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. 2022 Sep 20;20(1):53.
doi: 10.1186/s12959-022-00414-x.

Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study

Junichi Nakamura  1 , Ichizo Tsujino  2   3 , Sen Yachi  4 , Makoto Takeyama  4 , Yuji Nishimoto  5 , Satoshi Konno  1 , Naoto Yamamoto  6 , Hiroko Nakata  7 , Satoshi Ikeda  8 , Michihisa Umetsu  9 , Shizu Aikawa  10 , Hiroya Hayashi  11 , Hirono Satokawa  12 , Yoshinori Okuno  13 , Eriko Iwata  14 , Yoshito Ogihara  15 , Nobutaka Ikeda  16 , Akane Kondo  17 , Takehisa Iwai  18 , Norikazu Yamada  19 , Tomohiro Ogawa  20 , Takao Kobayashi  6 , Makoto Mo  21 , Yugo Yamashita  13 ; CLOT-COVID Study Investigators
Affiliations

Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study

Junichi Nakamura et al. Thromb J. .

Abstract

Background: The coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear.

Method: The CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events.

Results: Among 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6-14] vs 28 [19-43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001).

Conclusions: In the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19.

Keywords: Anticoagulant; Bleeding; COVID-19; Hospitalization; Mortality; Severity.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Sites of major bleeding. The bleeding sites in the 57 major bleeding events are shown
Fig. 2
Fig. 2
Number of major bleeding events according to COVID-19 severity. The proportion of patients with major bleeding among patients with mild, moderate, and severe COVID-19 is shown COVID-19, coronavirus disease 2019
Fig. 3
Fig. 3
Incidence of major bleeding according to the calculated risk score. The proportion of patients with major bleeding according to the total risk score of major bleeding is shown. The risk score was calculated by summing the points described below. History of major bleeding: no, 0 point; yes, 1 point. COVID-19 severity at admission: mild, 0 point; moderate, 1 point; severe, 2 points. Anticoagulant regimen: no anticoagulants, 0 point; prophylactic dose of parenteral anticoagulant (unfractionated heparin or low molecular weight heparin) or therapeutic dose of warfarin/DOAC, 1 point; therapeutic dose of unfractionated heparin, 2 points. COVID-19, coronavirus disease 2019; LMWH, low-molecular-weight heparin; UFH, unfractionated heparin; DOAC, direct oral anticoagulant
See this image and copyright information in PMC

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