A Rare Thrombophilic Occurrence: Dural Venous Sinus Thrombosis in a Patient with Significant Family History of Protein S Deficiency

Abstract

Protein S is a potent anticoagulant that downregulates thrombin formation and is a vitamin K-dependent glycoprotein which is primarily synthesized in the liver. A deficiency in this protein or decreased activity, as seen in hereditary protein S deficiency, can lead to life-threatening thrombosis. Hereditary protein S deficiency is a rare disease as listed by the National Organization for Rare Disorders (NORD). It is known to cause venous as well as arterial thromboembolic events commonly occurring in the deep leg and pelvic veins. Dural venous sinus thrombosis is a rare consequence of protein S deficiency and is associated with a risk of increased morbidity and mortality. We report a case of dural venous sinus thrombosis in a patient with a family history of protein S deficiency in nine family members. A 53-year-old female presented to the ED with a three-day history of persistent left-sided headache, left facial numbness with tingling, and photophobia. She denied any visual disturbances, slurring of speech, and/or unilateral weakness. Some 10 years prior to this episode, she was placed on warfarin therapy for deep vein thrombosis (DVT) of lower extremity, but she discontinued it after three years of treatment without consulting her treating physician. She was taking oral contraceptive pills (OCPs) for two years and discontinued one month ago. She has nine family members with protein S deficiency, but the patient was never screened for a hypercoagulable state. On admission, her vital signs were within normal limits. Pupils were round and reactive to light, neck was supple, there was a sensory deficit for pinprick on the left V2-V3 distribution, and remainder of the cranial nerves and neurologic examination was unremarkable. CT scan of the head demonstrated a hyper-density within the left transverse and sigmoid sinus suspicious for dural venous sinus thrombosis. This was confirmed by CT angiogram showing a filling defect throughout the transverse sinus and sigmoid sinus extending below the jugular bulb into the superior aspect of the jugular vein. Intravenous heparin and warfarin were initiated. As the patient had severe trypanophobia and IV heparin required frequent activated partial thromboplastin time (APTT) monitoring, this was later changed to subcutaneous low-molecular-weight heparin and warfarin. Subsequent thrombosis panel showed a reduced protein S activity of 15% and low levels of total and free protein S antigens. She was discharged home with life-long warfarin therapy. In conclusion, cerebral dural venous sinus thrombosis is a rare and potentially life-threatening condition that can be seen in hereditary protein S deficiency. A high degree of suspicion in young females with worsening headache and neurologic signs and symptoms will help with timely diagnosis and management avoiding serious consequences. In a patient with a family history of thrombophilia, as seen in our patient, screening is important in order to confirm an underlying thrombophilic state...