ARTICLE IN PRESS

Cerebral Venous Thrombosis Associated with Intracranial
Hemorrhage and Timing of Anticoagulation after
Hemicraniectomy
Michael A. Pizzi, DO, PhD,*† David A. Alejos, MD,† Jason L. Siegel, MD,*
Betty Y.S. Kim, MD, PhD,‡ David A. Miller, MD,‡ and William D. Freeman, MD*†‡

Background: Cerebral venous thrombosis (CVT) is a rare cerebrovascular event
that can present with headache, seizure, and focal neurological deficits. Approximately 30%-40% of patients with CVT also present with intracranial hemorrhage.
Current guidelines recommend anticoagulation after CVT even in the setting of
intracranial hemorrhage, but the timing of initiation is unclear. We present a case
of CVT where timing of anticoagulation was unclear by current guidelines. Methods:
We conducted a literature search with search terms of “cerebral venous thrombosis,” “intracranial hemorrhage,” and “anticoagulation.” Abstracted information
included anticoagulation status and time of initiation of anticoagulation. We present
a 30-year-old woman with sudden onset of right hemiplegia, global aphasia, and
new-onset seizures diagnosed with left transverse and sigmoid sinus thrombosis
with intraparenchymal hemorrhage. The patient was treated with endovascular
thrombectomy and decompressive hemicraniectomy due to hemorrhage expansion, and anticoagulation was restarted 8 days after hemicraniectomy. Results: The
literature review demonstrated a wide variation of timing for anticoagulation initiation in patients with CVT and intracranial hemorrhage. Most started anticoagulation
within 24 hours of admission with similar functional neurological recovery. Current
guidelines on the treatment of CVT, even with intracranial hemorrhage, recommend anticoagulation. Most reports in the literature state initiation of anticoagulation
within 24 hours. However, the literature does not definitively state when to initiate anticoagulation in a patient with CVT, intracranial hemorrhage, thrombectomy,
and decompressive hemicraniectomy. Conclusion: This case illustrates the challenge of determining when to resume anticoagulation for CVT. Key Words: Cerebral
venous thrombosis—intracranial hemorrhage—anticoagulation—craniectomy.
© 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Introduction

From the *Departments of Neurology, Mayo Clinic, Jacksonville,
Florida; †Department of Critical Care, Mayo Clinic, Jacksonville, Florida;
and ‡Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida.
Received March 16, 2016; revision received May 12, 2016; accepted
May 17, 2016.
Address correspondence to William D. Freeman, MD, Mayo
Clinic, 4500 San Pablo Road, Jacksonville, FL 32224. E-mail:
Freeman.william1@mayo.edu.
1052-3057/$ - see front matter
© 2016 National Stroke Association. Published by Elsevier Inc. All
rights reserved.
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.05.025

Cerebral venous thrombosis (CVT) is a rare form of
stroke, constituting .5%-1.0% of all cerebral strokes. The
symptoms and clinical outcome are highly variable.1 The
incidence is approximately 3 patients out of 1 million,
and approximately 76% of the patients are female. Several
potential risk factors have been identified including surgery,
trauma, pregnancy, puerperium, antiphospholid syndrome, cancer, exogenous hormones, and thrombophilia.2
The mortality of CVT has decreased over the last few
decades and is currently 5%-10%,3 and this is because
of increased awareness of the diagnosis, improved
neuroimaging techniques, and more effective treatment.1

