In Reply to Michael Levine, Published December 2022, Pages 525-572

Abstract

We read the response by Drs. Watkins and Smelski1Watkins S. Smelski G. Epic fail? Try again.Ann Emerg Med. 2023; 81: 765-766Abstract Full Text Full Text PDF Google Scholar and appreciate their interest in our manuscript. Drs. Watkins and Smelski discuss that there is no universal definition of thrombocytopenia. Although we generally agree, we do feel that most clinicians would define platelets of 102,000/μL, and certainly 80,000/μL, as thrombocytopenic. The landmark study comparing Crotalidae polyvalent immune Fab (ovine) [marketed as CroFab®; FabAV] with crotalidae immune F(ab’)2 (equine) [marketed as Anavip®; F(ab’)2AV] defined thrombocytopenia as platelet counts less than 150,000/μL.2Bush S.P. Ruha A.M. Seifert S.A. et al.Comparison of F(ab’)2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial.Clin Toxicol. 2015; 53: 37-45Crossref PubMed Scopus (70) Google Scholar This was supported by another study by Dr. Smelski.3Dudley S. Smelski G. Massey D.J. et al.Fashionably late: A characterization of late coagulopathies in rattlesnake envenomations between Fab and F(ab’)2 antivenoms.Toxicon. 2022; 212: 49-54Crossref Scopus (0) Google Scholar Drs. Smelski and Watkins also mention that some patients have resolution of thrombocytopenia with a single dose of antivenom and others need multiple doses. Furthermore, they questioned if the inability to achieve control was the result of several smaller doses rather than a few larger doses. One of the advantages of F(ab’)2AV compared with FabAV is the longer half-life. Our patient received 52 vials of F(ab’)2AV in 44 hours. In fact, one reviewer on our original submission commented that the dose was “large (one would suggest excessive) amount of antivenom.” We agree with that statement. Thus, it is highly unlikely that underdosing was the reason for our inability to achieve control. Even with smaller aliquots, at the end of 44 hours, there should have been more than enough circulating antivenom to have achieved a desirable effect given the antivenom’s long half-life. We are concerned that Drs. Smelski and Watson are confusing early and late hematologic toxicity. These are entirely different entities, and achieving control has nothing to do with late hematologic toxicity. We cannot comment on unpublished data but would caution against using unpublished data without knowledge of total antivenom dose to make determinations. As stated, many patients respond to one dose, whereas others may need multiple doses. Thus, it is difficult to comment on unpublished data without knowing total antivenom doses. However, if one-third of patients exhibit inadequate response to an appropriate dose of antivenom, that should be published. In addition, Drs. Watkins and Smelski commented that their unpublished data included 23 years of experience. Most of that 23 years would have nearly certainly involved the use of FabAV, not F(ab’)2AV, as was used in this case. The latter was not available for use until recently. Lastly, drawing any conclusions from Arizona data to this case report should be limited because the southern pacific rattlesnake, C. helleri, is not found in Arizona.