Harmonized D-dimer levels upon admission for prognosis of COVID-19 severity: Results from a Spanish multicenter registry (BIOCOVID-Spain study)

J Thromb Thrombolysis. 2022 Jan;53(1):103-112. doi: 10.1007/s11239-021-02527-y. Epub 2021 Jul 16.


Coagulopathy is a key feature of COVID-19 and D-dimer has been reported as a predictor of severity. However, because D-dimer test results vary considerably among assays, resolving harmonization issues is fundamental to translate findings into clinical practice. In this retrospective multicenter study (BIOCOVID study), we aimed to analyze the value of harmonized D-dimer levels upon admission for the prediction of in-hospital mortality in COVID-19 patients. All-cause in-hospital mortality was defined as endpoint. For harmonization of D-dimer levels, we designed a model based on the transformation of method-specific regression lines to a reference regression line. The ability of D-dimer for prediction of death was explored by receiver operating characteristic curves analysis and the association with the endpoint by Cox regression analysis. Study population included 2663 patients. In-hospital mortality rate was 14.3%. Harmonized D-dimer upon admission yielded an area under the curve of 0.66, with an optimal cut-off value of 0.945 mg/L FEU. Patients with harmonized D-dimer ≥ 0.945 mg/L FEU had a higher mortality rate (22.4% vs. 9.2%; p < 0.001). D-dimer was an independent predictor of in-hospital mortality, with an adjusted hazard ratio of 1.709. This is the first study in which a harmonization approach was performed to assure comparability of D-dimer levels measured by different assays. Elevated D-dimer levels upon admission were associated with a greater risk of in-hospital mortality among COVID-19 patients, but had limited performance as prognostic test.

Keywords: COVID-19; D-dimer; Harmonization; Mortality; Prognosis.

Publication types

  • Multicenter Study

MeSH terms

  • Biomarkers / blood
  • COVID-19* / diagnosis
  • Fibrin Fibrinogen Degradation Products / analysis*
  • Humans
  • Prognosis
  • Registries
  • Retrospective Studies
  • Severity of Illness Index
  • Spain / epidemiology


  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D