Post-Anticoagulant D-dimer as a Highly Prognostic Biomarker of COVID-19 Mortality

Song, X.; Ji, J.; Reva, B.; Joshi, H.; Calinawan, A. P.; Mazumdar, M.; Taioli, E.; Wang, P.; Veluswamy, R.

Importance: Clinical biomarkers that accurately predict mortality are needed for the effective management of patients with severe COVID-19 illness. Objective: To determine whether D-dimer levels after anticoagulation treatment is predictive of in-hospital mortality. Design: Retrospective study using electronic health record data. Setting: A large New York City hospital network serving a diverse, urban patient population. Participants: Adult patients hospitalized for severe COVID-19 infection who received therapeutic anticoagulation for thromboprophylaxis between February 25, 2020 and May 31, 2020. Exposures: Mean and trend of D-dimer levels in the 3 days following the first therapeutic dose of anticoagulation. Main Outcomes: In-hospital mortality versus discharge. Results: 1835 adult patients (median age, 67 years [interquartile range, 57-78]; 58% male) with PCR-confirmed COVID-19 who received therapeutic anticoagulation during hospitalization were included. 74% (1365) of patients were discharged and 26% (430) died in hospital. The study cohort was divided into four groups based on the mean D-dimer levels and its trend following anticoagulation initiation, with significantly different in-hospital mortality rates (p<0.001): 49% for the high mean-increase trend (HI) group; 27% for the high-decrease (HD) group; 21% for the low-increase (LI) group; and 9% for the low-decrease (LD) group. Using penalized logistic regression models to simultaneously analyze 67 variables (baseline demographics, comorbidities, vital signs, laboratory values, D-dimer levels), post-anticoagulant D-dimer groups had the highest adjusted odds ratios (ORadj) for predicting in-hospital mortality. The ORadj of in-hospital death among patients from the HI group was 6.58 folds (95% CI 3.81-11.16) higher compared to the LD group. The LI (ORadj: 4.06, 95% CI 2.23-7.38) and HD (ORadj: 2.37; 95% CI 1.37-4.09) groups were also associated with higher mortality compared to the LD group. Conclusions and Relevance: D-dimer levels and its trend following the initiation of anticoagulation have high and independent predictive value for in-hospital mortality. This novel prognostic biomarker should be incorporated into management protocols to guide resource allocation and prospective studies for emerging treatments in hospitalized COVID-19 patients.