Mild antithrombin deficiency and risk of recurrent venous thromboembolism: a prospective cohort study.

BACKGROUND Antithrombin deficiency, defined by antithrombin levels of <70%, is a major thrombophilic condition associated with an increased risk of venous thromboembolism (VTE). No prospective data are available about the risk of recurrent VTE associated with mildly decreased antithrombin levels (70-80%). METHODS AND RESULTS Consecutive patients with a first VTE were stratified according to functional antithrombin levels (<70%, 70-80%, >80%) and were followed up for a mean of 8.70 years to assess the incidence of VTE recurrence. A total of 823 patients (mean age, 48.3 years; 41.9% male) were enrolled. Recurrent VTE occurred in 253 patients (3.53% per patient-year). With stratification for antithrombin levels, VTE recurrence occurred in 19 patients with antithrombin levels <70% (5.90% per patient-year), in 20 patients with antithrombin levels 70% to 80% (5.35% per patient-year), and in 214 patients with antithrombin levels >80% (3.31% per patient-year). After adjustment for major VTE risk factors and for anticoagulation duration, the risk of VTE recurrence was significantly higher in patients with antithrombin levels <70% (hazard ratio, 3.48; 95% confidence interval, 2.16-5.61) and antithrombin levels 70% to 80% (hazard ratio, 2.40; 95% confidence interval, 1.51-3.80) compared with patients with antithrombin levels >80%. When the population was stratified according to the presence or absence of major risk factors for the index event, the association remained significant only in patients with unprovoked VTE. CONCLUSIONS The presence of mild antithrombin deficiency (70-80% antithrombin) in patients with unprovoked VTE is associated with a significantly increased risk of recurrence and should be taken into account when the duration of secondary prevention is determined. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01382550.