D-Dimer Level and Neutrophils Count as Predictive and Prognostic Factors of Pulmonary Embolism in Severe Non-ICU COVID-19 Patients

Abstract

The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19). We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients. In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion. Baseline data, laboratory biomarkers, treatments, and outcomes were collected. Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively. A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55–77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed. PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6–4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1–537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4–29.5]). The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5–67.8], p < 0.01). In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively.

Mortality Predictors in Severe COVID-19 Patients from an East European Tertiary Center: A Never-Ending Challenge for a No Happy Ending Pandemic

“…Concerning our study, we found that an even lower cut-off value for CRP (23 mg/L) is significantly associated with severe outcome (i.e., ICU admission). D-Dimers represent another well-established predictive factor in COVID-19, with generally accepted high-risk cut-offs ranging from 1 to 3 mg/L [ 31 , 32 ], values which are similar to the results (0.41–2.05) predicting a negative prognosis in patients included in our study.…”

Meta-Analysis and Systematic Review of Coagulation Disbalances in COVID-19: 41 Studies and 17,601 Patients

“…As confirmed by autopsy results, the elevated DD levels can be associated with fibrin deposits within pulmonary extravascular space and alveoli ( 67 ), but they may be non-specific to intravascular fibrin formation ( 87 ). High DD levels, together with elevated neutrophils, were reported to be predictive factors of pulmonary embolism in COVID-19 patients ( 88 ). DD and FIB levels are elevated in both COVID-19 and thromboembolism, and therefore as single tests are unspecific and unhelpful in the differentiation of these conditions.…”

“…DD and FIB levels are elevated in both COVID-19 and thromboembolism, and therefore as single tests are unspecific and unhelpful in the differentiation of these conditions. In part, it may be explained by the involvement in abnormal coagulation in COVID-19 of different systems, including endothelial cells, complement activation, and hypofibrinolysis resulting in changes undetected by routine tests ( 39 , 88 ).…”

“…DD and FIB levels are elevated in both COVID-19 and thromboembolism, and therefore as single tests are unspecific and unhelpful in the differentiation of these conditions. In part, it may be explained by the involvement in abnormal coagulation in COVID-19 of different systems, including endothelial cells, complement activation, and hypofibrinolysis resulting in changes undetected by routine tests (39,88). A significantly higher amount of neutrophil extracellular traps [and related markers such as cell-free DNA and myeloperoxidase-DNA (MPO-DNA)] was found when compared with non-COVID-19 thrombi (89).…”

Prevention of venous thromboembolism and haemostasis monitoring in patients with COVID-19: Updated proposals (April 2021)

“…Baseline D-dimers level above the upper limit of normal is associated with critical illness, thrombosis, acute kidney injury, and death [23] . In the CLOTVID cohort including non-ICU hospitalised patients, after adjustment of anticoagulant status and delay of follow-up, the combination of D-dimer level ≥2 µg/mL and neutrophils count ≥7.0 G/L on admission was associated with increased risk of death or ICU transfer [24] . The D-dimers level is related to thrombotic complications during COVID-19 but also the severity of the disease, especially the severity of lung injury.…”