Medically significant late bleeding after treated crotaline envenomation: a systematic review

Ann Emerg Med. 2014 Jan;63(1):71-78.e1. doi: 10.1016/j.annemergmed.2013.03.002. Epub 2013 Apr 6.


Study objective: We estimate the proportion of patients with crotaline snake envenomation who are treated with Crotalidae polyvalent immune Fab (ovine) antivenom and who develop medically significant late bleeding.

Methods: We performed a systematic review of all published cohort studies of North American crotaline snake envenomation patients treated with Fab antivenom. We searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to April 30, 2012. Data were extracted by 2 trained researchers. Late bleeding was defined as bleeding that began or recurred after initial control of the envenomation syndrome. Medically significant late bleeding was defined a priori as late bleeding treated with RBC transfusion, vasoactive drug infusion, surgery, or rehospitalization or associated with a hemoglobin decrease of greater than or equal to 3 g/dL, hematocrit decrease of greater than or equal to 8%, disability, or death. Summary incidence and 95% confidence intervals (CIs) were calculated with a random-effects Poisson regression model.

Results: Nineteen unique cohort studies were identified. Four studies collected data prospectively, and in 9 studies, patients were followed actively after hospital discharge. A total of 1,017 subjects were enrolled in these cohort studies. Late bleeding was reported in 9 subjects (0.9%; 95% CI 0.4% to 2.2%), of whom 5 subjects (0.5%; 95% CI 0.1% to 1.7%) had medically significant late bleeding. Three patients received RBC transfusion; no deaths or permanent sequelae were reported. Estimates of risk may be affected by underreporting.

Conclusion: Medically significant late bleeding appears to be uncommon in snakebite victims treated with Fab antivenom.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antivenins / adverse effects*
  • Antivenins / therapeutic use
  • Crotalid Venoms / antagonists & inhibitors*
  • Hemorrhage / etiology*
  • Humans
  • Immunoglobulin Fab Fragments / adverse effects*
  • Immunoglobulin Fab Fragments / therapeutic use
  • Snake Bites / complications*
  • Snake Bites / therapy


  • Antivenins
  • Crotalid Venoms
  • Crotalidae Polyvalent immune Fab
  • Immunoglobulin Fab Fragments