# Bite First, Bleed Later: How Philippine Trimeresurus Pit Viper Venoms Hijack Blood Clotting

## TL;DR

This study examines how Philippine pit viper venoms disrupt blood clotting and finds that non-specific antivenoms may help treat envenomation.

## Contribution

The study is the first to profile coagulopathic effects of Philippine pit viper venoms and test antivenom cross-neutralization.

## Key findings

- Venoms from Trimeresurus flavomaculatus and Trimeresurus mcgregori cause weak, transient fibrin clots and deplete fibrinogen.
- Venoms inhibit clotting factors fIXa and fXa, contributing to anticoagulation.
- Thai antivenoms, especially polyvalent ones, effectively neutralize venom effects and restore fibrinogen clotting.

## Abstract

The Philippines has a high diversity of venomous snake species, but there is minimal information on their envenomation effects. This is evidenced by the small number of case reports, the poor reporting of envenomation cases, and the absence of specific antivenoms apart from one against the Philippine cobra (Naja philippinensis). This study sought to profile the action of selected Philippine pit viper venoms on blood coagulation and to investigate whether commercially available non-specific antivenoms can provide adequate protection against these venoms. Venom from the pit vipers Trimeresurus flavomaculatus and Trimeresurus mcgregori were subjected to coagulation assays, antivenom cross-neutralization tests, and thromboelastography. Venoms from both species were able to clot human plasma and isolated human fibrinogen. Consistent with pseudo-procoagulant/thrombin-like activity, the resulting fibrin clots were weak and transient, thereby contributing to net anticoagulation through the depletion of fibrinogen levels. Clotting factors fIXa and fXa were also inhibited by the venoms, further contributing to the net anticoagulant activity. Monovalent and polyvalent antivenoms from the Thai Red Cross Society were effective against both venoms, indicating cross-neutralization of venom toxins; the polyvalent antivenom was able to rescue fibrinogen clotting to a greater degree than the monovalent antivenom. Our findings highlight the coagulopathic effects of these pit viper venoms and suggest the utility of procuring the non-specific antivenoms for areas in the Philippines with a high risk for pit viper envenomation.