D-dimer in COVID-19: A Guide With Pitfalls

D-dimers, as degradation products of fibrin, are widely used in the diagnosis (exclusion) of venous thrombosis. In addition, D-dimers have been shown to be of prognostic value in various diseases, including cancer and cardiovascular disease. There is plethora of data on the coagulation disturbances in patients with COVID-19, both clinically and by the use of various laboratory measurements.

D-dimers in predicting the severity of COVID-19

A high D-dimer at admission was an independent predictor for mortality in COVID-19 patients from Wuhan. Patients with a D-dimer ≥2.0 μg/ml had a much higher mortality incidence than those with levels ≤2.0 μg/ml (HR 51.5),¹ where the HR was 18.4 in D-dimers ≥1.0 μg/ml.² Also, D-dimers were able to distinguish patients with moderate from severe disease in 75 patients from China.³ Even more so, dynamic changes of D-dimer levels during the course of the disease was prognostic of poor outcome in 276 Chinese patients.⁴

D-dimers in predicting the occurrence of pulmonary embolism in patients with COVID-19

Higher D-dimer levels were associated with a greater probability of pulmonary embolism 3, 6, 9, and 12 days after determining D-dimer levels with an OR of 1.7, 2.0, 2.4, and 2.4, respectively in 21 patients from Spain.⁵ Similar results were found in 106 French patients, although the D-dimer threshold to exclude PE (2660 μg/L) was much higher than usual.⁶ A higher threshold was also suggested in 156 COVID-19 patients with asymptomatic deep venous thrombosis.⁷

D-dimers to guide anticoagulation

Anticoagulation therapy was associated with lower mortality in COVID-19 and this was especially true for patients with high D-dimers.⁸ As the relationship between D-dimers and the severity of COVID-19 and/or the occurrence of PE is evident and even appears to be dynamic, it is appealing to start an early intervention based on D-dimer levels. Several clinical guideline already advocate the use of different D-dimer cut-off levels to determine the anticoagulation dose.

However, as a recent review pointed out very clearly,⁹ there is a high variety of D-dimer tests with a large variability in the way they report their results. Most importantly, differences in the reported units (either D-Dimer Units [DDU]) or Fibrin Equivalent Units [FEU], the assay cut-off values and the absolute measuring units (mg/L, ng/mL, μ/mL) hamper generalisability of the results and the use of a clear cut-off point for decision making. The authors correctly call out for at least fully reporting the necessary variables to ensure study results can be translated to other clinics.

Therefore, although the role of D-dimers in guiding treatment of COVID-19 is attractive, clinicians should be aware of the details of their local D-dimer test before implementing standard cut-offs provided by others.