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

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.

Tixagevimab/Cilgavimab as pre-exposure prophylaxis against SARS-CoV-2 in patients with hematological malignancies

“…Patients with hematological malignancies who develop coronavirus infectious dis-ease (COVID-19) following infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually display an increased risk of hospitalization and intensive care unit (ICU) admission, with an estimated risk of death up to 34% (1)(2)(3)(4). This is likely due to the severe impairment of these patients' immune systems, weakened by the hematological diseases themselves as well as their treatments, which results in ineffective cellular (5)(6)(7) and humoral (8)(9)(10) responses to SARS-CoV-2.…”

Editorial: Covid-19 therapies in patients with hematologic malignancies

“…One of the key concerns for patients with hematological malignancies during the COVID-19 pandemic is the increased vulnerability to severe illness. The weakened immune response can make it difficult for these patients to fight the infection, including the respiratory complications associated with COVID-19, resulting in high rate of hospitalization, intensive care unit admission and death (1)(2)(3). Several studies also suggest that COVID-19 can exacerbate the complications of hematological malignancies, leading to disruptions in treatment schedules and heightened concerns about disease management.…”

Realizing precision medicine in chronic lymphocytic leukemia: Remaining challenges and potential opportunities

“…Swiftly conducted real‐world studies by ERIC and others during the COVID‐19 pandemic exemplify this potential, providing useful information on the outcomes of patients with CLL infected with SARS‐COV‐2 and their responses to COVID‐19 vaccines. 115 , 116 , 117 , 118 , 119 , 120 , 121 Last but not least, RWD has also been used in more elaborate approaches involving artificial intelligence (AI). Indicatively, Agius et al have reported a machine‐learning approach for identifying patients with a high risk of infection, underlining the myriad possibilities of utilizing RWD toward the realization of PM.…”