Abstract
Coronavirus disease 2019 (COVID-19) has been associated with increased mortality and morbidity from thromboembolism, but with limit data on systemic thromboembolism. The present study aimed to investigate the prevalence of systemic and venous thromboembolism, as well as major bleeding and mortality, in relation to underlying risk factors and the impact of anticoagulation use in hospitalized patients with COVID-19. Patients with COVID-19 admitted to Union Hospital, Wuhan, Hubei, China between January 08, 2020 to April 7, 2020, were enrolled into the respective study. Cox proportional hazard models were utilised to determine associated risk factors for clinical events, adjusting for the severity of COVID-19 infection, drug therapies, comorbidities, surgery, and the use of antithrombotic drugs. There were 1125 patients (49.9% male; mean age 58 (standard deviation, SD, 15 years) with a mean follow-up of 21(SD13) days. Of these, 408(36.3%) were aged over 65 years, 33 (2.9%) underwent surgery, and 249(22.1%) received anticoagulants. Of the latter, 87(7.7%) received oral anticoagulants, 209(18.6%) parenteral anticoagulants, and 47(4.2%) received oral plus parenteral anticoagulants. There were 82(7.3%) thromboembolism events (37 systemic, 45 venous), 128(11.4%) major bleeding events, and 91(8.1%) deaths. About 25(30%) patients with thromboembolism also suffered bleeding events. Age was an independent risk factor for thromboembolism, bleeding events, and death (all p<0.05). After adjusting for the severity of COVID-19 infection, comorbidities, surgery, antiviral drugs, immunomodulators, Chinese herb, and antithrombotic drugs, low lymphocyte counts (hazard ratio, HR, 95% confidence interval (CI), 1.03, 1.01-1.05, p=0.01) and surgery (HR 2.80, 1.08-7.29, p=0.03) independently predicted the risk for major bleeding, while liver dysfunction ( HR 4.13, 1.30-13.1, p=0.02) was an independent risk factor for patients with both thromboembolism and bleeding events. Atrial fibrillation/ irregular rhythm increased the risk for systemic thromboembolism (HR 3.16, 1.06-9.46, p=0.04). Both oral anticoagulant (HR 0.32, 0.19-0.53) and parenteral anticoagulant (HR 0.39, 0.22-0.70) use reduced the risk for thromboembolism (all p<0.001). After adjustment, parenteral anticoagulant use had a borderline effect on both thromboembolism and bleeding events (0.36, 0.13-1.01, P=0.053), but significantly reduced the risk for the composite outcome of thromboembolism, bleeding events and death ((HR 0.70, 0.51-0.95, p=0.02). Patients with COVID-19 were at high risk for thromboembolic and bleeding events, as well as mortality. Anticoagulant use, especially parenteral anticoagulants significantly reduced the risk for composite outcome of thromboembolism, bleeding events and death. The presence of AF was a contributor to systemic thromboembolism in COVID-19 patients.