Venous thrombosis in older people: prevalence of the factor V gene mutation Q506

Old age is usually considered to be a risk factor for venous thromboembolism, in conjunction with other factors such as heart failure, major surgery, cancer, long-term immobilization, and antiphospholipid antibodies. Genetic risk factors, especially inherited deficiencies in coagulation inhibitors, also play a role in the pathogenesis of thrombosis, but these are usually diagnosed in thrombophilic patients before the age of 50. The factor V Q506 mutation, responsible for activated protein C resistance, was recently linked to thromboembolic disease. We therefore investigated the prevalence of biological risk factors in older hospital patients with venous thromboembolism.

A 2-year study period.

Ivry sur Seine (Paris), France.

Seventy-nine geriatric patients (60 women and 19 men, mean age 83+/-6.8 years, range 70-102 years) who had had at least one proven episode of venous thromboembolism were enrolled over a 2-year period.

Lupus anticoagulant and antithrombin (AT), protein C (PC), and protein S (PS) levels were determined in plasma. The factor V Q506 mutation was detected on genomic DNA.

Lupus anticoagulant was detected in two women, one of whom also had a high level of anticardiolipin IgG, leading to the diagnosis of an antiphospholipid syndrome. No hereditary deficiency in AT, PC, or PS was found, but one patient had an acquired AT deficiency. Interestingly, nine of the 79 patients (11.4%, six women and three men) were heterozygous for the factor V Q506 mutation, although none were homozygous. The only major risk factor for thrombosis identified in these patients was prolonged immobilization in four cases. Four of the nine patients who were heterozygous for the factor V Q506 mutation had recurrent thromboembolism, and two of these patients had been immobilized for long periods.

This study confirms that hereditary deficiencies in coagulation inhibitors, and the lupus anticoagulant, are rarely involved in the pathogenesis of venous thromboembolism in older subjects. In contrast, the factor V Q506 mutation was frequently associated with thrombosis (11.4% of our patients) and should, therefore, be considered an important risk factor in the older people.