Abstract Number: PB0789
Meeting: ISTH 2020 Congress
Background: Snake venoms are complex mixtures of toxins that activate and/or inhibit coagulation, fibrinolysis and the inflammatory system. Bites by Bothrops snakes evoke an inflammatory reaction, marked by an increase in pro-inflammatory cytokines and acute phase proteins (APPs). This envenomation also induces hemostatic disturbances, as thrombocytopenia, consumption coagulopathy (characterized by decreased levels of factors II, VIII, X and fibrinogen) and secondary hyperfibrinolysis. The neutralization of the venom by the specific antivenom therapy allows the restoration of hemostatic parameters, including fibrinogen levels. However, the hepatic molecular mechanisms underlying these alterations and its interactions are still unclear.
Aims: To investigate the gene expression kinetics of important coagulation and inflammation factors synthetized by the liver in mice injected with Bothrops jararaca venom.
Methods: All procedures involving animals were approved by IACUC. Swiss mice were injected s.c. with saline or venom (1.6 mg/kg b.w, s.c.). After 3, 6 or 24 h, liver fragments were collected. Gene expression was assessed by Real-Time Quantitative PCR.
Results: Envenomation induced an important increase in mRNA levels of the positive APPs fibrinogen and haptoglobin, and also the transcription factor STAT3. Interestingly, mRNA levels of tissue factor decreased at 3 h. At 24 h, mRNA levels of FX increased and of antithrombin III and protein C decreased. No alterations were observed regarding the gene expression of the negative APP murinoglobin, the transcription factor NFκB-1 and most hemostasis-related genes, e.g., factors II and VIII, plasminogen and α2-antiplasmin. Nevertheless, significant correlations were observed among these genes.
Conclusions: Our results indicate that envenomation induces a rapid mRNA synthesis of fibrinogen chains, which could explain the fast recovery of hemostatic parameters in patients after the neutralization of the venom by specific antivenom. Moreover, important genes related to coagulation and inflammation display different patterns of expression and seem to have common regulatory mechanisms.
Funding: FAPESP, CNPq, CAPES, Fundação Butantan.
To cite this abstract in AMA style:Sachetto ATA, Jensen JR, Santoro ML. Coagulation and Inflammation Genes Are Differently Expressed during the Acquired Coagulation Disorder Induced by Snake Envenomation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/coagulation-and-inflammation-genes-are-differently-expressed-during-the-acquired-coagulation-disorder-induced-by-snake-envenomation/. Accessed January 28, 2022.
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