# Hematological and coagulation alterations and splenic response following Macrovipera lebetina obtusa envenomation: Evaluation of ovine-derived experimental antivenom

## TL;DR

This study examines the effects of Macrovipera lebetina obtusa venom on blood and tissues in animals and tests a sheep-based antivenom's effectiveness.

## Contribution

The study introduces an ovine-derived experimental antivenom and evaluates its partial efficacy against M. l. obtusa envenomation.

## Key findings

- Venom caused hemoconcentration and coagulopathy, with prolonged prothrombin time persisting after antivenom treatment.
- Tissue damage in the spleen and skin, including hemorrhage and lymphoid follicle hyperplasia, lasted up to seven days.
- The experimental antivenom provided partial systemic protection but failed to fully reverse tissue and coagulation abnormalities.

## Abstract

Macrovipera lebetina obtusa
(M. l. obtusa) is the most medically significant viper species in Armenia and the region, responsible for the majority of snakebite cases. This study investigated the hematological, coagulation, and histopathological effects of M. l. obtusa envenomation in rats and mice, and evaluated the therapeutic efficacy of an ovine-derived experimental antivenom. Hematological analysis revealed significant increases in red blood cell (RBC) count and hemoglobin (HGB) concentration following envenomation, suggestive of hemoconcentration likely due to vascular leakage. Coagulation studies demonstrated marked prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT), indicating venom-induced coagulopathy. Notably, PT was more severely affected, and its elevation persisted even after antivenom administration, suggesting incomplete neutralization of venom activity. Histopathological examination of spleen and skin tissues showed progressive structural disruption, including hemorrhage, edema, and lymphoid follicle hyperplasia, which remained evident up to seven days post-envenomation. While the experimental antivenom provided partial systemic protection and improved some hematological parameters, it was unable to reverse the venom-induced tissue and coagulation abnormalities fully. These findings highlight the complex pathophysiology of M. l. obtusa venom and underscore the need for adjunctive therapies targeting vascular integrity and immune regulation in the management of viper envenomation.

The blunt-nosed viper M. l. obtusa (Macrovipera lebetina obtusa) is the most dangerous snake in Armenia and surrounding areas, responsible for most local snakebite cases. Its venom can cause serious blood and tissue damage, which may not be fully reversed even with antivenom. In this study, we examined how the venom affects blood cells, blood clotting, and organ structure in laboratory rats and mice. We also tested an experimental antivenom made from sheep antibodies (ovine-derived) to see how well it could protect against these effects. The venom caused dehydration of the blood (hemoconcentration), likely due to leaky blood vessels, and triggered strong clotting disturbances. One clotting measure, the prothrombin time, stayed abnormal even after antivenom treatment, showing that the venom’s effects were only partly neutralized. Microscopic tissue analysis revealed bleeding, swelling, and immune-related changes in the spleen and skin that lasted for at least a week. While the ovine-derived antivenom improved some blood test results, it could not fully prevent tissue damage or restore normal clotting. These findings show why managing viper bites can be challenging and suggest that additional treatments may be needed alongside antivenom to protect patients.