Serial D-dimers after anticoagulant cessation in unprovoked venous thromboembolism: Data from the REVERSE cohort study.

Introduction: While several risk stratification tools have been developed to predict the risk of recurrence in patients with an unprovoked venous thromboembolism (VTE), only 1 in 4 patients are categorized as low-risk. Rather than a one-time measure, serial D-dimer assessment holds promise to enhance the prediction of VTE recurrence after oral anticoagulant (OAC) cessation.
Methods: Using the REVERSE cohort, we compared VTE recurrence among patients with normal D-dimer levels (<490 ng/mL among males under age 70, <500 ng/mL in others) at OAC cessation and 1-month follow-up, to those with an elevated D-dimer level at either timepoint. We also evaluated VTE recurrence based on absolute increase in D-dimer levels between the two timepoints (e.g., ∆D-dimer) according to quartiles.
Results: Among 214 patients with serial D-dimer levels measured at OAC cessation and 1-month follow-up, an elevated D-dimer level at either timepoint was associated with a numerically higher risk of recurrent VTE than patients with normal D-dimer levels at both timepoints (6.9 % vs. 4.2 % per year, hazard ratio 1.6; 95 % CI 0.9-2.7). Among women with <2 HERDOO2 criteria, a normal D-dimer level at both timepoints predicted a very low risk of recurrent VTE during follow-up (0.8 % per year, 95 % CI 0.1-2.8). Irrespective of baseline value, recurrent VTE risk was only 3 % per year (95 % CI 1.4-5.6) among patients in the lowest ∆D-dimer quartile.
Conclusion: Serial normal D-dimer levels have the potential to identify patients at a low risk of recurrent VTE. In addition, ∆D-dimer, irrespective of its elevation above cutoff threshold, may predict recurrent VTE.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Xu, Khan, Kovacs, Sabri, Righini, Kahn, Anderson, Chagnon, White, Rodger and Le Gal have no conflicts of interest to report. Dr. Carrier reports research funding from BMS, Leo Pharma, and Pfizer; and honoraria from Bayer, Pfizer, BMS, Leo Pharma, Servier, and Sanofi. Dr. Wells reports speaker honoraria from BMS and Bayer Healthcare and prior grant funding from BMS/Pfizer. Dr. Crowther reports honoraria from Pfizer, CSL Behring, and Diagnostica Stago; consultation services to/served on advisory boards for Servier Canada, Asahi Kasei, and Precision Biologics; serving on the data safety monitoring board for Bayer; stock ownership in Alnylam; and holds the Leo Pharma Chair in Thromboembolism research, the funding for which is held in perpetuity at McMaster University (the interest is used to support M.A.C.'s research activities).
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