Outcome in childhood cerebral venous thrombosis—new insights.

GERMANY; ISRAEL

BACKGROUND Cerebral venous thrombosis (CVT) in children is associated with considerable mortality and morbidity, but the long-term risk of a second cerebral or systemic venous thrombosis (VT) event has not received much attention in the literature. The effect of predisposing factors on the risk of recurrence is, therefore, unknown, and the guidelines for secondary prophylactic anticoagulation in children with CVT have been adapted from adult protocols. OBJECTIVE To determine the recurrence rate of symptomatic VT, and to identify predictors of VT recurrence. DESIGN AND INTERVENTION This European cohort study enrolled 396 consecutive patients from Belgium, Germany, Israel and the UK who had a first symptomatic CVT; patients were recruited regardless of the presence of prothrombotic risk factors. The enrollment period was July 1996 to August 2005. CVT was diagnosed using standard imaging methods, i.e. duplex sonography (in neonates only), MRI, and CT or magnetic resonance venography and angiography. Preterm infants and patients older than 19 years were excluded. Acute anticoagulation with unfractionated heparin or low-molecular-weight heparin (LMWH) was administered to 250(65%) children. Secondary anticoagulation prophyIaxis with LMWH or warfarin was provided in 165 (43%) cases. Surviving patients were followed up for a median of 36 months (range 0.1-85 months). The Cox proportional hazards model was used to evaluate the independent contributions of age at onset, underlying medical conditions, nonadministration of secondary prophylactic anticoagulation, neuroimaging data, and presence of prothrombotic risk factors to the risk of recurrent VT OUTCOME MEASURES The primary outcome measure was the recurrence rate of symptomatic VT per 1,000 person-years. Secondary outcome measures included the time to relapse and the relevance of clinical, laboratory and radiological risk factors to symptomatic recurrence. RESULTS Of the 396 children enrolled, 12 died immediately, so the final analysis included 384 patients (60% boys) with a median age of 5.2 years. A second VT event occurred in 22 of the surviving children, at a median of 6 months (range 0.1-85 months) after the index event. VT recurred only in patients who were older than 2 years (range 2.5-16.2 years) at the index event. The recurrence rate per 1,000 person-years was 21.2(95% 0113.9- 32.1) for the entire cohort and 29.1 (95% CI 18.9-44.7) for children older than 2 years. The risk of relapse was significantly increased in patients who did not receive anticoagulation before the relapse event (hazard ratio [HR] 11.2, 95% CI 3.4-37.0; P<0.0007), those with persistent occlusion on repeat venous imaging (HR 4.1, 95% CI 1.1-14.8; P=0.032), and those with heterozygosity for the G20210A mutation in factor II (HR 4.3, 95% CI 1.1-16.2; P=0.034). Underlying medical conditions had no effect on VT recurrence. CONCLUSION The risk of VT recurrence in children with CVT is increased in those who are older than 2 years, those who do not receive secondary anticoagulation prophylaxis, those who fail to recanalize, and those who have the G20210A mutation in factor II. [ABSTRACT FROM AUTHOR]

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