Head trauma in anticoagulated patients: Evidence guiding management

after an initial negative head CT

Eric Brown MD, Shauna Kern MD, Charles Soliman MD, Greg Starr MD
Resident Physicians, OU Department of Emergency Medicine

Background
Daily ED clinical practice demonstrates lack of consistency regarding the management of
head trauma in patients who are coagulopathic from physiologic (e.g. hemophilia) or pharmaco-
logic (e.g. warfarin) mechanisms. These anticoagulated individuals (hereafter denoted as “AC”
patients) tend to undergo initial cranial computed tomography (CCT) in the ED. However, the
post-imaging management (in patients with negative CCT) ranges from immediate discharge to
hospital admission and mandatory next-day imaging. In between these two ends of the man-
agement spectrum are intermediate approaches such as short-term observation or overnight
admission with repeat imaging only in the presence of abnormal neurological findings.
In an effort to optimize both medical care and resource utilization, the SJMC ED Attend-
ing group decided to assess the evidence basis for management of AC patients with head trau-
ma and an initial negative CCT. The SJMC ED Attendings asked the OUDEM to assess and pre-
pare a report on the available data, in order to inform a decision as to how best to generate a
clinical guideline for managing these patients.
The current report is structured along the lines of clinical questions. Each section ad-
dresses a particular question faced by clinicians, and summarizes the available evidence on the
subject. A final section of the report outlines the recommended course for management of AC
patients with initially negative CCT.

What is the overall risk associated with coagulopathy in head trauma?

It is well known that AC is associated with increased risk of post-traumatic intracranial
bleeding of clinical significance.1 One representative study reported that, as compared to pa-
tients without preinjury coagulopathy, patients with preinjury AC have a 4- to 5-fold increase in
mortality.2 Other evidence confirms the dramatic increase in head injury mortality in AC pa-
tients. A typical study reports a 50% excess brain injury mortality rate in AC patients, as com-
pared to non-AC patients with similar head injuries.3
The known risk of AC in the setting of head trauma means that clinicians should have a
low threshold for CCT when these patients are head-injured.4 A recommendation illustrative of
most literature is that all patients on warfarin have an INR performed, with CCT scan performed
in most anticoagulated patients. 5 This recommendation stems from knowledge that rapid con-
firmation of head bleeding with expedited CCT, combined with prompt reversal of anticoagula-
tion, decreases progression of bleeding and reduces mortality.6 The high risk of bleeding, and
the associated increased risk of mortality, combine to make a strong case for low-threshold CCT
imaging in AC patients with head injury.5
What about medications other than warfarin?
A previously mentioned study finding up to 5-fold mortality increase associated with AC
included in its at-risk group patients on aspirin, as well as those on warfarin. 2 Other studies de-
monstrating increases in head injury mortality have also identified non-warfarin pharmacologic
anticoagulation as problematic.
In patients who are elderly (a group often prescribed chronic antiplatelet agents), the
use of either aspirin or clopidogrel is demonstrated to be associated with higher mortality in the
setting of intracranial bleeds.7 The risk even extends to patients on low-dose aspirin therapy.8
There are also data showing that in cases where traumatic brain injury requires operative inter-
vention, post-operative rebleeding is more common in patients taking clopidogrel than in those
with no pre-injury AC.9
Therefore, the preponderance of the literature suggests that any anticoagulation, in-
cluding that with antiplatelet agents (and even low-dose aspirin), places patients at a significant-
ly higher risk for hemorrhagic head injury complications. The conclusion we draw is that pa-
tients should be considered a relatively higher risk, regardless of the pharmacologic mechanism
of anticoagulation. Of course, there are both physiologic and experience-based reasons to pre-
sume that patients with greater degrees of coagulopathy, will have greater degrees of risk for
hemorrhage after head injury.

