Role of genetic prothrombotic risk factors in childhood caval vein thrombosis

Abstract

Childhood caval vein thrombosis has a high incidence especially in the first year of life. Besides deficiencies of protein C, protein S, antithrombin and plasminogen, the factor (F) V G1691A mutation, the prothrombin (PT) G20210A variant, the methylenetetrahydro-folate reductase (MTHFR) TT677 genotype, or increased lipoprotein (Lp) (a)>30 mg/dl have emerged as important prothrombotic risk factors in childhood vascular accidents. 27 consecutive childhood patients with inferior caval vein thrombosis and 100 healthy age-matched controls were investigated for the presence of these prothrombotic risk factors with respect to the first thrombotic onset. In 19 out of 27, patients thrombosis occurred during infancy; the remaining vascular accidents were diagnosed during puberty. In 13 out of the 19 infants, vascular occlusion occurred spontaneously, five times associated with renal venous thrombosis. 68.4% of patients in the first year of life (n=13) showed at least one prothrombotic risk factor. The FV mutation (heterozygous n=4, homozygous n=1), Lp (a)>30 mg/dl and kringle 4 repeats <28 (n=4), MTHFR TT677 with mild hyperhomocysteinaemia (>95th age-dependent percentile, i.e. 8.5 μmol/l: n=3) and antithrombin deficiency type II (n=1) were diagnosed with an overall odds ratio/95% confidence interval of 9.2/3.1–27.4. In the adolescent group, genetic risk factors were found in 50% of patients investigated (FV mutation (n=1), PT variant (n=3); odds ratio/95% confidence interval: 4.2/0.97–18.6).

Conclusion Data presented here suggest that genetic prothrombotic risk factors play an important role in childhood caval vein thrombosis. Remarkably, during puberty and adolescence the predominant defect diagnosed was the PT G20210A variant, whereas the FV G1691A mutation had a higher incidence during infancy.