Effectiveness of fresh frozen plasma in the resolution of coagulopathy in human patients following hemotoxic snakebites: a systematic review and meta-analysis
Effectiveness of fresh frozen plasma in the resolution of coagulopathy in human patients following hemotoxic snakebites: a systematic review and meta-analysis
Abstract
Objective
To assess the effectiveness of fresh frozen plasma (FFP) as an adjunctive treatment to anti-snake venom (ASV) for resolving venom-induced consumption coagulopathy (VICC) in patients with hemotoxic snakebites.
Design
Systematic review and meta-analysis, reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Data sources
MEDLINE, ScienceDirect, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Europe PubMed Central, Directory of Open Access Journals, Google Scholar, ClinicalTrials.gov and WHO ICTRP were searched from inception to 30 July 2025 using multiple terms, including ‘fresh frozen plasma’, ‘plasma transfusion’, ‘hemotoxic snakebite’, ‘vasculotoxic snakebite’, ‘coagulopathy in snake bite’ and ‘venom-induced consumption coagulopathy’.
Eligibility criteria
We included randomised controlled trials and observational studies in the English language comparing antivenom alone with antivenom with FFP in patients with hemotoxic snakebite-induced coagulopathy. Studies must have reported coagulopathy resolution as measured by international normalised ratio (INR) normalisation or 20 min whole blood clotting test (WBCT) correction. Non-English publications, case reports, case series, reviews, conference abstracts, preclinical studies and studies lacking full-text availability or without quantitative INR or WBCT outcome data were excluded.
Data extraction and synthesis
Two independent reviewers extracted data using standardised extraction forms and assessed risk of bias using the Cochrane Risk of Bias 2 tool for randomised controlled trials and the Newcastle–Ottawa scale for observational studies. Data were pooled using random-effects meta-analysis and expressed as ORs with 95% CIs. Statistical heterogeneity was assessed using I² statistics, and the certainty of evidence was evaluated using the Grades of Recommendation, Assessment, Development and Evaluation approach.
Results
Four studies involving 370 patients were included (two randomised controlled trials and two prospective observational studies). The pooled analysis demonstrated that adjunctive FFP significantly increased the likelihood of coagulopathy resolution compared with antivenom alone (OR=7.71, 95% CI 2.20 to 27.04, p=0.001). No evidence of a significant difference in mortality was observed between groups (OR=4.96, 95% CI 0.55 to 44.60, p=0.15). High heterogeneity was noted among the four studies (I² = 67%), but a subgroup analysis of three studies, which used INR as the outcome assessment method, showed lower heterogeneity (I² = 25%). Adverse events were inconsistently reported across studies.
Conclusions
FFP as an adjunct to antivenom significantly improves coagulopathy resolution in patients with hemotoxic snakebite-induced coagulopathy. However, the certainty of evidence is very low because of methodological limitations, small sample sizes and significant heterogeneity. Although FFP shows promise for rapid coagulopathy correction, mortality benefits are not established, and it should not replace timely antivenom administration or comprehensive supportive care.
Effectiveness of fresh frozen plasma in the resolution of coagulopathy in human patients following hemotoxic snakebites: a systematic review and meta-analysis