Snake Venom PLA2 as Anticoagulant Agents: Role of Crotoxin, from Crotalus durissus Rattlesnake, in Hemostasis.
Lisele Maria Brasileiro-Martins, Greene Dias Marques, Jéssica Burlamaque Maciel, Márcia Neiva, Thaís Pinto Nascimento, David Jose Estrada Reyes, Alessandro Júnio Campelo Feitosa, Sofia Angiole-Cavalcante, Priscila Ferreira de Aquino, Jacqueline de Almeida Gonçalves Sachett, Wuelton Marcelo Monteiro, Marco Aurélio Sartim
Abstract
Open AccessSnake venoms are rich sources of bioactive molecules that modulate hemostasis and, among these, anticoagulant snake venom phospholipases A2 (sPLA2) are found in a range of snake venoms. Crotoxin (CTX), from the Crotalus durissus rattlesnake, is a heterodimeric PLA2 complex, and literature has reported its mechanisms in anticoagulant activity. The present review revisits the biological roles of anticoagulant sPLA2 and critically examines evidence on CTX in hemostatic regulation, aiming to clarify its mechanisms and therapeutic promise. CTX exerts anticoagulant activity via enzymatic hydrolysis of procoagulant phospholipids and direct interaction with coagulation factors, disrupting key complex assembly. It also counteracts inflammation-induced coagulation by modulating leukocyte- and endothelial-derived mediators, restoring balance among anticoagulant, procoagulant, and fibrinolytic pathways. Effects on platelet function appear comparatively modest, ranging from less potent pro-aggregatory activity to negligible aggregation. The dual anticoagulant and anti-inflammatory properties of CTX highlight its potential as a model for novel antithrombotic agents in hypercoagulable and inflammation-driven disorders, despite toxicological concerns that necessitate cautious pharmacological exploration.