Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations–State-of-the-Art

Dimakakos

et al. 2022

JCM

Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients.

Section: Results—key Questions and Practical Recommendationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials

Dimakakos

et al. 2022

JCM

“…In January 2022, the National Lung Cancer Audit reported on the negative impact of COVID-19 on LC diagnosis and treatment pathways within the NHS [159]. Both LC and COVID-19 are well-established risk factors for CAT, with mechanisms involving the interaction of cancer cells or SARS-CoV-2 with the coagulation system and the endothelial cells [160][161][162]. The incidences of CAT and arterial thromboembolic events (ATE) in the COVID-19 and Cancer Consortium registry cohort study were 7.6% and 3.9%, respectively [163].…”

Section: Lung Cancer Cat and Covid-19mentioning

confidence: 99%

“…Thromboprophylaxis for all hospitalized cancer patients with COVID-19 is recommended [162,[166][167][168]. Higher (therapeutic) doses of thromboprophylaxis are recommended for high-thrombotic-risk, non-critically ill patients [169]; yet, this recommendation has not been specifically investigated in cancer patients.…”

Section: Lung Cancer Cat and Covid-19mentioning

confidence: 99%

Lung Cancer Related Thrombosis (LCART): Focus on Immune Checkpoint Blockade

Charpidou,

Gerotziafas,

Popat

et al. 2024

Cancers

Self Cite

Cancer-associated thrombosis (CAT) is a common complication in lung cancer patients. Lung cancer confers an increased risk of thrombosis compared to other solid malignancies across all stages of the disease. Newer treatment agents, including checkpoint immunotherapy and targeted agents, may further increase the risk of CAT. Different risk-assessment models, such as the Khorana Risk Score, and newer approaches that incorporate genetic risk factors have been used in lung cancer patients to evaluate the risk of thrombosis. The management of CAT is based on the results of large prospective trials, which show similar benefits to low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs) in ambulatory patients. The anticoagulation agent and duration of therapy should be personalized according to lung cancer stage and histology, the presence of driver mutations and use of antineoplastic therapy, including recent curative lung surgery, chemotherapy or immunotherapy. Treatment options should be evaluated in the context of the COVID-19 pandemic, which has been shown to impact the thrombotic risk in cancer patients. This review focuses on the epidemiology, pathophysiology, risk factors, novel predictive scores and management of CAT in patients with active lung cancer, with a focus on immune checkpoint inhibitors.

“…COVID-19 patients with comorbidities, especially with preexisting CVD, are at a high risk level of a more severe course and even death [5]. Most recently, several studies have demonstrated that arterial and venous thromboembolic events (VTE) immediately increased after severe COVID-19, and thromboembolic disease increased mortality during the COVID-19 pandemic [6][7][8][9][10]. Besides, the ACE2 receptor, responsible for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry, also was reported as being expressed on the arterial and venous endothelium [11], which may partly explain higher incidences of heart failure-related events and acute coronary syndromes among individuals with COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Developing a Novel Immune-Related Seven-Gene Signature and Immune Infiltration Pattern in Patients with COVID-19 and Cardiovascular Disease

Zhang

et al. 2022

JCDD

Background: patients with pre-existence of cardiovascular disease (CVD) are vulnerable to coronavirus disease 2019 (COVID-19), and COVID-19 will cause long-term burden of CVD. However, the common pathogenic mechanisms are not fully elucidated. More detailed knowledge of linking biological molecules and the role of immune signature would allow more valuable and specific clinical management. Methods: the gene expression profiles of CVD and COVID-19 were retrieved from the GEO database. Common differentially expressed genes (DEGs) were screened with the Limma R package and the WGCNA algorithm, and then functional enrichment analysis, protein-protein interaction network, hub genes, and small therapeutic molecules analyses were performed. The hub immune-related genes (HIRGs) were intersected, and their associations with immune cells, expressional correlation, evaluated performance, and potential signal pathways were further investigated. Results: In total, 57 common DEGs were identified as a shared transcriptional signature between CVD and COVID-19, and 12 hub genes were screened using five topological algorithms. There are common altered immune responses in the response of these two diseases, and seven HIRGs, including C5AR1, MMP9, CYBB, FPR2, CSF1R, TLR2, and TLR4, were identified, with positive correlation to altered macrophages and neutrophils. Nine small molecular agents (SMAs) were detected as promising therapeutic drugs. These seven HIRGs mainly participated in the inflammatory immune response through activation of Il2 stat5 signaling and Tnfa signaling via nfκb pathways, and ROC curves confirmed their good discriminatory capacity in the two diseases. Conclusions: this study established the co-expression network and identified a new immune-related seven-gene signature as therapeutic targets, which may provide new insights into pathogenic mechanisms and novel clinical management strategies.