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■

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Mortality is usually attributed to transtentorial cerebral
herniation due to mass occupying lesions or generalized cerebral edema.4 Complications such as subarachnoid
hemorrhage (SAH)/intracerebral hemorrhage (ICH) are
rare but can further complicate treatment and prognosis.2,5
The most frequent, but not specific, symptom of CVT
is severe headache, which occurs in more than 90% of
adult patients.1 It usually progresses over days but can
sometimes present as a thunderclap headache.6 Most patients present with signs and symptoms of intracranial
hypertension (headache, visual disturbances, papilledema, focal neurological deficits, and/or seizures).7
Thrombosis of the deep venous system can cause bilateral thalamic lesions causing delirium, amnesia, mutism,
or even coma.8 Given the variety of possible presenting
symptoms, the diagnosis of CVT can easily be delayed.
According to the International Study on Cerebral Vein
and Dural Sinus Thrombosis (ISCVT), there are an average
of 4 days between the initial presentation of symptoms
and admission to a hospital and 7 days between the initial
presentation of symptoms and a diagnosis of CVT.9
Computed tomography (CT) or magnetic resonance
imaging can be used as the initial test. Magnetic resonance venography (MRV) is the most sensitive imaging
modality for CVT. Thrombosed sinuses are best demonstrated as hyperintensities on T1 and T2 sequences.1 When
computed tomography venography (CTV) and MRV are
equivocal, cerebral angiography may be indicated if clinical suspicion for CVT is high. A repeat CTV or MRV at
3-6 months is recommended to assess the recanalization
of the occluded cortical vein or sinuses in stable patients.2
The most recent guidelines state that once CVT has been
confirmed, treatment with anticoagulation should be initiated even in the setting of ICH.2 According to the
algorithm detailed in the American Heart Association
(AHA)/American Stroke Association (ASA) guidelines,
if neurological deterioration occurs despite anticoagulation for CVT, decompressive hemicraniectomy may be
considered. However, there are no recommendations for
when to resume anticoagulation in this specific patient
population.2 The lack of recommendations for when
to resume anticoagulation after decompressive
hemicraniectomy after CVT in current guidelines and the
paucity of published cases of CVT patients with ICH subsequently undergoing decompressive hemicraniectomy
prompted us to present this unique case and engage in

a discussion on when to resume anticoagulation in such
patients.

Case Presentation
A 30-year-old woman with a past medical history of
oral contraceptive use for dysmenorrhea developed severe
left-sided headache 4 days before admission. The patient
had been taking ibuprofen and naproxen for her headache without relief. On the day of admission, the patient
was witnessed by her spouse as having a vacant, unresponsive stare. The patient was noted to have an ataxic
gait followed by a witnessed generalized tonic–clonic
seizure. The patient had a second witnessed seizure en
route to the hospital, where she was intubated for airway
protection.
At an outside facility, noncontrast CT of the head demonstrated a 3.7 × 2.3 mm ICH in the lateral left partial lobe,
small adjacent SAH, and a left transverse and left sigmoid
sinus thrombus (Fig 1). The patient was transferred to
our institution for a possible interventional neurovascular procedure. Cerebral angiogram was performed,
revealing a venous thrombosis in the left vein of Labbé
and occlusion of the transverse and sigmoid sinuses (Fig 2).
Significant thrombus was removed, and sections of the
occluded sinuses were recanalized. No thrombolytics were
given due to recanalization after mechanical thrombectomy. Anticoagulation with intravenous (IV) heparin was
started. Within 12 hours of admission, the patient’s condition deteriorated, as noted by asymmetric pupils. Repeat
CT of the head was obtained 4.5 hours after endovascular
intervention, demonstrating expansion of the ICH (Fig 3).
Treatment with heparin was stopped, and the patient received emergent decompressive hemicraniectomy and
removal of a left temporal hematoma (Fig 4).
The patient was transferred to the ICU where she improved neurologically, reaching a Glasgow Coma Scale
score of 15. A noncontrast CT scan of the head was repeated 8 days after decompressive hemicraniectomy and
showed no increase in the size of the ICH. Based on our
patient’s consistent and stable neurological status and radiographic imaging, we decided to resume anticoagulation.
Treatment with IV heparin was then restarted 8 days after
decompressive hemicraniectomy. The patient continued
to show improvement, with expressive aphasia and dysarthria as her only residual symptoms. Anticoagulation

Figure 1. Initial computed tomography scan of
the head without contrast. (A) Hyperdensity in
the region of the left transverse sinus. (B)
Intraparenchymal hemorrhage of the left temporal lobe.

