Increased fasting total homocysteine plasma levels as a risk factor for thromboembolism in children.

Elevated total homocysteine (tHcy) concentrations are an independent risk factor for thromboembolic events in adults. In children with moderate hyperhomocysteinemia data are sparse. Therefore, between 1995 and 2002 we consecutively recruited 163 white pediatric patients with a first symptomatic thromboembolic event and 255 healthy controls (mean age: 6.4 years in patients vs. 6.6 years in controls, range: 3 months to 18 years) and measured fasting tHcy levels. Median tHcy levels in patients were significantly higher (6.6 micromol/l, range 2.9-20.4 micromol/l) than in controls (5.7 micromol/l, 2.0-14.0 micromol/l, p<0.0001). 48 of the 163 patients with thromboembolism (29.5%) versus 26 of the 255 controls (10.2%) had tHcy levels above the age-specific normal 90th percentile (OR 2.9, 95%CI: 1.7-4.8). The odds ratio for children in the highest quintile compared to children with levels in the lowest quintile was 4.3 (1.6-8.1; highest quintile: median tHcy level 9.6 micromol, range 8.0-20.4), showing a significantly increased risk for thromboembolic disease with even mild hyperhomocysteinemia. We conclude that hyperhomocysteinemia above the age-specific cut-off values is a risk factor for thromboembolic events in children. Therefore, screening for elevated fasting tHcy levels of patients with thromboembolism is recommended to stratify the risk of thromboembolism.