Byrnes et al.

World Journal of Emergency Surgery 2012, 7:25

http://www.wjes.org/content/7/1/25

WORLD JOURNAL OF
EMERGENCY SURGERY

RESEARCH ARTICLE

Open Access

Therapeutic anticoagulation can be safely

accomplished in selected patients with
traumatic intracranial hemorrhage
Matthew C Byrnes1,2,3*, Eric Irwin1, Robert Roach1, Molly James2, Patrick K Horst2 and Patty Reicks1

Abstract
Introduction: Therapeutic anticoagulation is an important treatment of thromboembolic complications, such as
DVT, PE, and blunt cerebrovascular injury. Traumatic intracranial hemorrhage has traditionally been considered to
be a contraindication to anticoagulation.
Hypothesis: Therapeutic anticoagulation can be safely accomplished in select patients with traumatic intracranial
hemorrhage.
Methods: Patients who developed thromboembolic complications of DVT, PE, or blunt cerebrovascular injury
were stratified according to mode of treatment. Patients who underwent therapeutic anticoagulation with a
heparin infusion or enoxaparin (1 mg/kg BID) were evaluated for neurologic deterioration or hemorrhage
extension by CT scan.
Results: There were 42 patients with a traumatic intracranial hemorrhage that subsequently developed a
thrombotic complication. Thirty-five patients developed a DVT or PE. Blunt cerebrovascular injury was diagnosed
in four patients. 26 patients received therapeutic anticoagulation, which was initiated an average of 13 days after
injury. 96% of patients had no extension of the hemorrhage after anticoagulation was started. The degree of
hemorrhagic extension in the remaining patient was minimal and was not felt to affect the clinical course.
Conclusion: Therapeutic anticoagulation can be accomplished in select patients with intracranial hemorrhage,
although close monitoring with serial CT scans is necessary to demonstrate stability of the hemorrhagic focus.

Introduction
Injury represents one of the most common causes of
morbidity and mortality in children and young adults.
Although many complications can be seen after injury,
venous thromboembolic disease can be among the most
vexing. Virchows triad involves venous stasis, endothelial injury, and hypercoaguability, which are often seen
in this patient population [1-3]. Injured patients often
require immobility as a result of critical illness or skeletal fractures. Endothelial injuries are caused by fractures or venous stretching, and hematologic alterations
associated with trauma result in hypercoagulability. The
* Correspondence: mbyrnes150@yahoo.com
1
Department of Trauma, North Memorial Medical Center, Robbinsdale, MN,
USA
2
Division of Critical Care and Acute Care Surgery, University of Minnesota,
Minneapolis, MN, USA
Full list of author information is available at the end of the article

risk of venous thromboembolism (VTE) is dependent

upon the specific injuries present in individual patients.
While a single site arm fracture is unlikely to lead to
VTE, a multisystem injury that includes a spinal cord
injury, head injury, and multiple long bone fractures is
very likely to lead to VTE [1]. The actual risks of VTE
have been estimated to vary between 7%58% [4].
A significant amount of study has been directed at
preventing VTE in injured patients. Prophylactic doses
of heparin or low molecular weight heparin have been
demonstrated to significantly reduce the risk of VTE
[4,5]. This intervention has been demonstrated to be safe
within days of the initial injury, with only a small risk of
bleeding complications. Once a thrombosis or embolus
has occurred, however, prophylactic doses of anticoagulation are no longer adequate.
Injured patients are also at risk of arterial thromboembolism (ATE). Patients with mitral valve replacements

2012 Byrnes et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Byrnes et al. World Journal of Emergency Surgery 2012, 7:25

http://www.wjes.org/content/7/1/25

are at risk of cerebrovascular accidents without anticoagulation. Patients with traumatic blunt cerebrovascular
injury are also at risk without anticoagulation.
The traditional treatment of VTE has been therapeutic
levels of anticoagulation [3]. The primary complication
of therapeutic anticoagulation is hemorrhage, which is
a significant consideration in injured patients. Patients
with intracranial hemorrhagic diatheses (traumatic and
nontraumatic) have been felt to be at an especially high
risk of developing complications of anticoagulation [2,6].
Extension of an intracranial bleed can be especially
troublesome and can potential lead to death or severe
disability. In the presence of a contraindication to anticoagulation, inferior vena cava filters have been recommended to prevent embolus of thrombi from the lower
extremity venous system to the pulmonary vasculature
[3]. While this approach is reasonable for many injured
patients, there are certain patient populations who
would benefit from anticoagulation. As such, it is
important to know the risks of therapeutic anticoagulation in patients with intracranial hemorrhage. Unfortunately, there is very literature to guide clinical decisions.
Expert recommendations have suggested that therapeutic
anticoagulation should be avoided, but no studies to date
have reported the safety profile of this intervention.
Herein, we developed a study with the following objectives: (1) to evaluate the likelihood of extension of intracranial bleeding after the introduction of therapeutic
anticoagulation; and (2) to evaluate the time course
associated with introduction of therapeutic anticoagulation after the initial injury.

