☆ 4.4 Review

Immune Checkpoint Inhibitors-Associated Thrombosis: Incidence, Risk Factors and Management

CURRENT ONCOLOGY (2023)

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Article Hematology

Clinical impact of venous thromboembolism in non-small cell lung cancer patients receiving immunotherapy

Birgitte Bjornhart et al.

Summary: This study aimed to investigate cancer-associated venous thromboembolism (VTE) in non-small cell lung cancer (NSCLC) patients during treatment with immune checkpoint inhibitors (ICIs). The study found that the incidence of VTE in this population was significantly higher than reported in clinical trials and retrospective studies, and it significantly impaired patients' overall survival. Therefore, more attention should be given to the prevention and management of VTE during ICI treatment.

THROMBOSIS RESEARCH (2023)

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Article Oncology

Venous thromboembolism incidence and risk factors associated with immune checkpoint inhibitors among patients with advanced non-small cell lung cancer

Alok A. Khorana et al.

Summary: This study assessed the incidence and risk factors of venous thromboembolism (VTE) in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The study found that ICI-based regimens were associated with lower risk of VTE compared to chemotherapy (chemo), while the risk of VTE with ICI+chemo regimens was similar to chemo. Previous radiation and severe obesity were also associated with VTE.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2023)

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Article Cardiac & Cardiovascular Systems

The predictive value of high sensitivity troponin measurements in patients treated with immune checkpoint inhibitors

Barliz Waissengein et al.

Summary: This study aimed to evaluate the changes in high sensitivity-Troponin (hs-Tn) levels in cancer patients treated with pembrolizumab and found that abnormally elevated hs-TnI was a significant predictor for the development of major adverse cardiac events (MACE) and all-cause mortality.

CLINICAL RESEARCH IN CARDIOLOGY (2023)

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Article Cardiac & Cardiovascular Systems

ESC 2022 guidelines on cardio-oncology in collaboration with the European Hematology Association (EHA), European Society of Therapeutic Radiology and Oncology (ESTRO) and International Cardio-Oncology Society (IC- OS) developed by the Cardio-Oncology Task Force of the European Society of Cardiology (ESC)

Alexander R. Lyon et al.

GIORNALE ITALIANO DI CARDIOLOGIA (2023)

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Article Cardiac & Cardiovascular Systems

Incidence of venous thromboembolism and discriminating capacity of Khorana score in lung cancer patients treated with immune checkpoint inhibitors

Stancu Alma et al.

Summary: Lung cancer patients treated with immune-checkpoint inhibitors (ICIs) have an increased risk of venous thromboembolism (VTE), which negatively impacts survival. The current VTE prediction models do not perform well in this population.

JOURNAL OF THROMBOSIS AND THROMBOLYSIS (2022)

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Article Hematology

Old is new again: Emergence of thromboembolic complications in cancer patients on immunotherapy

Keith R. McCrae et al.

Summary: Cancer immunotherapy, particularly treatment with immune checkpoint inhibitors (ICI), has become a significant new approach for cancer treatment. However, the occurrence of ICI-Associated Thrombosis (IAT) has become a major clinical concern. The mechanisms of IAT are not well understood but may involve the activation of blood and vascular cells leading to thromboinflammation. Elevated levels of myeloid derived suppressor cells and inflammatory cytokines may serve as biomarkers of IAT.

THROMBOSIS RESEARCH (2022)

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Article Oncology

C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer

Niklas Kluemper et al.

Summary: Early dynamics of C reactive protein (CRP) can serve as a predictive biomarker for response to anti-PD-1 immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC). CRP flare-responders can predict ICB response and survival as early as 4 weeks after therapy initiation. Early CRP kinetics have no predictive value for chemoimmunotherapy or when steroids are administered concurrently.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Article Hematology

Risk of Thromboembolic Events in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-analysis of Randomized Controlled Trials

Zhuo Ma et al.

Summary: This study assessed the risk of major thromboembolic events (TEEs) associated with immune checkpoint inhibitors (ICIs). The results showed that there was no significant increase in the overall risk of venous thromboembolism (VTE) in patients treated with ICIs. However, special attention should be given to the risk of VTE in PD-1/PD-L1 inhibitor and CTLA-4 inhibitor combination therapy, as well as pulmonary embolism (PE) in lung cancer patients. PD-L1 inhibitors were associated with a significant increase in arterial thromboembolism (ATE).

THROMBOSIS AND HAEMOSTASIS (2022)

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Article Hematology

The Khorana score and venous and arterial thrombosis in patients with cancer treated with immune checkpoint inhibitors: A Danish cohort study

Thure F. Overvad et al.

