The Current Status of Thrombosis and Anticoagulation Therapy in patients with COVID-19 in Japan: From the CLOT-COVID Study

ABSTRACT

Background: Data on thrombosis and current real-world management strategies for anticoagulation therapy are important for an optimal management of patients with coronavirus disease 2019 (COVID-19) Methods: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. Also subanalysis is performed for D-dimer at the admission and influence of sex with adjustment confounders with multivariable logistic regression model. Result(s) Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. During the hospitalization, 38 patients (1.3%)and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrastenhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism(71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4%withmoderate COVID-19, and 9.5%with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. The higher D-dimer levels in the 3rd tertile (>=1.1 mug/mL) in 2,771 patients who had D-dimer levels measured at admission. were independently associated with a higher risk of VTE during hospitalization (adjusted odds ratio 4.83 [95% confidence interval 1.93-12.11;P<0.001];reference=1st tertile).Men had more severe status of the COVID-19 at admission compared with women (Mild 57% versus 66%, Moderate 34% versus 29%, and Severe 9.1% versus 5.7%, P < 0.001). During the hospitalization, men more often developed thrombosis than women (2.5% [95%CI, 1.9-3.3%] versus 0.8% [95%CI, 0.4- 1.6%], P = 0.001). Men had numerically higher incidences of thrombosis than women in all subgroups of the worst severity of COVID-19during the hospitalization (Mild 0.3% versus 0.0%, Moderate 1.6% versus 1.0%, and Severe 11.1% versus 4.3%) Conclusion(s) In the large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients was common especially in patients with severe COVID-19. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19 in Japan. In contrast to previous studies outside Japan, the risk of thrombosis in Japanese patients with COVID-19 may be relatively low, and racial differences may have to be considered. In subanalysis higher D-dimer levels at admission were associated with a higher risk of VTE events during hospitalization. Men had more severe status of the COVID-19 than women, and the risk of development of thrombosis was higher in men compared with women.