Methods
Medical records of patients admitted to a university
affiliated Level I trauma center were reviewed. Patients
who had both a thrombotic complication and an intracranial hemorrhage were selected for inclusion. The
thrombotic events that were incorporated in the study
included: deep venous thrombosis (DVT), pulmonary
embolus (PE), and blunt cerebrovascular injury. Patient
demographics and CT scan results were noted. Patients
were stratified according to the decision to use therapeutic anticoagulation vs. another treatment modality.
Mortality and expansion of hemorrhage on CT scan
were compared between the groups.
All patients were admitted to the trauma service. All
patients received a head CT on admission and neurosurgery was subsequently consulted. There were four
trauma surgeons during the study period that served
as the core of the program and there were two neurosurgeons that were consulted on all patients with
neurologic injuries. Patients who had leg swelling or
unexplained hypoxia were evaluated for DVT or PE. This
was done with bedside sonography and CT angiography.

Page 2 of 5

During the study period, we did not perform screening

sonography, so all the DVT in the study were initially
suspected based upon symptoms. We currently screen
patients who do not receive prophylactic anticoagulation every four days, but this protocol was developed
after this study was completed. We developed a formal
screening criterion to evaluate for blunt cerebrovascular
injury during the study time period. These criteria
included a fracture of C1 through C4, LeFort 3 fracture,
unexplained neurologic deficit, and fracture through the
vascular foramen.
All patients in this study were regularly discussed with
the neurosurgical service. When a diagnosis of DVT, PE,
or blunt cerebrovascular injury was made, a discussion
was held regarding the appropriateness of anticoagulation. After reviewing the radiologic images and the
clinical course, the neurosurgeon determined whether or
not anticoagulation could be safely administered. These
decisions were made on a case by case basis. There was
not a specific protocol for obtained follow up head CT
scans after anticoagulation was started, but this was
typically done 14 days later.
Data were analyzed with Analyse-It (Leeds, England).
Categorical data were analyzed with chi-square tests and
continuous data were analyzed with t-tests. Permission
to conduct the study was obtained from the institutional
review board at North Memorial Medical Center, which
includes an ethical review of the research protocol.

Results
During the study period, there were 42 patients who
had both an ICH and an indication for anticoagulation.
The average patient age was 50 years. 31% were female.
The average injury severity score was 30.7.
Patients who received therapeutic anticoagulation were
compared with patients who were treated without anticoagulation (Table 1). Twenty-six patients received
anticoagulation, and 16 patients were treated without
anticoagulation. The average age was similar in both
groups. The gender distribution was identical in each
group. The average length of stay was higher in the
patients receiving anticoagulation (30 days vs. 20.9 days,
p = 0.01). The thrombotic events were primarily composed of DVT and PE, with two cases of blunt cerebrovascular injury in each group.
As noted by the high injury severity scores, most of
the patients had significant injuries beyond the traumatic
head injury. Concomitant injuries included 16 patients
with skull fractures, 17 with spinal cord injuries, 8 with
long bone fractures, 20 with at least one known rib fracture, 2 blunt liver injuries and 5 splenic injuries.
Overall, 62% of patients received therapeutic anticoagulation for treatment of their thrombotic complication
(Table 2). All patients receiving anticoagulation received

Byrnes et al. World Journal of Emergency Surgery 2012, 7:25

http://www.wjes.org/content/7/1/25

Page 3 of 5

Table 1 Patient characteristics

Table 3 Decision to anticoagulate

Anticoagulation

No Anticoagulation

26

16

Mean Age

51

48

p
0.43

Gender**
M

18 (69%)

11 (69%)

8 (31%)

5 (31%)

1.0

No Anticoagulation

0.54

Subdural

13

0.75

SAH

20

13

1.0

Contusion

14

12

0.21

Marshall Score

Mean ISS

31.1

30.1

0.95

Mortality

2 (7.7%)

2 (12.5%)

0.63

Mean LOS

30.0

20.9

0.01

PE

16

0.53

DVT

15

1.0

BCVI

0.63

Thrombosis*

*some pts had more than one type of thrombosis (DVT and PE). Blunt
cerebrovascular injury (BCVI).

