Antivenin Therapy for Rattlesnake and Cottonmouth Envenomation

The previously available antivenin, derived from horse serum product, was antivenin (Crotalidae) polyvalent (ACP). Acute reactions occurred in 20% to 25% of patients, and serum sickness in 50% to 75% of patients treated with the equine product (22).

In December 2000, Crotalidae polyvalent immune Fab (ovine) (CroFab ®; FabAV) became commercially available in the United States. FabAV is derived from sheep hyperimmunized against Crotalus atrox (western diamondback), C. adamanteus (eastern diamondback), C. scutulatus (Mojave rattlesnake), and Agkistrodonpiscivorus (cottonmouth). Similar to digoxin Fab, these antibodies are treated with papain to cleave off the Fc portions of the molecule. The possibility of hypersensitivity reactions still exists, but these reactions may be easily treated and additional Fab antivenom products can be safely given along with histamine receptor blockers and epinephrine as needed (67,68).

FabAV was shown in the clinical studies to be effective when given within 6 hours of snakebite, but recently, FabAV has been shown to be effective starting at 52 hours after envenomation from a rattlesnake (C. concolor). The recommended initial dose is 4 to 6 vials. The patient should be observed for up to 1 hour following the completion of this first dose to determine if initial control has been achieved (complete arrest of local manifestations and return of coagulation tests and systemic signs to normal). If initial control is not achieved by the first dose, an additional dose of 4 to 6 vials should be repeated until initial control of envenomation has been achieved. Recurrence of effects of venom after completion of the FabAV treatment, including limb swelling and hypofibrinogenemia, has been observed. Additional 2-vial doses of FabAV at 6, 12, and 18 hours after achieving initial control has effectively prevented recurrence (68-70).

FabAV can neutralize the toxic effects of all North American crotalidae venoms. Southern Pacific rattlesnake (Crotalus helleri) venom is not one of the four venoms used to produce FabAV. In standard treatment doses though, it was efficacious for bites of this species (71).

Postmarketing experience with FabAV found that control of coagulopathy was difficult, and delayed-onset hematotoxicity was common. Because hypofibrinogenemia and prothrombin time prolongation in patients experiencing rattlesnake bites do not result in spontaneous bleeding, observation might be all that is needed in the absence of active bleeding. When managing coagulopathy and thrombocytopenia, a trend toward normalization of laboratory values might be a more reasonable end point for FabAV treatment than actual attainment of normal reference values. Every effort should be made to repeat coagulopathy studies within 2 to 3 days after treatment with FabAV (72,73).

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