Delayed Traumatic ICH and Oral Anticoagulants

Washington University Emergency Medicine Journal Club – May 19th, 2022


You are working a moonlighting shift at a local level II trauma center when you meet Mr. X, a 68-year-old gentleman with a history of atrial fibrillation, for which he takes diltiazem for rate control and apixaban for anticoagulation. This morning, while walking his dog, a rare crossbreed known as a great yorkie (a cross between a great Dane and a Yorkshire terrier), he was tripped up by the leash and fell forward, striking his forehead on the concrete. He suffered no loss of consciousness, has a mild headache, and has had no nausea or vomiting. His wife states that he has had no altered mental status since the fall. 

On exam he has a GCS of 15, a superficial abrasion to his forehead with a small 4 cm hematoma, no cervical spine pain or tenderness, and a normal neurologic examination. Being an astute reader of the literature, you remember that the studies on the Canadian Head CT rules excluded patients on anticoagulation, and proceed to order a head CT, which is read as normal by the attending radiologist (not a neuroradiologist). 

After updating the patient’s tetanus booster you discharge him home in the care of his wife. That night after your shift, you begin to worry about your patient and his risk of delayed intracranial hemorrhage given his anticoagulant use. You are aware of a prior journal club that found a low risk of delayed bleed with warfarin use, but you wonder if the results apply to patients taking Xa inhibitors and direct thrombin inhibitors. Unable to sleep, you head online and begin to search the literature for answers. 

PICO Question

Population: Patients taking a direct oral anticoagulant (DOAC) presenting with a minor
head injury and normal initial head CT

Intervention: Observation and/or repeat CT scan of the head CT

Comparison: Discharge after normal initial head CT

Outcome: Risk of delayed intracranial hemorrhage, need foe neurosurgical intervention,

Search Strategy

Pubmed was searched using the terms “(DOAC or “direct oral anticoagulant” or
“novel anticoagulation”) AND head trauma” ( This
resulted in 52 citations, from which 3 primary studies and a systematic review and
meta-analysis were chosen. Review of the systematic reviews bibliography did not
identify more relevant articles. Search of the Cochrane Database of Systematic
Reviews did not reveal any other relevant reviews.

Article 1: Cohan CM, Beattie G, Bowman JA, Galante JM, Kwok AM, Dirks RC, Kornblith LZ, Plevin R, Browder TD, Victorino GP. Repeat computed tomography head scan is not indicated in trauma patients taking novel anticoagulation: A multicenter study. J Trauma Acute Care Surg. 2020 Aug;89(2):301-310. doi: 10.1097/TA.0000000000002760. PMID: 32332255. Answer Key.

Article 2:Puzio TJ, Murphy PB, Kregel HR, Ellis RC, Holder T, Wandling MW, Wade CE, Kao LS, McNutt MK, Harvin JA. Delayed Intracranial Hemorrhage after Blunt Head Trauma while on Direct Oral Anticoagulant: Systematic Review and Meta-Analysis. J Am Coll Surg. 2021 Jun;232(6):1007-1016.e5. doi: 10.1016/j.jamcollsurg.2021.02.016. Epub 2021 Mar 22. PMID: 33766725; PMCID: PMC8722268. Answer Key.

Article 3: Mourad M, Senay A, Kharbutli B. The utility of a second head CT scan after a negative initial CT scan in head trauma patients on new direct oral anticoagulants (DOACs). Injury. 2021 Sep;52(9):2571-2575. doi: 10.1016/j.injury.2021.05.039. Epub 2021 Jun 1. PMID: 34130854. Answer Key.

Article 4: Turcato G, Cipriano A, Zaboli A, Park N, Riccardi A, Santini M, Lerza R, Ricci G, Bonora A, Ghiadoni L. Risk of delayed intracranial haemorrhage after an initial negative CT in patients on DOACs with mild traumatic brain injury. Am J Emerg Med. 2022 Mar;53:185-189. doi: 10.1016/j.ajem.2022.01.018. Epub 2022 Jan 15. PMID: 35063890. Answer Key.

