Prevalence of mild hyperhomocysteinaemia and association with thrombophilic genotypes (factor V Leiden and prothrombin G20210A) in Italian patients with venous thromboembolic disease

Mild hyperhomocysteinaemia is an established risk factor for deep vein thro mbosis (DVT); few data concerning its potential interaction with thrombophi lic genotypes are available at the present time. We investigated 121 thromb osis-free individuals and 111 patients with at least one objectively confir med episode of DVT. A thrombophilic condition (deficiency in antithrombin, protein C and S, factor V Leiden, prothrombin G20210A) was detected in 15.2 % of the patients: mutant factor V or prothrombin genotypes were present in 6.6% of the controls. Hyperhomocysteinaemia was found in 14.4% of patients and 3.3% of the controls, with a 3.7-fold increase in risk for DVT (95% CI 1.1-12.3), Adoption of different cut-off levels for definition of hyperhom ocysteinaemia did not substantially change the magnitude of the risk. Carri ership of both hyperhomocysteinaemia and factor V Leiden or prothrombin G20 210A was detected in 2.7% of patients for each combination and in none of t he controls, An approximate estimate of 30-fold increased risk in carriers of both hyperhomocysteinaemia and factor V Leiden and 50-fold increased ris k In carriers of both hyperhomocysteinaemia and prothrombin G20210A was cal culated, suggesting a synergistic interaction between hyperhomocysteinaemia and such thrombophilic genotypes, Yet statistical analysis is highly unsta ble due to the small number of individuals with combined defects. Further i nvestigations on large series of patients are needed.