No abstract

V enous thromboembolism is a common, potentially fatal, yet treatable, condition. The risk of a recurrent venous thromboembolic event after 3-6 months of oral anticoagulant therapy varies. Some groups of patients (e.g., those who had a venous thromboembolism after surgery) have a very low annual risk of recurrence (< 1%), 1 and they can safely discontinue anticoagulant therapy. 2 However, among patients with an unprovoked thromboembolism who discontine anticoagulation therapy after 3-6 months, the risk of a recurrence in the first year is 5%-27%. 3-6 In the second year, the risk is estimated to be 5%, 3 and it is estimated to be 2%-3.8% for each subsequent year. 5,7 The casefatality rate for recurrent venous thromboembolism is between 5% and 13%. 8,9 Oral anticoagulation therapy is very effective for reducing the risk of recurrence during therapy (> 90% relative risk [RR] reduction); 3,4,10,11 however, this benefit is lost after therapy is discontinued. 3,10,11 The risk of major bleeding with ongoing oral anticoagulation therapy among venous thromboembolism patients is 0.9-3.0% per year, 3,4,6,12 with an estimated case-fatality rate of 13%. 13 Given that the long-term risk of fatal hemorrhage appears to balance the risk of fatal recurrent pulmonary embolism among patients with an unprovoked venous thromboembolism, clinicians are unsure if continuing oral anticoagulation therapy beyond 6 months is necessary. 2,14 Identifying subgroups of patients with an annual risk of less than 3% will help clinicians decide which patients can safely discontinue anticoagulant therapy.

Summary.  Background: The post‐thrombotic syndrome is a chronic, poorly understood complication of deep venous thrombosis (DVT). Objectives: To evaluate predictors of the post‐thrombotic syndrome, including intensity of long‐term anticoagulation, and to assess the impact of the post‐thrombotic syndrome on quality of life. Patients and methods: The setting was 13 Canadian hospitals and one US hospital. One hundred and forty‐five patients with an unprovoked episode of proximal DVT who were initially treated with 3 months of conventional‐intensity warfarin [target International Normalized Ratio (INR) of 2.5] then participated in a trial comparing two intensities of long‐term warfarin therapy (target INR 2.5 vs. INR 1.7). Post‐thrombotic syndrome was assessed at the end of the trial using a validated clinical scale. Generic and venous disease‐specific quality of life was compared in patients with and without the post‐thrombotic syndrome. Multivariable regression analyses were performed to identify predictors of the post‐thrombotic syndrome and of its severity. Results: After an average follow‐up of 2.2 years, the prevalence of post‐thrombotic syndrome was 37% and of severe post‐thrombotic syndrome was 4%. Quality of life was worse in patients with the post‐thrombotic syndrome compared with patients who did not have it. The presence of factor (F)V Leiden or the prothrombin gene mutation was an independent predictor of both a lower risk (P = 0.006) and reduced severity (P = 0.045) of the post‐thrombotic syndrome. Intensity of anticoagulation did not influence the risk of developing the post‐thrombotic syndrome. Conclusions: The post‐thrombotic syndrome is a frequent and burdensome complication of proximal DVT, even among patients maintained on long‐term oral anticoagulation. While the presence of FV Leiden or prothrombin gene mutation appears to be associated with a reduced risk of post‐thrombotic syndrome, this finding requires further evaluation in prospective studies.