Increased lipoprotein(a) is an important risk factor for venous thromboembolism in childhood

Background-Serum levels of lipoprotein(a) [Lp(a)] are determined largely by genetic variation in the gene encoding for apolipoprotein(a) [apo(a)], the specific protein component of Lp(a) that is very homologous to plasminogen . High plasma levels of Lp(a) increase the risk for premature atherosclerot ic vessel diseases. We investigated the little-characterized role of Lp(a) as a risk factor for venous thromboembolic diseases, alone and in conjuncti on with established thrombophilic risk factors of proteins regulating blood coagulation and fibrinolysis. Methods and Results-Serum levels of Lp(a) and lipids, protein C, protein S, and antithrombin, as well as the size of apo(a) isoforms and the presence of the factor V:Q(506) mutation, were determined in 186 consecutively admit ted children from neonates to 18 years old with a history of venous thrombo sis and in 186 age- and disease-matched control subjects, Children with a h istory of venous thrombosis had a significantly higher median Lp(a) level ( 19 versus 4.4 mg/dL) than control subjects. The risk for thromboembolic eve nts in children with Lp(a) levels in the upper quartile, ie, >30 mg/dL, was 7.2 (95% CI, 3.7 to 14.5). The size of apo(a) isoforms was inversely relat ed to Lp(a) levels and to the risk for thromboembolic events. Compared with the highest quartile of the apo(a) size distribution, the lowest quartile was associated with a risk of 8.2. In addition, multivariate statistical an alysis gives evidence that the factor V:Q(506) mutation (OR/CI, 2.8/1.6 to 4.9), protein C (OR/CI, 6.5/2.1 to 19), and antithrombin deficiency (OR/CI, 10.4/1.2 to 90) were independent risk factors of childhood venous thrombos is. Coincidence of elevated Lp(a) with factor V:Q(506) mutation or deficien cies of protein C or antithrombin further increased the risk for thromboemb olic events to 8.4. Conclusions-Lp(a) >30 mg/dL is a risk factor for venous thromboembolism in childhood. Lp(a) measurements should be included in the screening of causal factors in children with venous thromboembolic events.