What evidence addresses the need for observation and/or repeat CCT?
The major decision to be made after an initially negative CCT in a head-injury patient is
“Can I discharge this patient?” Of course, decision-making must be individualized, but there are
data available to guide the treating clinician. The following discussion is provided as a guide,
rather than as a “protocol.”
Perhaps the easiest case is the decision as to whether to admit/observe the AC patient
who is supratherapeutic (i.e. on warfarin). In these cases, admission for observation is the mi-
nimally acceptable approach. (For this scenario, and indeed for this entire discussion, the pa-
tient is assumed to have something constituting “significant” head trauma.) Authorities clearly
recommend that any patient who is supratherapeutic (on warfarin therapy) must be admitted
for neurologic observation.5
Another simple decision is presented by the patient with a non-surgical abnormality on
initial CCT. Both the literature and common sense dictate that such patients be admitted for
observation at the least.5
In patients who are not supratherapeutic, the literature seems to indicate that observa-
tion (at minimum) is the wisest course. Reasoning for this includes concern about diagnoses
such as “DASH” (delayed acute subdural hematoma). DASH risks are highest in elderly patients,
and anticoagulation is demonstrated to raise that risk.10 In addition, other clinically significant
delayed-positive CCT findings (i.e. requiring craniotomy) have also been shown to be correlated
with pre-injury AC status.11, 12
The available data are thus fairly consistent in an indication that AC patients are not only
at high risk for an initially positive CCT, but that these patients are also at higher risk (as com-
pared to non-AC patients) for delayed-diagnosis bleeds. Thus, admission/observation of these
patients is the prudent course even if there is an initially negative CCT.
The next question is, is there a need for repeat CCT after the observation period? (On a
related point, it should be acknowledged that the observation period is not necessarily consis-
tent across the literature. The most common approach seems to be the “overnight” observation
– which can of course be anywhere from 12-24 hours.) Whatever the observation time frame
might be, there are cases in which the EM specialist may be either responsible for the plan (e.g.
if the patient is “observed” in the ED or in an associated ED Observation Unit) or may be asked
by an admitting hospitalist about the need for repeat CT. Thus we will address the question of
repeat CCT.
One common-sense approach would be to reserve utilization of the CT resource, for
cases in which there is neurological abnormality or other clinical worsening. Unfortunately, the
reliance upon the neurological examination in AC patients may fail to detect up to 30% of intra-
cranial bleeds.13 Studies consistently indicate a noteworthy risk of delayed-positive CCT in AC
patients, especially the elderly. It is in these patients that the neurological assessment (includ-
ing a normal GCS and nonfocal exam) is associated with a relatively high false-negative rate.10, 11
The message from the literature seems to be that a repeat CCT is clearly the most appropriate
approach in the geriatric AC patient with negative initial imaging.
Although advanced age is a factor in delayed-positive CCT, the parameter of anticoagu-
lation remains an independent risk factor for concerning findings on repeat CT. In fact, in multi-
variate analysis adjusting for age, AC is also found to be an independent predictor of follow-up
CCT’s identification of need for craniotomy, in patients with initially negative imaging. 11, 12
Therefore, while there is a gray area in the literature with respect to whether repeat CCT is
needed in the non-geriatric patient, the prudent course appears to be to re-image.

What about patients with nonpharmocologic coagulopathy?

Most of the coagulopathy-outcomes data in the head trauma literature address use of
pharmacologic agents. With that acknowledgment, it remains the case that the literature focus-
ing on anticoagulants consistently reports an association between increasing INR and worse
outcomes.5, 12 Therefore, it seems reasonable (given the paucity of directly applicable data) to
work under the assumption that any condition increasing INR places patients at increased risk
for post-traumatic head bleed and complications.
One of the most common nonpharmacologic conditions causing coagulopathy is hemo-
philia. Given the prevalence of hemophilia, it is a bit surprising that the literature reveals no
consistency in management of hemophiliacs suffering head trauma.14 There are virtually no da-
ta guiding other causes of nonpharmacologic coagulopathy. However, there is strong physiolog-
ic basis to presume that the AC patient is at some level of increased risk for post-traumatic in-
tracranial bleeding, regardless of the etiology of the AC state. This presumption is bolstered by
the evidence (cited above) that the AC state’s risk for intracranial bleeding is shared across all
drugs inducing coagulopathy. The most prudent course is to practice with an assumption that
the reason for the AC state is not a critical factor in determining disposition of the ED patient
with head injury and an initially negative CCT.

Conclusions and recommendations

While the evidence is not ideal, available data support some preliminary conclusions:
 First, AC from any cause seems a virtual certainty to increase the risk of clinically
significant abnormalities on CCT.
 Second, although the degree of coagulopathy is related to the likelihood of clinically
significant findings, the evidence points to concern even in cases where there is lit-
tle or no detectable coagulopathy (e.g. low-dose aspirin therapy). This translates to
a concern in any condition causing alterations in coagulation (e.g. liver disease).
 Third, the minimal approach to the AC patient with head injury and a negative initial
CCT is admission for 12-24 hours’ observation and reassessment. Elderly patients
should nearly always undergo repeat CCT, and this appears to be the most prudent
course even in the non-geriatric population.
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