Arterial and Venous Thrombosis Complicated in COVID-19: A Retrospective Single Center Analysis in Japan

Abstract

Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients.Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests.Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08–42.3, and 1.06–9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics.Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19.

The current status of thrombosis and anticoagulation therapy in patients with COVID-19 in Japan: From the CLOT-COVID study

“…In line with the previous studies [ 17 , 19 , 24 , 25 ], the present study from Japan showed a lower incidence of VTE in hospitalized patients with COVID-19 than that in the studies from Western countries [ 7 , 9 , 10 ]. The interpretation of the present results should be taken with caution because the number of patients that underwent imaging examinations was small, which may have been partly due to the difficulty in diagnosing VTE in patients with COVID-19 from the following perspectives: 1) the symptoms of COVID-19, such as fever, dyspnea, and tachypnea, mimic those of PE [ 26 ], 2) a major influence of COVID-19 on the hemodynamic status and oxygenation could mask the suspicion of VTE leading to imaging examinations, and 3) a high threshold for imaging examinations due to isolation [ 27 ].…”

Full Characterization of Thrombotic Events in All Hospitalized COVID-19 Patients in a Spanish Tertiary Hospital during the First 18 Months of the Pandemic

“…Lodigiani et al recorded 28 events (7.7%) in 388 Italian patients, most of them diagnosed at hospital admission [ 30 ]. Oba et al studied 516 patients in Tokyo, of whom 42 patients (6.20%) suffered a TE [ 31 ]. Furthermore, Klok et al described a TE incidence of 31% in ICU patients with COVID-19 [ 13 ].…”

“…The occurrence of thrombotic events is more frequently associated with advanced age, male sex, and the presence of TE risk factors [ 14 , 30 , 31 ]. These are essentially the same factors that are associated with severe COVID-19 [ 1 , 5 , 33 , 34 ].…”

COVID-19-related thrombotic complications experience before and during delta wave

“…Moreover, 69% of the patients on early DVT prophylaxis still showed thrombotic complications despite adequate preventive measures. Previous literature also described this phenomenon ( 27 ); it highlights the need to develop a standardized protocol for early antithrombotic regimens in COVID-19 patients.…”