Coagulation parameters in copperhead compared to other Crotalinae envenomation: secondary analysis of the F(ab’)₂ versus Fab antivenom trial

Context: Coagulation derangements in copperhead envenomation are considered less severe than other crotaline envenomations, resulting in recommendations to limit both coagulation testing and antivenom treatment. A prospective, blinded, multicenter, randomized clinical trial comparing the effectiveness of F(ab’)₂ versus Fab antivenom in crotaline envenomation patients was completed in 2011. We determined the difference between coagulation parameters in copperhead compared to other crotaline envenomations. Methods: We performed a post hoc analysis comparing the coagulation parameters (platelets and fibrinogen) prospectively obtained in the aforementioned trial. All the patients received antivenom in one of three treatment arms [F(ab’)₂ with maintenance, F(ab’)₂ with placebo maintenance, or Fab with maintenance]. Coagulation parameters were measured at pretreatment baseline, during acute hospitalization, day 5, day 8, and day 15 post-envenomation. Mean platelet count and fibrinogen levels for the copperhead and other crotaline groups were compared. The platelet and fibrinogen point estimates with distribution are presented graphically over time. Results: 122 patients were enrolled in the study. There were 22 patients with copperhead envenomation, 93 with other crotaline envenomations, and 7 that could not be definitively determined. The mean age was 42 (SD 20) years. There was a minor pretreatment difference in mean baseline platelet count between the copperhead group (246 × 109/L 95% CI 215, 277) compared to other crotaline envenomation patients (184 × 109/L 95% CI 167, 202). There was a modest pretreatment difference in mean fibrinogen level between copperhead patients (345 mg/dL 95% CI 277, 415) and other crotaline patients (261mg/dL 95% CI 241, 281). Pretreatment coagulation parameter means were normal and converged post treatment. Conclusion: On average, copperhead envenomations have less severe initial coagulation derangements. However, in mild envenomations, differences in laboratory values are minimal and there is substantial variation in individual patients regardless of species. Species alone should not be used to determine the need for laboratory testing or treatment in crotaline snakebite.