D-dimer and Factor VIII are Independent Risk Factors for Recurrence After Anticoagulation Withdrawal for a First Idiopathic Deep Vein Thrombosis

Abstract

Conclusion: Elevated levels of D-dimer and factor VIII at 30 ± 10 days after cessation of vitamin K antagonist (VKA) therapy for a first episode of idiopathic proximal deep venous thrombosis (DVT) are independent risk factors for recurrent venous thromboembolism (VTE). Summary: The optimal duration of VKA therapy after a first episode of VTE is unknown. It appears VKA extension after unprovoked VTE can reduce the risk of recurrent VTE but at the potential price of increased bleeding. There is therefore intense interest in stratifying patients with idiopathic VTE with respect to risk factors that may increase rates of recurrence. The specific objective of this study was to assess the risk of recurrence of VTE associated with elevated D-dimer levels and factor VIII levels after withdrawal of VKA therapy for symptomatic idiopathic proximal VTE. Consecutive outpatients with the first episode of idiopathic proximal DVT were enrolled into the study after cessation of VKA therapy. At 30 ± 10 days after cessation of VKA therapy, levels of D-dimer (cutoff value, 500 ng/mL) and chromogenic factor VIII, as well as inherited thrombophilias were determined. Follow-up extended for 2 years. Overall recurrence rate of VTE was 16.4% (55 of 336; 95% confidence interval [CI], 13%-21%). The multivariate hazard ratio for recurrence was 2.45 (95% CI, 1.24-4.99) for abnormal D-dimer and 2.76 (95% CI, 1.57-4.85) for factor VIII >75th percentile (2.42 μ/mL). The values were adjusted for age, sex, and thrombophilia. Compared with normal levels of D-dimer and factor VIII, the multivariate hazard ratio was 4.5 (95% CI, 1.7-12.2) for normal D-dimer levels with factor VIII >2.42 U/mL, and 2.7 (95% CI, 1.2-6.6) and 7.1 (95% CI, 2.8-17.6) for abnormal D-dimer with factor VIII, respectively, below and above 2.42 U/mL. Comment: The appropriate length of treatment with VKA therapy for patients with idiopathic VTE is unknown. The data suggest the longer the treatment period with VKA, the less the recurrence rates of VTE. Of course, VKAs are associated with increased risk of bleeding and are inconvenient for the patient. There is therefore intense interest in stratifying risk among those patients with idiopathic VTE. This is another study that attempts to do just that. The percentage of patients with both normal D-dimer and factor VIII <75th percentile was 37%. This implies that at least a third of patients with idiopathic VTE have a low risk of VTE recurrence. Larger studies are warranted to determine if the combination of factor VIII and D-dimer analysis can be used to tailor duration of VKA therapy after idiopathic VTE.