a b s t r a c t

OBJECTIVE: To report a case of successful use of unfractionated heparin (UFH) infusion to treat cerebral 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 h. The patient was on a home regimen of enoxaparin 1.5 mg/kg subcutaneously 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 h 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 may be considered as one of the pharmacolog- ical 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 and 0.7 units/mL.

(C) 2017

The estimated annual incidence of CVST is between 2 and 4 per mil- lion 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 intrave- nous UFH dosing [1]. Clinical trials assessing current Pharmacological management strategies for CVST are lacking due to the rarity of the dis- ease. Pertinent literature was identified through PubMed using MeSH terms heparin and CVST. Only articles written in 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, sweating and generalized head- ache that had been worsening over three days. The patient denied experiencing any Seizure activity or loss of consciousness. She also de- nied having acute Nuchal rigidity or fever. The patient was alert and ori- ented with normal speech and mentation. Her motor and sensory functions were intact. The patient’s past medical history was significant for history of Deep vein thrombosis , recent pulmonary embolism (PE) while therapeutic on warfarin and ovarian cancer treated pallia- tively. Pertinent medication prior to admission includes enoxaparin 90 mg (1.5 mg/kg) subcutaneously daily. At presentation, the vital

* Corresponding author.

E-mail addresses: [email protected] (A. Fernandez), [email protected] (V. Nair), [email protected] (J. Ho).

signs included blood pressure of 139/75, heart rate of 75, and a respira- tory rate of 18. Baseline laboratory studies were unremarkable. A head CT scan showed an acute superior sagittal sinus thrombosis with in- volvement of the torcula and proximal transverse sinuses, consistent with cerebral venous thrombosis. The patient was subsequently trans- ferred to the neurology floor from the ED on a reduced UFH infusion rate of 850 units/h (15 units/kg/h). The patient’s heparin infusion was monitored every 6 h and titrated per an 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 ev- idenced by the reported pain score decreasing from 5 to 1. Heparin infu- sion was continued for approximately 48 h and was discontinued upon discharge. The patient was transitioned back to enoxaparin, but since her CVST occurred while on enoxaparin 90 mg (1.5 mg/kg) subcutane- ously once daily, the dose was increased to 60 mg (1 mg/kg) subcutane- ously twice daily for long term anticoagulation.

Multiple treatment strategies may be considered for CVST manage- ment including local thrombolysis, anticoagulation, Mechanical thrombectomy, and endoVascular procedures. Initial treatment of CVST in anticoagulant naive patients usually does not include thrombol- ysis 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

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heparin infusion is an effective treatment in this patient population [2]. Another randomized trial that looked at anticoagulation in CVST con- cluded that anticoagulation in CVST resulted in a more favorable out- come than no anticoagulation [3].

Based on results from randomized controlled trials and data from observational studies on outcomes and bleeding complica- tions, anticoagulation continues to be a mainstay of treatment for CVST [3]. The 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 and pulmonary embolism (PE). Catheter directed thrombolysis, thrombectomy, and Endovascular therapy have been considered as treatment op- tions 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 [4]. Geisbusch et al. [5] 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 concluded that rivaroxaban may be considered in patients with CVST.

In the case of our patient, neurology was consulted. Since the patient had received enoxaparin prior to admit, heparin bolus was not adminis- tered and the infusion rate was reduced from the recommended full dose rate of 18 units/kg/h to 15 units/kg/h. The patient’s symptoms sub- sided after about 48 h of heparin initiation. Patient was switched back to LMWH after approximately 16 h from symptom resolution. Patient was discharged to home on long term anticoagulation with LMWH to pre- vent recurrence of CVST or systemic venous thromboembolism. Warfa- rin was not used for this patient’s long-term anticoagulation therapy as the patient previously suffered a PE while therapeutic on warfarin ther- apy and enoxaparin is the preferred anticoagulant in the setting of cancer.

In conclusion, ED providers should be cognizant that initial treat- ment of CVST is not the same as treatment for ischemic stroke in antico- agulant naive patients. Anticoagulation with full dose UFH or LMWH is considered the gold standard of treatment for CVST [1]. Following initial treatment, patients will require long term anticoagulation to prevent re- current thrombosis. The duration of treatment is dependent on individ- ual patient risk factors.

Appendix A. Providence St. Peter Hospital heparin protocol

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References

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