Prothrombotic risk factors in children with spontaneous venous thrombosis and their asymptomatic parents: A family study

The present study was designed to assess to what extent single and combined clotting abnormalities influence spontaneous vascular accidents in pediatr ic patients, and how the children affected differ in their prothrombotic ri sk profiles from their biological first-degree family members. In addition, this study was performed to investigate if relatively mild thrombophilic p olymorphisms not leading to thrombosis in the parents cause severe clinical expression when coinherited with an established prothrombotic risk factor. The factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, t he methylenetetrahydrofolate reductase (MTHFR) T677T genotype, the plasmino gen activator inhibitor (PAI)-1 promoter polymorphism, lipoprotein (Lp)(a), antithrombin, protein C, and protein S were investigated in 48 childhood p atients aged neonate to <18 years (median 0.5 years) with spontaneous venou s thromboembolism (SVT) compared with the carrier status of their first-deg ree family members. In 19 of the 48 patients (39.6%), one prothrombotic ris k factor was diagnosed, and in 27 of the 48 subjects (56.3%) at least two p rothrombotic defects/alleles. In the majority of cases with SVT, the FV G16 91A mutation was involved either with a second mutated allele or combined w ith elevated Lp(a), the 4G/4G genotype of the PAI-1 promoter polymorphism, and the T677T MTHFR genotype. The rate of combined prothrombotic risk facto rs was significantly higher in childhood patients compared with their paren ts (p=0.0004). In conclusion, based on the data presented here we suggest t hat early-onset SVT in childhood patients is mainly caused by combinations of at least two prothrombotic risk factors. (C) 2000 Elsevier Science Ltd. All rights reserved.