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

Abstract

Venom-induced consumption coagulopathy (VICC) is a major effect of snake envenoming. To investigate whether fresh frozen plasma (FFP) given after antivenom resulted in more rapid correction of coagulation. This was a multicenter open-label randomized controlled trial in patients with VICC of FFP vs. no FFP within 4h of antivenom administration. Patients (>2years) 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 6h after antivenom administration. Secondary outcomes included time from antivenom administration to discharge, adverse effects, major hemorrhage, and death. 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 interval23-73%; P=0.0002). The median time from antivenom administration to discharge was similar (34h, range14-230h vs. 39h, range14-321h; 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 6h after FFP administration. Posthoc analysis showed that the median time from bite to FFP administration was significantly shorter for non-responders to FFP than for responders (4.7h, interquartile range [IQR]4.2-6.7h vs. 7.3h, IQR6.1-8h; P=0.002). 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 (<6-8h) post-bite is less likely to be effective.