Objectives: To assess the possible association between inherited thrombophilic alterations and the severity of peripheral arterial disease (PAD).
Design: A case-control study.
Methods: We evaluated the presence of G20210A prothrombin (FII) and R506Q FV Leiden mutations, antithrombin, protein C and S deficiencies in 176 patients with PAD at Fontaine's stage II and in 106 patients with critical limb ischaemia (Fontaine's stage III/IV) consecutively referred to our unit. As control group, we studied 209 apparently healthy subjects.
Results: The prevalence of G20210A prothrombin mutation was similar in PAD patients and controls (odds ratio (OR): 1.361; 95% confidence interval (CI): 0.552-3.355; p=0.503 after adjustment for age, sex, smoking and presence of diabetes), but was significantly higher in patients with Fontaine's stage III/IV vs. those with stage II and controls (10.4% vs. 3.4% vs. 4.3%; p=0.02, respectively). According to a logistic multivariate model that included all patients with PAD, the presence of the FII G20210A mutation (OR: 4.621; 95% CI: 1.548-13.789; p=0.006) was associated with critical limb ischaemia after adjustment for age, sex, smoking, presence of diabetes and the use of platelet aggregation inhibitors. The prevalence of the other thrombophilic alterations was not different in patients with Fontaine's stage III/IV, in patients with stage II and in controls.
Conclusion: These hypothesis-generating data suggest that the FII 20210A allele may be considered as a genetic marker predisposing critical ischaemia in patients with PAD, justifying larger longitudinal studies.