D-dimer at hospital admission for COVID-19 are associated with in-hospital mortality, independent of venous thromboembolism: Insights from a French multicenter cohort study

Abstract

Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders, in particular high concentrations of D-dimers, and increased frequency of venous thromboembolism. Aim: To explore the association between D-dimers at admission and in-hospital mortality in patients hospitalized for COVID-19, with or without symptomatic venous thromboembolism. Methods: From 26 February to 20 April 2020, D-dimer concentration at admission and outcomes (in-hospital mortality or venous thromboembolism) of patients hospitalized for COVID-19 in medical wards were analysed retrospectively in a multicentre study in 24 French hospitals. Results: Among 2878 patients enrolled in the study, 1154 (40.1%) patients had D-dimer measurement at admission. Receiver operating characteristic curve analysis identified a D-dimer concentration > 1128 ng/mL as the optimum cut-off value for in-hospital mortality (area under the curve 64.9%, 95% confidence interval [CI] 0.60–0.69), with a sensitivity of 71.1% (95% CI 0.62–0.78) and a specificity of 55.6% (95% CI 0.52–0.58), which did not differ in the subgroup of patients with venous thromboembolism during hospitalization. Among 545 (47.2%) patients with D-dimer concentration > 1128 ng/mL at admission, 86 (15.8%) deaths occurred during hospitalization. After adjustment, in Cox proportional hazards and logistic regression models, D-dimer concentration > 1128 ng/mL at admission was also associated with a worse prognosis, with an odds ratio of 3.07 (95% CI 2.05–4.69; P < 0.001) and an adjusted hazard ratio of 2.11 (95% CI 1.31–3.4; P < 0.01). Conclusions: D-dimer concentration > 1128 ng/mL is a relevant predictive factor for in-hospital mortality in patients hospitalized for COVID-19 in a medical ward, regardless of the occurrence of venous thromboembolism during hospitalization.

Harmonized D-dimer levels upon admission for prognosis of COVID-19 severity: Results from a Spanish multicenter registry (BIOCOVID-Spain study)

“…In our study, a higher harmonized D-dimer (≥ 0.945 mg/L FEU) on admission was also associated with greater risk of all-cause mortality. However, D-dimer, as an isolated measure evaluated by a ROC curve analysis, was not a reliable tool for predicting mortality among COVID-19 patients, showing a low AUC (0.66), similar to those recently reported by Chocron et al [ 37 ] (0.65) and Naymagon et al [ 40 ] (0.69), but significantly lower than reported by Yao et al (0.85) [ 39 ] and Zhang et al (0.89) [ 38 ]. According to Gris et al [ 30 ], selection bias would be a major confounding factor affecting the results in Chinese populations, with mortality rates (3.8% [ 38 ] and 6.9% [ 39 ], respectively) being lower than those found in western cohorts (14.3% in ours).…”

“…D-dimer was one of the first biomarkers reported as useful for the prediction of a poor prognosis at an early stage in COVID-19 patients [ 3 ]. Subsequent studies confirmed the significant association of D-dimer levels with greater risk of all-cause mortality, with a wide variety of optimal cut-off values reported as predictors of death, including 1128 ng/mL [ 37 ], 2.00 μg/mL [ 38 ], 2.14 mg/L [ 39 ] and 2.38 μg/mL [ 40 ], although an association was not detected by Martín-Rojas et al [ 4 ]. In our study, a higher harmonized D-dimer (≥ 0.945 mg/L FEU) on admission was also associated with greater risk of all-cause mortality.…”

COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects

“…Mauri et al reported in six out of seven such COVID-19 patients’ large ventilation/perfusion mismatch, with a median (IQR) dead space fraction of 22% [ 221 ]. Comparable results were reported in 15 other patients: median (IQR) dead space fraction of 27% [ 23 – 36 ] [ 222 ]. Importantly, the percentage of dead space measured by EIT differs from the measures provided by capnography, because it refers to dead space inside the lungs (minimizing the contribution of instrumental and anatomical dead space), with lung aerated volume (and not tidal volume) as the reference value.…”

“…Furthermore, while 30–40% of septic shock patients develop DIC [ 28 ], few COVID-19 patients were diagnosed with DIC according to the International Society on Thrombosis and Hemostasis or the Japanese Association for Acute Medicine diagnosis scores for DIC [ 9 , 13 ], unless COVID-19 was secondarily complicated by bacterial sepsis, septic shock or multiple organ failure. D-dimer increase has thus been widely assessed in COVID-19 patients and has been correlated to disease severity and mortality [ 33 – 36 ]. Therefore, monitoring of D-dimers has been proposed by several guidelines but no clear data exist to date on a reliable cut-off to predict mortality risk or to guide the choice of initiating therapeutic anticoagulation [ 37 ].…”

COVID-19 pneumonia imaging follow-up: when and how? A proposition from ESTI and ESR

“…The 2020 advice from the European Society of Radiology and the European Society of Thoracic Imaging was to consider performing an additional contrast-enhanced CT acquisition for patients requiring supplementary oxygen if there was limited disease extension on the unenhanced CT [16]. D-dimer elevation has been recognized as a useful biomarker of poor prognosis; D-dimer levels are now almost invariably checked in COVID-19 pneumonia patients [62]. This greatly increases the referral rate for CTPA, with a risk of over-use.…”