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

Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937

Informations de publication

Date de publication:
26 08 2022
Historique:
received: 19 04 2022
accepted: 08 08 2022
entrez: 26 8 2022
pubmed: 27 8 2022
medline: 31 8 2022
Statut: epublish

Résumé

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. 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. 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). 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.

Sections du résumé

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.

Identifiants

pubmed: 36028857
doi: 10.1186/s13045-022-01333-0
pii: 10.1186/s13045-022-01333-0
pmc: PMC9415249
doi:

Substances chimiques

Anticoagulants 0
Heparin, Low-Molecular-Weight 0

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

116

Informations de copyright

© 2022. The Author(s).

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Auteurs

Darko Antic (D)

Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia. darko.antic1510976@gmail.com.
Faculty of Medicine, University of Belgrade, Belgrade, Serbia. darko.antic1510976@gmail.com.

Natasa Milic (N)

Department of Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Thomas Chatzikonstantinou (T)

Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.
Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece.

Lydia Scarfò (L)

Università Vita-Salute San Raffaele and IRCC Ospedale San Raffaele, Milan, Italy.

Vladimir Otasevic (V)

Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia.

Nina Rajovic (N)

Department of Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

David Allsup (D)

Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Hull, UK.

Alejandro Alonso Cabrero (A)

Haematology Department, Hospital Universitario de La Princesa, Madrid, Spain.

Martin Andres (M)

Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Monica Baile Gonzales (M)

Hematology Department, University Hospital of Salamanca-IBSAL, Salamanca, Spain.

Antonella Capasso (A)

IRCSS Ospedale San Raffaele, Milan, Italy.

Rosa Collado (R)

Department of Hematology, Hospital General Universitario, Valencia, Spain.
Fundación de Investigación del Hospital General Universitario, Valencia, Spain.

Raul Cordoba (R)

Department of Hematology, Health Research Institute IIS-FJD, Fundacion Jimenez Diaz University Hospital, Madrid, Spain.

Carolina Cuéllar-García (C)

Hematology Unit Terrassa Hospital, Terrassa, Spain.

Juan Gonzalo Correa (JG)

Hospital Clínic de Barcelona, Barcelona, Spain.

Lorenzo De Paoli (L)

Division of Internal Medicine, Hematology Unit, ASL Vercelli, Vercelli, Italy.

Maria Rosaria De Paolis (MR)

UOC Ematologia PO Vito Fazzi Lecce, Lecce, Italy.

Giovanni Del Poeta (G)

Department of Biomedicine and Prevention Hematology, University Tor Vergata, Rome, Italy.

Maria Dimou (M)

1st Internal Medicine Department, Propaedeutic, Hematology Clinical Trial Unit, National and Kapodistrian University of Athens, Athens, Greece.

Michael Doubek (M)

Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno, Czechia.
Department of Medical Genetics and Genomics, Faculty of Medicine, Masaryk University, Brno, Czechia.

Maria Efstathopoulou (M)

Department of Haematology Athens Medical Center-Psychikon Branch, Athens, Greece.

Shaimaa El-Ashwah (S)

Clinical Hematology Unit, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.

Alicia Enrico (A)

Hospital Italiano La Plata, La Plata, Argentina.

Blanca Espinet (B)

Department of Hematology, Hospital del Mar, Barcelona, Spain.

Lucia Farina (L)

Hematology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Angela Ferrari (A)

Hematology Unit, Azienda Unità Sanitaria Locale - IRCCS, Reggio Emilia, Italy.

Myriam Foglietta (M)

SC Ematologia, AO S. Croce e Carle, Cuneo, Italy.

Alberto Lopez-Garcia (A)

Department of Hematology, Health Research Institute IIS-FJD, Fundacion Jimenez Diaz University Hospital, Madrid, Spain.

José A García-Marco (JA)

Hematology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.

Rocío García-Serra (R)

Department of Hematology, Hospital General Universitario, Valencia, Spain.
Fundación de Investigación del Hospital General Universitario, Valencia, Spain.

Massimo Gentile (M)

Hematology Unit AO Cosenza, Cosenza, Italy.

Eva Gimeno (E)

Department of Hematology, Hospital del Mar, Barcelona, Spain.

Maria Gomes da Silva (MG)

Hematology Department, Portuguese Institute of Oncology Lisbon, Lisbon, Portugal.

Odit Gutwein (O)

Department of Hematology, Shamir Medical Center, Zerifin, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Yervand K Hakobyan (YK)

Hematology Center after Prof. Yeolyan MH RA, Yerevan, Armenia.

Yair Herishanu (Y)

Department of Hematology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

José Ángel Hernández-Rivas (JÁ)

Department of Hematology, Infanta Leonor University Hospital, Madrid, Spain.

Tobias Herold (T)

Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.

Gilad Itchaki (G)

Division of Hematology, Rabin Medical Center, Petah Tikva, and the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.

Ozren Jaksic (O)

Department of Hematology, University Hospital Dubrava, Zagreb, Croatia.

Ann Janssens (A)

Department of Hematology, Universitaire Ziekenhuizen Leuven, Leuven, Belgium.

Olga B Kalashnikova (OB)

Federal State Budgetary Educational Institution of Higher Education Academician I.P. Pavlov, First St. Petersburg State Medical University of the Ministry of Healthcare of Russian Federation, St. Petersburg, Russia.

Elżbieta Kalicińska (E)

Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wrocław, Poland.

Arnon P Kater (AP)

Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Sabina Kersting (S)

Department of Hematology, Haga Teaching Hospital, The Hague, The Netherlands.

