The present study was designed to assess to what extent single and combined clotting abnormalities influence spontaneous vascular accidents in pediatric patients, and how the children affected differ in their prothrombotic risk profiles from their biological first-degree family members. In addition, this study was performed to investigate if relatively mild thrombophilic polymorphisms 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, the methylenetetrahydrofolate reductase (MTHFR) T677T genotype, the plasminogen activator inhibitor (PAI)-1 promoter polymorphism, lipoprotein (Lp)(a), antithrombin, protein C, and protein S were investigated in 48 childhood patients aged neonate to18 years (median 0.5 years) with spontaneous venous thromboembolism (SVT) compared with the carrier status of their first-degree family members. In 19 of the 48 patients (39.6%), one prothrombotic risk factor was diagnosed, and in 27 of the 48 subjects (56.3%) at least two prothrombotic defects/alleles. In the majority of cases with SVT, the FV G1691A mutation was involved either with a second mutated allele or combined with elevated Lp(a), the 4G/4G genotype of the PAI -1 promoter polymorphism, and the T677T MTHFR genotype. The rate of combined prothrombotic risk factors was significantly higher in childhood patients compared with their parents. In conclusion, based on the data presented here we suggest that early-onset SVT in childhood patients is mainly caused by combinations of at least two prothrombotic risk factors.