either enoxaparin at a dose of 1 mg/kg BID or a heparin

drip with a goal PTT between 60 and 80 s (our high
intensity protocol). The average time to instituting anticoagulation was 11.9 days after admission. Nearly onequarter of the patients received full anticoagulation
within the first 7 days of admission. Among these
patients, two were anticoagulated within 24 h of injury,
two were anticoagulated on day 4, and two were anticoagulated on day 6. Approximately 30% of patients were
not anticoagulated until two weeks after their injury.
The decision to anticoagulate was not protocolized.
Rather, the decision was left to the discretion of the
attending neurosurgeon, in discussion with the trauma
surgeon. The distribution of intracranial hemorrhage is
listed in Table 3. The frequency of epidural, subdural,
and intraparenchymal hemorrhage was similar between
the groups. The average size of extra-axial hemorrhage
was 9.48 mm in the group receiving anticoagulation
and 9.89 mm in the group that did not receive anticoagulation. There was not a difference in rate of craniotomy for the treatment of the intracranial hemorrhage
between the groups (30.8% vs. 56.6%, p = 0.19).
There was extension of intracranial hemorrhage after
institution of anticoagulation in only one patients. 96%
of patients had no change in the volume of intracranial
bleeding after initiation of anticoagulation. The extension of bleeding was very minor in one patient
Table 2 Anticoagulation characteristics
Percent receiving anticoagulation

Anticoagulation
Epidural

62%

Mean time until anticoagulation

11.9 days (range: 024)

Percent <7 days

23.1%

Percent 714 days

46.2%

Percent >14 days

30.7%

(1-2 mm growth in intraparenchymal hemorrhage), and

the clinical course was felt to be unaffected. This was
noted on follow up imaging 6 days after initiation of
anticoagulation.
There were two deaths in each group of patients. The
causes of death related to brain injury and multisystem
organ failure. There were no deaths strictly from the
thrombotic complications.

Discussion
Injured patients are at significant risk of both hemorrhagic
and thrombotic complications. These divergent risks
create a therapeutic conundrum for trauma surgeons. Use
of anticoagulation can lead to potential exsanguination
and death, while avoidance of anticoagulation can lead
to thrombotic complications and death [7]. Our data
represents a novel report that suggests that therapeutic
anticoagulation can be safely accomplished in select
patients with intracranial hemorrhage.
There is very little to guide trauma surgeons in the
safety profile of therapeutic anticoagulation. A recent
review by Golob, et. al. evaluated the safety of initiating
therapeutic anticoagulation in multi-injured trauma
patients [7]. They noted that 21% of patients had complications from the therapy. The most common complication was an acute drop in hemoglobin requiring a
blood transfusion; three patients died as a result of
hemorrhage. Clinical factors associated with a higher risk
of complications were COPD, low platelet count before
therapy, and the use of unfractionated hemorrhage. This
study, however, did not include any patients with head
injuries, so extrapolation to this population is difficult.
Injured patients are at significant risk of thrombotic
complications. Patients with multisystem trauma may
develop DVT at a rate of 58%, while a quarter of patients
with isolated intracranial hemorrhage may develop DVT
[1]. This has led to significant study evaluating medical
DVT prophylaxis in head injured patients. These studies
have evaluated both low dose heparin and low molecular
weight heparin. Norwood, et.al. noted that enoxaparin
could be safely administered to select patients within
24 h of craniotomy for trauma [8]. In a separate report,
this group noted a 3.4% progression rate of intracranial
hemorrhage after institution of prophylactic doses of
anticoagulants [2].

Byrnes et al. World Journal of Emergency Surgery 2012, 7:25

http://www.wjes.org/content/7/1/25

These reports were highly important in that they dispelled the traditional viewpoint that prophylactic anticoagulation is unsafe after brain trauma. They do not,
however, speak to the safety profile of therapeutic anticoagulation. Traditional recommendations suggest that
therapeutic anticoagulation is unsafe after traumatic
intracranial hemorrhage. Textbooks have noted that
anticoagulation should be delayed for 3 days to 6 weeks
after injury depending on local customs (although no
references were cited to support this recommendation)
[9]. Our data suggests that anticoagulation in the earlier
portion of this window may be safe.
Much of the hesitation to use therapeutic anticoagulation after brain trauma likely stems from studies on preinjury use of anticoagulants. Cohen, et.al. reported
mortality rates of 84%91% among patients who were
anticoagulated prior to an intracranial bleed [10]. Mina,
et.al. compared anticoagulated patients to matched controls and found an absolute increase in mortality of 30%
among the anticoagulated patients [11]. Another study
evaluated the effect of rapid reversal of coagulopathy.
Patients who underwent a rapid, protocolized reversal of
coagulopathy had a 38% absolute reduction in mortality
compared to historical controls [12]. Although these
studies clearly indicated higher risks of death and disability among patients exposed to anticoagulants before
the time of injury, they do not speak to the risks of
administration of anticoagulants in a delayed fashion.
While many thrombotic complications can be treated
without anticoagulation, there are specific scenarios
in which anticoagulation has the potential to markedly
improve a treatment regimen. Inferior vena cava (IVC) filters are the mainstay of treatment of both DVT and PE in
patients with a contraindication to anticoagulation [3].
There are certain situations, however, in which IVC filters
are not adequate. The filters do not prevent propagation
of a thrombus that has already embolized to the pulmonary vasculature. A saddle PE requires very little propagation to result in lethal shock, so anticoagulation in this
population is critical. Similarly, the long term morbidity
of phlegmasia cerulean dolens is reduced with anticoagulation. Further, there is a small, but defined, risk of
thrombosis of the IVC after placement of a filter [6]. This
situation also requires anticoagulation. A final venous
thrombosis that that is not amenable to treatment with
an intravascular filter is an upper extremity DVT. Superior vena cava filters are uncommon and would lead to
fatal intracranial swelling in the event of filter thrombosis.
There is only one report that has attempted to define
the optimal treatment regimen of DVT or PE after intracranial hemorrhage [6]. This report focused on nontraumatic hemorrhage, so the generalizability may be
limited. The authors conducted a review of the literature
and were unable to develop firm recommendations.

