Title: Cerebral Venous Thrombosis: Acute Vision Loss in a Patient with PAI-1 4G/4G Gene Mutation A

Authors: Ayesha Khadka, MD, and Gregory Polcha, DO.

Email: akhadka@mercy.com

Introduction: Dural venous thrombosis predominantly occurs in females and has an annual incidence of 1.16 – 2.02 cases per 100,000 every year.  It is associated with OCP use, pregnancy, cancer, trauma, or genetic prothrombotic states, including deficiency in proteins (antithrombin III, protein C, or protein S) or genetic mutations (Factor V Leiden, prothrombin 20210A allele, and MTHFR). Factor V Leiden and prothrombin G20210 A mutations account for 50-60% of cases.  Thrombosis pertaining to Plasminogen activator inhibitor-1 (PAI-1) gene mutations is understudied and information on its significance is still being evaluated. We present a case of dural thrombosis in a patient with multiple genetic mutation.

Case: A 31-year-old male presented with vomiting, subconjunctival hemorrhage, and blurry vision.   MRV head without contrast showed thrombosis of left transverse sinus while MRI of orbits showed flattening of optic disks.   Systemic anticoagulation with heparin was initiated and left transverse thrombectomy with stent placements was urgently performed.  Patient was transitioned to oral ticagrelor and rivaroxaban prior to discharge and had complete resolution of symptoms.   Ultimately, thrombophilia panel showed homozygous PA1 4G/4G mutation and heterozygous MHFTR gene mutation.

Discussion: PAI-1 is the major inhibitor of tissue type plasminogen activator. It is postulated that increased plasma PAI-1 levels results in thrombosis due to reduced fibrinolytic effects.  Meta-analyses pose that intact PAI-1 4G allele reduces risk of CVA, TIA, and cardiovascular mortality and mutations in the 4G/4G allele resulted in a 20% increased risk of myocardial infarction.  Dural thrombosis is diagnostically challenging and requires a multidisciplinary approach and long term follow up to monitor for appropriate treatment of the disease.  Current guidelines by American Heart Association and American Stroke Associations suggest that any patient with dural thrombosis must be investigated for both acquired and inherited pro thrombotic states.  Inherited thrombophilia necessitates lifelong anticoagulation.