Post-anticoagulant D-dimer is a highly prognostic biomarker of COVID-19 mortality

Abstract

Clinical biomarkers that accurately predict mortality are needed for the effective management of patients with severe coronavirus disease 2019 (COVID-19) illness. In this study, we determine whether changes in D-dimer levels after anticoagulation are independently predictive of in-hospital mortality. Adult patients hospitalised for severe COVID-19 who received therapeutic anticoagulation for thromboprophylaxis were identified from a large COVID-19 database of the Mount Sinai Health System in New York City (NY, USA). We studied the ability of post-anticoagulant D-dimer levels to predict in-hospital mortality, while taking into consideration 65 other clinically important covariates including patient demographics, comorbidities, vital signs and several laboratory tests. 1835 adult patients with PCR-confirmed COVID-19 who received therapeutic anticoagulation during hospitalisation were included. Overall, 26% of patients died in the hospital. Significantly different in-hospital mortality rates were observed in patient groups based on mean D-dimer levels and trend following anticoagulation: 49% for the high mean-increase trend group; 27% for the high-decrease group; 21% for the low-increase group; and 9% for the low-decrease group (p<0.001). Using penalised logistic regression models to simultaneously analyse 67 clinical variables, the high increase (adjusted odds ratios (OR_adj): 6.58, 95% CI 3.81-11.16), low increase (OR_adj: 4.06, 95% CI 2.23-7.38) and high decrease (OR_adj: 2.37; 95% CI 1.37-4.09) D-dimer groups (reference: low decrease group) had the highest odds for in-hospital mortality among all clinical features. Changes in D-dimer levels and trend following anticoagulation are highly predictive of in-hospital mortality and may help guide resource allocation and future studies of emerging treatments for severe COVID-19.

FIGURE 1

Selection of study cohort to evaluate role of post-anticoagulant D-dimer as predictive biomarker for mortality.

FIGURE 2

D-dimer distribution and its association with patient outcomes. a) Boxplot of baseline and post-anticoagulation (post-A/C) D-dimer values. b) receiver operating characteristic curves of prediction models with baseline D-dimer, post-anticoagulation D-dimer and both (area under the curve (AUC) 0.59, 0.76 and 0.76, respectively).

FIGURE 3

In-hospital mortality and baseline patient characteristics of four post-anticoagulation D-dimer groups. a) In-hospital mortality rates by post-anticoagulation D-dimer groups. b) Baseline characteristics of patients with different D-dimer groups after anticoagulation therapy. HI: high increase; HD: high decrease; LI: low increase; LD: low decrease; EGFR: estimated glomerular filtration rate; LDH: lactate dehydrogenase.

FIGURE 4

A multivariate prediction model for patients’ outcome. a) ORs estimates (95% CI), for variables selected in the post-anticoagulation model (post-A/C). b) Area under the curve (AUC) differences between leave-one-predictor-out models and the full model for variables selected in the post-anticoagulation model. c) Comparison of 10-fold cross-validation AUCs between baseline model and post-anticoagulation model in 100 bootstrap samples. HI: high increase; HD: high decrease; LI: low increase; LD: low decrease; LDH: lactate dehydrogenase.