Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Thrombophilic factors in idiopathic intracranial hypertension: a report of 51 patients and a meta-analysis Anat Kesler a , Efrat Kliper a , Einor Ben Assayag b , Eti Zwang c , Varda Deutsch c , Uriel Martinowitz e , Aharon Lubetsky e,1 and Shlomo Berliner d,1 Several studies have suggested that thrombophilic risk factors are more prevalent in individuals with idiopathic intracranial hypertension (IIH), and that a prothrombic state may be involved in the etiopathogenesis of this disease. We examine thrombophilic factors in a group of patients with IIH in relation to obesity. In addition, we reviewed the relevant literature and performed a meta-analysis. Thrombophilia work-up was performed on 51 patients with IIH at least 1 month following their first episode. Samples for the analysis of factor V Leiden (FVL), prothrombin gene variant (PGV) G20210A and methylenetetrahydrofolate reductase (MTHFR) were available in an additional 30 patients, that is 81 patients in all. Meta-analysis was performed. Of the 51 patients 40 were obese. Increased concentrations of fibrinogen, D-Dimer, factor VIII, factor IX and factor XI were found in 15, 7, 7, 6 and 2 patients, respectively, all obese. The circulating anticoagulant, measured by dilute Russell’s viper venom time (dRVVT assay), found mainly in obese. All 51 patients were negative for the anticardiolipin antibody (IgG immunoglobulin G) and IgG anti-b2 glycoprotein I. In the meta-analysis antiphospholipid antibodies were significantly associated with IIH [odds ratio (OR) of 4.25 (1.68 – 12.60)], similar to the association with high factor VIII [OR U 16.17 (2.87–91.01)], higher plasminogen activator inhibitor-1 (PAI-1) levels [OR U 6.91 (2.28–20.91)], and high lipoprotein (a) [LP(a)] [OR U 3.54 (1.54–8.70)]. Obesity often observed in IIH patients is frequently linked with thrombophilic factors. Thus, we believe that dysmetabolism could be the thrombophilic target for treatment in patients with IIH. Blood Coagul Fibrinolysis 21:328–333 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Blood Coagulation and Fibrinolysis 2010, 21:328–333 Keywords: coagulation, idiopathic intracranial hypertension, obesity a Department of Ophthalmology, b Department of Neurology, c Department of Hematology, d Medicine ‘E’, Tel Aviv Sourasky Medical Center and e Institute of Thrombosis and Hemostasis, and the National Hemophilia Center, The Chaim Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Correspondence to Anat Kesler, Neuro-Ophthalmology Unit, Department of Ophthalmology, Tel Aviv -Sourasky Medical Center, Tel Aviv, Israel Tel: +972 3 6973408; fax: +972 3 9340520; e-mail: kesler@netvision.net.il Received 7 July 2009 Revised 12 January 2010 Accepted 19 January 2010 Introduction Idiopathic intracranial hypertension (IIH) is a disorder associated with increased intracranial pressure without any clinical, laboratory, or radiological evidence of a space-occupying lesion. The cause and mechanism of this syndrome is obscure, and it has been suggested that cerebrospinal fluid (CSF) drainage is impeded by a venous occlusive disorder. This is supported by the higher preva- lence of thrombophilic risk factors in cohorts of IIH patients compared to the normal population [1–6]. In addition, our recent finding of increased red blood cell aggregation in IIH provides additional support and mech- anism for veno-occlusive cause [7]. The present study was designed to further investigate the association between thrombophilic risk factors and IIH. Due to the relatively small cohorts in our study (51 patients) and in the litera- ture, a meta-analysis was performed on the available literature. Patients and methods Patients Fifty-one consecutive patients (50 females and 1 male, mean age ¼ 31.9 years, range ¼ 18–57 years), with well established IIH according to the modified Dandy criteria [8], were recruited to the neuro-ophthalmology unit, Tel Aviv Sourasky Medical Center (excluding the patients from our previous study [7]). All patients were in the stable state of their disease, and undergone a full exam- ination by a senior neuro-ophthalmologist (A.K.). Inclusion criteria were age above 18 and below 68 years, normal brain neuroimaging, intracranial pressure greater than 250 mm H 2 O with normal CSF, bilateral papillo- dema, and nonfocal neurologic examination, except for isolated abducens paresis. Exclusion criteria included sinus vein thrombosis and pregnancy. The study was approved by the Tel Aviv Sourasky Medical Center Ethics Committee. A written informed consent was obtained from all participants. In addition to the present cohort, we used previous data for the three coagulation polymorphisms from additional 30 patients with IIH (26 females and 4 males, mean age ¼ 39.5 years, range ¼ 23–68 years) who gave their consents. Blood sampling and plasma preparation Venous blood samples were obtained from fasting patients at least 1 month after the clinical event. Blood was collected into a 0.109 mol/l buffered citrate in a ratio 328 Original article 1 A.L. and S.B. contributed equally to the writing of this article. 0957-5235 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/MBC.0b013e328338ce12