Systematic vitamin K antagonist reversal with prothrombin complex concentrate in patients with mild traumatic brain injury: randomized controlled trial.

Abstract

Traumatic brain injury (TBI) in patients on vitamin K antagonists (VKAs) is linked to a high rate of intracranial hemorrhage (ICH). Rapid reversal can reduce ICH progression and mortality, but its effectiveness depends on the time between bleeding onset and coagulation normalization. The PREVACT study aimed to assess the efficacy and safety of prompt systematic reversal of anticoagulation in patients presenting to emergency departments (EDs) for recent mild-TBI while receiving a VKA. A randomized, open-label, blinded-endpoint clinical trial was conducted in 21 French EDs. Patients receiving a VKA, having experienced a TBI within the last 6 h, and presenting a Glasgow Coma Score ≥13 were included. Patients were randomized to systematic immediate VKA reversal with 25 IU/kg of four-factor prothrombin complex concentrate (4f-PCC) before any investigation (intervention group) or standard-of-care signifying reversal only if the initial cranial computed tomography (CT) scan indicated ICH (control group). The primary outcome was the rate of ICH detected on a cranial CT scan 24 h post-inclusion. The study was prematurely stopped for logistic reasons after the randomization of 202 patients (101 and 101 in the intervention and control groups, respectively, mean age 90; 51.8% female). On the 24-h cranial CT scan, 6 of 98 patients (6.1%) in the intervention group manifested ICH vs. 12 of 99 patients (12.1%) in the control group [odds ratio: 0.47 (95% confidence interval: 0.14-1.44); P = 0.215]. In patients with recent mild-TBI receiving a VKA, systematic prompt reversal with 4f-PCC did not statistically significantly reduce ICH rate at 24 h. However, the study was prematurely stopped and does not exclude a clinically relevant benefit of the strategy tested. Clinicaltrials.gov (NCT01961804).