Accepted Manuscript

Pharmacological management of cerebral venous sinus

thrombosis with full-dose IV heparin infusion and its clinical
outcomes

Andrea Fernandez, Vidya Nair, Anna Mckeone, Joseph Ho

PII: S0735-6757(17)30207-3
DOI: doi: 10.1016/j.ajem.2017.03.041
Reference: YAJEM 56559
To appear in:
Received date: 9 March 2017
Revised date: 15 March 2017
Accepted date: 16 March 2017

Please cite this article as: Andrea Fernandez, Vidya Nair, Anna Mckeone, Joseph Ho
, Pharmacological management of cerebral venous sinus thrombosis with full-dose IV
heparin infusion and its clinical outcomes. The address for the corresponding author
was captured as affiliation for all authors. Please check if appropriate. Yajem(2017), doi:
10.1016/j.ajem.2017.03.041

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 ACCEPTED MANUSCRIPT

Pharmacological Management of Cerebral Venous Sinus Thrombosis with Full-

Dose IV Heparin Infusion and Its Clinical Outcomes
Andrea Fernandez, PharmD1,2 – corresponding author
Vidya Nair, PharmD1,3
Anna Mckeone, MD, FACEP1,4
Joseph Ho, MD, PhD1,5
1
Providence St. Peter Hospital, 413 Lily Rd NE Olympia, WA 98506

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2
andreacamille.fernandez@providence.org
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vidya.nair@providence.org
4
anna.mckeone@yahoo.com
5

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joseph.ho@providence.org

Abstract
OBJECTIVE: To report a case of successful use of unfractionated heparin (UFH) infusion to treat cerebral

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venous sinus thrombosis (CVST). CASE SUMMARY: A 54-year-old female with a history of ovarian cancer
addressed through palliative care, presents to the Emergency Department complaining of nausea, vomiting and
headache for the last 72 hours. The patient was on a home regimen of enoxaparin 1.5 mg/kg subcutaneously
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daily for recent pulmonary embolism and deep vein thrombosis that developed while on warfarin therapy
previously. CT scan showed superior sagittal sinus thrombosis. UFH infusion was initiated and continued for
48 hours until the headache dissipated. DISCUSSION: Stable CVST may be treated with UFH infusion;
however, there is limited literature that describes UFH dosing for CVST management. CONCLUSIONS: UFH
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may be considered as one of the pharmacological agents to manage CVST. The dosing for UFH bolus and
infusion is similar to treatment dose for pulmonary embolism/deep vein thrombosis management with goal
anti-Xa between 0.3-0.7 units/mL.
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Key words:
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CVST
Heparin
Thrombosis
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Full-dose heparin
Cerebral sinus thrombosis
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CVST Management with Full-Dose IV UFH

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Pharmacological Management of Cerebral Venous Sinus Thrombosis with Full-Dose IV Heparin

Infusion and Its Clinical Outcomes

The estimated annual incidence of CVST is between 2 to 4 per million per year.1 Unlike ischemic stroke
which affects the arterial blood flow to the brain, CVST affects the venous side blocking blood flow out
of the brain. There are guidelines broadly recommending anticoagulation for CVST; however, there are
no literature specifically guiding intravenous UFH dosing.1 Clinical trials assessing current
pharmacological management strategies for CVST are lacking due to the rarity of the disease. Pertinent

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literature was identified through PubMed using MeSH terms heparin and CVST. Only articles written in

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the English language and evaluating human subjects were used.

A 54-year-old Caucasian female weighing 56.7 kg presented to ED with complaints of nausea, vomiting,

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sweating and generalized headache that had been worsening over three days. The patient denied
experiencing any seizure activity or loss of consciousness. She also denied having acute nuchal rigidity
or fever. The patient was alert and oriented with normal speech and mentation. Her motor and sensory

