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

Abstract

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.

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Funding

The work was supported by the National Key R&D Program of China (2017YFC1307500, 2017YFC1307504) and Science and Technology Project of Huizhou City (2017C0416032).

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Correspondence to Yamei Tang.

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Pan, R., Cheng, J., Lai, K. et al. Efficacy and safety of prothrombin complex concentrate for vitamin K antagonist-associated intracranial hemorrhage: a systematic review and meta-analysis. Neurol Sci 40, 813–827 (2019). https://doi.org/10.1007/s10072-019-3726-x

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  • DOI: https://doi.org/10.1007/s10072-019-3726-x

Keywords

  • Intracranial hemorrhage
  • Vitamin K antagonists
  • Prothrombin complex concentrate
  • Meta-analysis