Clinically applicable laboratory end-points for treating snakebite coagulopathy.
OBJECTIVE
To determine which coagulation tests best reflect the return of clotting function after snakebite venom induced consumptive coagulopathy (VICC).


METHODS
Cases of snake envenoming were prospectively recruited to the Australian Snakebite Project (ASP). This study examined cases with VICC treated with antivenom and monitored with serial measures of clottable fibrinogen, prothrombin time (PT) and activated partial thromboplastin time (aPTT). The main outcome measures were times from antivenom treatment until a moderate recovery in the PT (<24 seconds), a measurable aPTT and detectable fibrinogen.


RESULTS
Forty-six cases were examined, including 27 brown snakes with proven complete venom neutralisation by antivenom in 25, 16 tiger snake group and three taipans. The times from initial antivenom dose to recovery were: PT<24 seconds, median 9.2 hours (IQR 6.2-11.3 hours); measurable aPTT, median 5.2 hours (IQR 3.4-8.8 hours); and detectable fibrinogen, median 8.8 hours (IQR 5.4-11.7 hours). In 10 cases where fibrinogen was detectable earlier than recovery of the PT, the mean fibrinogen was 0.25 g/L (SD 0.10) compared with 0.6 g/L (SD 0.28) in the remaining 36 cases (p<0.0001), reflecting differing sensitivities between laboratories. In only three patients (7%) was fibrinogen measurable before the other two outcomes, using highly sensitive fibrinogen assays.


CONCLUSIONS
The combination of the PT and aPTT is an effective, clinically available and cost-effective end-point for treating VICC, and may take longer to return to normal after venom neutralisation than previously believed. The fibrinogen assays that are generally in use do not provide any additional useful information.
Isbister
Geoffrey K
GK
Tropical Toxinology Unit, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia. geoffrey.isbister@menzies.edu.au
Williams
Vaughan
V
Brown
Simon G A
SG
White
Julian
J
Currie
Bart J
BJ
D000328:Adult; D000997:Antivenins / Q000627:therapeutic use; D001777:Blood Coagulation / Q000502:physiology; D001780:Blood Coagulation Tests / Q000191:economics / Q000379:methods*; D003362:Cost-Benefit Analysis; D023381:Endpoint Determination / Q000191:economics / Q000379:methods*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time / Q000191:economics / Q000379:methods; D011446:Prospective Studies; D011517:Prothrombin Time / Q000191:economics / Q000379:methods; D012680:Sensitivity and Specificity; D012909:Snake Bites / Q000097:blood* / Q000628:therapy*
D000997:Antivenins; D005340:Fibrinogen