title: Medically significant late bleeding after treated crotaline envenomation: a systematic review.
abstract: 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.
  
  
  CONCLUSIONS
  Medically significant late bleeding appears to be uncommon in snakebite victims treated with Fab antivenom.
authors.affiliation: Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO; Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO. Electronic address: eric.lavonas@rmpdc.org.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lavonas
authors.affiliation: Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Khatri
authors.affiliation: BTG International, Inc., West Conshohocken, PA.
authors.forename: Claire
authors.initials: C
authors.lastname: Daugherty
authors.affiliation: Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO.
authors.forename: Becki
authors.initials: B
authors.lastname: Bucher-Bartelson
authors.affiliation: BTG International, Inc., West Conshohocken, PA.
authors.forename: Thomas
authors.initials: T
authors.lastname: King
authors.affiliation: Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO; Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Dart
mesh_terms: D000997:Antivenins / Q000009:adverse effects* / Q000627:therapeutic use; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors*; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects* / Q000627:therapeutic use; D012909:Snake Bites / Q000150:complications* / Q000628:therapy
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; C431183:Crotalidae Polyvalent immune Fab; D007140:Immunoglobulin Fab Fragments