Change in D-Dimer and Mortality in Patients admitted with Coronavirus Disease 19 (COVID19)

Abstract

Background: Coronavirus disease 19 is a complex multisystem disease that continues to spread rapidly across the world. It is associated with elevations in inflammatory markers including the one produced during fibrinolysis, namely D-Dimer. Reports have shown marked elevations in this protein fragment particularly in severe disease. We report our observations regarding change in D-Dimer and effect on mortality over time. Methods: We analyzed all adults between March and September 2020 who were admitted or managed in the emergency department for COVID19 infection within the University Hospitals Health System in Northeast Ohio. Delta d-dimer was defined as the change in d-dimer (Δd-dimer) from day of presentation to the maximum value between day 1 to 6 post admissions. Kaplan-Meier and cox regression analyses were performed to explore the association with mortality. Receiver operating characteristics were used to estimate discrimination power for mortality. Results: A total of 442 patients were included. Mean age was 64±16 years. A total of 93 patients were managed in the intensive care unit, 324 were managed as inpatient, and 25 patients were managed in the emergency department. The median admission d-dimer was 1169 [645-2208] ng/ml, and Δd-dimer was 75 [-334 to 717]. At a median follow-up of 108 days, 100 patients died (30-day mortality of 21%). The 30-day mortality was 12.3% for tertile 1, 12.2% for tertile 2, and 39.1% for tertile 3 of Δd-dimer, (Figure). Compared with tertile 1, patients in tertile 3 of Δd-dimer had 4-fold higher mortality (age-adjusted HR 3.77 [2.30-6.18], P<0.001). In multivariable analysis, Δd-dimer but not admission d-dimer (P=0.36) was associated with mortality after adjusting for age (per 1000 ng/mL increase: HR 1.017 [1.008-1.027], P<0.001). Δd-dimer had a good discriminative power for mortality (AUC=0.70). An increase in d-dimer of 540 ng/ml was determined to be the best threshold for mortality (sensitivity of 62% and specificity of 80%). Conclusions: Serial monitoring of D-Dimer during hospitalization to assess for change over time is a reliable prognostic marker for mortality in COVID-19 patients. Using it as an indicator to initiate therapeutic anticoagulation requires investigation.