Antivenom

Anti-venom: Alpha-gal is present in anti-venom formulations because these purified fragments are derived from venom-immunized non-primate mammals. There has been at least one case report of an acute reaction to CroFab in a patient with AGS. Despite this report, we advise administration of CroFab if clinically indicated even in patients with AGS as the risk of reaction to anti-venom has not been established in this scenario and may be quite low while, on the contrary, the therapeutic benefit of anti-venom is high.

Antivenoms are produced in horses and sheep (nonprimate mammals) as polyclonal IgG preparations. Previous studies have reported IgE to a-GAL and increased rates of hypersensitivity reactions to Fab administration. Investigators noticed higher rates of hypersensitivity reactions to Fab in Virginia compared to Arizona, where a-GAL sensitization would be rare because it lacks the tick A. americanum. An abstract from the manufacturer of Fab shows that both Fab and F(ab’)2 antivenoms contain a-GAL. Quantitative analysis of the western blots suggested approximately 3-fold more a-GAL was present on F(ab’)2 compared to Fab antivenom per unit weight.
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In this study, we demonstrate a high frequency of adverse drug reactions (37.8%) and presumed anaphylaxis (21.6%) in subjects receiving F(ab’)2 in Arkansas. Other national and regional studies (specifically from the southwestern United States) report that 0 to 2.5% of patients receiving F(ab’)2 experienced immediate hypersensitivity reactions.2,3 Our data also indicate that 5.9% of the subjects had any adverse drug reaction to the Fab antivenom. These findings align with those from Virginia, Arkansas, and Oklahoma, all states with high rates of a-GAL sensitization.
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Notably, subjects with adverse drug reactions to snake antivenom with IgE testing available in the poison control narratives were all positive for a-GAL.
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However, the relationship between adverse drug reaction propensity and severity remains unclear. Only 1 subject with a positive IgE for a-GAL had a history of allergic responses to red meat. The other 4 subjects with a positive IgE for a-GAL and adverse drug reactions to F(ab’)2 or Fab were reportedly consuming red meat without symptoms.

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These data suggest that exposure to a-GAL antigen in the bloodstream (through intravenous injection) could cause anaphylaxis, even when oral exposure to red meat does not occur.

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In conclusion, our findings demonstrate a high rate of adverse drug reactions and presumed anaphylaxis to crotaline antivenoms in an area where a-GAL IgE sensitization is common. In our cohort, reactions to F(ab’)2 were more common than for Fab antivenoms, but more work is needed with prospective studies to evaluate these outcomes. Although administering antivenoms remains essential in managing some snake envenomations, clinicians practicing in a-GAL endemic regions may wish to exercise increased vigilance and prepare for adverse drug reactions and anaphylaxis, especially when treating patients with a history of red meat allergy.

Recent evidence from our group in collaboration with Dr. Joshua Kennedy in Little Rock shows that ANAVIP has far greater activity than CroFab in the basophil activation test (BAT) using blood taken from patients with AGS [77] (Figure 7).

If an envenomation requires antivenom, you treat with antivenom. There is no absolute contraindication.

All antivenoms have alpha-gal to some extent. We have two options when treating an AGS patient with antivenom. We can monitor really carefully and treat if/when signs and symptoms develop, or we can pre-medicate with antihistamines +/- steroids with epinephrine available. You never want to withhold antivenom when it is really necessary. We can treat an allergic reaction.