Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors

Abstract

Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous. The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis. In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included. A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected. Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected. Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis. D-dimers at baseline were significantly higher in patients with DVT (p < 0.001). Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE. The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE. The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively. The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer. Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients. Increased D-dimer concentrations of more than 1.0 μg/ml predict the risk of venous thromboembolism. D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.

Keywords: COVID-19; D-dimer; Pulmonary embolism; Venous thromboembolism.

Fig. 1

correlation between D-dimer levels and venous thromboembolic events in the 65 COVID-19 patients who had a D-dimer level measurement on admission. (a, top left) Baseline (admission) D-dimer levels according to thromboembolism events. Stars represent pulmonary embolism. (b, top right) Risk of deep venous thrombosis and pulmonary embolism according to baseline D-dimer levels. (c, bottom, left) D-dimer levels kinetics between baseline and the latest value before the venous duplex ultrasonography in the 15 patients with D-dimer levels monitoring. 7 patients with no VTE, median [IQR] admission D-dimer: 0.62 [0.41–1.34], median [IQR] last-value: 0.66 [0.61–0.89]; 8 patients with VTE, median [IQR] admission D-dimer: 2.01 [0.62–4.30], median [IQR] last-value: 4.75 [2.98–6.42] (d, bottom, right) Risk of deep venous thrombosis and pulmonary embolism according to the latest D-dimer levels. VTE venous thromboembolic events, DVT deep venous thrombosis, PE pulmonary embolism. **p < 0.01