Incidence and Clinical Features of Venous Thromboembolism in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) in Japan

Yamashita, Yugo; Maruyama, Yuuki; Satokawa, Hirono; Nishimoto, Yuji; Tsujino, Ichizo; Sakashita, Hideaki; Nakata, Hiroko; Okuno, Yoshinori; Ogihara, Yoshito; Yachi, Sen; Toya, Naoki; Shingaki, Masami; Ikeda, Satoshi; Yamamoto, Naoto; Aikawa, Shizu; Ikeda, Nobutaka; Hayashi, Hiroya; Ishiguro, Shingo; Iwata, Eriko; Umetsu, Michihisa; Kondo, Akane; Iwai, Takehisa; Kobayashi, Takao; Mo, Makoto; Yamada, Norikazu

doi:10.1253/circj.cj-21-0169

Cited by 33 publications

(34 citation statements)

References 34 publications

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“…Our study revealed that thrombotic complications developed more frequently in patients with a severe respiratory disease on admission and were associated with death, consistent with the previous findings in the Japanese population (16). Additionally, elevated D-dimer and ferritin levels on admission were the risk factors for the development of thrombosis.…”

Section: Discussionsupporting

confidence: 91%

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

Oba

Hosoya

Amamiya

et al. 2021

Front. Cardiovasc. Med.

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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.

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Section: Discussionsupporting

confidence: 91%

“…So far, there is limited evidence about the incidence of thrombosis and the association of biomarkers in Japanese population, except a few (15)(16)(17)(18). The objective of the current study was to identify the risk factors for the development of thrombosis.…”

Section: Introductionmentioning

confidence: 97%

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

Oba

Hosoya

Amamiya

et al. 2021

Front. Cardiovasc. Med.

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“…Yamashita et al, conducting questionnaire surveillance involving 1243 patients with COVID-19 among 77 institutions in Japan, reported a low prevalence of venous thrombosis (0.6%, 7/1243) and PE (0.4%, 5/1243) [10]. In line with our data that the proportion of thromboembolic events was up to 44.4% (4/9) in patients with severe COVID-19 infection requiring mechanical ventilation, one Japanese multicenter cohort study with 1236 patients with COVID-19 infection found that the prevalence of CTproven venous thromboembolism was up to 40% in those with severe COVID-19 infection requiring mechanical ventilation [22]. Therefore, more studies for thromboembolic events are warranted to address the epidemiology of thromboembolic events among patients with COVID-19 in Asian populations, particularly studies with active surveillance.…”

Section: Discussionsupporting

confidence: 88%

“…However, recent studies have shown that the incidence of VTE in Asian countries, including Taiwan, has risen in the past two decades, and the increased incidence may be attributed to increased vigilance for VTE, ageing population, increased patients with cancer, and altered lifestyle [17][18][19][20]. Notably, accumulating evidence have shown the highly prevalent thromboembolic events in patients including the Asian population with COVID-19 infection, particularly those with high disease severity and elevated levels of D-dimer [4,8,21,22]. Ren et al carried out a cross-sectional study with a routine survey for DVT using compression ultrasound examinations among 48 patients with severe COVID-19 infection requiring ICU admission in Wuhan [4].…”

Section: Discussionmentioning

confidence: 99%

Association between Early Absolute Neutrophil Count and Level of D-Dimer among Patients with COVID-19 Infection in Central Taiwan

Chao

Huang

et al. 2021

JCM

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Thromboembolism is a critical event in patients with coronavirus disease (COVID)-19 infection and highly associated with neutrophil extracellular traps. D-dimer has been found to be an essential thromboembolism-associated biomarker; however, the association between absolute neutrophil count (ANC) and level of D-dimer in patients with COVID-19 infection remains unclear. In this study, we enrolled consecutive patients with COVID-19 admitted to Taichung Veterans General Hospital (TCVGH), a referral center in central Taiwan with 20 airborne infection isolation rooms. Spearman correlation was used to determine the association between ANC and level of D-dimer in distinct time periods. A total of 28 consecutive patients with COVID-19 infection were enrolled, and 32.1% (9/28) of them required mechanical ventilation. Patients requiring mechanical ventilation had a higher ANC (8225 vs. 3427/µL, p < 0.01) and levels of D-dimer (6.0 vs. 0.6 mg/L, p < 0.01) compared with those without mechanical ventilation. Notably, we identified five patients with image-proven thromboembolic events during the hospital course, with the number of patients with pulmonary embolism, venous thrombosis and acute ischemic stroke were 2, 1, and 2, respectively. We found that ANC within 4 days correlated with the level of D-dimer to a moderate level (r = 0.71, p < 0.05), and the association between ANC and D-dimer no longer exist after day 5. In conclusion, we found highly prevalent thromboembolic events among patients with severe COVID-19 infection in central Taiwan and identified the association between early ANC and D-dimer. More studies are warranted to elucidate the underlying mechanism.

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“…Considering the high risk of VTE in COVID-19 patients, it could be important for clinicians to conduct an appropriate imaging examination of these patients when they are suspected of VTE during the course of COVID-19 treatment to avoid under-diagnosis of VTE. However, a previous study reported that only a small number of patients were evaluated with contrastenhanced computed tomography (CT) examination in real-world clinical practice, which suggests some reluctance to conduct imaging examinations due to the risk of infection to healthcare providers (2). Thus, practical diagnostic strategies for VTE could be clinically relevant.…”

Section: Covid-19 and Venous Thromboembolismmentioning

confidence: 99%

Editorial: COVID-19 and Venous Thromboembolism

Yamashita

2021

Front. Cardiovasc. Med.

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Incidence and Clinical Features of Venous Thromboembolism in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) in Japan

Cited by 33 publications

References 34 publications

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

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

Association between Early Absolute Neutrophil Count and Level of D-Dimer among Patients with COVID-19 Infection in Central Taiwan

Editorial: COVID-19 and Venous Thromboembolism

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