Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users who are carriers of hereditary prothrombotic conditions

Objective: To investigate whether users of oral contraceptives who are carriers of a hereditary prothrombotic condition (factor V Leiden mutation, protein C, S, or antithrombin deficiency) have an increased risk of cerebral sinus thrombosis. Design: Comparison of a prospective series of cases of cerebral sinus thrombosis with population data. Setting: Neurological teaching hospitals from different regions in the Netherlands (cases) and a representative sample of the non-institutionalised Dutch population (controls). Subjects: 40 women aged 18-54 years with cerebral sinus thrombosis (cases) and 2248 women aged 18-49 years (controls). Main outcome measure: Current use of oral contraceptives at the time of the thrombosis (cases) or at the time of the questionnaire (controls). Prevalences of a hereditary prothrombotic condition in patients and in the population with odds ratios. Results: 34 of 40 (85%) women with cerebral sinus thrombosis used oral contraceptives, versus 1007 of 2248 (45%) of the control women; the age adjusted odds ratio was 13 (95% confidence interval 5 to 37). Seven of 36 patients (19%) had a prothrombotic deficiency, versus 7% expected in the population; this corresponds to a threefold to fourfold increase in risk. In women who used oral contraceptives and also carried a prothrombotic defect, the odds ratio for cerebral sinus thrombosis was about 30 relative to women who had neither risk factor. Conclusion: The use of oral contraceptives and being a carrier of a hereditary prothrombotic condition increase the risk of and interact in a multiplicative way in the development of cerebral sinus thrombosis. Introduction Epidemiological studies have shown that oral contraceptives carry a small but increased risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism). Furthermore, women who use oral contraceptives and carry the factor V Leiden mutation have a higher risk of venous thromboembolism than expected from the mere addition of these risks. Although the association between oral contraceptives and venous thromboembolism is generally accepted, there remains discussion about possible sources of bias that might influence the magnitude of the risk. Cerebral venous sinus thrombosis is a relatively rare disease, often with cerebral infarcts, which may lead to seizures, other neurological symptoms, or death. Patients with sinus thrombosis, however, may recover completely. Oral contraceptives and hereditary prothrombotic conditions, such as protein C, S, and antithrombin deficiency and factor V Leiden mutation, have been reported as possible causes of cerebral sinus thrombosis. We compared a series of patients with cerebral venous sinus thrombosis from a prospective treatment trial with population data from the Netherlands to investigate the risk of oral contraceptive use and prothrombotic conditions for cerebral sinus thrombosis. Patients and methods Cases Cases were patients with cerebral sinus thrombosis (newly diagnosed) who participated in a treatment trial from July 1992 to November 1996 that compared low molecular weight heparin in a therapeutic dose with placebo in a randomised double blind design. Patients Papers Department of Neurology, Academic Medical Centre, PO Box 22700, 1100 DE Amsterdam, Netherlands S F T M de Bruijn, senior registrar in neurology J Stam, professor of neurology Department of Vascular Medicine, Academic Medical Centre, Amsterdam M M W Koopman, internist Department of Clinical Epidemiology, University hospital, Postbus 9600, 2300 RC Leiden, Netherlands J P Vandenbroucke, professor of clinical epidemiology Correspondence to: Professor Stam [email protected]