Summary: The Khorana score can stratify patients with cancer treated with immune checkpoint inhibitors according to the 6-month risk of thromboembolic events. The risk of venous thromboembolism in this population was lower than in randomized thromboprophylaxis trials, which raises questions about the absolute benefit of routine primary thromboprophylaxis for these patients. Higher Khorana risk categories were also associated with a higher 6-month risk of arterial thrombosis and any thromboembolic events.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2022)

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Article Oncology

Thromboembolism in Patients with Metastatic Urothelial Cancer Treated with Immune Checkpoint Inhibitors

Iris Y. Sheng et al.

Summary: This study investigated the incidence of thromboembolism events in patients with metastatic urothelial cancer treated with immune checkpoint inhibitors and found a high risk of thromboembolism and worsened survival associated with immune checkpoint inhibitors.

TARGETED ONCOLOGY (2022)

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Meeting Abstract Hematology

Early Dynamics of C-Reactive Protein Predict Risk of Venous Thromboembolism in Patients with Cancer Treated with Immune Checkpoint Inhibitors

Florian Moik et al.

BLOOD (2022)

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Meeting Abstract Hematology

Identification of Risk Factors for and Development of a Predictive Model for Immunotherapy-Associated Venous Thromboembolism (VTE) in Patients with Non-Small Cell Lung Cancer

Kristen M. Sanfilippo et al.

BLOOD (2022)

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Meeting Abstract Hematology

Venous Thromboembolism Risk in Cancer Patients Receiving First-Line Immune Checkpoint Inhibitor Vs. Chemotherapy

Sarah B. May et al.

BLOOD (2022)

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Article Cardiac & Cardiovascular Systems

2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS) Developed by the task force on cardio-oncology of the European Society of Cardiology (ESC)

Alexander R. Lyon et al.

EUROPEAN HEART JOURNAL (2022)

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Article Oncology

Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group

Manuel Sanchez Canovas et al.

Summary: This study found that immune checkpoint inhibitors (ICI) can increase the risk of thrombotic events in patients with lung cancer and melanoma, which also impact overall survival. Blood indicators such as neutrophil/lymphocyte ratio (NLR), anemia, and history of thrombosis before ICI treatment could predict the occurrence of thrombotic events.

CLINICAL & TRANSLATIONAL ONCOLOGY (2022)

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Article Hematology

Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy

Florian Moik et al.

Summary: The study found that cancer patients undergoing therapy with immune checkpoint inhibitors were at a high risk of thromboembolism, particularly venous thromboembolism (VTE). The occurrence of VTE was associated with increased mortality. Patients with a history of VTE were more likely to develop VTE, and distant metastasis may be related to VTE risk.

BLOOD (2021)

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Article Medicine, General & Internal

Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors

Serena Petricciuolo et al.

Summary: The study found that baseline hs-TnT can predict cardiovascular events and progression of cardiac involvement in patients receiving ICIs. A cut-off value of 14ng/L was identified as the best predictor, with high sensitivity and specificity.

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION (2021)

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Review Oncology

Vascular events with immune checkpoint inhibitors in melanoma or non-small cell lung cancer: A systematic review and meta-analysis

Michela Giustozzi et al.

Summary: This study demonstrated a significant rate of vascular events in patients with melanoma and NSCLC treated with ICIs, including venous and arterial thromboembolic events.

CANCER TREATMENT REVIEWS (2021)

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Review Hematology

Discordant reporting of VTE in pancreatic cancer: A systematic review and meta-analysis of thromboprophylaxis versus chemotherapeutic trials

Thita Chiasakul et al.

Summary: The incidence of VTE reported in chemotherapy RCTs in pancreatic cancer is significantly lower than what is reported in thromboprophylaxis studies. This indicates a lack of recognition of VTE in chemotherapeutic trials and underscores the importance of standardizing approaches to monitoring and reporting VTE in clinical trials.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2021)

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Article Oncology

Immune checkpoint inhibitors for cancer and venous thromboembolic events

Jingyi Gong et al.

Summary: The study found that the risk of VTE was 7.4% at 6 months and 13.8% at 1 year after starting an ICI, with a significantly increased rate of VTE. Factors such as age, medical history, and underlying diseases can predict the risk of VTE in patients receiving ICIs.

EUROPEAN JOURNAL OF CANCER (2021)

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Article Oncology

Incidence of thromboembolism in patients with melanoma on immune checkpoint inhibitor therapy and its adverse association with survival

Tamara A. Sussman et al.

Summary: This study found a high incidence of thromboembolism in melanoma patients receiving immune checkpoint inhibitor therapy, especially with combination regimens. Thromboembolism was associated with significantly worse survival outcomes. Further research is needed to understand the underlying mechanisms and develop preventive strategies.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Hematology

Prognostic impact and risk factors of cancer-associated thrombosis events in stage-IV cancer patients treated with immune checkpoint inhibitors

Tariq Kewan et al.

