Venous thromboembolism in neonates and children.

Thrombosis in children is gaining increased awareness, as advanced medical care has increased treatment intensity of hospitalized pediatric patients. Guidelines for diagnosis and treatment of children and neonates with venous thromboembolism (VTE) are mostly extrapolated from adult data, despite the uniqueness of their hemostatic system. Whereas inherited thrombophilia (IT) have been established as risk factors for VTE in adults, in children with idiopathic VTE and in pediatric populations in which thromboses were associated with medical diseases, IT have been described as additional risk factors. Follow-up data for VTE recurrence in children suggest a recurrence rate between 3% (neonates) and 21% (idiopathic VTE). Apart from underlying medical conditions, recently reported systematic reviews on pediatric VTE and stroke have shown significant associations between thrombosis and presence of factor V G1691A, factor II G20210A, protein C-, protein S- and antithrombin deficiency, even more pronounced when combined IT were involved. The pooled odds ratios (OR: single IT) for VTE onset ranged from 2.4 for the factor II G20210A mutation (cerebrovascular occlusion) to 9.4 in children with antithrombin deficiency (venous VTE). In addition, the pooled OR for persistent antiphospholipid antibodies/lupus anticoagulants was 6.6 for children with cerebrovascular occlusion and 4.9 for pediatric cases with venous VTE. The factor II G20210A mutation (OR: 2.1), protein C- (OR: 2.4), S- (OR: 3.1), and antithrombin deficiency (OR: 3.0) did also play a significant role at recurrence. Among primarily asymptomatic family members of pediatric VTE index cases annual VTE incidences were 2.82% (95% confidence interval [95% CI], 1.63-4.80%) in carriers of antithrombin, protein C, or protein S-deficiency, 0.42% (0.12-0.53%) for factor II G202010A, 0.25% (0.12-0.53%) for factor V G1691A, and 0.10% (0.06-0.17%) in relatives with no IT. Based on these data diagnosis, screening and treatment issues will be discussed.