Prothrombin Complex Concentrates are Superior to Fresh Frozen Plasma for Emergency Reversal of Vitamin K Antagonists: A Meta-Analysis in 2606 Subjects

Background Urgent reversal of vitamin K antagonists (VKAs) is required for major bleeding or urgent surgery by intravenous vitamin K with either prothrombin complex concentrates (PCCs) or fresh frozen plasma (FFP). However, there is lack of consensus regarding the superiority of either reversal agent. We sought to compare the performance of PCC and FFP in urgent reversal of VKA. Methods A meta-analysis was conducted up to November 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results Seventeen studies comprising 2606 participants met the inclusion criteria. Compared with FFP treatment, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.60, 95% CI 0.40-0.90, p = 0.01), better reversal of INR (OR 7.36, 95% CI 4.18-12.98; p < 0.00001) and lower risk of at least one treatment-related adverse event (OR 0.45, 95% CI 0.26-0.80, p = 0.006). Among patients with VKA-associated intracranial haemorrhage, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.58, 95% CI 0.35-0.94, p = 0.03) and better reversal of INR (OR 6.52, 95% CI 1.66-25.59, p = 0.007). There were no differences between these two agents in thrombogenicity, requirement for and quantity of red blood cell transfusions, all adverse events, fluid overload or disability on discharge or at 90 days. Conclusions As an agent for urgent reversal of VKA, PCC outperforms FFP in 90-day all-cause mortality including those with VKA-related intracranial haemorrhage, INR reversal and treatment-related adverse events.