Guideline-Concordant Administration of Prothrombin Complex Concentrate and Vitamin K is Associated with Decreased Mortality in Patients with Severe Bleeding under Vitamin K Antagonist Treatment (EPAHK study)

Purpose: In vitamin K antagonist (VKA)-treated patients with severe haemorrhage, guidelines recommend prompt VKA reversal with prothrombin complex concentrate (PCC) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on 7-day mortality. Methods: Datas from consecutive patients treated with were prospectively collected in 44 emergency departments. Type of haemorrhage, coagulation parameters, type of treatment and 7day mortality were recorded. Guideline-concordant administration of PCC and vitamin K (GC-PCC-K) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of 8 hours after admission. Multivariate analysis was used to assess the effect of appropriate reversal on 7-day mortality in all patients and in those with intracranial haemorrhage (ICH). Results: Data from 822 VKA-treated patients with severe haemorrhage were collected over 14 months. Bleeding was gastrointestinal (32%), intracranial (32%), muscular (13%), and "other" (23%). Seven-day mortality was 13% in the whole cohort and 33% in patients with ICH. GC-PCC-K was performed in 38% of all patients and 44% of ICH patients. Multivariate analysis showed a two-fold decrease in 7-day mortality in patients with GC-PCC-K (OR = 2.15 [1.20-3.88]; P = 0.011); this mortality reduction was also observed when only ICH was considered (OR = 3.23 [1.53-6.79]; P = 0.002). Conclusion: Guideline-concordant VKA reversal with PCC and vitamin K within 8 hours after admission was associated with a significant decrease in 7-day mortality.