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Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Antic, Darko; Milic, Natasa; Chatzikonstantinou, Thomas; Scarfò, Lydia; Otasevic, Vladimir; Rajovic, Nina; Allsup, David; Alonso Cabrero, Alejandro; Andres, Martin; Baile Gonzales, Monica; Capasso, Antonella; Collado, Rosa; Cordoba, Raul; Cuéllar-García, Carolina; Correa, Juan Gonzalo; De Paoli, Lorenzo; De Paolis, Maria Rosaria; Del Poeta, Giovanni; Dimou, Maria; Doubek, Michael; Efstathopoulou, Maria; El-Ashwah, Shaimaa; Enrico, Alicia; Espinet, Blanca; Farina, Lucia; Ferrari, Angela; Foglietta, Myriam; Lopez-Garcia, Alberto; García-Marco, José A; García-Serra, Rocío; Gentile, Massimo; Gimeno, Eva; Gomes Da Silva, Maria; Gutwein, Odit; Hakobyan, Yervand K; Herishanu, Yair; Hernández-Rivas, José Ángel; Herold, Tobias; Itchaki, Gilad; Jaksic, Ozren; Janssens, Ann; Kalashnikova, Olga B; Kalicińska, Elżbieta; Kater, Arnon P; Kersting, Sabina; Koren-Michowitz, Maya; Labrador, Jorge; Lad, Deepesh; Laurenti, Luca; Fresa, Alberto; Levin, Mark David; Mayor Bastida, Carlota; Malerba, Lara; Mar...

Authors

Darko Antic

Natasa Milic

Thomas Chatzikonstantinou

Lydia Scarfò

Vladimir Otasevic

Nina Rajovic

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Dr David Allsup D.J.Allsup@hull.ac.uk
Senior Lecturer in Haematology and Honorary Consultant

Alejandro Alonso Cabrero

Martin Andres

Monica Baile Gonzales

Antonella Capasso

Rosa Collado

Raul Cordoba

Carolina Cuéllar-García

Juan Gonzalo Correa

Lorenzo De Paoli

Maria Rosaria De Paolis

Giovanni Del Poeta

Maria Dimou

Michael Doubek

Maria Efstathopoulou

Shaimaa El-Ashwah

Alicia Enrico

Blanca Espinet

Lucia Farina

Angela Ferrari

Myriam Foglietta

Alberto Lopez-Garcia

José A García-Marco

Rocío García-Serra

Massimo Gentile

Eva Gimeno

Maria Gomes Da Silva

Odit Gutwein

Yervand K Hakobyan

Yair Herishanu

José Ángel Hernández-Rivas

Tobias Herold

Gilad Itchaki

Ozren Jaksic

Ann Janssens

Olga B Kalashnikova

Elżbieta Kalicińska

Arnon P Kater

Sabina Kersting

Maya Koren-Michowitz

Jorge Labrador

Deepesh Lad

Luca Laurenti

Alberto Fresa

Mark David Levin

Carlota Mayor Bastida

Lara Malerba

Roberto Marasca

Monia Marchetti

Juan Marquet

Biljana Mihaljevic

Ivana Milosevic

Fatima Mirás

Marta Morawska

Marina Motta

Talha Munir

Roberta Murru

Raquel Nunes

Jacopo Olivieri

Miguel Arturo Pavlovsky

Inga Piskunova

Viola Maria Popov

Francesca Maria Quaglia

Giulia Quaresmini

Gianluigi Reda

Gian Matteo Rigolin

Amit Shrestha

Martin Šimkovič

Svetlana Smirnova

Martin Špaček

Paolo Sportoletti

Oana Stanca

Niki Stavroyianni

Doreen Te Raa

Kristina Tomic

Sanne Tonino

Livio Trentin

Ellen Van Der Spek

Michel van Gelder

Marzia Varettoni

Andrea Visentin

Candida Vitale

Vojin Vukovic

Ewa Wasik-Szczepanek

Tomasz Wróbel

Lucrecia Yáñez San Segundo

Mohamed Yassin

Marta Coscia

Alessandro Rambaldi

Emili Montserrat

Robin Foà

Antonio Cuneo

Marc Carrier

Paolo Ghia

Kostas Stamatopoulos



Abstract

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Citation

Antic, D., Milic, N., Chatzikonstantinou, T., Scarfò, L., Otasevic, V., Rajovic, N., …Stamatopoulos, K. (2022). Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL. Journal of Hematology & Oncology, 15(1), Article 116. https://doi.org/10.1186/s13045-022-01333-0

Journal Article Type Article
Acceptance Date Aug 8, 2022
Online Publication Date Aug 26, 2022
Publication Date 2022
Deposit Date Sep 1, 2022
Publicly Available Date Sep 1, 2022
Journal Journal of hematology & oncology
Electronic ISSN 1756-8722
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 15
Issue 1
Article Number 116
DOI https://doi.org/10.1186/s13045-022-01333-0
Keywords CLL; COVID-19; Thrombosis; Bleeding; D-dimer; Anticoagulation therapy; Thromboprophylaxis; LMWH; Age
Public URL https://hull-repository.worktribe.com/output/4063771

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Copyright Statement
© The Author(s) 2022.
Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.





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