# Fibrinogen supplementation enhances antivenom efficacy in treating coagulopathy due to hemotoxic snakebite envenoming by Trimeresurus and Agkistrodon species in Yunnan, China

## TL;DR

Adding fibrinogen to antivenom treatment improves coagulopathy recovery and shortens hospital stays in patients bitten by certain snakes in Yunnan, China.

## Contribution

This study demonstrates that fibrinogen supplementation enhances antivenom efficacy in treating snakebite-induced coagulopathy.

## Key findings

- Patients receiving fibrinogen had significantly higher fibrinogen levels closer to the physiological range at discharge.
- The combination therapy reduced hospital stay duration compared to antivenom alone.
- Fibrinogen supplementation improved multiple coagulation parameters in hemotoxic snakebite cases.

## Abstract

Timely administration of antivenom remains the cornerstone of treatment for hemotoxic snakebite envenoming, primarily aimed at neutralizing circulating toxins and halting the progression of venom-induced consumption coagulopathy (VICC), thus facilitating gradual recovery of the hemostatic system. However, immediate access to antivenom is not always possible, and variations in venom composition among snake species, along with individual patient differences, can result in significant morbidity (including persistent complications of coagulopathy) and mortality.

This retrospective study evaluated 116 cases of hemotoxic snakebite envenoming caused by Trimeresurus stejnegeri, T. mucrosquamatus, and Agkistrodon halys at three hospitals in Yunnan Province, China (The First People's Hospital of Yunnan Province 63 cases, The People's Hospital of Linxiang District 28 cases, and The First People's Hospital of Xuanwei City 25 cases). Among these, thirty-three patients consented to receive adjunctive therapy with fibrinogen (Fg) in addition to standard antivenom treatment (Agkistrodon acutus antivenom or Agkistrodon halys antivenom), while the remaining 83 received antivenom alone. Coagulation parameters were measured at admission and discharge. Statistical analyses were performed using IBM SPSS Statistics and GraphPad Prism, employing the Mann-Whitney U test for non-normally distributed data and Student's t-test for normally distributed data.

In the antivenom-only group, significant reductions were observed in prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and D-dimer (DD2) levels (all P < 0.05), accompanied by increases in Fg and fibrin degradation products (FDP; P < 0.05). Patients receiving the combined regimen demonstrated decreases in PT, INR, thrombin time (TT), APTT, FDP, and DD2 (all P < 0.05), along with a significant rise in Fg levels (P < 0.05). Those who received Fg presented with more severe coagulation deficits at baseline. Despite this, by the time of discharge, the median Fg level in the combination group [1.94 (1.52–2.20) g/L] was significantly higher than in the antivenom-only group [0.84 (0.68–1.17) g/L] (P < 0.0001), and closer to the physiological range (2–4 g/L). Moreover, the hospital stay in the combination group (4.88 ± 1.47 days) was significantly shorter than in the antivenom-only group (7.07 ± 2.02 days; P < 0.0001).

These findings suggest that adjunctive Fg supplementation may improve the laboratory parameters of coagulopathy and reduce the length of hospital stay in hemotoxic snakebite envenoming. However, further clinical evaluations are needed to support the use of Fg as an adjuvant in the management of hemotoxic snakebite envenoming.