Summary: During ICIs treatment, risk factors for CAT in cancer patients include anticoagulation use and melanoma. Khorana score is a good predictor of mortality but not CAT risk. Further studies with control groups are needed to better identify risk factors for CAT.

EUROPEAN JOURNAL OF HAEMATOLOGY (2021)

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Article Hematology

Venous thromboembolism incidence and risk assessment in lung cancer patients treated with immune checkpoint inhibitors

Oded Icht et al.

Summary: VTE rates were higher among NSCLC patients treated with platinum-based chemotherapy compared to those treated with ICI. The Khorana Score did not effectively identify high-risk ICI-treated patients, suggesting the need for an ICI-specific risk model.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2021)

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Article Medicine, Research & Experimental

Treatment with therapeutic anticoagulation is not associated with immunotherapy response in advanced cancer patients

Paul Johannet et al.

Summary: The study found that patients receiving anticoagulation therapy did not experience better treatment outcomes when receiving immune checkpoint inhibitors, and were instead more likely to suffer from major or clinically relevant bleeding complications.

JOURNAL OF TRANSLATIONAL MEDICINE (2021)

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Article Oncology

Thromboembolism in Patients with Metastatic Renal Cell Carcinoma Treated with Immunotherapy

Iris Y. Sheng et al.

Summary: Patients with mRCC treated with IO have a high incidence of TE, which is associated with risk of treatment delay, hospitalization, and mortality, while TE, IMDC poor risk, and Khorana score >= 2 are predictors of worse survival. Further research is needed to investigate the benefits of primary thromboprophylaxis in this population.

TARGETED ONCOLOGY (2021)

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Article Hematology

Venous thromboembolism incidence and risk factors in non-small cell lung cancer patients receiving first-line systemic therapy

Hailey Hill et al.

Summary: This study evaluated the incidence and predictive factors of venous thromboembolism (VTE) in non-small cell lung cancer (NSCLC) patients receiving first-line therapies. The findings suggest that treatment type and smoking status can predict the time to VTE, with the highest incidence observed in patients receiving TTs and combination chemotherapy plus ICI.

THROMBOSIS RESEARCH (2021)

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Article Oncology

Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab

Shohei Fukuda et al.

Summary: The study found that the CRP flare-response group among mRCC patients was associated with significant tumor shrinkage and improved survival outcomes compared to the other two groups. Early CRP kinetics may be useful for evaluating the efficacy of nivolumab treatment.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Hematology

American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer

Gary H. Lyman et al.

Summary: These evidence-based guidelines aim to support decision-making on the prevention and treatment of VTE in cancer patients, covering mechanical and pharmacological prophylaxis, as well as recommendations for initial, short-term, and long-term treatment based on patient risk and treatment circumstances. Recommendations vary depending on patient risk level and treatment situation.

BLOOD ADVANCES (2021)

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Article Hematology

Venous thromboembolism in cancer patients: a population-based cohort study

F. Mulder et al.

Summary: Over the past decade, the incidence of venous thromboembolism (VTE) in cancer patients may have changed due to novel cancer therapies, improved survival, and high-resolution imaging. The risk of VTE in cancer patients is steadily increasing and is ninefold higher than in the general population.

BLOOD (2021)

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Article Oncology

Anticoagulation with Factor Xa Inhibitors Is Associated with Improved Overall Response and Progression-Free Survival in Patients with Metastatic Malignant Melanoma Receiving Immune Checkpoint Inhibitors-A Retrospective, Real-World Cohort Study

Maximilian Haist et al.

Summary: The study provides clinical evidence that the clinical application of FXa inhibitors may enhance the efficacy of ICI therapy by restoring anti-tumor immunity, while patients who received FXa inhibitors were not more likely to experience bleeding complications.

CANCERS (2021)

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Article Hematology

Thromboembolic risk in patients with lung cancer receiving systemic therapy

Cecelia J. Madison et al.

Summary: The study revealed that both chemotherapy and immunotherapy were associated with an increased risk of thrombosis in US Veterans with lung cancer. Factors such as the Khorana score, vascular disease, and metastases were also found to be related to higher risk of thrombosis. Further research is needed to identify ways to reduce this risk for patients.

BRITISH JOURNAL OF HAEMATOLOGY (2021)

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Article Hematology

Venous thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: A retrospective multicentric cohort study

Xavier Deschenes-Simard et al.

Summary: This study found that the incidence of VTE in NSCLC patients treated with immune checkpoint inhibitors is comparable to other cohorts of patients treated with chemotherapy. VTE was not associated with decreased survival or response to therapy, while younger age and higher PD-L1 expression in tumors were identified as risk factors for VTE under ICIs.

THROMBOSIS RESEARCH (2021)

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Review Oncology

Thrombotic Complications Associated with Immune Checkpoint Inhibitors

Tzu-Fei Wang et al.

