Efficacy and Safety of Recombinant Activated Factor VII versus Activated Prothrombin Complex Concentrate for Bleeding Control in Acquired Haemophilia A: A Systematic Review and Meta-Analysis

Abstract

Introduction:  Acquired haemophilia A is a rare autoimmune coagulopathy with reported mortality of 3.3 to 22 per cent, in which uncontrolled haemorrhage is the principal cause of early death. International guidelines have endorsed both recombinant activated factor VII and activated prothrombin complex concentrate as first-line bypassing therapy without explicit preference, yet the comparative efficacy of these two agents has not previously been quantified by formal meta-analysis.

Methods: A systematic review and random-effects meta-analysis was conducted in line with the PRISMA 2020 guideline. PubMed/MEDLINE, Scopus, and Web of Science Core Collection were searched on 1 May 2026 for primary cohort, registry, and observational comparative studies of adults with acquired haemophilia A treated with recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrate (aPCC). Bleeding-control proportions per arm were converted to Hedges g via the Cox–Hasselblad–Hedges transformation, and were pooled under DerSimonian–Laird and restricted maximum-likelihood random-effects models. As co-primary metrics, pooled risk ratio and pooled risk difference were computed. Risk of bias was appraised with a modified Newcastle–Ottawa Scale, and certainty of evidence was rated with GRADE.

Results: Ten primary studies were retained for qualitative synthesis and nine of these were eligible for quantitative meta-analysis (916 patient-arm data points; rFVIIa arm n = 531; aPCC arm n = 385). Bleeding control was achieved in 474 of 531 patients (89.27 per cent) treated with rFVIIa and 343 of 385 patients (89.09 per cent) treated with aPCC. The pooled Hedges g was 0.026 (95 per cent confidence interval −0.232 to +0.285; p = 0.84). The pooled risk ratio was 1.00 (95 per cent confidence interval 0.95 to 1.06) and the pooled risk difference was +0.18 percentage points (95 per cent confidence interval −4.5 to +4.6). Heterogeneity was low (I² = 5.8 per cent; τ² = 0.009). Findings were robust across leave-one-out, EACH2-restricted, regional, design, and quality-stratified subgroup analyses. The certainty of evidence was rated low.

Conclusion: rFVIIa and aPCC produced clinically equivalent bleeding-control rates in adults with acquired haemophilia A. Selection should be informed by availability, acquisition cost, and individual safety profile rather than by presumed efficacy advantage of either agent.