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• W1698259584 abstract "Prothrombin G20210A mutation, factor (F)V Leiden mutation and oral contraceptive (OC) use were previously shown to be associated with an increased risk of cerebral venous thrombosis (CVT) [1Martin P.J. Enevoldson T.P. Cerebral venous thrombosis.Postgrad Med J. 1996; 72: 72-6Crossref PubMed Google Scholar, 2Reuner K.H. Ruf A. Grau A. Rickmann H. Stolz E. Juttler E. Druschky K.F. Patscheke H. Prothrombin gene G20210→A transition is a risk factor for cerebral venous thrombosis.Stroke. 1998; 29: 1765-9Crossref PubMed Google Scholar, 3Martinelli I. Sacchi E. Landi G. Taioli E. Duca F. Mannucci P.M. High risk of cerebral vein thrombosis in carriers of a prothrombin‐gene mutation and in users of oral contraceptives.N Engl J Med. 1998; 338: 1793-7Crossref PubMed Scopus (0) Google Scholar]. We investigated the prevalences of prothrombin G20210A mutation, FV Leiden mutation and OC use in 42 consecutive patients with objectively confirmed diagnosis of CVT (median age of 28 years and 67% being women), and compared them with 134 healthy subjects, recruited from biologically unrelated acquaintances or partners of patients without history of venous thromboembolism (VTE) or known systemic diseases (median age of 34 years and 60% being women). Prothrombin G20210A mutation was found in 16.7% of patients and 0.7% of the control group, yielding an odds ratio (OR) for CVT of 26.6 [95% confidence interval (CI): 3.2‐223.5]. FV Leiden mutation was detected in 4.8% of patients and in 2.2% of the control group (OR: 2.2, 95% CI: 0.4–13.5). It is noteworthy that the majority of carriers of prothrombin G20210A mutation and FV Leiden mutation were Caucasian. Our prevalence of prothrombin G20210A mutation was similar to an Italian study (20%) [3Martinelli I. Sacchi E. Landi G. Taioli E. Duca F. Mannucci P.M. High risk of cerebral vein thrombosis in carriers of a prothrombin‐gene mutation and in users of oral contraceptives.N Engl J Med. 1998; 338: 1793-7Crossref PubMed Scopus (0) Google Scholar], and to a previous Brazilian report with 14 CVT patients (14.3%) [4Voetsch B. Damasceno B.P. Camargo E.C. Massaro A. Bacheschi L.A. Scaff M. Annichino‐Bizzacchi J.M. Arruda V.R. Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults.Thromb Haemost. 2000; 83: 229-33Crossref PubMed Google Scholar]. In accordance to previous reports [2Reuner K.H. Ruf A. Grau A. Rickmann H. Stolz E. Juttler E. Druschky K.F. Patscheke H. Prothrombin gene G20210→A transition is a risk factor for cerebral venous thrombosis.Stroke. 1998; 29: 1765-9Crossref PubMed Google Scholar, 3Martinelli I. Sacchi E. Landi G. Taioli E. Duca F. Mannucci P.M. High risk of cerebral vein thrombosis in carriers of a prothrombin‐gene mutation and in users of oral contraceptives.N Engl J Med. 1998; 338: 1793-7Crossref PubMed Scopus (0) Google Scholar], prothrombin G20210A mutation was a significant risk factor for CVT. The proportion of patients carrying FV Leiden was also similar to the previous Brazilian report (7.1%) [4Voetsch B. Damasceno B.P. Camargo E.C. Massaro A. Bacheschi L.A. Scaff M. Annichino‐Bizzacchi J.M. Arruda V.R. Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults.Thromb Haemost. 2000; 83: 229-33Crossref PubMed Google Scholar], but lower as compared with the Italian series (15%) [3Martinelli I. Sacchi E. Landi G. Taioli E. Duca F. Mannucci P.M. High risk of cerebral vein thrombosis in carriers of a prothrombin‐gene mutation and in users of oral contraceptives.N Engl J Med. 1998; 338: 1793-7Crossref PubMed Scopus (0) Google Scholar]. The high prevalence of the prothrombin G20210A mutation in Brazilian patients may derive from the ethnic background of the study populations. Brazilian general population has an extremely heterogeneous ethnic composition, unevenly distributed in the country with variable degrees of admixtures. Brazilian citizens of Caucasian descent originate mainly from Southern Europe (specially Portugal, Italy and Spain), where prevalence of the prothrombin G20210A mutation is twice as high as compared to Northern Europe [5Rosendaal F.R. Doggen C.J. Zivelin A. Arruda V.R. Aiach M. Siscovick D.S. Hillarp A. Watzke H.H. Bernardi F. Cumming A.M. Preston F.E. Reitsma P.H. Geographic distribution of the 20210 G to A prothrombin variant.Thromb Haemost. 