Cerebral Venous Sinus Thrombosis in Pregnancy

Anesthesiology News

---

Case Presentation

A 22-year-old woman, with a body mass index of 35 kg/m², presented to the emergency department with altered consciousness, 6 days after the uneventful delivery of a full-term healthy infant. According to her husband, less than 1 hour before admission, she experienced a sudden, severe thunderclap headache, rapidly progressing to confusion. At admission, blood pressure was 180/110 mm Hg, heart rate was 51 beats per minute, and the neurologic examination revealed bilateral papilledema. Rapid mental status deterioration to a Glasgow Coma Scale score of 7 prompted immediate endotracheal intubation, after administration of IV lidocaine, propofol, and rocuronium. Non-contrast CT of the brain showed hyperdensity of the right transverse sinus. Cerebral venous sinus thrombosis (CVST) was suspected and the diagnosis was confirmed with magnetic resonance venography, which showed thrombosis along the right transverse sinus with evidence of venous infarction without hemorrhage.

The patient was treated with heparin infusion and showed significant clinical improvement after 4 days. She was extubated and discharged home on warfarin therapy with recommendations for thrombophilia screening after discontinuation of the anticoagulation.

According to the CDC, venous thromboembolism accounts for 9.2% of maternal deaths in the United States.^1,2 In the general population, CVST is very rare, with an incidence of 3 to 4 in 1 million. Risk is significantly increased during the third trimester of pregnancy and in the peripartum period, to an incidence of 12 in 100,000, which accounts for 2% of strokes during this period.^3-5 The transverse sinus is most commonly affected.

The significantly increased risk during pregnancy and in the peripartum period can be explained by pregnancy-induced hematologic changes, which continue for 6 to 8 weeks postpartum. Pregnancy is a known hypercoagulable, prothrombotic state due to increased levels of procoagulant factors (factors II, VII, VIII, X, XII, and XII, and von Willebrand factor); increased fibrinogen levels (by approximately 50%); and increased platelet aggregation and decreased anticoagulant factors (protein S, increase in activated protein C resistance).^2,6 The risk for CVST is further increased by prothrombotic conditions (eg, factor V Leiden gene mutation leading to resistance to activated protein C, protein S and C deficiencies, antithrombin III deficiency, and hyperhomocysteinemia).⁷ Hypovolemia is an additional risk factor.⁷

Clinical Signs

The clinical signs largely vary with the site of the thrombosis and the presence or absence of parenchymal damage, ranging from headache to coma. Venous thrombosis causes decreased venous drainage, resulting in increased intracranial pressure (ICP), focal brain injury, and encephalopathy. Approximately 30% of patients can present with intracerebral hemorrhage.⁸

ache is the most frequent presenting symptom, with a frequency of 90%; and it can be mild, diffuse, and progressive, or sudden (ie, a thunderclap headache).⁵ Patients with CVST can also present with altered consciousness, seizures, and/or focal neurologic signs.

Diagnosis, Treatment, and Prognosis

The clinical suspicion of CVST should be confirmed by neuroimaging. Non-contrast CT can show hyperdensity of a cortical vein or dural sinus, suggesting venous obstruction in only 30% of cases.⁵ To confirm the diagnosis of CVST, venographic CT or MRI studies are recommended.^5,9Increased D-dimer level can support the diagnosis; however, normal values do not rule out CVST.¹⁰

To recanalize the obstructed vein or sinus, anticoagulation with unfractionated heparin or low-molecular-weight heparin (LMWH) should be started immediately after confirming the CVST diagnosis, including in patients with intracerebral hemorrhage. LMWH is preferred to unfractionated heparin during pregnancy and in the postpartum period, with the therapeutic aim of achieving an international normalized ratio of 2.0 to 3.0.^5,9

The optimal duration of therapeutic anticoagulation is based on underlying patient characteristics. For patients with a provoked event (those with a transient risk factor, such as postpartum state), 3 to 6 months of therapeutic anticoagulation is advised. Treatment duration may be extended up to 6 to 12 months for patients with an unprovoked event or may be of indefinite duration for those with recurrent events or with evidence of thrombophilia.⁵

The results of an international study on cerebral vein and dural sinus thrombosis, which included 624 patients in 89 centers located in 21 countries, indicate a mortality rate of 8%.¹¹

One month after discontinuation of anticoagulation therapy, and at least 6 weeks after delivery, thrombophilia screening is recommended for all patients with CVST.⁴ Antithrombotic prophylaxis with LMWH should be considered for future pregnancies to prevent recurrence of CVST.⁹