Summary: Cancer patients often develop blood clots, with immune checkpoint inhibitors increasing the risk. Studies have shown a connection between immune checkpoint inhibitors and venous and arterial thrombosis, with further investigation needed on risk factors and optimal prevention and treatment strategies.

CANCERS (2021)

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Article Oncology

Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus

Marc Carrier et al.

Summary: Patients with CAT are at high risk for complications, and anticoagulant therapy should be tailored based on factors such as bleeding risk, cancer type, and drug interactions. The treatment algorithm should be adapted as the patient's cancer status and management evolve.

CURRENT ONCOLOGY (2021)

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Article Medicine, Research & Experimental

Increased incidence of venous thromboembolism with cancer immunotherapy

Joanna Roopkumar et al.

Summary: The study reveals a potential association between cancer immunotherapy and venous thromboembolism, impacting overall survival. Higher levels of interleukin-8 and myeloid-derived suppressor cells may play a role in the pathogenesis of venous thromboembolism in individuals undergoing immunotherapy.

MED (2021)

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Article Oncology

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update

Nigel S. Key et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Oncology

Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors

Yosuke Ando et al.

INVESTIGATIONAL NEW DRUGS (2020)

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Article Oncology

Is There an Interplay between Immune Checkpoint Inhibitors, Thromboprophylactic Treatments and Thromboembolic Events? Mechanisms and Impact in Non-Small Cell Lung Cancer Patients

Federico Nichetti et al.

CANCERS (2020)

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Editorial Material Medicine, General & Internal

Immune checkpoint inhibitors in cancer immunotherapy

Megan E. Himmel et al.

CANADIAN MEDICAL ASSOCIATION JOURNAL (2020)

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Article Cardiac & Cardiovascular Systems

Association Between Immune Checkpoint Inhibitors With Cardiovascular Events and Atherosclerotic Plaque

Zsofia D. Drobni et al.

CIRCULATION (2020)

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Article Hematology

Coagulation signaling and cancer immunotherapy

Wolfram Ruf et al.

THROMBOSIS RESEARCH (2020)

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Review Hematology

Venous and arterial thromboembolic events with immune checkpoint inhibitors: A systematic review

Cinzia Solinas et al.

THROMBOSIS RESEARCH (2020)

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Article Medicine, General & Internal

Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer

A. A. Khorana et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Article Immunology

Myeloid cell-synthesized coagulation factor X dampens antitumor immunity

Claudine Graf et al.

SCIENCE IMMUNOLOGY (2019)

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Article Oncology

Acute vascular events as a possibly related adverse event of immunotherapy: a single-institute retrospective study

Jair Bar et al.

EUROPEAN JOURNAL OF CANCER (2019)

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Review Hematology

Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms

Shaun P. Jackson et al.

BLOOD (2019)

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Review Hematology

The Khorana score for prediction of venous thromboembolism in cancer patients: a systematic review and meta-analysis

Frits I. Mulder et al.

HAEMATOLOGICA (2019)

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Article Medicine, General & Internal

Apixaban to Prevent Venous Thromboembolism in Patients with Cancer

Marc Carrier et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Article Medicine, General & Internal

Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs

Alyson Haslam et al.

JAMA NETWORK OPEN (2019)

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Article Medicine, General & Internal

Pembrolizumab-induced acute thrombosis: A case report

Kei Kunimasa et al.

MEDICINE (2018)

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Article Oncology

Patients' Experience of Living with Cancer-associated thrombosis in Spain (PELICANOS)

Carme Font et al.

SUPPORTIVE CARE IN CANCER (2018)

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Article Economics

What Impact Does Venous Thromboembolism and Bleeding Have on Cancer Patients' Quality of Life?

Andrew J. Lloyd et al.

VALUE IN HEALTH (2018)

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Meeting Abstract Oncology

Incidence and impact of thromboembolic events in lung cancer patients treated with nivolumab

Aparna Madhukeshwar Hegde et al.

JOURNAL OF CLINICAL ONCOLOGY (2017)

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Article Multidisciplinary Sciences

Programmed Cell Death-1 Deficiency Exacerbates T Cell Activation and Atherogenesis despite Expansion of Regulatory T Cells in Atherosclerosis-Prone Mice

Clement Cochain et al.

PLOS ONE (2014)

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Article Oncology

Venous Thromboembolism Risk in Patients With Cancer Receiving Chemotherapy: A Real-World Analysis

Gary H. Lyman et al.

ONCOLOGIST (2013)

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Article Hematology

Prediction of venous thromboembolism in cancer patients

Cihan Ay et al.

BLOOD (2010)

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Article Hematology

Development and validation of a predictive model for chemotherapy-associated thrombosis

Alok A. Khorana et al.

BLOOD (2008)

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Letter Hematology

Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy

A. A. Khorana et al.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2007)

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