ACMT Toxicology Visual Pearl: Pit Viper

4. Phospholipase A2

Background [1-3]

Bothriechis schlegelii is a venomous snake in the Viperidae family native to the rainforests of Central and South America. Like many of its subfamily, Crotalidae, it shares a triangular-shaped head, elliptical pupils, and retractable fangs associated with venom-producing glands.  The presence of pit-like depressions adjacent to the nostrils serves as a heat-sensing organ for the detection of prey. Snakes that share these “pits” are often grouped together as “pit vipers.” Bothriechis schlegelii is colloquially referred to as the “eyelash pit viper” due to its distinctive supraocular scales that resemble eyelashes (see photo). These scales protect the snake’s eyes from sunlight, rain, and debris, enhancing its ability to hunt in adverse conditions.

Its striking features, vibrant coloration, manageable size (averaging 2-3 feet in length), and generally calm temperament may give the impression of being a desirable household pet. Of the 77 species of exotic snake envenomations represented in the National Poison Data System (NPDS) dataset from 1995-2004, 24.7% were native to Latin America (encompassing Central and South America). Over 50% of cases sought hospital evaluation; 28.7% of which were admitted to the Intensive Care Unit, and 26% were treated with antivenom. The eyelash pit viper contributes to US non-native snakebite envenomations reported to the North American Snake Bite Registry. (4)

What is the mechanism of action of the Eyelash Pit Viper’s venom? [5-11]

Eyelash pit viper venom contains numerous components that are cytotoxic and coagulopathic:

• Snake Venom Metalloproteinases (SVMPs): Responsible for the destruction of vascular endothelium, leading to hemorrhage and tissue necrosis
• Phospholipase A2 (PLA2): Causes coagulopathy from phospholipid sequestration and tissue damage, and myotoxicity from destruction of cell membranes
• C-type Lectin-Like Proteins (“SNAke C-type LECtinS” or snaclecs): In the early phase, snaclecs bind to glycoprotein 1b platelet receptors and von Willebrand factor, causing microvascular thrombosis followed by inhibition of thrombin and clotting factor inactivation, resulting in late phase hypocoagulability.
• Serine Proteases: Induce edema, fibrinolysis, platelet aggregation, and coagulopathy by binding to plasma proteins such as fibrinogen.

What is the initial management for pit viper envenomation? [12-15]

• Close monitoring of local swelling and progression
  • Hourly measurements of the affected area
• Close monitoring for the development of systemic symptoms such as hypotension, dyspnea, vomiting, and diarrhea
• Elevation of extremities to at least 45 degrees and in full extension
• Removal of constriction points, such as jewelry
• Update tetanus if needed
• Laboratory evaluation for coagulopathy, including CBC with platelets, PT/INR, and fibrinogen
• For exotic snake species, antivenom can be located via the AntiVenom Index (Antivenom Index) accessible through your local poison control center or Association of Zoos and Aquariums (AZA) member institutions.
• Some exotic snake owners may stock their own personal antivenom after completing an FDA BB-IND. They may bring this supply for pharmacy verification upon presentation.
• North American Pit Vipers can be treated with Crotalidae polyvalent immune Fab (CroFab) and Crotalidae immune F(ab’)₂ (ANAVIP), and these have also been used successfully for non-native pit vipers.
  • CroFab (Crotalidae polyvalent immune Fab): A polyvalent, ovine-derived antivenom that is derived from Eastern diamondback rattlesnake (Crotalus adamanteus), Western diamondback rattlesnake (Crotalus atrox), cottonmouth (Agkistrodon piscivorus), and Mojave rattlesnake (Crotalus scutulatus).
    • Acute and delayed hypersensitivity reactions reported
    • Papaya allergy is a relative contraindication due to papain use in production
  • ANAVIP (Crotalidae immune F(ab’)₂): A polyvalent, equine-derived antivenom derived from Fer-de-lance (Bothrops asper) and the Central American rattlesnake (Crotalus simus).
    • Acute and delayed hypersensitivity reactions reported
    • Longer half-life relative to CroFab, which may prevent rebound coagulopathy
  • Indications for antivenom:
    • Progression of swelling
    • Significant coagulopathy or thrombocytopenia
    • Hemodynamic compromise
  • Timely administration of antivenom will not reverse the observed clinical features but may mitigate the progression of symptoms.
  • Consultation with a medical toxicologist is recommended, as they can assist with antivenom acquisition and guide the appropriate use of antivenom.

Bedside Pearls

• Eyelash pit viper and other non-native, exotic snakes are increasingly implicated in U.S. envenomations.
• The venom causes coagulopathy, tissue damage, and, in some cases, systemic effects such as hypotension
• The Antivenom Index (Antivenom Index) is an important resource for obtaining exotic antivenoms, if required.
• Despite being labeled for North American pit vipers, Crotalidae polyvalent immune Fab (CroFab) and Crotalidae immune F(ab’)₂ (ANAVIP) have been successfully used in non-native pit viper envenomation.