Venous thrombosis, thromboembolism and biomarkers of inflammation and coagulation in COVID-19

Thondapu, Vikas; Montes, Daniel; Rosovsky, Rachel; Dua, Anahita; McDermott, Shaunagh; Lu, Michael T.; Ghoshhajra, Brian; Hoffmann, Udo; Gerhard-Herman, Marie Denise; Hedgire, Sandeep

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with abnormal inflammatory and coagulation markers, potentially mediating thrombotic events. The objective was to investigate the incidence, time course, laboratory features, and in-hospital outcomes of COVID-19 patients with suspected venous thromboembolism (VTE). METHODS: A retrospective observational cohort study was conducted in patients hospitalized with COVID-19 undergoing ultrasound imaging for suspected VTE between March 13 to May 18, 2020. Medical records of included patients were reviewed for D-dimer, fibrinogen, prothrombin time, partial thromboplastin time, platelet count, C-reactive protein (CRP), and high-sensitivity troponin T at admission and up to 7 timepoints before and after ultrasound. Clinical outcomes included superficial venous thrombosis (SVT), deep venous thrombosis (DVT), pulmonary embolism (PE), intubation, and death. Mixed-effects logistic, linear, and Cox proportional hazards methods were used to evaluate the relation between laboratory markers with VTE and other in-hospital outcomes. RESULTS: Of 138 patients undergoing imaging, 44 (31.9%) had evidence of VTE. In univariable analysis, elevated admission CRP ([for every 10-unit increase in CRP] odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.09, p=0.02), platelets ([for every 1000-unit increase in platelets] OR 1.48, 95% CI 1.04-2.12, p=0.03), and male sex (OR 2.64, 95% CI 1.19-5.84, p=0.02), were associated with VTE. However only male sex remained significant in multivariable analysis (OR 2.37, 95% CI 1.01-5.56, p=0.048). Independent predictors of death included older age (HR 1.04, 95% CI 1.00-1.07, p=0.04), active malignancy (HR 4.39, 95% CI 1.39-13.91, p=0.01), elevated admission D-dimer (HR 1.016, 95% CI 1.003-1.029, p=0.02), and evidence of disseminated intravascular coagulation (DIC) (HR 4.81, 95% CI 1.76-13.10, p=0.002). CONCLUSIONS: Male sex, elevated CRP and platelet count at admission are associated with VTE in univariable analysis, but only male sex remained significant in multivariable analysis. Older age, active malignancy, DIC and elevated D-dimer at admission are independently associated with death in patients hospitalized with COVID-19.