Abstract Number: PB1671
Meeting: ISTH 2020 Congress
Background: Thrombocytopenia is frequently encountered in patients bitten by Bothrops jararaca snakes. Although various proteins that activate or inhibit platelets in vitro have been isolated and characterized from B. jararaca venom (BjV), it has not been determined which ones account for the development of thrombocytopenia in vivo. We showed previously that BjV incubated with catalytic inhibitors of metalloproteinases or serine proteinases, and/or anti-botrocetin (a VWF-dependent C-type lectin-like protein, CTLP) antibodies, and injected in rats and mice, still evoked platelet consumption.
Aims: To identify and characterize BjV toxins that cause thrombocytopenia in vivo.
Methods: Proteins were purified using ultrafiltration and liquid chromatography, and their primary structures were characterized by mass spectrometry. The biological activity of venom fractions was tested in vivo and in vitro. All procedures involving the use of animals or human donors were approved by IACUC from Instituto Butantan and Plataforma Brasil, respectively.
Results: By ultrafiltration, we observed that only venom components passing 50-kDa molecular weight cutoff membranes caused thrombocytopenia in mice, and this activity was completely independent of the hemorrhagic or coagulant activity of BjV. Ultrafiltered proteins were further separated by hydrophobic interaction, ion exchange and reversed-phase chromatography. Two 30-kDa proteins that induced thrombocytopenia in mice were isolated, and they showed primary structures similar to CTLPs, and were called CTLP-D and CTLP-E. Surprisingly, they did not induce platelet aggregation in platelet rich plasma or whole blood from humans or mice. Currently, experiments are being carried out to understand the mechanisms of action of CTLP-D and -E.
Conclusions: These findings reinforce previous results that thrombocytopenia occurs simultaneously to hemorrhage and coagulation following snakebites, but they are independent phenomena. Such results are important to understand the pathophysiology of B. jararaca envenomation, particularly of hemostatic disorders that may complicate the clinical picture of bitten patients. Funding: FAPESP, CNPq, CONICET, CAPES, Fundação Butantan.
To cite this abstract in AMA style:Sachetto ATA, Peichoto ME, Rosa JG, Torquato RJS, Silva DT, Serrano SMT, Tanaka AS, Santoro ML. C-type Lectin-like Proteins D and E, but Not Botrocetin, Cause Thrombocytopenia during Bothrops jararaca Snakebite Envenomation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/c-type-lectin-like-proteins-d-and-e-but-not-botrocetin-cause-thrombocytopenia-during-bothrops-jararaca-snakebite-envenomation/. Accessed February 21, 2024.
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