Fashionably late: A characterization of late coagulopathies in rattlesnake envenomations between Fab and F(ab’)2 antivenoms

Abstract

BackgroundRattlesnake envenomation may lead to a multitude of clinical effects, including a late onset hemorrhage. Laboratory values such as platelets and fibrinogen are commonly used to assess the risk of developing a life-threatening bleed. To date, no specific threshold has been identified that links a lab value to the risk of bleeding. This has led to widespread practice variability among clinicians managing snake bites. In assessing risk for patients, we apply the concept that the more abnormal the lab values are, the higher the risk probably is. Late onset coagulopathies pose a unique clinical challenge because they indicate the potential risk for a life-threatening hemorrhage, yet they have been identified after hospital discharge. There are currently two antivenom (AV) products on the US market to treat rattlesnake envenomations, a Fab product, CroFab® (BTG, UK) and a F (ab’)2 product, Anavip® (Bioclon, Mexico). ObjectiveThis study intended to characterize the incidence and severity of late coagulopathies reported to a Regional Poison Center (RPC) and hypothesized that late coagulopathies occur at rates higher than previously reported in the literature. Additionally, we sought to compare rates of late coagulopathy between Fab and F (ab’)2 AV. MethodsThe investigators performed an in-depth review of all suspected snakebite envenomations from 2018 to 2020 that presented to an Arizona healthcare facility in the RPC's catchment area between January 2018 through December of 2020. Patients were excluded from analysis if they did not receive any antivenom, had an incomplete medical record with the APDIC, were diagnosed as something other than a rattlesnake bite or had a known medical history that clouded the diagnosis or assessment of a rattlesnake envenomation. ResultsIn total, 522 records were reviewed of which 283 patients met the inclusion criteria. There were 149 patients who received Fab AV and 134 who received F (ab’)2. No significant baseline or demographic differences existed between the groups. 95 of the 283 patients developed a late onset coagulopathy. 39% of the late onset coagulopathies were delayed, 32% were recurrent and 29% were persistent. When comparing the two different AV products, delayed or recurrent coagulopathies occurred in 36% of Fab AV- and 10% of F (ab’)2 treated patients. Persistent coagulopathies occurred in 17% of Fab AV- and 8% of F (ab’)2 treated patients. Interestingly, there were zero cases of late hypofibrinogenemia in any of the 134 F (ab’)2 treated patients compared to 26% of all Fab treated ones. The average onset of late coagulopathy post-bite was 8 days for Fab AV and 7 for F (ab’)2. ConclusionThe results from this study suggest the total rate of late onset coagulopathies may be underestimated. Additionally, our results suggest the potential that F (ab’)2 AV may be associated with fewer late onset coagulopathies, especially late onset hypofibrinogenemia.