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A

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B

C

Figure 2. Cerebral angiogram. (A) Lack of filling of left transverse and sigmoid sinus consistent with thrombosis. (B) Filling defect noted in left vein of
Labbé (arrow). (C) Restoration of venous flow in left transverse and sigmoid sinuses after mechanical thrombectomy.

with warfarin was started, and the patient was sent to
an inpatient rehabilitation center. Three months after discharge, our patient had a modified Rankin Scale (mRS)
score of 3 and persistent moderate expressive aphasia.
The patient remains on lifelong anticoagulation based on
the life-threatening nature of her unprovoked event, as
recommended by our hematology colleagues.

Discussion and Literature Review
Our case report demonstrates the clinical dilemma of
starting anticoagulation in the setting of SAH and ICH.
In our case, we resumed anticoagulation 8 days after decompressive hemicraniectomy and based this decision
mainly on clinical and radiographic stabilization of the
ICH. The current guidelines proposed by the AHA recommend the use of heparin in the acute phase of CVT
with concurrent ICH, but there are no specific recommendations about the timing of anticoagulation. 1
Furthermore, there are no specific guidelines about the
timing of anticoagulation for CVT after hemicraniectomy
for the treatment of refractory intracranial hypertension.
We reviewed the literature in the PubMed and Google
Scholar databases describing CVT patients presenting with
ICH to better characterize the timing of anticoagulation
in this particular patient population. Using the search key
words of “cerebral venous thrombosis,” “intracranial hemorrhage,” and “anticoagulation” we identified 2 prospective
observational studies, 3 retrospective studies, and 6 case
reports. The anticoagulation regimen of these studies is
described below.

A
Figure 3. Noncontrast computed tomography
scan of the head 4.5 hours after endovascular intervention. (A and B) Increased edema and
intraparenchymal hemorrhage with 6 mm from the
left to the right midline shift.

In a prospective observational study of 102 CVT patients presenting with ICH and/or SAH, 52 were initially
treated with IV heparin and 50 were treated with
enoxaparin.10 However, this study did not specifically state
when anticoagulation was started in these patients.
Girot et al11 aimed to identify predictors of outcome
in patients included in the ISCVT with ICH. This prospective observational study compared early intracerebral
hemorrhage (e-ICH), which is defined as ICH identified
on imaging at the time of CVT diagnosis, and delayed
ICH, which is defined as ICH identified on subsequent
imaging after diagnosis of CVT had occurred. The outcome
at 6 months was assessed with the mRS. A total of 624
patients were included in ISCVT, 245 (39%) of which had
an e-ICH. In the e-ICH group, 178 patients were treated
with IV or subcutaneous therapeutic heparin initiated
within the first 24 hours after diagnosis. Assessment of
the e-ICH group at 6 months demonstrated that 190 patients (79%) were found to have an mRS score of 0-2,
and 51 patients (21%) were found to have an mRS score
of 3-6.11 This is the only study that mentions the specific timing of when anticoagulation therapy was initiated,
and good outcomes were reported for patients treated
with heparin within the first 24 hours. However, the choice
of treatment was left to the discretion of the treating
physician.
A retrospective study looking at outcomes on CVT patients treated with heparin consisted of a total of 102
patients, 43 of which were noted to have ICH. Out of
the 43 patients with ICH, 27 received dose-adjusted IV

B

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M.A. PIZZI ET AL.

