D-dimer to Predict Recurrence in Patients With Multiple Episodes of Venous Thromboembolism

The Negative Predictive Value of D-dimer on the Risk of Recurrent Venous Thromboembolism in Patients With Multiple Previous Events: a Prospective Cohort Study

Optimal duration of oral anticoagulant therapy in patients with recurrent episodes of venous thromboembolism (VTE) is a matter of debate and recommendations are based on inadequate evidence. More than 12 months of treatment are currently recommended, and the grade of recommendation is low.

The PROLONG study has recently evaluated the predictive role of D-dimer measurement after withholding oral anticoagulant treatment in patients with a first episode of VTE. Patients with a positive D-dimer had a significantly higher incidence of VTE recurrences than patients with a negative D-dimer and required resumption of the antithrombotic treatment. Based on the results of this and of previous cohort studies, it appears safe to withhold treatment in patients with negative D-dimer values and to continue treatment in patients with altered D-dimer levels.

Aim of this study is therefore to assess the negative predictive value of D-dimer also in patients with recurrent VTE and to evaluate the clinical utility of this approach in this patient setting.

Inclusion Criteria:

• Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism)
• Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases
• Age > 18 years
• Informed consent provided

Exclusion Criteria:

• Pregnancy/puerperium
• One or more episodes of massive pulmonary embolism
• Last event isolated idiopathic pulmonary embolism
• Two or more idiopathic VTE events
• First degree relatives with recurrent VTE
• Right ventricular disfunction or pulmonary hypertension
• Active cancer
• Antiphospholipid antibodies syndrome
• Antithrombin deficiency
• Homozygous Factor V Leiden or G20210A prothrombin mutation
• Heterozygous Factor V Leiden and G20210A prothrombin mutation
• Concomitant congenital thrombophilic mutations
• Concomitant indications to long term oral anticoagulant treatment
• Severe cardiorespiratory insufficiency
• Severe liver or renal disease (creatinine clearance > 2 mg/dL)
• Limited life expectancy
• Geographic inaccessibility