A randomized controlled trial of fresh frozen plasma for treating venom-induced consumption coagulopathy in cases of Australian snakebite (ASP-18)

Authors

  • G. K. Isbister,

    Corresponding author
    1. NSW Poisons Information Centre, Sydney Children's Hospital Network, Sydney, NSW
    • Department of Clinical Toxicology and Pharmacology, School of Medicine and Public Health, University of Newcastle, Calvary Mater Newcastle, Newcastle, NSW
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  • N. A. Buckley,

    1. NSW Poisons Information Centre, Sydney Children's Hospital Network, Sydney, NSW
    2. Medical Professorial Unit, Prince of Wales Hospital Medical School, University of New South Wales, Sydney, NSW
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  • C. B. Page,

    1. Department of Clinical Toxicology and Pharmacology, School of Medicine and Public Health, University of Newcastle, Calvary Mater Newcastle, Newcastle, NSW
    2. NSW Poisons Information Centre, Sydney Children's Hospital Network, Sydney, NSW
    3. Emergency Department, Princess Alexandra Hospital, Brisbane, Queensland
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  • F. E. Scorgie,

    1. Hunter Haematology Research Group, Calvary Mater Newcastle, Newcastle, NSW
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  • L. F. Lincz,

    1. Hunter Haematology Research Group, Calvary Mater Newcastle, Newcastle, NSW
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  • M. Seldon,

    1. Hunter Haematology Research Group, Calvary Mater Newcastle, Newcastle, NSW
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  • S. G. A. Brown,

    1. Centre for Clinical Research in Emergency Medicine, Western Australian Institute for Medical Research, Royal Perth Hospital and the University of Western Australia, Perth, WA, Australia
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  • the ASP Investigators


  • Manuscript handled by: I. Pabinger Final decision: F.R. Roseridaal, April 2013

Correspondence: Geoffrey K Isbister, c/o Calvary Mater Newcastle, Edith St, Waratah NSW 2298, Australia.

Tel.: +612 4921 1211; fax: +612 4921 1870.

E-mail: geoff.isbister@gmail.com

Summary

Background

Venom-induced consumption coagulopathy (VICC) is a major effect of snake envenoming.

Objectives

To investigate whether fresh frozen plasma (FFP) given after antivenom resulted in more rapid correction of coagulation.

Patients/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.

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