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Prothrombotic Factors are Highly Associated with Cerebral Venous Sinus Thrombosis
Abstract & Commentary
Source: Cakmak S, et al. Cerebral venous thrombosis: Clinical outcome and systemic screening of prothrombotic factors. Neurology. 2003;60:1175-1178.
Cerebral venous thrombosis (CVT) is a stroke syndrome characterized by headache, seizures, and hemorrhagic infarction. Compared with conventional ischemic stroke, CVT has an excellent prognosis, especially when it is recognized rapidly with early initiation of anticoagulant therapy. CVT may be associated with a known hypercoagulable state such as malignancy or with certain exposures, such as the combination of cigarette smoking and oral contraceptive use. Infections such as chronic mastoiditis may precipitate CVT, a phenomenon known as "otitic hydrocephalus." Pregnancy and the postpartum state also elevate CVT risk.
Cakmak and associates report a series of 16 patients with CVT with an aim toward identifying underlying prothrombotic factors. Outcome, as expected, was generally excellent (in 87.5% of patients), even in the setting of hemorrhagic infarction at presentation. More interestingly, 9 of 12 patients were found to have an identifiable hypercoagulable factor. An elevated factor VIII level (with a functional level > 150%) was diagnosed in 8 of these 9. This was even more notable in that factor VIII levels were only measured in 11 of the 16 patients. Of note, 3 patients developed CVT after treatment with corticosteroids for multiple sclerosis or optic neuritis, each undergoing lumbar puncture as part of their prior workup. CSF hypotension and steroids are noted by Cakmak et al as possible contributors to CVT in these cases.
It has been well demonstrated (but perhaps not that widely recognized) that elevations in factor VIII levels increase the risk of venous thromboembolism. Factor VIII levels above the 90th percentile increase DVT and PE risk by as much as 14-fold.1 Factor VIII appears to be a similarly potent risk factor for cerebral venous clotting, along with other newly recognized factors such as the G20210A prothrombin gene polymorphism and factor V Leiden. These data on factor VIII suggest that with ongoing advances in molecular genetics, there may soon be no such thing as an "idiopathic" venous clot.
Even in the absence of a positive finding on hypercoagulable workup, patients who have had a DVT or PE may have nevertheless "declared" themselves as an at-risk subject. Recent data suggest that long-term treatment with warfarin (at low dose and possibly at full levels) may be indicated in patients with DVT or PE regardless of whether they have a hypercoagulable state.2
Despite these data, it is less clear how these venous phenomena apply to arterial clot, such as in cryptogenic stroke, where platelet aggregation may play an important role. Warfarin therapy may be beneficial in selected cases of cryptogenic stroke, but this hypothesis has never been demonstrable in any large-scale randomized trial. — Alan Z. Segal
Dr. Segal is Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Presbyterian Hospital.
1. Kyrle PA, et al. N Engl J Med. 2000;343:457-462.
2. Ridker PM, et al. N Engl J Med. 2003;348:1425-1434.