Maya Koren-Michowitz (M)

Department of Hematology, Shamir Medical Center, Zerifin, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Jorge Labrador (J)

Hematology Department, Unit Research, Complejo Asistencial Universitario de Burgos, Burgos, Spain.

Deepesh Lad (D)

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Luca Laurenti (L)

Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Alberto Fresa (A)

Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Mark-David Levin (MD)

Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands.

Carlota Mayor Bastida (C)

Haematology Department, Hospital Universitario de La Princesa, Madrid, Spain.
Spanish Society of Haematology and Hemotherapy (SEHH: Sociedad Española de Hematología y Hemoterapia), Madrid, Spain.

Lara Malerba (L)

Hematology and Stem Cell Transplant Center Marche Nord Hospital, Pesaro, Italy.

Roberto Marasca (R)

Section of Hematology, Department of Medical Sciences, University of Modena and Reggio E., Modena, Italy.

Monia Marchetti (M)

Hematology Unit & TMO Center, AO SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.

Juan Marquet (J)

Hematology Department, Ramón y Cajal University Hospital, Madrid, Spain.

Biljana Mihaljevic (B)

Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia.
Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Ivana Milosevic (I)

Clinical Centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.

Fatima Mirás (F)

Hematology Department, Hospital Universitario 12de Octubre, Madrid, Spain.

Marta Morawska (M)

Experimental Hematooncology Department, Medical University of Lublin, Lublin, Poland.
Hematology Department, St. John's Cancer Center, Lublin, Poland.

Marina Motta (M)

S.C. Ematologia ASST Spedali Civili Brescia, Brescia, Italy.

Talha Munir (T)

Consultant Haematologist, St James's Hospital, Leeds, LS9 7TF, UK.

Roberta Murru (R)

Hematology and Stem Cell Transplantation Unit, Ospedale Oncologico A. Businco, ARNAS "G. Brotzu", Cagliari, Italy.

Raquel Nunes (R)

Hematology Department, Portuguese Institute of Oncology Lisbon, Lisbon, Portugal.

Jacopo Olivieri (J)

Hematology Clinic, ASUFC, Udine, Italy.

Miguel Arturo Pavlovsky (MA)

FUNDALEU, Clinical Research Center Buenos Aires, Buenos Aires, Argentina.

Inga Piskunova (I)

Consultative Hematology Department with a Day Hospital for Intensive High-Dose Chemotherapy, National Research Center for Hematology, Moscow, Russia.

Viola Maria Popov (VM)

Hematology Department, Colentina Clinical Hospital, Bucharest, Romania.

Francesca Maria Quaglia (FM)

Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.

Giulia Quaresmini (G)

Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy.

Gianluigi Reda (G)

Hematology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, Milan, Italy.

Gian Matteo Rigolin (GM)

St. Anna University Hospital, Ferrara, Italy.

Amit Shrestha (A)

Hematology Unit, Nepal Cancer Hospital and Research Center, Lalitpur, Nepal.

Martin Šimkovič (M)

4th Department of Internal Medicine - Haematology, Faculty of Medicine in Hradec Králové, University Hospital and Charles University in Prague, Hradec Kralove, Czech Republic.

Svetlana Smirnova (S)

Consultative Hematology Department with a Day Hospital for Intensive High-Dose Chemotherapy, National Research Center for Hematology, Moscow, Russia.

Martin Špaček (M)

1st Department of Medicine - Hematology, First Faculty of Medicine, Charles University and General Hospital in Prague, Prague, Czech Republic.

Paolo Sportoletti (P)

Department of Medicine and Surgery, Institute of Hematology and Center for Hemato-Oncological Research, Ospedale S. Maria della Misericordia, Perugia, Italy.

Oana Stanca (O)

Hematology Department from Coltea Clinical Hospital, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.

Niki Stavroyianni (N)

Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.

Doreen Te Raa (D)

Department of Hematology, Gelderse Vallei Ede, Ede, The Netherlands.

Kristina Tomic (K)

Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia.

Sanne Tonino (S)

Department of Hematology, Lymmcare, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Livio Trentin (L)

Hematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padua, Italy.

Ellen Van Der Spek (E)

Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands.

Michel van Gelder (M)

Department Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.

Marzia Varettoni (M)

Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Andrea Visentin (A)

Hematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padua, Italy.

Candida Vitale (C)

Division of Hematology, A.O.U. Cittàdella Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.

Vojin Vukovic (V)

Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia.

Ewa Wasik-Szczepanek (E)

Department Hematooncology and Bone Marrow Transplantation, Medical University in Lublin, Lublin, Poland.

Tomasz Wróbel (T)

Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wrocław, Poland.

Lucrecia Yáñez San Segundo (LYS)

University Hospital and Research Institute of Marqués de Valdecilla (IDIVAL), Santander, Spain.

Mohamed Yassin (M)

Hematology Section, Department of Medical Oncology, National Center for Cancer Care and Research, Doha, Qatar.

Marta Coscia (M)

Division of Hematology, A.O.U. Cittàdella Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.

Alessandro Rambaldi (A)

Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy.

Emili Montserrat (E)

Hospital Clínic de Barcelona, Barcelona, Spain.

Robin Foà (R)

Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.

Antonio Cuneo (A)

St. Anna University Hospital, Ferrara, Italy.

Marc Carrier (M)

Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.

Paolo Ghia (P)

Università Vita-Salute San Raffaele and IRCC Ospedale San Raffaele, Milan, Italy.

Kostas Stamatopoulos (K)

Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece.

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