Journal Article

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

Allsup, David, Lopez-Garcia, Alberto, Otasevic, Vladimir, Capasso, Antonella, García-Serra, Rocío, Janssens, Ann, Morawska, Marta, Gimeno, Eva, Te Raa, Doreen, Vitale, Candida, Gentile, Massimo, Fresa, Alberto, Stanca, Oana, Lad, Deepesh, Marchetti, Monia, Foà, Robin, Koren-Michowitz, Maya, Stavroyianni, Niki, Correa, Juan Gonzalo, Kersting, Sabina, Tomic, Kristina, Farina, Lucia, Rajovic, Nina, Munir, Talha, Stamatopoulos, Kostas, Mihaljevic, Biljana, Hernández-Rivas, José Ángel, Milosevic, Ivana, Šimkovič, Martin, Visentin, Andrea, De Paoli, Lorenzo, Del Poeta, Giovanni, Van Der Spek, Ellen, Scarfò, Lydia, Alonso Cabrero, Alejandro, Laurenti, Luca, Chatzikonstantinou, Thomas, Kalicińska, Elżbieta, Yassin, Mohamed, Andres, Martin, Wróbel, Tomasz, Varettoni, Marzia, Kalashnikova, Olga B., Cuneo, Antonio, Pavlovsky, Miguel Arturo, Nunes, Raquel, Efstathopoulou, Maria, Espinet, Blanca, Herold, Tobias, Hakobyan, Yervand K., Levin, Mark-David, Špaček, Martin, da Silva, Maria Gomes, Collado, Rosa, Antic, Darko, García-Marco, José A., Motta, Marina, Enrico, Alicia, Piskunova, Inga, Herishanu, Yair, Cuéllar-Ga

2022

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Anticoagulation therapy / Bleeding / Blood clot / C-reactive protein / Cancer / Cancer Research / Cardiovascular disease / Care and treatment / Chronic lymphocytic leukemia / CLL / Comorbidity / Complications and side effects / Coronaviruses / COVID-19 / D-dimer / Data collection / Heart attacks / Hematology / Hemodialysis / Heparin / Hospitalization / Immunodeficiency / Intensive care / Leukemia / Medicine / Medicine & Public Health / Multivariate analysis / Observational studies / Oncology / Oncology, Experimental / Oxygen / Pandemics / Patients / Pharynx / Polymerase chain reaction / Pulmonary embolisms / Risk factors / Severe acute respiratory syndrome coronavirus 2 / Statistical analysis / Supplements / Thromboembolism / Thrombosis / Variables