Publication details

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

Authors	ANTIC Darko MILIC Natasa CHATZIKONSTANTINOU Thomas SCARFO Lydia OTASEVIC Vladimir RAJOVIC Nina ALLSUP David CABRERO Alejandro Alonso ANDRES Martin GONZALES Monica Baile CAPASSO Antonella COLLADO Rosa CORDOBA Raul CUELLAR-GARCIA Carolina CORREA Juan Gonzalo LORENZO De Paoli ROSARIA De Paolis Maria GIOVANNI Del Poeta DIMOU Maria DOUBEK Michael EFSTATHOPOULOU Maria EL-ASHWAH Shaimaa ENRICO Alicia ESPINET Blanca FARINA Lucia FERRARI Angela FOGLIETTA Myriam LOPEZ-GARCIA Alberto GARCIA-MARCO Jose A GARCIA-SERRA Rocio GENTILE Massimo GIMENO Eva GOMES da Silva Maria GUTWEIN Odit HAKOBYAN Yervand K HERISHANU Yair HERNANDEZ-RIVAS Jose Angel HEROLD Tobias ITCHAKI Gilad JAKSIC Ozren JANSSENS Ann KALASHNIKOVA Olga B KALICINSKA Elzbieta KATER Arnon P KERSTING Sabina KOREN-MICHOWITZ Maya LABRADOR Jorge LAD Deepesh LAURENTI Luca FRESA Alberto LEVIN Mark-David BASTIDA Carlota Mayor MALERBA Lara MARASCA Roberto MARCHETTI Monia MARQUET Juan MIHALJEVIC Biljana MILOSEVIC Ivana MIRAS Fatima MORAWSKA Marta MOTTA Marina MUNIR Talha MURRU Roberta NUNES Raquel OLIVIERI Jacopo PAVLOVSKY Miguel Arturo PISKUNOVA Inga POPOV Viola Maria QUAGLIA Francesca Maria QUARESMINI Giulia REDA Gianluigi RIGOLIN Gian Matteo SHRESTHA Amit SIMKOVIC Martin SMIRNOVA Svetlana SPACEK Martin SPORTOLETTI Paolo STANCA Oana STAVROYIANNI Niki DOREEN Te Raa TOMIC Kristina TONINO Sanne TRENTIN Livio ELLEN Van der Spek MICHEL van Gelder VARETTONI Marzia VISENTIN Andrea VITALE Candida VUKOVIC Vojin WASIK-SZCZEPANEK Ewa WROBEL Tomasz YANEZ San Segundo Lucrecia YASSIN Mohamed COSCIA Marta RAMBALDI Alessandro MONTSERRAT Emili FOA Robin CUNEO Antonio CARRIER Marc GHIA Paolo STAMATOPOULOS Kostas
Year of publication	2022
Type	Article in Periodical
Magazine / Source	JOURNAL OF HEMATOLOGY & ONCOLOGY
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01333-0
Doi	http://dx.doi.org/10.1186/s13045-022-01333-0
Keywords	CLL; COVID-19; Thrombosis; Bleeding; D-dimer; Anticoagulation therapy; Thromboprophylaxis; LMWH; Age
Description	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.