Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients.

Tihana Kurtović,Miran Brvar,Damjan Grenc,Beata Halassy,Svjetlana Karabuva,Mojca Dobaja Borak,Boris Lukšić,Igor Križaj

doi:10.3390/toxins13040279

Abstract

Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab’)2 fragments (European viper venom antiserum, also called “Zagreb” antivenom) in V. ammodytes-envenomed patients. This was a prospective study of V. ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab’)2 fragments that were given intramuscularly only on admission. F(ab’)2 fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 h, respectively). In V. ammodytes-envenomed patients, the intramuscular use of specific F(ab’)2 fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented.

Highlights

Snake envenoming is a rather uncommon but potentially severe injury in Europe, 1
Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented
F(ab’)2 fragments raised against V. ammodytes venom should be used for patients that are envenomed by V. ammodytes, but Fab fragments raised against V. berus venom could give satisfactory

Summary

Introduction

Snake envenoming is a rather uncommon but potentially severe injury in Europe, 1. Introduction which is estimated to affect 0.4 to 1.1 people per 100,000 population per year [1,2]. Vipera ammodytes (V. ammodytes or nose-horned viper, Figure 1a) is the most dangerous of the which is estimated to affect 0.4 to 1.1 people per 100,000 population per year [1,2]. Figure most and dangerous of the (up to cm), long fangs (up to mm) and venom toxicity induced by proteolytic, haemorrhagic and neurotoxic components [3]. It high venom toxicity induced by proteolytic, haemorrhagic and neurotoxic components [3]. Inhabits southern Europe, mainly the Balkans peninsula, including coastal and central arIt inhabits southern Europe, mainly the Balkans peninsula, including coastal and central eas of Slovenia and Croatia (Figure 1b).

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