Recurrent thromboembolism in infants and children suffering from symptomatic neonatal arterial stroke - A prospective follow-up study

Background and Purpose - The present study was performed to evaluate the rate of recurrent symptomatic thromboembolism with respect to prothrombotic risk factors and underlying clinical conditions. Methods - In a series of 215 consecutively enrolled neonates with arterial ischemic stroke ( AIS), the factor V G1691A mutation, factor II G20210A variant, methylenetetrahydrofolate reductase ( MTHFR) T677T genotype, lipoprotein ( Lp) ( a), antithrombin, protein C, protein S, and anticardiolipin antibodies ( ACA) were investigated. Patient median follow- up was 3.5 years ( range, 1 to 8 years). Results - During follow- up, 7 infants and children ( 3.3%) showed recurrent symptomatic thromboembolism ( AIS, n = 4; venous sinus thrombosis, n = 2; deep vein thrombosis of the leg, n = 1). The factor V mutation, factor II variant, elevated Lp( a) > 30 mg/ dL, protein C deficiency, and protein S or antithrombin deficiency were associated with first stroke onset. In 5 of 7 cases ( 71.4%), prothrombotic risk factors [ MTHFR T677T, elevated Lp( a), hyperhomocysteinemia, protein C deficiency] were involved at the time of recurrence. Furthermore, a second thromboembolic event was triggered additionally by underlying diseases ( 71%), eg, cardiac malformation and immobilization, diarrhea, mastoiditis, and moyamoya syndrome. Conclusions - Data shown here give evidence that symptomatic recurrent thromboembolism is not common in children with neonatal AIS. The risk of a second event, however, is increased when underlying diseases occur and prothrombotic risk factors are involved.