Summary
We hypothesized that increased prothrombin levels associated with G20210A prothrombin
gene mutation could affect the results of activated protein C (APC) resistance phenotype
and increase the risk of venous thrombosis (VT). The increasing addition of purified
prothrombin in plasma of 90 normal subjects resulted in a parallel significant increase
of APC resistance. Significantly different mean n-APC-SR in 879 GG20210 subjects compared
to 27 heterozygous carriers of isolated G20210A mutation was observed (1.0 ± 0.12
vs. 0.95 ± 0.11; P = 0.02) in a random sample of 906 normal population subjects. Twenty-seven
families with VT and isolated G20210A mutation consecutively diagnosed during 1998-1999
were evaluated. Mean n-APC-SR was significantly lower in the 80 G20210A carriers compared
to 58 GG 20210 relatives investigated, even after sex and age adjustment (0.92 ± 0.08
vs. 1.05 ± 0.13; P < 0.0001). A strong relationship between plasma prothrombin level
and n-APC-SR was observed in the families. When n-APC-SR values were grouped in tertiles,
the odds ratio for VTE, after exclusion of the index cases and adjustment for 20210
status, for subjects in the lowest tertile (n-APC-SR 0.73-0.90) was 4.58 (95% CI 0.78-26.88)
compared to upper tertile (n-APC-SR 1.01-1.30). In conclusion, in subjects with G20210A
mutation APC resistance is significantly increased, correlates with plasma prothrombin
level and the carriers with the lowest APC resistance values have an increased risk
of VTE.
Keywords
Venous thrombosis - FV Leiden - APC resistance - thrombophilia - prothrombin