Platelet dysfunction during Bothrops jararaca snake envenomation in rabbits.
Despite being well established that snake envenomation causes blood coagulation and fibrinolysis disturbances, scant information is available about blood platelet disorders. Herein we show that experimentally Bothrops jararaca-envenomed rabbits presented thrombocytopenia, hypofibrinogenemia, elevation of von Willebrand factor plasma levels, platelet hypoaggregation in platelet rich plasma and whole blood, normoaggregation in washed platelet suspensions, decreased platelet ATP secretion, normal plasma levels of platelet factor 4, and constant intraplatelet serotonin levels. Furthermore, by flow cytometric analyses, platelets displayed a significant decrease in the expression of a GPIIb-IIIa epitope recognized by P2 monoclonal antibody (p< 0.05) and an increased expression of a ligand-induced binding site (LIBS-1) of GPIIIa (p< 0.05), but total GPIIb-IIIa expression, evaluated with specific polyclonal antibodies, was normal. Fibrinogen and fibrin(ogen) degradation product (FfDP) expression on platelet surface showed no significant alteration. Nonetheless, significant elevations of platelet P-selectin were noticed on circulating platelets. The percentage of circulating reticulated platelets and the survival time of biotinylated platelets of envenomed rabbits were not statistically different from control animals. We suggest that thrombin engendered by procoagulating components of B. jararaca venom has an essential role in the pathogenesis of platelet and coagulation disorders in this experimental model. Increased expression of P-selectin in the experimental group demonstrates that platelets of envenomed rabbits are indeed activated in circulation, and that decreased fibrinogen or increased FfDP levels are not the primary cause of platelet dysfunction. These results imply the existence of an inhibitor in plasma that interferes with platelet aggregation in bothropic envenomation.
Laboratory of Pathophysiology, Institute Butantan, São Paulo, Brazil. santoro@butantan.gov.br
Marcelo Larami
ML
Santoro
Ida Sigueko
IS
Sano-Martins
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D001791:Blood Platelet Disorders; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D017837:Bothrops; D003094:Collagen / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000096:biosynthesis / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000473:pathology; D019007:P-Selectin / Q000097:blood; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry; D011817:Rabbits; D012909:Snake Bites; D012910:Snake Venoms / Q000378:metabolism; D013921:Thrombocytopenia / Q000209:etiology; D013997:Time Factors; D014841:von Willebrand Factor / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D000939:Epitopes; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012910:Snake Venoms; D014841:von Willebrand Factor; D005337:Fibrin; D005340:Fibrinogen; D003094:Collagen