title: Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicentre cohort study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Israel National Haemophilia Centre, Sheba Medical Centre, Tel-Hashomer, Israel.
authors.forename: Gili
authors.initials: G
authors.lastname: Kenet
authors.forename: Fenella
authors.initials: F
authors.lastname: Kirkham
authors.forename: Thomas
authors.initials: T
authors.lastname: Niederstadt
authors.forename: Achim
authors.initials: A
authors.lastname: Heinecke
authors.forename: Dawn
authors.initials: D
authors.lastname: Saunders
authors.forename: Monika
authors.initials: M
authors.lastname: Stoll
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brenner
authors.forename: Christoph
authors.initials: C
authors.lastname: Bidlingmaier
authors.forename: Christine
authors.initials: C
authors.lastname: Heller
authors.forename: Ralf
authors.initials: R
authors.lastname: Knöfler
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Schobess
authors.forename: Barbara
authors.initials: B
authors.lastname: Zieger
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sébire
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nowak-Göttl
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007391:International Cooperation; D020767:Intracranial Thrombosis / Q000150:complications* / Q000453:epidemiology; D008297:Male; D010372:Pediatrics; D012008:Recurrence; D012307:Risk Factors; D020246:Venous Thrombosis / Q000453:epidemiology / Q000209:etiology*