Despite anticoagulation, 9% to 13% of patients will experience clinical deterioration, and endovascular therapy may be warranted when standard treatment fails. Options for endovascular therapy include fibrinolytic therapy and/or mechanical clot retrieval. The optimal method is not defined and determination of treatment modality is at the discretion of the clinician. There are no randomized controlled trials to support one type of therapy over another, but guidelines advise use of these methods only when deterioration occurs in spite of intensive anticoagulation.⁵

In some cases presenting large venous infarctions or large hemorrhages, cerebral edema may be a complicating factor, and acetazolamide is recommended for treatment of increased ICP. There may be rare cases in which increased ICP leads to severe neurologic deterioration. In these situations, decompressive hemicraniectomy can be a lifesaving procedure.⁵

Airway Management in a Postpartum Patient With Increased ICP

Airway changes during pregnancy and labor are progressive and persist into the postpartum period. For that reason, the same planning and precautions taken for airway management in the prepartum patient should be followed for at least 48 hours after delivery.

Difficult face mask ventilation or endotracheal intubation can aggravate hypoxemic changes and lead to a further increase in ICP. Elevated head position facilitates venous drainage and can help decrease the ICP before induction.12 Preoxygenation with fraction of inspired oxygen is mandatory. The benefits of manual hyperventilation before intubation should be considered, as opposed to rapid sequence induction in a postpartum patient who presents with an increased risk for pulmonary aspiration of gastric contents. It is not clear whether video laryngoscopy is superior to direct laryngoscopy in minimizing hemodynamic changes during induction of anesthesia. Post-intubation positive pressure ventilation can decrease venous drainage from the cerebral vasculature.

Neuraxial Anesthesia in CVST

Spinal anesthesia is generally contraindicated in patients with focally induced increased ICP, because of an increased risk for brain stem herniation. Month and Vaida reported a parturient with CVST undergoing cesarean delivery under spinal anesthesia. The anesthetic was complicated by post-spinal bradycardia, possibly attributable to Cushing’s reflex.13

Conclusion

Pregnancy-induced hypercoagulability significantly increases the risk for CVST. Headache is the most frequent presenting symptom. General anesthesia is indicated in patients with increased ICP due to focal lesions. Blunting hemodynamic changes at endotracheal intubation and extubation in these patients is critical.

---

Dr Ermak is an assistant professor of neurology, Department of Neurology. Dr Vaida is a professor of anesthesiology, obstetrics, and gynecology; vice chair of research; and the director of obstetric anesthesia, Department of Anesthesiology. Both are at Penn State College of Medicine, Penn State Health Milton S. Hershey Medical Center, in Hershey, Pennsylvania. Drs Ermak and Vaida reported no relevant financial disclosures.

References

1. CDC. Pregnancy Mortality Surveillance System. 2017. www.cdc.gov/ reproductivehealth/ maternalinfanthealth/ pmss.html. Accessed July, 2017.
2. Leffert L, Butwick A, Carvalho B, et al; members of the SOAP VTE Taskforce. The Society for Obstetric Anesthesia and Perinatology consensus statement on the anesthetic management of pregnant and postpartum women receiving thromboprophylaxis or higher dose anticoagulants. Anesth Analg. 2018;126(3):928-944.
3. Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med. 2005;352(17):1791-1798.
4. Davie CA, O’Brien P. Stroke and pregnancy. J Neurol Neurosurg Psychiatry. 2008;79(3):240-245.
5. Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke.2011;42(4):1158-1192.
6. Hill CC, Pickinpaugh J. Physiologic changes in pregnancy. Surg Clin N Am. 2008;88(2):391-401.
7. Holzman RS, Bessim S. Regional anesthesia for a parturient with venous sinus thrombosis and placental abruption undergoing fractional heparin therapy. Anesthesiology. 2006;105(2):423-424.
8. Wasay M, Bakshi R, Bobustuc G, et al. Cerebral venous thrombosis: analysis of a multicenter cohort from the United States. J Stroke Cerebrovasc Dis. 2008;17(2):49-54.
9. Ferro JM, Bousser MG, CanhÃo P, et al; European Stroke Organization. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis – endorsed by the European Academy of Neurology. Eur J Neurol. 2017;24(10):1203-1213.
10. Bouser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol. 2007;6(2):162-170.
11. Ferro JM, CanhÃo P, Stam J, et al; ISCVT investigators. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke. 2004;35(3):664-670.
12. Anson J, Vaida S, Giampetro D, et al. Anesthetic management of labor and delivery in patients with elevated intracranial pressure. Int J Obstet Anesth. 2015;24(2):147-160.
13. Month R, Vaida S. Spinal anesthesia for cesarean delivery in a patient with cerebral venous sinus thrombosis. Can J Anaesth. 2008;55(9):658-659.