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functions were intact. The patient’s past medical history was significant for history of deep vein
thrombosis (DVT), recent pulmonary embolism (PE) while therapeutic on warfarin and ovarian cancer
treated palliatively. Pertinent medication prior to admission includes enoxaparin 90 mg (1.5 mg/kg)
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subcutaneously daily. At presentation, the vital signs included blood pressure of 139/75, heart rate of
75, and a respiratory rate of 18. Baseline laboratory studies were unremarkable. A head CT scan
showed an acute superior sagittal sinus thrombosis with involvement of the torcula and proximal
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transverse sinuses, consistent with cerebral venous thrombosis. The patient was subsequently
transferred to the neurology floor from the ED on a reduced UFH infusion rate of 850 units/hour (15
units/kg/hour). The patient’s heparin infusion was monitored every 6 hours and titrated per an
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institution-specific protocol (Appendix A). She was monitored to ensure her symptoms did not worsen
and the duration of the heparin infusion was determined by the clinical improvement of her headache.
The patient had significant improvement in her headache after one day of heparin treatment as
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evidenced by the reported pain score decreasing from 5 to 1. Heparin infusion was continued for
approximately 48 hours and was discontinued upon discharge. The patient was transitioned back to
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enoxaparin, but since her CVST occurred while on enoxaparin 90 mg (1.5mg/kg) subcutaneously once
daily, the dose was increased to 60 mg (1mg/kg) subcutaneously twice daily for long term
anticoagulation.
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Multiple treatment strategies may be considered for CVST management including local thrombolysis,
anticoagulation, mechanical thrombectomy, and endovascular procedures. Initial treatment of CVST in
anticoagulant naïve patients usually does not include thrombolysis as seen with arterial strokes, but is
more commonly treated with full dose heparin infusion as seen with DVT or PE.1

The first randomized controlled trial conducted in 1991 that studied anticoagulation in CVST patients
demonstrated that dose-adjusted heparin infusion is an effective treatment in this patient population.3
Another randomized trial that looked at anticoagulation in CVST concluded that anticoagulation in CVST
resulted in a more favorable outcome than no anticoagulation.4

Based on results from randomized controlled trials and data from observational studies on outcomes
and bleeding complications, anticoagulation continues to be a mainstay of treatment for CVST.4 The

CVST Management with Full-Dose IV UFH

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anticoagulation treatment may consist of therapeutic doses of UFH or LMWH. If heparin is used,
patients should receive an initial bolus followed by a continuous infusion at DVT/PE treatment dose
(Appendix A). The goal of initial anticoagulation is to prevent thrombus extension, aid in thrombus
resolution, and prevent systemic deep vein thrombosis (DVT) and pulmonary embolism (PE). Catheter
directed thrombolysis , thrombectomy, and endovascular therapy have been considered as treatment
options if the patient continues to deteriorate despite adequate anticoagulation.

Recent case reports have found that newer oral anticoagulants can be an option for treating CVST.5
Geisbusch et al6 looked at rivaroxaban and warfarin for the treatment and prevention of CVST in 16
patients. The study showed that the patients who received rivaroxaban had a survival rate of 93.8 % and

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concluded that rivaroxaban may be considered in patients with CVST.

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In the case of our patient, neurology was consulted. Since the patient had received enoxaparin prior to
admit, heparin bolus was not administered and the infusion rate was reduced from the recommended

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full dose rate of 18 units/kg/hour to 15 units/kg/hour. The patient’s symptoms subsided after about 48
hours of heparin initiation. Patient was switched back to LMWH after approximately 16 hours from
symptom resolution. Patient was discharged to home on long term anticoagulation with LMWH to

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prevent recurrence of CVST or systemic venous thromboembolism. Warfarin was not used for this
patient’s long-term anticoagulation therapy as the patient previously suffered a PE while therapeutic on
warfarin therapy and enoxaparin is the preferred anticoagulant in the setting of cancer.
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In conclusion, ED providers should be cognizant that initial treatment of CVST is not the same as
treatment for ischemic stroke in anticoagulant naïve patients. Anticoagulation with full dose UFH or
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LMWH is considered the gold standard of treatment for CVST.1 Following initial treatment, patients will
require long term anticoagulation to prevent recurrent thrombosis. The duration of treatment is
dependent on individual patient risk factors.
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CVST Management with Full-Dose IV UFH

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References

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Tsai, F. Y. (2011). Diagnosis and management of cerebral venous thrombosis: A statement for
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2. Star, M., & Flaster, M. (2013). Advances and controversies in the management of cerebral venous
thrombosis. Neurologic Clinics. http://doi.org/10.1016/j.ncl.2013.03.013

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3. Einh??upl, K. M., Villringer, A., Mehraein, S., Garner, C., Pellkofer, M., Haberl, R. L., … Meister, W.

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(1991). Heparin treatment in sinus venous thrombosis. The Lancet, 338(8767), 597–600.
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4. Coutinho, J. M., & Stam, J. (2010). How to treat cerebral venous and sinus thrombosis. Journal of
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7. Ferro, J. M., Canhão, P., Stam, J., Bousser, M.-G., & Barinagarrementeria, F. (2004). Prognosis of
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cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and
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http://doi.org/10.1161/01.STR.0000117571.76197.26
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Appendix A. Providence St. Peter Hospital Heparin Protocol

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CVST Management with Full-Dose IV UFH