Dose response relationship between D-dimer level and mortality in critically ill COVID-19 patients: a retrospective observational study

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic. Coagulopathy is one of the most common complications characterized by increased D-dimer level. We aimed to investigate the dose-response relationship between elevated D-dimer level and mortality in critically ill COVID-19 patients. Methods: This was a retrospective observational study in 259 critically ill COVID-19 patients requiring intensive care unit admission between March and December 2020. We compared the mortality rate between patients with and without elevated D-dimer. Receiver operating characteristic (ROC) curve analysis, Fagan’s nomogram, and dose-response relationship were performed to determine the association between D-dimer level and mortality. Results: Overall mortality rate was 40.9% (106 patients). Median D-dimer level was higher in non-survivor group (10,170 ng/mL vs 4,050 ng/mL, p=0.028). The association remained significant after multivariate logistic regression analysis (p=0.046). The optimal cut-off for D-dimer level to predict mortality from ROC curve analysis was 9,020 ng/mL (OR (odds ratio) 3.73 [95% CI (confidence interval) 1.91 – 7.28], p<0.001). D-dimer level >9,020 ng/mL confers 67% posterior probability of mortality and D-dimer level <9,020 ng/mL had 35% probability of mortality. Conclusions: There was a non-linear dose-response relationship between D-dimer level and mortality with P _nonlinearity of 0.004. D-dimer level was associated with mortality in critically ill COVID-19 patients in the non-linear dose-response relationship.