Safety of D-Dimer As a Stand-Alone Test for the Exclusion of Deep Vein Thrombosis Compared to Other Strategies

Abstract

BackgroundTogether with clinical decision rules, D-dimer testing has long been the mainstay of diagnostic work-up of suspected deep vein thrombosis (DVT). Advantages of D-dimer measurement include wide availability, low costs and high sensitivity. Age-adjusted D-dimer cut-off values have been suggested to improve specificity of D-dimer testing, defining a positive D-dimer as age multiplied by 0.01 mg/L at or over fifty years of age. Age-adjusted cut-off values have been found to increase specificity without compromising safety in the setting of acute pulmonary embolism, but have not been extensively evaluated in DVT.In this study, we aimed to evaluate and compare the diagnostic performance of fixed versus age-adjusted D-dimer thresholds in patients with suspected DVT, as a stand-alone test or in combination with pre-test probability assessment.MethodsWe included 973 consecutive outpatients referred to Østfold Hospital, Norway, with suspected first or recurrent lower extremity DVT, between 2015 and 2017. STA®-Liatest® Plus D-Dimer assay was performed and Wells clinical score assessed in all patients. Patients with positive fixed D-dimer (≥0.5 mg/L) were referred for whole-leg compression ultrasonography (CUS), whereas patients with negative D-dimer were not, irrespective of the clinical pre-test probability. Failure rate was defined as patients with negative D-dimer at baseline remaining untreated and diagnosed with symptomatic venous thromboembolism during 3-month follow-up. We compared diagnostic indices of both D-dimer thresholds with or without initial pre-test probability assessment.ResultsDVT was diagnosed in 177 out of 973 patients (18%).The fixed D-dimer cut-off was associated with a sensitivity of 99.4% (95% CI 96.9 to 99.9%) for one diagnostic failure (0.3%) (not adjudicated as of print). Adding the Wells score would have detected this one case at a cost of 90 additional CUS examinations. Age-adjusted D-dimer as a stand-alone test was associated with 6 diagnostic failures (1.5%) for a sensitivity of 96.6% (95% CI 92.8 to 98.8%). Age-adjusted D-dimer combined with Wells score yielded a sensitivity of 99.4% (95% CI 96.9 to 99.9%), with one diagnostic failure (0.4%) and 714 patients referred for CUS.ConclusionOur results suggest that the fixed D-dimer as a stand-alone test without Wells score is a safe and efficient diagnostic strategy. Combining age-adjusted D-dimer with Wells score was equally safe, but was not associated with a lower number of necessary CUS examinations. DisclosuresFronas:Bayer AG: Other: Bayer AG contributed with financial support in conducting the study; South-Eastern Norway Regional Health Authority: Other: Grant in conducting the study. Tøvik Jørgensen:Bayer AG: Other: Bayer AG contributed with financial support in conducting the study; South-Eastern Norway Regional Health Authority: Other: Grant for conducting the study. Ghanima:Bayer, BMS, Novartis: Research Funding; Amgen, Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.