Admission D-dimer levels, D-dimer trends, and outcomes in COVID-19

Abstract

Observational data suggest an acquired prothrombotic state may contribute to the pathophysiology of COVID-19. These data include elevated D-dimers observed among many COVID-19 patients. We present a retrospective analysis of admission D-dimer, and D-dimer trends, among 1065 adult hospitalized COVID-19 patients, across 6 New York Hospitals. The primary outcome was all-cause mortality. Secondary outcomes were intubation and venous thromboembolism (VTE). Three-hundred-thirteen patients (29.4%) died, 319 (30.0%) required intubation, and 30 (2.8%) had diagnosed VTE. Using Cox proportional-hazard modeling, each 1 μg/ml increase in admission D-dimer level was associated with a hazard ratio (HR) of 1.06 (95%CI 1.04-1.08, p < 0.0001) for death, 1.08 (95%CI 1.06-1.10, p < 0.0001) for intubation, and 1.08 (95%CI 1.03-1.13, p = 0.0087) for VTE. Time-dependent receiver-operator-curves for admission D-dimer as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.694, 0.621, and 0.565 respectively. Joint-latent-class-modeling identified distinct groups of patients with respect to D-dimer trend. Patients with stable D-dimer trajectories had HRs of 0.29 (95%CI 0.17-0.49, p < 0.0001) and 0.22 (95%CI 0.10-0.45, p = 0.0001) relative to those with increasing D-dimer trajectories, for the outcomes death and intubation respectively. Patients with low-increasing D-dimer trajectories had a multivariable HR for VTE of 0.18 (95%CI 0.05-0.68, p = 0.0117) relative to those with high-decreasing D-dimer trajectories. Time-dependent receiver-operator-curves for D-dimer trend as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.678, 0.699, and 0.722 respectively. Although admission D-dimer levels, and D-dimer trends, are associated with outcomes in COVID-19, they have limited performance characteristics as prognostic tests.

Keywords: Admission; COVID-19; D-dimer; Outcomes; Thrombosis; Trend.

Fig. 1

The results of joint latent class modeling (JLCM) of D-dimer trend and its association with the primary outcome of all-cause mortality are depicted. D-dimer level is expressed in units of μg/ml. The two distinct D-dimer trajectories (increasing and stable) are shown in the upper left corner. Survival curves for these two groups are shown in the upper-right corner. The results of Cox proportional hazards models are shown in the lower panel (* the multivariable model adjusted for race and anticoagulant use prior to diagnosis, as these were the only baseline characteristics different between groups). Abbreviations: CI – confidence interval; HR – hazard ratio.

Fig. 2

The results of joint latent class modeling (JLCM) of D-dimer trend and its association with the secondary outcome of need for mechanical ventilation are depicted. D-dimer level is expressed in units of μg/ml. The two distinct D-dimer trajectories (increasing and stable) are shown in the upper left corner. Curves depicting proportion of patients not on mechanical ventilation over time are shown in the upper-right corner. The results of Cox proportional hazards models are shown in the lower panel (* the multivariable model adjusted for age, and Charlson Comorbidity Index, as these were the only baseline characteristics different between groups). Abbreviations: CI – confidence interval; HR – hazard ratio; MV – mechanical ventilation.

Fig. 3

The results of joint latent class modeling (JLCM) of D-dimer trend and it association with the secondary outcome of diagnosed VTE are depicted. D-dimer level is expressed in units of μg/ml. The two distinct D-dimer trajectories (low-increasing and high-decreasing) are shown in the upper left corner. Curves depicting proportion of patients remaining venous-thrombosis-free over time are shown in the upper-right corner. The results of Cox proportional hazards models are shown in the lower panel (* the multivariable model adjusted for race as this was the only baseline characteristic different between groups). Abbreviations: CI – confidence interval; HR – hazard ratio.

Fig. 4

A forest plot depicting the unadjusted and adjusted HRs (with corresponding 95% CIs) comparing D-dimer trajectories for each outcome of interest. HRs represent the hazard of event in the lower and more stable D-dimer group relative to the hazard of event in higher increasing D-dimer group. All depicted HRs were significant. Abbreviations: HR – hazard ratio; LCL – lower confidence limit; UCL – upper confidence limit.