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Figure 4. Intraoperative anatomy during decompressive hemicraniectomy.
Abbreviation: ICH, intracerebral hemorrhage.

heparin. Of the 27 patients with CVT treated with IV
heparin, four died (15% mortality) and 14 experienced
complete recovery. Thirteen patients with CVT who were
not administered heparin demonstrated 69% mortality,
one had minor neurological deficits, and three completely recovered. Three patients received low-dose heparin
after ICH. This study demonstrated that anticoagulation with heparin is effective in treating patients with CVT
and ICH, and in particular showed less mortality in patients treated with dose-adjusted IV heparin.12 The authors
do not report the timing when they initiated the anticoagulation therapy, but the results support the decision
to anticoagulate despite the presence of ICH.
In a retrospective case series of CVT patients, 4 out
of 16 patients (25%) had concurrent ICH.13 Patients with
CVT and ICH were initially anticoagulated for 5 days
with heparin before transitioning to oral anticoagulation with either vitamin K antagonist or rivaroxaban. A
similar retrospective study looking at CVT patients (n = 15)
with ICH (7 patients) were either started on dabigatran
or warfarin after approximately 14 days of initial anticoagulation with heparin.14 Both of these studies did not
specify when initial anticoagulation with heparin was
started in these CVT patients presenting with ICH.
Of the case reports involving CVT patients presenting with ICH, the range of time initiating anticoagulation
ranged from immediately upon diagnosis of CVT and
ICH,15-17 to the second day of admission,18 and up to 1
month after diagnosis.18 One case report stated that anticoagulation with low–molecular-weight heparin was
maintained for 2 weeks before starting dabigatran, but
there was no statement on when low–molecular-weight
heparin was initially started.19

There are currently no guidelines regarding the timing
of resuming anticoagulation in CVT patients who have
undergone decompressive hemicraniectomy. There is only
1 small case series in the literature addressing the timing
of resuming anticoagulation in this unique patient population. In a case series of 3 consecutive CVT patients
presented by Coutinho et al,20 the patients were treated
immediately with low–molecular-weight heparin, and when
presented with severe herniation, they performed decompressive hemicraniectomy. Prophylactic low–molecular
weight heparin was started after decompressive
hemicraniectomy. Twenty-four hours after surgery, fulldose low–molecular-weight heparin was started. Two
patients had excellent recovery with minimal residual
symptoms 12 months after the incident with an mRS score
of 1, and the third patient died despite immediate
hemicraniectomy. Taking the above studies into account,
we based our decision on resuming anticoagulation on
repeated clinical exams and repeat imaging. Our patient’s
neurological examination results remained stable after decompressive hemicraniectomy. A follow-up noncontrast
CT of the head 7 days after decompressive
hemicraniectomy demonstrated stabilization of the hematoma. After consultation with our neurosurgery
colleagues, the team decided to resume anticoagulation
on day 8 after decompressive hemicraniectomy. Therefore, our timing to resume anticoagulation was based on
the stabilization of our patient’s neurological examination and brain imaging; however, despite the small number
of published cases resuming anticoagulation 24 hours after
surgery, we did not feel comfortable resuming anticoagulation until at least 7 days after surgery.

Conclusion
Current AHA/ASA guidelines recommend anticoagulation for patients with CVT and ICH; however, there is
a lack of data supporting the optimum timing of starting anticoagulation as well as resuming anticoagulation
after decompressive hemicraniectomy. In a small case series
of 3 patients with CVT undergoing decompressive
hemicraniectomy, anticoagulation was resumed 24 hours
after surgery. In this case of CVT with ICH and subsequent decompressive hemicraniectomy, anticoagulation was
resumed 8 days after decompressive hemicraniectomy
based on consistent and stable neurological examinations, stable intracranial hematoma on noncontrast CT head,
and previous published case reports resuming anticoagulation in similar patients. There is currently no other
data in the literature that help guide the exact time to
resume anticoagulation in these challenging patients.
Further studies are needed to establish the best time to
resume anticoagulation in CVT patients with ICH that
require decompressive hemicraniectomy. Until prospective data are established, individualization of management
is suggested based on recurrent CVT versus bleeding risks.

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