25
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicentre cohort study

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Background

          The relative importance of previous diagnosis and hereditary prothrombotic risk factors for cerebral venous thrombosis (CVT) in children in determining risk of a second cerebral or systemic venous thrombosis (VT), compared with other clinical, neuroimaging, and treatment variables, is unknown.

          Methods

          We followed up the survivors of 396 consecutively enrolled patients with CVT, aged newborn to 18 years (median 5·2 years) for a median of 36 months (maximum 85 months). In accordance with international treatment guidelines, 250 children (65%) received acute anticoagulation with unfractionated heparin or low-molecular weight heparin, followed by secondary anticoagulation prophylaxis with low-molecular weight heparin or warfarin in 165 (43%).

          Results

          Of 396 children enrolled, 12 died immediately and 22 (6%) had recurrent VT (13 cerebral; 3%) at a median of 6 months (range 0·1–85). Repeat venous imaging was available in 266 children. Recurrent VT only occurred in children whose first CVT was diagnosed after age 2 years; the underlying medical condition had no effect. In Cox regression analyses, non-administration of anticoagulant before relapse (hazard ratio [HR] 11·2 95% CI 3·4–37·0; p<0·0001), persistent occlusion on repeat venous imaging (4·1, 1·1–14·8; p=0·032), and heterozygosity for the G20210A mutation in factor II (4·3, 1·1–16·2; p=0·034) were independently associated with recurrent VT. Among patients who had recurrent VT, 70% (15) occurred within the 6 months after onset.

          Conclusion

          Age at CVT onset, non-administration of anticoagulation, persistent venous occlusion, and presence of G20210A mutation in factor II predict recurrent VT in children. Secondary prophylactic anticoagulation should be given on a patient-to-patient basis in children with newly identified CVT and at high risk of recurrent VT. Factors that affect recanalisation need further research.

          Related collections

          Most cited references48

          • Record: found
          • Abstract: found
          • Article: not found

          Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT).

          The natural history and long-term prognosis of cerebral vein and dural sinus thrombosis (CVT) have not been examined previously by adequately powered prospective studies. We performed a multinational (21 countries), multicenter (89 centers), prospective observational study. Patients were followed up at 6 months and yearly thereafter. Primary outcome was death or dependence as assessed by modified Rankin Scale (mRS) score >2 at the end of follow-up. From May 1998 to May 2001, 624 adult patients with CVT were registered. At the end of follow-up (median 16 months), 356 patients (57.1%) had no symptom or signs (mRS=0), 137 (22%) had minor residual symptoms (mRS=1), and 47 (7.5%) had mild impairments (mRS=2). Eighteen (2.9%) were moderately impaired (mRS=3), 14 (2.2%) were severely handicapped (mRS=4 or 5), and 52 (8.3%) had died. Multivariate predictors of death or dependence were age >37 years (hazard ratio [HR]=2.0), male sex (HR=1.6), coma (HR=2.7), mental status disorder (HR=2.0), hemorrhage on admission CT scan (HR=1.9), thrombosis of the deep cerebral venous system (HR=2.9), central nervous system infection (HR=3.3), and cancer (HR=2.9). Fourteen patients (2.2%) had a recurrent sinus thrombosis, 27 (4.3%) had other thrombotic events, and 66 (10.6%) had seizures. The prognosis of CVT is better than reported previously. A subgroup (13%) of clinically identifiable CVT patients is at increased risk of bad outcome. These high-risk patients may benefit from more aggressive therapeutic interventions, to be studied in randomized clinical trials.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cerebral sinovenous thrombosis in children.

            Cerebral sinovenous thrombosis in children is a serious disorder, and information is needed about its prevention and treatment. The Canadian Pediatric Ischemic Stroke Registry was initiated in 1992 at the 16 pediatric tertiary care centers in Canada. Children (newborn to 18 years of age) with symptoms and radiographic confirmation of sinovenous thrombosis were included. During the first six years of the registry, 160 consecutive children with sinovenous thrombosis were enrolled, and the incidence of the disorder was 0.67 cases per 100,000 children per year. Neonates were most commonly affected. Fifty-eight percent of the children had seizures, 76 percent had diffuse neurologic signs, and 42 percent had focal neurologic signs. Risk factors included head and neck disorders (in 29 percent), acute systemic illnesses (in 54 percent), chronic systemic diseases (in 36 percent), and prothrombotic states (in 41 percent). Venous infarcts occurred in 41 percent of the children. Fifty-three percent of the children received antithrombotic agents. Neurologic deficits were present in 38 percent of the children, and 8 percent died; half the deaths were due to sinovenous thrombosis. Predictors of adverse neurologic outcomes were seizures at presentation and venous infarcts. Sinovenous thrombosis in children affects primarily neonates and results in neurologic impairment or death in approximately half the cases. The occurrence of venous infarcts or seizures portends a poor outcome.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome.

