title: A randomized controlled trial of fresh frozen plasma for treating venom-induced consumption coagulopathy in cases of Australian snakebite (ASP-18).
abstract: BACKGROUND
  Venom-induced consumption coagulopathy (VICC) is a major effect of snake envenoming.
  
  
  OBJECTIVE
  To investigate whether fresh frozen plasma (FFP) given after antivenom resulted in more rapid correction of coagulation.
  
  
  METHODS
  This was a multicenter open-label randomized controlled trial in patients with VICC of FFP vs. no FFP within 4 h of antivenom administration. Patients (> 2 years) recruited to the Australian snakebite project with VICC (International Normalized Ratio [INR] > 3) were eligible. Patients were randomized 2 : 1 to receive FFP or no FFP. The primary outcome was the proportion with an INR of < 2 at 6 h after antivenom administration. Secondary outcomes included time from antivenom administration to discharge, adverse effects, major hemorrhage, and death.
  
  
  RESULTS
  Of 70 eligible patients, 65 consented to be randomized: 41 to FFP, and 24 to no FFP. Six hours after antivenom administration, more patients randomized to FFP had an INR of < 2 (30/41 [73%] vs. 6/24 [25%]; absolute difference, 48%; 95% confidence interval 23-73%; P = 0.0002). The median time from antivenom administration to discharge was similar (34 h, range 14-230 h vs. 39 h, range 14-321 h; P = 0.44). Seven patients developed systemic hypersensitivity reactions after antivenom administration - two mild and one severe (FFP arm), and three mild and one severe (no FFP). One serious adverse event (intracranial hemorrhage and death) occurred in an FFP patient with pre-existing hypertension, who was hypertensive on admission, and developed a headache 6 h after FFP administration. Post hoc analysis showed that the median time from bite to FFP administration was significantly shorter for non-responders to FFP than for responders (4.7 h, interquartile range [IQR] 4.2-6.7 h vs. 7.3 h, IQR 6.1-8 h; P = 0.002).
  
  
  CONCLUSIONS
  FFP administration after antivenom administration results in more rapid restoration of clotting function in most patients, but no decrease in discharge time. Early FFP administration (< 6-8 h) post-bite is less likely to be effective.
authors.affiliation: Department of Clinical Toxicology and Pharmacology, School of Medicine and Public Health, University of Newcastle, Calvary Mater Newcastle, Newcastle, NSW, Australia. geoff.isbister@gmail.com
authors.forename: G K
authors.initials: GK
authors.lastname: Isbister
authors.forename: N A
authors.initials: NA
authors.lastname: Buckley
authors.forename: C B
authors.initials: CB
authors.lastname: Page
authors.forename: F E
authors.initials: FE
authors.lastname: Scorgie
authors.forename: L F
authors.initials: LF
authors.lastname: Lincz
authors.forename: M
authors.initials: M
authors.lastname: Seldon
authors.forename: S G A
authors.initials: SG
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000997:Antivenins / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D001777:Blood Coagulation / Q000187:drug effects*; D001803:Blood Transfusion / Q000379:methods*; D003131:Combined Modality Therapy; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D019934:International Normalized Ratio; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010351:Patient Discharge; D010949:Plasma; D012909:Snake Bites / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D012910:Snake Venoms; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000997:Antivenins; D012910:Snake Venoms
keywords: antivenom; consumption coagulopathy; envenomation; plasma; snakebites