title: Factor deficiencies in venom-induced consumption coagulopathy resulting from Australian elapid envenomation: Australian Snakebite Project (ASP-10).
abstract: BACKGROUND
  Limited information exists on the dynamics of hemostasis in patients with venom-induced consumption coagulopathy (VICC) from snake envenomation.
  
  
  OBJECTIVE
  The aim of the present study was to investigate specific factor deficiencies and their time course in Australasian elapid envenomation.
  
  
  METHODS
  We measured coagulation parameters and factor concentrations in patients recruited to the Australian Snakebite Project, an observational cohort study. There were 112 patients with complete VICC, defined as an international normalized ratio (INR) > 3, and 18 with partial VICC. Serial citrated plasma samples were collected from 0.5 to 60 h post-bite. INR, activated partial thromboplastin time (aPTT), coagulation factors (F)I, II, V, VII, VIII, IX, X, von Willebrand factor antigen (VWF:Ag) and D-dimer concentrations were measured.
  
  
  RESULTS
  Complete VICC was characterized by near/total depletion of fibrinogen, FV and FVIII, with an INR and aPTT that exceeded the upper limits of detection, within 2 h of snakebite. Prothrombin levels never fell below 60% of normal, suggesting that the toxins were rapidly eliminated or inactivated and re-synthesis of clotting factors occurred irrespective of antivenom. Partial VICC caused limited depletion of fibrinogen and FV, and almost complete consumption of FVIII. Onset of VICC was more rapid with brown snake (Pseudonaja spp.) venom, which contains a group C prothrombin activator toxin, compared with the tiger snake group, which contains a group D prothrombin activator toxin and requires human FVa formation. Resolution of VICC occurred within 24-36 h irrespective of snake type.
  
  
  CONCLUSIONS
  These results suggest that Australasian elapid prothrombin activators have a potent but short duration of action. Antivenom is unlikely to be administered in time to prevent VICC.
authors.affiliation: School of Medicine and Public Health, University of Newcastle, NSW, Australia. geoff.isbister@gmail.com
authors.forename: G K
authors.initials: GK
authors.lastname: Isbister
authors.forename: F E
authors.initials: FE
authors.lastname: Scorgie
authors.forename: M A
authors.initials: MA
authors.lastname: O'Leary
authors.forename: M
authors.initials: M
authors.lastname: Seldon
authors.forename: S G A
authors.initials: SG
authors.lastname: Brown
authors.forename: L F
authors.initials: LF
authors.lastname: Lincz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D001315:Australia; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000209:etiology; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D012909:Snake Bites / Q000097:blood*; D013997:Time Factors; D014688:Venoms
chemical_list: D000997:Antivenins; D001779:Blood Coagulation Factors; D014688:Venoms