Clinical evaluation of eight different D-dimer tests for the exclusion of deep venous thrombosis in primary care patients

Abstract

D-dimer tests are an essential element in the diagnostic work-up of deep venous thrombosis (DVT). However, the poor standardization amongst assays necessitates clinical validation before implementation in daily practice. We therefore evaluated the analytical and diagnostic performance of eight D-dimer tests in a representative group of 290 prospectively identified consecutive primary care patients with suspected DVT. Seven quantitative D-dimer assays, and a qualitative test, Simplify, were evaluated. Correlation between assays was generally poor and several assays showed a significant bias in the method comparison. Nevertheless, the Vidas D-dimer, Innovance D-dimer (CA1500 and BCS), Pathfast D-dimer, and HemosIL HS500 (ACL TOP), all displayed 100% (95% CI: 85-100%) sensitivity. Tina-quant (Modular), AQT90 D-dimer, and Liatest (STA(®)) D-dimer tests showed a slightly lower sensitivity of 95% (78-100%). and the Simplify test reached a sensitivity of 91% (72-99%) that was further improved in combination with a clinical decision rule to 95% (76-100%). In concert with the low (8.2%) prevalence of proximal DVT, diagnosed by compression ultrasonography, in our study, all test reached a negative predictive value (NPV) of at least 99%. The user friendliness of the assays differed mainly by stability of reagents, calibration frequency, time required to obtain a test result and costs of a test. In conclusion, despite considerable analytical differences, in our low-risk population all tests evaluated displayed an excellent NPV. In combination with a validated clinical decision rule to identify low-risk patients, even a straightforward POC solution could safely and cost-efficiently rule out DVT.

D-dimer: Preanalytical, analytical, postanalytical variables, and clinical applications

“…whilst others recommend only citrate anticoagulated blood (e.g. [38]. Schutgens et al observed a higher mean D-dimer concentration (Tina-quant V R D-dimer) in heparin collection tubes (2510 mg/L), compared to citrate (2060 mg/L) albeit the difference did not achieve statistical significance [39].…”

“…This assay displayed sensitivity and specificity similar to those of microplate ELISAs, with the great advantage of being automated, thus generating more precise results in a shorter time (30 min) [3,58]. The Vidas V R assay is still considered the reference commercial quantitative immunoassay [84][85][86] and is the most clinically validated D-dimer measurement technique [38,48,85,[87][88][89].…”

“…More recent studies also found optimal diagnostic performance for current laboratory D-dimer immunoassays (e.g. STA- [38,48,84,112,114,167,168]. Not all POC Ddimer assays are appropriate to be used to exclude VTE [107].…”

Clinical effects of antiplatelet drugs and statins on D‐dimer levels

“…However, all were contemporary, well-validated high-sensitive quantitative D-dimer assays with similar fixed cut-off levels. 29 Based on our results, we conclude that use of statins is associated with a 15% decrease in D-dimer levels. In our cohort, this was not associated with an increase in falsenegative test results, compared to nonusers.…”

Policies and practices in haemostasis testing among laboratories in Croatia: a survey on behalf of a Working Group for Laboratory Coagulation of the Croatian Society of Medical Biochemistry and Laboratory Medicine

“…Evidences obtained in both surveys underline the need for further standardization in D-dimer result reporting. In general, D-dimer testing lacks standardization all over the world since there is still no standardized measurement unit, unique monoclonal antibody and calibrator ( 32 , 33 ). Thus results, RI and clinical cut-off values cannot be extrapolated between methods.…”