Thrombocytopenia and platelet hypoaggregation induced by Bothrops asper snake venom. Toxins involved and their contribution to metalloproteinase-induced pulmonary hemorrhage.
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 alpha2-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.
Rucavado
Alexandra
A
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica. arucavad@cariari.ucr.ac.cr
Soto
Mónica
M
Escalante
Teresa
T
Loría
Gilbert D
GD
Arni
Raghuvir
R
Gutiérrez
José María
JM
D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets; D017837:Bothrops; D004305:Dose-Response Relationship, Drug; D005338:Fibrin Fibrinogen Degradation Products; D006470:Hemorrhage; D006801:Humans; D008168:Lung / Q000473:pathology*; D008666:Metalloendopeptidases / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism*; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D012910:Snake Venoms; D013921:Thrombocytopenia / Q000139:chemically induced / Q000473:pathology*; D013997:Time Factors; D000511:alpha-Macroglobulins / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D005338:Fibrin Fibrinogen Degradation Products; D012910:Snake Venoms; D000511:alpha-Macroglobulins; C036309:fibrin fragment D; D014841:von Willebrand Factor; D045726:Metalloproteases; D008666:Metalloendopeptidases; C069317:hemorrhagic metalloproteinase