Page 4 of 5

Blunt cerebrovascular injury is another event that may

require anticoagulation despite the presence of an intracranial hemorrhage [13]. Dissection of the carotid or vertebral arteries can lead to disabling or fatal stroke events,
which may be prevented by adequate anticoagulation.
Although much of the focus of treatment has shifted to
antiplatelet regimens, there is a role for heparin in select
cases. Our data suggests that therapeutic anticoagulation
can be safely given to select patients with blunt cerebrovascular injury and intracranial hemorrhage.
Patients with mechanical cardiac valves represent a significant challenge to trauma surgeons [14-17]. The risk
of artificial valves appears to be the highest in patients with
a cage/ball valve in the mitral position. Atrial fibrillation
and reduced left ventricular function add to the risk of
stroke without anticoagulation. The natural history of these
patients is unclear, as they are generally on anticoagulants,
but we can glean some estimate of risk from studies that
have evaluated temporarily discontinuing anticoagulation
after intracranial hemorrhage. It appears safe to discontinue anticoagulation for brief periods of time [14,15].
Most of this work has been conducted in patients with
spontaneous intracranial hemorrhage. It is possible that
traumatic hemorrhage is a different entity, as injured
patients are more hypercoaguable than then general population. Our data represents an important adjunct to these
studies, in that we have demonstrated that early reintroduction of anticoagulation can be safely accomplished.
There are limitations of this study worth noting. We
did not have a protocolized approach to management of
anticoagulation. Rather, we consulted with the neurosurgeons on a daily basis and we started anticoagulation
when their clinical judgment indicated it was safe to do
so. As such, we are likely dealing with a highly select
patient population. Additionally, our sample size is limited. It is possible that we would have yielded different
results with a larger sample size. Finally, some of our
patients received anticoagulation for uncomplicated PE
rather than the extreme examples listed in this discussion. This does not detract from our results demonstrating safety of anticoagulation, however.
In conclusion, selected patients with brain injury may
safely be anticoagulated to prevent the propagation of
thrombotic complications. Our data does not provide
definitive evidence of the safety profile. Rather, this
manuscript provides initial evidence that suggests that
traditional beliefs about anticoagulation in patients with
brain injuries may be incorrect. Our data should be used
a springboard to develop further study on this issue, so
that the specific groups that would most benefit from
anticoagulation could be defined.
Competing interests
None of the authors have any conflicts of interest or special declarations to
make regarding the contents of this manuscript.

Byrnes et al. World Journal of Emergency Surgery 2012, 7:25

http://www.wjes.org/content/7/1/25

Authors contribution
MB directed the design of the study, data interpretation, and was involved in
the drafting and revision of the manuscript. EI was involved in the study
design and the manuscript revision. PR was involved in the data acquisition,
study planning, and manuscript revision. RR was involved in the data
interpretation and manuscript revision. PH was involved with the data
acquisition and the data interpretation. All authors read and approved the
final manuscript.

Page 5 of 5

doi:10.1186/1749-7922-7-25
Cite this article as: Byrnes et al.: Therapeutic anticoagulation can be
safely accomplished in selected patients with traumatic intracranial
hemorrhage. World Journal of Emergency Surgery 2012 7:25.

Author details
1
Department of Trauma, North Memorial Medical Center, Robbinsdale, MN,
USA. 2Division of Critical Care and Acute Care Surgery, University of
Minnesota, Minneapolis, MN, USA. 3North Memorial Medical Center, Division
of Trauma, 3300 Oakdale Avenue, Robbinsdale, MN 55422, USA.
Received: 8 February 2012 Accepted: 6 July 2012
Published: 23 July 2012

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