A Web of Coagulotoxicity: Failure of Antivenom to Neutralize the Destructive (Non-Clotting) Fibrinogenolytic Activity of <i>Loxosceles</i> and <i>Sicarius</i> Spider Venoms

• Main Authors: Dwin Grashof, Christina N. Zdenek, James S. Dobson, Nicholas J. Youngman, Francisco Coimbra, Melisa Benard-Valle, Alejandro Alagon, Bryan G. Fry
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Series: Toxins
• Subjects: venom; antivenom; fibrinogen; coagulopathy; spider
• Online Access: https://www.mdpi.com/2072-6651/12/2/91

Envenomations are complex medical emergencies that can have a range of symptoms and sequelae. The only specific, scientifically-validated treatment for envenomation is antivenom administration, which is designed to alleviate venom effects. A paucity of efficacy testing exists for numerous antivenoms worldwide, and understanding venom effects and venom potency can help identify antivenom improvement options. Some spider venoms can produce debilitating injuries or even death, yet have been largely neglected in venom and antivenom studies because of the low venom yields. Coagulation disturbances have been particularly under studied due to difficulties in working with blood and the coagulation cascade. These circumstances have resulted in suboptimal spider bite treatment for medically significant spider genera such as <i>Loxosceles</i> and <i>Sicarius</i>. This study identifies and quantifies the anticoagulant effects produced by venoms of three <i>Loxoscles</i> species (<i>L. reclusa</i>, <i>L. boneti,</i> and <i>L. laeta</i>) and that of <i>Sicarius terrosus</i>. We showed that the venoms of all studied species are able to cleave the fibrinogen A&#945;-chain with varying degrees of potency, with <i>L. reclusa</i> and <i>S. terrosus</i> venom cleaving the A&#945;-chain most rapidly. Thromboelastography analysis revealed that only <i>L. reclusa</i> venom is able to reduce clot strength, thereby presumably causing anticoagulant effects in the patient. Using the same thromboelastography assays, antivenom efficacy tests revealed that the commonly used <i>Loxoscles-</i>specific SMase D recombinant based antivenom failed to neutralize the anticoagulant effects produced by <i>Loxosceles</i> venom. This study demonstrates the fibrinogenolytic activity of <i>Loxosceles</i> and <i>Sicarius</i> venom and the neutralization failure of <i>Loxosceles</i> antivenom, thus providing impetus for antivenom improvement.