              Neuroimaging and management advances require review of indications for excluding cerebral venous sinus (sinovenous) thrombosis (CSVT) in children. Our goals were to examine (i) clinical presentations of CSVT, (ii) prothrombotic risk factors and other predisposing events, (iii) clinical and radiological features of brain lesions in CSVT compared with arterial stroke, and (iv) predictors of outcome. We studied 42 children with CSVT from five European paediatric neurology stroke registries. Patients aged from 3 weeks to 13 (median 5.75) years (27 boys; 64%) presented with lethargy, anorexia, headache, vomiting, seizures, focal signs or coma and with CSVT on neuroimaging. Seventeen had prior chronic conditions; of the 25 previously well patients, 23 had recent infections, eight became dehydrated and six had both. Two children had a history compatible with prior CSVT. Anaemia and/or microcytosis (21 probable iron deficiency, five haemolytic, including two with sickle cell disease and one with beta-thalassaemia) was as common (62%) as prothrombotic disorder (13/21 screened). High factor VIII and homozygosity for the thermolabile methylene tetrahydrofolate reductase polymorphism were the commonest prothrombotic disorders. The superficial venous system was involved in 32 patients, the deep in six, and both in four. Data on the 13 children with bland infarction and the 12 with haemorrhage in the context of CSVT were compared with those from 88 children with ischaemic (AIS) and 24 with haemorrhagic (AHS) arterial stroke. In multiple logistic regression, iron deficiency, parietal infarction and lack of caudate involvement independently predicted CSVT rather than arterial disease. Five patients died, three acutely, one after recurrence and one after 6 months being quadriparetic and blind. Follow-up ranged from 0.5 to 10 (median 1) years. Twenty-six patients (62%) had sequelae: pseudotumour cerebri in 12 and cognitive and/or behavioural disabilities in 14, associated with epilepsy in three, hemiparesis in two and visual problems in two. Eighteen patients, including six with haemorrhage, were anticoagulated. Older age [odds ratio (OR) 1.54, 95% confidence limits (CI) 1.12, 2.13, P = 0.008], lack of parenchymal abnormality (OR 0.17, 95% CI 0.02, 1.56, P = 0.1), anticoagulation (OR 24.2, 95% CI 1.96, 299) and lateral and/or sigmoid sinus involvement (OR 16.2, 95% CI 1.62, 161, P = 0.02) were independent predictors of good cognitive outcome, although the last predicted pseudotumour cerebri. Death was associated with coma at presentation. Of 19 patients with follow-up magnetic resonance (MR) venography, three had persistent occlusion, associated with anaemia and longer prodrome. A low threshold for CT or MR venography in children with acute neurological symptoms is essential. Nutritional deficiencies may be modifiable risk factors. A paediatric anticoagulation trial may be required, after the natural history has been further established from registries of cases with and without treatment.
                Bookmark

                Author and article information

                Contributors
                Journal
                Lancet Neurol
                Lancet Neurology
                Lancet Pub. Group
                1474-4422
                1474-4465
                July 2007
                July 2007
                : 6
                : 7
                : 595-603
                Affiliations
                [a ]Israel National Haemophilia Centre, Sheba Medical Centre, Tel-Hashomer, Israel
                [b ]Neurosciences Unit, Institute of Child Health, University College London, London, UK
                [c ]Department of Child Health, Southampton General Hospital, Southampton, UK
                [d ]Institute of Clinical Radiology/Neuroradiology, University Hospital Münster, Germany
                [e ]Department of Medical Informatics and Biomathematics, University Hospital Münster, Münster, Germany
                [f ]Department of Paediatric Haematology/Oncology, University Hospital Münster, Münster, Germany
                [g ]Department of Radiology, Great Ormond Street Hospital, London, UK
                [h ]Leibniz-Institute for Arteriosclerosis Research, University of Münster, Münster, Germany
                [i ]Department of Haematology, Rambam Medical Centre, Israel
                [j ]Department of Paediatrics, University Hospital Munich, Germany
                [k ]Department of Paediatric Haematology/Oncology, University Hospital Frankfurt am Main, Germany
                [l ]Department of Paediatrics, University Hospital Dresden, Dresden, Germany
                [m ]Department of Paediatrics, University Hospital Halle, Halle, Germany
                [n ]Department of Paediatric Haematology/Oncology, University Hospital Freiburg, Freiburg, Germany
                [o ]Services de Neuropédiatrie, Université de Sherbrooke, Canada
                [p ]Université Catholique de Louvain, Louvain-La-Neuve Belgium
                Author notes
                [* ]Correspondence to: Professor U Nowak-Göttl, Department of Paediatric Haematology and Oncology, University Hospital of Münster, D-48149 Münster, Germany leagottl@ 123456uni-muenster.de
                Article
                LANEUR70131
                10.1016/S1474-4422(07)70131-X
                1906729
                17560171
                40ded4c4-b3c0-46e9-94c0-c8d5c5d27954
                .

                This document may be redistributed and reused, subject to certain conditions.

                History
                Categories
                Fast track — Articles

                Neurology
                Neurology

                Comments

                Comment on this article