Abstract and Introduction
Herein, we present the case of a 22-year old obese Caucasian woman female with no acquired thrombophilic risk factors who was diagnosed with extensive cerebral sinus thrombosis. A detailed thrombophilia workup demonstrated persistently elevated plasminogen activator inhibitor 1 (PAI-1) activity levels, with an elevated PAI-1 antigen concentration and homozygosity for the PAI-1 4G allele (4G/4G genotype). The patient was treated with indefinite warfarin anticoagulation medication due to the unprovoked nature of her thrombotic event. Disturbances in the fibrinolytic system, in particular PAI-1, have been related to an increased risk of arterial and venous thrombosis. In this article, we discuss the pathophysiology of hypofibrinolysis associated with elevated PAI-1 levels and the PAI-1 4G/5G polymorphism.
A 22-year old obese Caucasian woman with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 34.3 kg per m2 and no significant past medical history arrived at the emergency department (ED) in early September 2014 seeking treatment for left-sided facial droop. She was diagnosed with Bell's palsy and started on oral corticosteroid therapy. A routine laboratory workup for conditions such as Lyme disease testing yielded negative results. During the next 2 to 3 weeks, the patient developed left-sided ptosis, left lateral and upper gaze paralysis, progressive left-sided visual loss, and partial right-sided visual obscuration. She also reported pulsating tinnitus and bifrontal morning headaches. Her primary care physician referred her to the ED, where she underwent an extensive workup.
The patient reported no fever, chills, sweating, or other systemic symptoms. She had no history of recent travel and no previous pregnancies; she reported that she was not sexually active. She also reported that she was not taking oral contraceptive pills, any other estrogen containing contraceptive chemicals, or other medications. A careful history did not identify any other provoking factors for thrombosis. She has a family history of type II diabetes mellitus and provoked deep venous thrombosis (DVT) postoperatively in her maternal grandfather. The differential diagnosis featured a space-occupying lesion; infection, including fungal disease; cerebral sinus thrombosis; paraneoplastic syndrome; central nervous system (CNS) autoimmune disease, and vasculitis.
Lab Med. 2016;47(3):223-240. © 2016 American Society for Clinical Pathology