Vitamin K Antagonists and TBI: A Deadly Combination?

Kelli Whitlock Burton

July 11, 2022

Patients with a traumatic brain injury (TBI) are significantly more likely to die or need acute neurosurgery in the month following the injury if they have a history of taking vitamin K antagonists (VKA), new research suggests.

Preinjury use of direct oral anticoagulants (DOAC) was also associated with worse outcomes, although not nearly as high as use of VKA. Adenosine diphosphate inhibitors (ADPi) were not linked to higher rates of death or surgery at 30 days.

The large-scale, nationwide, population-based study offers a clearer picture of the effect OAC and ADPi use may have on outcomes following TBI, an issue clinicians are seeing more frequently with an aging population, researchers note.

"These results indicate the relative safety of direct anticoagulants or adenosine diphosphate inhibitors in patients at risk of head trauma and encourage the choice of direct anticoagulants when oral anticoagulation is required," co-investigator Jussi Posti, MD, PhD, head of department and neurosurgery consultant at Turku University Hospital and adjunct professor of neurosurgery at University of Turku, Finland, told Medscape Medical News.

The findings were published online June 28 in Neurology.

Growing Concern

Individuals aged 60 years and older are expected to make up 22% of the world's population by 2040, which is nearly double what it was in 2015.

Older adults have a higher risk for atrial fibrillation and cardioembolic events, increasing the likelihood of OAC and ADPi use. This population is also at higher risk for mild TBI, which can be complicated by medications affecting blood clotting due to the increased risk for intracranial hemorrhaging.

Earlier studies have yielded conflicting results, leaving uncertainty about the best course of action in these patients.

To explore the issue, researchers analyzed data from 57,056 patients with TBI, most of whom were diagnosed with concussion or mild TBI. Overall, 0.9% were treated with DOAC, 7.1% with VKA (all warfarin), and 2.3% an ADPi.

Mortality at 30 days was 15.4% in the VKA group, 8.4% in the DOAC group, and 7.1% in patients without OAC.

Participants treated with VKA had a significantly higher risk for death within 30 days of TBI vs those without OAC (adjusted hazard risk [aHR], 1.35; P < .0001) or those taking DOAC (aHR, 0.62; P = .005).

ADPis were not associated with mortality after multivariable analysis, and mortality was not significantly different between patients treated with DOAC and those who did not receive oral anticoagulation.

"We concluded that patients at risk for head trauma who require anticoagulants should have their medications reviewed," Posti said.

Limitations within the coding system used in the study meant researchers couldn't assess true TBI severity. Instead, they used the need for acute neurosurgery and length of stay as markers of severity, an approach used in related studies.

"This approach has previously been considered acceptable in the literature," Posti said, "and because of the large number of patients in each group studied, it is highly unlikely that the severities as measured by the Glasgow Coma Scale, posttraumatic amnesia, and functional outcome differed between the groups of patients studied."

Although there was no significant difference among groups in hospital stay, patients taking VKA were significantly more likely to need acute neurosurgery than patients without OAC (aOR, 1.33; P < .0001). There were no differences in surgery risk among other patient groups.

The study did not explore whether reversing the effects of VKA would affect mortality rates or the need for acute neurosurgery.

More Data Needed

Commenting on the findings for Medscape Medical News, Ritvij Bowry, MD, an assistant professor of neurosurgery in neurocritical care with McGovern Medical School at UTHealth Houston in Texas, noted that "from a clinical practice perspective," reversal is a part of the medical armamentarium of managing patients with TBI — whether it is with VKAs or DOACs.

Bowry, who was not involved with the research, noted there has been an increase in older patients with TBI, many of whom are taking VKAs or DOACs for atrial fibrillation. Studies such as this that offer data that could influence clinical decisions are important, but more information is needed, he said.

"Which patients should be reversed and should it be based on the radiological criteria, clinical criteria, hematological criteria, or whether these patients require imminent surgery?" he asked.

"VKA reversal should always be considered but it's unclear from this data whether that's an absolute and whether that's really going to be associated with better outcomes," Bowry said.

Posti reported funding from the Academy of Finland, the Maire Taponen Foundation, and Turku University Hospital in Finland, but has disclosed no relevant financial relationships. Bowry also has disclosed no relevant financial relationships.

Neurology. Published online June 28, 2022. Abstract

Kelli Whitlock Burton is a reporter for Medscape Medical News who covers psychiatry and neurology.

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