Thrombocytopenia and platelet hypoaggregation induced by Bothrops asper snake venom

Alexandra Rucavado; Mónica Soto; Teresa Escalante; Gilbert D. Loría; Raghuvir Arni; José María Gutiérrez

doi:10.1160/TH05-02-0112

Thrombosis and Haemostasis, Table of Contents

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

Authors

Alexandra Rucavado

¹Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica
Mónica Soto

¹Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica
Teresa Escalante

¹Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica
Gilbert D. Loría

¹Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica

²Departamento de Microbiología e Inmunología, Facultad de Microbiología, Universidad de Costa Rica, Costa Rica
Raghuvir Arni

³Department of Physics, IBILCE/UNESP, Sao José de Rio Preto, Brazil
José María Gutiérrez

¹Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica

Abstract

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

Full Text

References

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