Efficacy and safety of prothrombin complex concentrate for vitamin K antagonist-associated intracranial hemorrhage: a systematic review and meta-analysis

Background Prothrombin complex concentrate (PCC) is the treatment of choice in vitamin K antagonist-associated intracranial hemorrhage (VKA-ICH). However, the efficiency and safety associated with their use remain unclear. Aims This study aimed to assess the current evidence of the clinical outcomes in patients with VKA-ICH treated with or without PCC. Summary of review A meta-analysis was conducted. Two randomized controlled trials and 19 observational studies were included. PCC use demonstrated a significant increased likelihood of international normalized ratio (INR) normalization (OR=3.76; 95% CI 1.74-8.12), shortened time to INR correction (MD=-1.30; 95% CI -2.08 to -0.53) and reduction of hematoma expansion (HE) rate (OR=0.37; 95% CI 0.23-0.60). Although PCC use revealed a statistical reduction at 30-day mortality (OR=0.62; 95% CI 0.50-0.78), the result was inconsistent with mortality at discharge (OR=1.03; 95% CI 0.68-1.57) and 90-day follow-up (OR=0.50; 95% CI 0.24-1.07), both of which yielded no significant difference. When subgroup analyses were performed focus on PCC only treatment with FFP, no statistically significant difference was observed in 30-day mortality (OR=0.43; 95% CI 0.11-1.71) as well. Besides, significant difference was not found in neurologic improvement at discharge (OR=1.85; 95% CI 0.32-10.75), 30-day follow-up (OR=3.00; 95% CI 0.93-9.70), or 90-day follow-up (OR=1.55; 95% CI 0.84-2.86). No statistically significant difference was noted in the risk of thromboembolism following PCC administration (OR=0.61; 95% CI 0.23-1.63). Conclusions PCC use for VKA-ICH reversal was associated with a significant reduction in INR and HE rate, without an increased risk of thromboembolic events. However, this reduction was not associated with improvement in neurologic deficits or overall survival. Well-designed randomized trials with special considerations to the aspect are necessary.