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Received: 17 August 2022    Accepted: 31 August 2022

DOI: 10.1002/rth2.12817

LETTER TO THE EDITOR

How to use and report data on D-­dimer testing in the

COVID-­19 era?

We read with interest the study published in the recent issue by a previous official communication (Thachil J et al.) from the ISTH
Woller and colleagues,1 entitled “Biomarker derived risk scores pre- Scientific and Standardization Subcommittee on fibrinolysis.5
dict venous thromboembolism and major bleeding among patients
with COVID-­19.” We appreciated that they introduced D-­dimer to R E L AT I O N S H I P D I S C LO S U R E
the study to improve the predictiveness of the biomarkers score. The authors declare that they have no conflicts of interest regarding
However, we noticed that there was a little deficiency in the use and this article.
report of D-­dimer testing in this article.
It is well known that the standardization and harmonization of AU T H O R C O N T R I B U T I O N S
D-­dimer testing are poor, and fibrinogen equivalent units (FEU) and LZ and XL drafted the manuscript, and ZZ participated in discussion
D-­dimer units (DDU) are the two units commonly used to report D-­ and critical editing of the manuscript.
dimer levels. However, there is a huge difference in D-­dimer results
between these two reporting systems. 2 Therefore, the D-­
dimer F U N D I N G I N FO R M AT I O N
results among institutions are significantly different and have little This work was supported by the Hubei Provincial Nature Science
comparability. In Woller's study, the participants were assigned into Foundation of China (2020CFB865) and 2020 Wuhan Young &
three categories based on D-­dimer levels: D-­dimer <0.5, 0.5–­2.0, Middle-­age Medical Backbone Training Programme.
and greater than 2.0  μg/ml. However, using the absolute D-­dimer
values in the analysis would limit the use of the biomarker score K E Y WO R D S
model for the hospitals using different D-­dimer reagents. Thus, we COVID-­19, D-­dimer, D-­dimer ratio, report, standardization
suggest using the D-­dimer ratio (DDR) instead of absolute D-­dimer
values to stratify the patients in their study. DDR means the ratio of Litao Zhang MD1,2
the D-­dimer value to the upper limit of the normal range (ULN) for Xiaohui Liu MD2
the current D-­dimer assay (DDR = D-­dimer/ULN). Using the DDR Zhenlu Zhang PhD1,2
reporting system, the three categories in Woller's study could be
1
translated into DDR less than 1.0, 1.0–­4.0, and greater than 4.0, with Clinical Laboratory, Wuhan Asia General Hospital Affiliated to
the ULN of 0.5 μg/ml stated in the study. DDR can show the propor- Wuhan University of Science and Technology, Wuhan, China
2
tional level of D-­dimer elevation, independent of the unit type used, Laboratory Medicine, Wuhan Asia Heart Hospital, Wuhan,
and accounts for the cutoff value used. This is a simple and helpful China
transformation to apply the predictive model more widely. The DDR
Handling Editor: Dr Henri Spronk
had been employed in several multicenter clinical trials on COVID-­19
(the RAPID, ATTACC, ACTIV-­4a, and REMAP-­C AP studies) to ensure
comparable D-­dimer results across institutions.3,4 Correspondence
Additionally, the details of the D-­dimer assay in Woller's study Zhenlu Zhang, Laboratory Medicine, Wuhan Asia Heart
were not described clearly. We speculated that it would be an FEU Hospital, No. 753 Jinghan Avenue, Wuhan 430022, China.
reagent since the ULN is 0.5 μg/ml, which should be declared in the Email: zhenluzhangwh@163.com
paper. Furthermore, the authors should also provide the analytical
performance of the D-­dimer assay because it is important for read- ORCID
ers to know the potential statistical bias of the predictive model. Litao Zhang  https://orcid.org/0000-0003-4918-611X
We suggest that the authors refer to the recommendations from Zhenlu Zhang  https://orcid.org/0000-0002-1999-6536

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis
and Haemostasis (ISTH).

Res Pract Thromb Haemost. 2022;6:e12817.  |

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2 of 2       LETTER TO THE EDITOR
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