Mild Antithrombin Deficiency and the Risk of Recurrent Venous Thromboembolism: A Prospective Cohort Study
Background—Antithrombin (AT) deficiency, defined by AT levels of less than 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 AT levels (70-80%).
Methods and Results—Consecutive patients with a first VTE were stratified according to functional AT 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, males 41.9%) were enrolled. Recurrent VTE occurred in 253 patients (3.53% patients-year). Stratifying for AT levels, VTE recurrence occurred in 19 (5.90% patients-year) <70%AT patients, in 20 (5.35% patients-year) of the 70-80%AT patients and in 214 patients (3.31% patient-year) with >80%AT. After adjusting for major VTE risk factors and for anticoagulation duration, the risk of VTE recurrence was significantly higher in patients with <70%AT (HR: 3.48, 95%CI: 2.16-5.61) and 70-80%AT (HR: 2.40, 95%CI: 1.51-3.80) as compared to >80%AT patients. 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 AT deficiency (70%-80% AT) in patients with unprovoked VTE is associated with a significantly increased risk of recurrence and should be taken into account when deciding the duration of secondary prevention.
Clinical Trial Registration Information—ClinicalTrials.gov; Unique Identifier: NCT01382550.
- Received May 13, 2013.
- Revision received September 8, 2013.
- Accepted October 7, 2013.