To the Editor:
We read with great interest the study “Comparison of F(ab’)2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial.”Citation1 The authors designed a rigorous phase three study; however, their work conjures several questions.
This is a superiority trial in which the authors seek to demonstrate that F(ab’)2 is more efficient than Fab because it has a longer half-life in the serum compartment. They conclude that F(ab’)2 is superior to Fab in preventing delayed coagulopathy with a reported number needed to treat of 4–5.Citation1 Delayed coagulopathy was defined mainly by laboratory abnormalities including a platelet count less than 150,000/mm3 or a fibrinogen level less than 150 mg/dL. The authors do not report any evidence of active bleeding in these patients and the lowest platelet count reported is 40,000/mm3. Thus, the clinical relevance of envenomation that induces thrombocytopenia without any evidence of bleeding and with a platelet level higher than the threshold that usually prompts platelet transfusion is in question. Furthermore, in one systematic review that evaluates delayed bleeding in snakebite envenomation, medically significant, delayed bleeding is uncommon in victims treated with Fab.Citation2 Is this new antidote really necessary?
The authors also report that six of 43 patients in the F(ab’)2/F(ab’)2 group and one of 37 in the F(ab’)2/placebo group experience serious adverse events, but they do not provide a description of these adverse events. One patient in the F(ab’)2/F(ab’)2 died reportedly from injuries of a motor vehicle collision—could this have been from the complications of unrecognized delayed coagulopathy? A list of these serious adverse events would be useful information for clinicians who are considering to treat patients with F(ab’)2.
We hope that evaluating the above points proves beneficial in the process of treating cases of pit viper envenomation and choosing the best management strategy for each individual patient.
Declaration of interest
The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References
- Bush SP, Ruha AM, Seifert SA, Morgan DL, Lewis BJ, Arnold TC, et al. Comparison of F(ab’)2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial. Clin Toxicol (Phila) 2015; 53:37–45.
- Lavonas EJ, Khatri V, Daugherty C, Bucher-Bartelson B, King T, Dart RC. Medically significant late bleeding after treated crotaline envenomation: a systematic review. Ann Emerg Med 2014; 63: 71–78.e1.