Bottom Line

Traumatic brain injury results in just over 1.3 million emergency department (ED)
visits, 275,000 hospitalizations, and 52,000 deaths annually in the United States
alone, with an increase in the combined rate of ED visits, hospitalization, and death
from 521 per 100,000 in 2001 to 823.7 per 100,000 in 2010 (CDC TBI Report). In
elderly patients suffering a fall, long-term anticoagulation has been shown to
increase not only the incidence of intracranial hemorrhage (ICH) compared to those
not on anticoagulation (8.0% vs. 5.3%, p < 0.0001), but to also increase mortality in
those with ICH (21.9% vs. 15.2%, p = 0.04) (Pieracci 2007).
While the risk of delayed intracranial hemorrhage (ICH) following an initial negative
CT among patients taking warfarin appears to be low, with no evidence that routine
observation and repeat scanning improves outcome (see May 2017 Journal Club),
the use of warfarin has declined as more and more patients being started on direct
oral anticoagulants (DOACs) such as apixaban, dabigatran, and rivaroxaban. While
typically felt to be safer, with a lower risk of hemorrhage compared with warfarin
(Yinogradova 2018, Carnicelli 2022), DOACs nonetheless carry an increased risk of
hemorrhage. We therefore sought to evaluate the risk of delayed ICH among such
patients following minor head injury and an initial negative head CT.
We initially reviewed three retrospective studies conducted in a variety of settings.
The first of these included 777 anticoagulated patients seen in any of 5 level 1
trauma centers in Northern California (Cohan 2020). Of these, 431 were taking
warfarin an d 346 were taking a DOAC. The risk of delayed ICH was 4.1% among
patients taking warfarin (95% CI 2.0% to 7.4%) and 2.3% among patients taking a
DOAC (95% CI 0.62% to 5.7%). More importantly, none of the patients in the DOAC
group required a neurosurgical intervention and none died. This study was
primarily limited by the fact that 45% of patients not undergoing repeat head CT
due to physical discretion. It is therefore possible that some delayed ICH cases were
therefore missed.
The second study was a retrospective chart review conducted at Henry Ford
Wyandotte Hospital, a Level III trauma center in Wyandotte, MI (Mourad 2021).
Among 400 patients included, all of whom were taking a DOAC, a positive head CT
following an initial negative CT was only observed in 2 cases (risk 0.5%, 95% CI
0.06% to 1.7%). Neither of these patients required a neurosurgical intervention and
one presented with a GCS of 10.
Out third retrospective study was conducted in the EDs of 5 hospitals in Northern,
Italy (Turcato 2022). By protocol at all 5 hospitals, patients with MTBI on oral
anticoagulation underwent CT scan on arrival to the ED, followed by a 24-hour
observation period. A repeat CT scan could be done prior to discharge at the
discretion of the treating physician, but this was not required. Out of 1426 patients
enrolled, 85 (6%) had an ICH seen on the initial CT scan. Of the remaining patients,
916 (68.3%) underwent a repeat CT scan at 24 hours, with 14 of these (1.5%, 95%
CI 0.84% to 2.6%) demonstrated a delayed ICH. None of these patients died or
required neurosurgical intervention. Among the 424 patients who did not undergo
repeat scanning, 1 presented 8 days later with an ICH, resulting in death. It is
unclear if there was any further trauma in this patient.
In addition to these retrospective studies, we reviewed a systematic review and
meta-analysis on this topic (Puzio 2021). There were 12 included articles
comprising 5289 individual patient encounters involving patients with blunt head
trauma taking anticoagulants. The patient was taking a DOAC in 1263 (23.9%) of
these encounters, while the patient was taking warfarin in 1788 (33.8%) of the
encounters. A delayed ICH was observed in 25 patients on a DOAC, for a pooled risk
of 2.43% (95% CI 1.31-3.88%). A delayed ICH was observed in 44 patients on
warfarin, for a pooled risk of 2.31% (95% CI 1.26-3.66%). Four patients required a
neurosurgical intervention, although the authors do not report how many of these
were on a DOAC versus warfarin. The overall crude rate of mortality was 0.16% in
the DOAC group and 0.45% in the warfarin group. There was a moderate degree of
heterogeneity for both sets of outcomes and the included studies were overall of
moderate to poor quality.
Overall, this data suggests that the risk of a delayed ICH among patients taking a
DOAC and suffering minor head trauma is low following an initial negative CT. More
importantly, the risk of requiring a neurosurgical intervention or having an adverse
outcome as a result was even lower in all of these studies. While it seems prudent to
maintain caution in such patients, particularly in elderly patients who live alone, it
does not seem necessary to routinely admit all such patients for observation or
repeat CT scanning. Strict return precautions should be given to those patients who
are discharged home following a negative initial CT scan, and select inpatient or ED
observation is reasonable depending on severity of injury and social situation.