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, Natasa MILIC, Thomas CHATZIKONSTANTINOU, Lydia SCARFO, Vladimir OTASEVIC et. al.
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 (guarantor), Natasa MILIC, Thomas CHATZIKONSTANTINOU, Lydia SCARFO, Vladimir OTASEVIC, Nina RAJOVIC, David ALLSUP, Alejandro Alonso CABRERO, Martin ANDRES, Monica Baile GONZALES, Antonella CAPASSO, Rosa COLLADO, Raul CORDOBA, Carolina CUELLAR-GARCIA, Juan Gonzalo CORREA, De Paoli LORENZO, De Paolis Maria ROSARIA, Del Poeta GIOVANNI, Maria DIMOU, Michael DOUBEK (203 Czech Republic, belonging to the institution), Maria EFSTATHOPOULOU, Shaimaa EL-ASHWAH, Alicia ENRICO, Blanca ESPINET, Lucia FARINA, Angela FERRARI, Myriam FOGLIETTA, Alberto LOPEZ-GARCIA, Jose A GARCIA-MARCO, Rocio GARCIA-SERRA, Massimo GENTILE, Eva GIMENO, da Silva Maria GOMES, Odit GUTWEIN, Yervand K HAKOBYAN, Yair HERISHANU, Jose Angel HERNANDEZ-RIVAS, Tobias HEROLD, Gilad ITCHAKI, Ozren JAKSIC, Ann JANSSENS, Olga B KALASHNIKOVA, Elzbieta KALICINSKA, 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 MIRAS, 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 SIMKOVIC, Svetlana SMIRNOVA, Martin SPACEK, Paolo SPORTOLETTI, Oana STANCA, Niki STAVROYIANNI, Te Raa DOREEN, Kristina TOMIC, Sanne TONINO, Livio TRENTIN, Van der Spek ELLEN, van Gelder MICHEL, Marzia VARETTONI, Andrea VISENTIN, Candida VITALE, Vojin VUKOVIC, Ewa WASIK-SZCZEPANEK, Tomasz WROBEL, San Segundo Lucrecia YANEZ, Mohamed YASSIN, Marta COSCIA, Alessandro RAMBALDI, Emili MONTSERRAT, Robin FOA, Antonio CUNEO, Marc CARRIER, Paolo GHIA and Kostas STAMATOPOULOS
Edition
JOURNAL OF HEMATOLOGY & ONCOLOGY, LONDON, BMC, 2022, 1756-8722
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30205 Hematology
Country of publisher
United Kingdom of Great Britain and Northern Ireland
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.
ANTIC, Darko, Natasa MILIC, Thomas CHATZIKONSTANTINOU, Lydia SCARFO, Vladimir OTASEVIC, Nina RAJOVIC, David ALLSUP, Alejandro Alonso CABRERO, Martin ANDRES, Monica Baile GONZALES, Antonella CAPASSO, Rosa COLLADO, Raul CORDOBA, Carolina CUELLAR-GARCIA, Juan Gonzalo CORREA, De Paoli LORENZO, De Paolis Maria ROSARIA, Del Poeta GIOVANNI, Maria DIMOU, Michael DOUBEK, Maria EFSTATHOPOULOU, Shaimaa EL-ASHWAH, Alicia ENRICO, Blanca ESPINET, Lucia FARINA, Angela FERRARI, Myriam FOGLIETTA, Alberto LOPEZ-GARCIA, Jose A GARCIA-MARCO, Rocio GARCIA-SERRA, Massimo GENTILE, Eva GIMENO, da Silva Maria GOMES, Odit GUTWEIN, Yervand K HAKOBYAN, Yair HERISHANU, Jose Angel HERNANDEZ-RIVAS, Tobias HEROLD, Gilad ITCHAKI, Ozren JAKSIC, Ann JANSSENS, Olga B KALASHNIKOVA, Elzbieta KALICINSKA, 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 MIRAS, 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 SIMKOVIC, Svetlana SMIRNOVA, Martin SPACEK, Paolo SPORTOLETTI, Oana STANCA, Niki STAVROYIANNI, Te Raa DOREEN, Kristina TOMIC, Sanne TONINO, Livio TRENTIN, Van der Spek ELLEN, van Gelder MICHEL, Marzia VARETTONI, Andrea VISENTIN, Candida VITALE, Vojin VUKOVIC, Ewa WASIK-SZCZEPANEK, Tomasz WROBEL, San Segundo Lucrecia YANEZ, Mohamed YASSIN, Marta COSCIA, Alessandro RAMBALDI, Emili MONTSERRAT, Robin FOA, Antonio CUNEO, Marc CARRIER, Paolo GHIA and Kostas STAMATOPOULOS. 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. LONDON: BMC, 2022, vol. 15, No 1, p. 1-13. ISSN 1756-8722. Available from: https://dx.doi.org/10.1186/s13045-022-01333-0.
