Comprehensive Summary
This multicenter, randomized, open-label, blinded-endpoint trial investigated the safety and efficacy of vitamin K antagonist (VKA) reversal in patients presenting to the emergency department (ED) with mild traumatic brain injury (TBI). In the treatment group, participants received immediate VKA reversal with 25 IU/kg of four-factor prothrombin complex concentrate (4f-PCC) prior to imaging. Patients in the control group received standard-of-care unless reversal was indicated by intracranial hemorrhage (ICH) on the initial CT scan. The primary endpoint was detection of ICH on a follow-up CT scan 24 hours after enrollment. Due to logistical challenges, the study was terminated early after randomizing 202 patients equally between the two groups. The study found no significant difference in ICH detection between the intervention and control groups on the 24 hour CT scan (odds ratio: 0.47, p = 0.215).
Outcomes and Implications
Patients presenting with TBI on anticoagulants such as VKAs are at increased risk for ICH. Current clinical guidelines recommend performing a CT scan to confirm ICH before administering reversal therapy. However, immediate reversal of VKAs after TBI, without waiting for CT confirmation, could potentially reduce ICH progression and mortality. This study showed that immediate administration of the VKA reversal agent 4f-PCC did not significantly reduce ICH incidence at 24 hours compared with standard care, in which reversal was initiated only if ICH was indicated on the initial ED CT scan. However, the results may be inconclusive due to the study’s premature termination and lack of statistical power. Further research is warranted to provide clarity on the effects of immediate anticoagulation reversal in patients with TBI.