model was developed in mice to study the effects of B. asper venom in platelet numbers and function. Intravenous administration of this venom induces rapid and prominent thrombocytopenia and ex vivo platelet hypoaggregation. The drop in platelet numbers was primarily due to aspercetin, a protein of the C-type lectin family which induces von Willebrand factor-mediated platelet aggregation/agglutination. In addition, the effect of class P-III hemorrhagic metalloproteinases on the microvessel wall also contributes to thrombocytopenia since jararhagin, a P-III metalloproteinase, reduced platelet counts. Hypoaggregation was associated with the action of procoagulant and defibrin(ogen)ating proteinases jararacussin-I (a thrombin-like serine proteinase) and basparin A (a prothrombin activating metalloproteinase). At the doses which induced hypoaggregation, these enzymes caused defibrin(ogen)ation, increments in fibrin(ogen) degradation products and D-dimer and prolongation of the bleeding time. Incubation of B. asper venom with batimastat and α2-macroglobulin abrogated the hypoaggregating activity, confirming the role of venom proteinases in this effect. Neither aspercetin nor the defibrin(ogen)ating and hypoaggregating components induced hemorrhage upon intravenous injection. However, aspercetin, but not the thrombin-like or the prothrombin-activating proteinases, potentiated the hemorrhagic activity of two hemorrhagic metalloproteinases in the lungs.

Keywords

Snake venom - coagulopathy - defibrin(ogen)ation - thrombocytopenia - hypoaggregation
 

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