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

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. Key Points Question Are D-dimer levels following therapeutic anticoagulation predictive of mortality in hospitalized COVID-19 patients? Finding In a retrospective study of 1835 adult COVID-19 patients who received therapeutic anticoagulation for thromboprophylaxis during hospitalization, 1365 (74%) patients were discharged and 470 (26%) died. Post-anticoagulant D-dimer levels and trends were significantly and independently predictive of mortality. Meaning Active monitoring of post-anticoagulant D-dimer levels in hospitalized COVID-19 patients is a novel strategy for stratifying individual risk of in-hospital mortality that can help guide resource allocation and prospective studies for emerging treatments for severe COVID-19 illness.