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Advances in D-dimer testing: progress in harmonization of clinical assays and innovative detection methods

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Abstract

The D-dimer is a sensitive indicator of coagulation and fibrinolysis activation, especially valuable as a biomarker of intravascular thrombosis. Measurement of plasma D-dimer levels plays a crucial role in the diagnosis and monitoring of conditions such as deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation. A variety of immunoassays, including enzyme-linked immunosorbent assays, latex-enhanced immunoturbidimetric assays, whole-blood aggregation analysis, and immunochromatography assays, are widely used in clinical settings to determine D-dimer levels. However, the results obtained from different D-dimer assays vary significantly. These assays exhibit intra-method coefficients of variation ranging from 6.4% to 17.7%, and the measurement discrepancies among different assays can be as high as 20-fold. The accuracy and reliability of D-dimer testing cannot be guaranteed due to the lack of an internationally endorsed reference measurement system (including reference materials and reference measurement procedures), which may lead to misdiagnosis and underdiagnosis, limiting its full clinical application. In this review, we present an in-depth analysis of clinical D-dimer testing, summarizing the existing challenges, the current state of metrology, and progress towards harmonization. We also review the latest advancements in D-dimer detection techniques, which include mass spectrometry and electrochemical and optical immunoassays. By comparing the basic principles, the definition of the measurand, and analytical performance of these methods, we provide an outlook on the potential improvements in D-dimer clinical testing.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (grant no. 2022YFF0710301) and National Platform for Reference Material Resources (grant no. APT2302-1)

Funding

National Platform for Reference Material Resources, APT2302-1, National Key Research and Development Program of China, 2022YFF0710301

Author information

Authors and Affiliations

  1. National Institute of Metrology, Beijing, 100029, China

    Rong Zhao, Peng Xiao, Dewei Song & Hongmei Li

  2. Key Laboratory of Chemical Metrology and Applications on Nutrition and Health for State Market Regulation, Beijing, 100029, China

    Rong Zhao, Peng Xiao & Hongmei Li

  3. Beijing University of Chemical Technology, Beijing, 100029, China

    Mengran Li

Authors
  1. Rong Zhao
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  2. Mengran Li
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  3. Peng Xiao
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  4. Dewei Song
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  5. Hongmei Li
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Contributions

Rong Zhao and Hongmei Li conceived the idea for the study. Rong Zhao performed the literature search and data analysis, and drafted the paper. Mengran Li performed the literature search. Peng Xiao and Dewei Song revised the paper. Hongmei Li supervised the work, and critically reviewed and revised the paper.

Corresponding author

Correspondence to Hongmei Li.

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Zhao, R., Li, M., Xiao, P. et al. Advances in D-dimer testing: progress in harmonization of clinical assays and innovative detection methods. Anal Bioanal Chem (2024). https://doi.org/10.1007/s00216-024-05207-x

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  • DOI: https://doi.org/10.1007/s00216-024-05207-x

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