Venous Thrombosis and Procoagulant Factors in High-risk Neuroblastoma

Abstract

The mechanism of increased thrombin production has been investigated in children with high-risk neuroblastoma (NB), to detect any possible association between catheter- related venous thrombosis (VT) and prothrombotic factors. Consecutive children with high-risk NB were studied by color-doppler ultrasonography of the upper vein system and thrombophilia factors assessment. Plasma levels of Tissue Factor (TF), Vascular Endothelial Growth Factor (VEGF), Prothrombin Activation Fragment 1+2, and Thrombin-Antithrombin Complex were evaluated. Moreover, inherited thrombophilia factors (homocystein, antithrombin, protein C, protein S, factor V Leiden, activated protein C resistence, mutation H1299R and G1691A of factor V, mutation G20210A of prothrombin, mutation T677 and A1298C of methylenetetrahydrofolate reductase, and allele 4G of plasminogen activator inhibitor-1) were tested to exclude congenital disorders. Six patients with mean age: 48.8 months---were studied. Five patients were affected by stage 4 NB and another one by stage 3 NB with Myc-N amplification. All children had a central venous line (mean duration: 8.5 mos). Four patients (67%) had asymptomatic catheter-related VT visualized by color-doppler ultrasonography. No patient had major inherited thrombophilia factors. The levels of plasma TF and plasma VEGF were found elevated in all patients. Mean value of TF (nv 20.3+/-6.6) was 82 pg/mL with a range of 39 to 131 pg/mL. Mean value of VEGF (nv 24.3 pg/mL) was 78.5 pg/mL with a range of 31 to 142 pg/mL. The increased risk of catheter-related VT detected in our small series of high-risk NB patients, was associated with elevated levels of circulating TF and VEGF. Further studies are needed to evaluate if elevated levels of TF/VEGF are involved both in the hypercoagulable state and in advanced childhood cancer.