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Bleeding and thrombotic events and intensity of heparin therapy in the two first waves of COVID-19

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Abstract

A systemic inflammatory response occurs during SARS-CoV2 infection and is associated with hypercoagulability and thrombotic events. From March 2020 in our hospital different dosages of low-molecular weight heparin (LMWH) were introduced according to the level of patient care intensity. Because bleeding episodes occurred in hospitalized COVID-19 patients on heparin, the dosage of LMWH at the end of first wave was tailored on the severity of COVID-19. The aim of this study is to describe bleeding and thrombotic events in patients hospitalized with SARS-CoV2 infection on LMWH therapy in the two waves of COVID-19 and analyze the factors associated with these events. Among 1143 patients enrolled in the COVID-19 Network registry, 912 were included in the analysis, 537 of them admitted during the first wave and 375 during the second. Bleeding events were 30 (3.3%): 22 (2.4%) major and 8 (0.9%) non-major. Arterial and venous thrombotic events were 6 (0.7%) and 24 (2.6%). The incidence of venous thrombotic events was higher in the first than in the second wave (0.29% [95% CI 0.20–0.45] events/day vs. 0.05% [95% CI 0.02–0.16]), with a 71% risk reduction (95% CI 22%—94%). The incidence of bleeding was 0.33% (95% CI 0.22–0.50) vs 0.14% events/day (95% CI 0.07–0.28), with no statistical between-wave difference (HR 0.41 95% CI 0.16–1.08). After adjusting for the competing risks of death and comorbidities, patients in the second wave had lower odds to have thrombotic events than in the first wave (0.24 HR [95% C.I. 0.07–0.89]). In this retrospective study on COVID-19 we found a low rate of hemorrhagic and thrombotic events, that may be explained by the absence in the case material of patients admitted to intensive care unit.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors gratefully acknowledge P.M. Mannucci for his critical revision. The study was partially supported by the Italian Ministry of Health – Bando Ricerca Corrente 2023. The Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico is member of the European Reference Network (ERN) EuroBloodNet.

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Ricerca corrente 2023.

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Authors and Affiliations

  1. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Sforza 35, Milan, Italy

    Raffaella Rossio, Roberta Gualtierotti, Andrea Giachi & Flora Peyvandi

  2. Department of Pathophysiology and Transplantation, Università Degli Studi Di Milano, Milan, Italy

    Roberta Gualtierotti, Adriana Torri & Flora Peyvandi

  3. Laboratory of Geriatric Epidemiology, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy

    Mauro Tettamanti, Alessia Antonella Galbussera & Alessandro Nobili

  4. Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, 20122, Milan, Italy

    Nicola Montano

  5. Department of Pathophysiology and Transplantation, Unit of Metabolic and Internal Medicine, University of Milan, Milan, Italy

    Anna Ludovica Fracanzani

  6. Infectious Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Alessandra Bandera

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  1. Raffaella Rossio
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the COVID-19 Network

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Correspondence to Raffaella Rossio.

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Conflict of interests

R.G. has received honoraria for participating as a speaker in education meetings organized by Pfizer, Novo Nordisk, Sobi, Takeda, and Roche and is a member of the scientific advisory boards of Bayer, Sobi, Roche, and Pfizer. F.P. has received honoraria for participating as a speaker in education meetings and symposia organized by Takeda and Spark. She is a consultant/member of the advisory boards for CSL Behring, Biomarin, Roche, Sanofi, and Sobi. The remaining authors declare no competing financial interests.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Ospedale Maggiore Policlinico.

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The authors state that this research was conducted in accordance with the Helsinki Declaration as revised in 2008.

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Rossio, R., Tettamanti, M., Galbussera, A. et al. Bleeding and thrombotic events and intensity of heparin therapy in the two first waves of COVID-19. Intern Emerg Med (2024). https://doi.org/10.1007/s11739-024-03635-2

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