1998; 79: 706-8Crossref PubMed Google Scholar]. Patients and controls had a heterogeneous ethnic distribution: among patients, 55% were Caucasians and 43% were of Caucasian and Black descent and among controls, 20% were Caucasians and 80% were of Caucasian and Black descent. It is important to point out that the high OR for the prothrombin G20210A mutation may be in part attributable to the relatively low frequency of Caucasians among controls, since carriers of prothrombin G20210A mutation were in general Caucasians. Eighty‐nine percent of women had thrombosis between 20 and 50 years of age (Fig. 1). For this age group, 60% of the patients were OC users and 20% were in the puerperium when CVT was diagnosed. Among the five women with inherited thrombophilia, there were four who were also OC users. Among patients, 60% were OC users as compared to 12.5% of a historical control group of 40 consecutive women aged 20–50 that came as outpatients for reasons other than thrombosis (OR = 10.5, 95% CI: 3.1–36.0). Our results confirmed previous findings of a higher frequency of CVT in women than in men, mostly during reproductive age when there is an excessive exposure to exogenous (OC) and endogenous (pregnancy‐related) sex hormones [1Martin P.J. Enevoldson T.P. Cerebral venous thrombosis.Postgrad Med J. 1996; 72: 72-6Crossref PubMed Google Scholar, 3Martinelli I. Sacchi E. Landi G. Taioli E. Duca F. Mannucci P.M. High risk of cerebral vein thrombosis in carriers of a prothrombin‐gene mutation and in users of oral contraceptives.N Engl J Med. 1998; 338: 1793-7Crossref PubMed Scopus (0) Google Scholar]. Eleven patients had acquired disorders that might be associated with CVT such as nephrotic syndrome, bacterial meningitis, antiphospholipid syndrome, Behçet's disease, Crohn's disease, sinusitis, homocystinuria, essential thrombocythemia and breast cancer. Both cases of CVT associated with meningitis were male patients with prothrombin G20210A mutation, and the patient with Crohn's disease was also OC user. The prevalence of acquired disorders was higher in men (50%) than in women (14%), P = 0.02. Overall, we found that among 42 consecutive patients with CVT, 72% had at least one acquired risk factor or predisposing condition for venous thromboembolism, six of whom were also carriers of prothrombin G20210A mutation (n = 5) and FV Leiden mutation (n = 1). Only 28% of patients had CVT spontaneously. Among the seven carriers of prothrombin G20210A mutation, only two subjects had no other known acquired predisposing condition for venous thromboembolism, suggesting that this mutation is usually associated with other risk factors in patients with CVT. Patients were re‐evaluated 30 days after CVT diagnosis by two neurologists unaware of the genotypic results, and the functional clinical outcome was graded on the modified Rankin Scale [6Wilson J.T. Hareendran A. Grant M. Baird T. Schulz U.G. Muir K.W. Bone I. Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin scale.Stroke. 2002; 33: 2243-6Crossref PubMed Scopus (483) Google Scholar]. Most patients (71%) had no activity limitations. There was no relationship between prothrombin G20210A mutation and FV Leiden mutation and clinical outcome: 21% of patients without limitations carried those mutations, as compared to 25% of patients with sequelae (Fisher's test, P = 1.00). Our data did not confirm the findings of a German study [7Stolz E. Kemkes‐Matthes B. Potzsch B. Hahn M. Kraus J. Wirbartz A. Kaps M. Screening for thrombophilic risk factors among 25 German patients with cerebral venous thrombosis.Acta Neurol Scand. 2000; 102: 31-6Crossref PubMed Scopus (0) Google Scholar] including 10 patients who had poor clinical outcome among 25 patients with CVT. Inherited thrombophilia (including protein C, protein S and plasminogen deficiencies) were more common among patients with limitations than in those with better outcome. However, that series was smaller than ours and there were more patients with limitations (40%) than in our series. In conclusion, most cases of CVT are associated with at least one inherited or acquired risk factor for venous thrombosis. In Brazilian subjects, the prothrombin G20210A mutation and OC use are significant risk factors for CVT, whereas isolated FV Leiden mutation does not show significant association. We are indebted to Dr Gisele Sampaio Silva and Dr Márcia Mayumi Fukujima for the expert neurological assistance." @default.
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• W1698259584 title "Prothrombin G20210A mutation, and not factor V Leiden mutation, is a risk factor for cerebral venous thrombosis in Brazilian patients" @default.
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