@article{2251393, author = {Antic, Darko and Milic, Natasa and Chatzikonstantinou, Thomas and Scarfo, Lydia and Otasevic, Vladimir and Rajovic, Nina and Allsup, David and Cabrero, Alejandro Alonso and Andres, Martin and Gonzales, Monica Baile and Capasso, Antonella and Collado, Rosa and Cordoba, Raul and CuellarandGarcia, Carolina and Correa, Juan Gonzalo and Lorenzo, De Paoli and Rosaria, De Paolis Maria and Giovanni, Del Poeta and Dimou, Maria and Doubek, Michael and Efstathopoulou, Maria and ElandAshwah, Shaimaa and Enrico, Alicia and Espinet, Blanca and Farina, Lucia and Ferrari, Angela and Foglietta, Myriam and LopezandGarcia, Alberto and GarciaandMarco, Jose A and GarciaandSerra, Rocio and Gentile, Massimo and Gimeno, Eva and Gomes, da Silva Maria and Gutwein, Odit and Hakobyan, Yervand K and Herishanu, Yair and HernandezandRivas, Jose Angel and Herold, Tobias and Itchaki, Gilad and Jaksic, Ozren and Janssens, Ann and Kalashnikova, Olga B and Kalicinska, Elzbieta and Kater, Arnon P and Kersting, Sabina and KorenandMichowitz, Maya and Labrador, Jorge and Lad, Deepesh and Laurenti, Luca and Fresa, Alberto and Levin, MarkandDavid and Bastida, Carlota Mayor and Malerba, Lara and Marasca, Roberto and Marchetti, Monia and Marquet, Juan and Mihaljevic, Biljana and Milosevic, Ivana and Miras, Fatima and Morawska, Marta and Motta, Marina and Munir, Talha and Murru, Roberta and Nunes, Raquel and Olivieri, Jacopo and Pavlovsky, Miguel Arturo and Piskunova, Inga and Popov, Viola Maria and Quaglia, Francesca Maria and Quaresmini, Giulia and Reda, Gianluigi and Rigolin, Gian Matteo and Shrestha, Amit and Simkovic, Martin and Smirnova, Svetlana and Spacek, Martin and Sportoletti, Paolo and Stanca, Oana and Stavroyianni, Niki and Doreen, Te Raa and Tomic, Kristina and Tonino, Sanne and Trentin, Livio and Ellen, Van der Spek and Michel, van Gelder and Varettoni, Marzia and Visentin, Andrea and Vitale, Candida and Vukovic, Vojin and WasikandSzczepanek, Ewa and Wrobel, Tomasz and Yanez, San Segundo Lucrecia and Yassin, Mohamed and Coscia, Marta and Rambaldi, Alessandro and Montserrat, Emili and Foa, Robin and Cuneo, Antonio and Carrier, Marc and Ghia, Paolo and Stamatopoulos, Kostas}, article_location = {LONDON}, article_number = {1}, doi = {http://dx.doi.org/10.1186/s13045-022-01333-0}, keywords = {CLL; COVID-19; Thrombosis; Bleeding; D-dimer; Anticoagulation therapy; Thromboprophylaxis; LMWH; Age}, language = {eng}, issn = {1756-8722}, journal = {JOURNAL OF HEMATOLOGY & ONCOLOGY}, title = {Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL}, url = {https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01333-0}, volume = {15}, year = {2022} }
TY - JOUR ID - 2251393 AU - 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 PY - 2022 TI - Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL JF - JOURNAL OF HEMATOLOGY & ONCOLOGY VL - 15 IS - 1 SP - 1-13 EP - 1-13 PB - BMC SN - 17568722 KW - CLL KW - COVID-19 KW - Thrombosis KW - Bleeding KW - D-dimer KW - Anticoagulation therapy KW - Thromboprophylaxis KW - LMWH KW - Age UR - https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01333-0 N2 - 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. ER -
ANTIC, Darko, Natasa MILIC, Thomas CHATZIKONSTANTINOU, Lydia SCARFO, Vladimir OTASEVIC, Nina RAJOVIC, David ALLSUP, Alejandro Alonso CABRERO, Martin ANDRES, Monica Baile GONZALES, Antonella CAPASSO, Rosa COLLADO, Raul CORDOBA, Carolina CUELLAR-GARCIA, Juan Gonzalo CORREA, De Paoli LORENZO, De Paolis Maria ROSARIA, Del Poeta GIOVANNI, Maria DIMOU, Michael DOUBEK, Maria EFSTATHOPOULOU, Shaimaa EL-ASHWAH, Alicia ENRICO, Blanca ESPINET, Lucia FARINA, Angela FERRARI, Myriam FOGLIETTA, Alberto LOPEZ-GARCIA, Jose A GARCIA-MARCO, Rocio GARCIA-SERRA, Massimo GENTILE, Eva GIMENO, da Silva Maria GOMES, Odit GUTWEIN, Yervand K HAKOBYAN, Yair HERISHANU, Jose Angel HERNANDEZ-RIVAS, Tobias HEROLD, Gilad ITCHAKI, Ozren JAKSIC, Ann JANSSENS, Olga B KALASHNIKOVA, Elzbieta KALICINSKA, 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 MIRAS, 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 SIMKOVIC, Svetlana SMIRNOVA, Martin SPACEK, Paolo SPORTOLETTI, Oana STANCA, Niki STAVROYIANNI, Te Raa DOREEN, Kristina TOMIC, Sanne TONINO, Livio TRENTIN, Van der Spek ELLEN, van Gelder MICHEL, Marzia VARETTONI, Andrea VISENTIN, Candida VITALE, Vojin VUKOVIC, Ewa WASIK-SZCZEPANEK, Tomasz WROBEL, San Segundo Lucrecia YANEZ, Mohamed YASSIN, Marta COSCIA, Alessandro RAMBALDI, Emili MONTSERRAT, Robin FOA, Antonio CUNEO, Marc CARRIER, Paolo GHIA and Kostas STAMATOPOULOS. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL. \textit{JOURNAL OF HEMATOLOGY \&{} ONCOLOGY}. LONDON: BMC, 2022, vol.~15, No~1, p.~1-13. ISSN~1756-8722. Available from: https://dx.doi.org/10.1186/s13045-022-01333-0.