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Clinical Outcomes, Symptoms and Quality of Life in Cancer Patients with Incidental Pulmonary Embolism

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Clinical Outcomes, Symptoms and Quality of Life in Cancer Patients with Incidental Pulmonary Embolism A STUDY OF CLINICOPATHOLOGICAL CHARACTERISTICS, SYMPTOMS AND PATIENTS EXPERIENCES RELATED TO OUTCOMES IN PEOPLE WITH CANCER AND I-PE Naima E Benelhaj PhD The University of Hull and The University of York Hull York Medical School July 2019 Abstract Background: The clinical course of incidental pulmonary embolism in cancer population represents an area of controversy. It presents a growing challenge for clinicians because of a lack of prospective data. Aim: This research aims to investigate the impact of an incidentally diagnosed pulmonary embolism on cancer population’ outcomes and to explore their experience of living with cancer and i-PE. The second aim was to explore the role of the key thrombogenic biomarkers as a predictive biomarker of thrombosis. Methods: Mixed method research with critical integrative analysis. A systematic literature review and qualitative analysis to examine patients’ experience of living with cancer-associated thrombosis. A prospective observational case-controlled cohort study with embedded semi-structured interview study to investigate the quality of life and patients’ experience of living with cancer and incidental pulmonary embolism. A retrospective case control-study and scientific analysis of defined biological key factors associated with thrombosis. Results: The diagnosis of cancer-associated thrombosis including incidental pulmonary embolism negatively affect patients’ life, and patients experience this diagnosis in the context of living with cancer. Yet it is a diagnosis that often misattributed, misdiagnosed and associated with lack of information among patients and some of the clinical care professionals. The scientific analysis of the biological biomarkers illustrates the potential role of TF-mRNA as a predictive biomarker for cancer- associated incidental pulmonary embolism and the role of anti-factor ten anticoagulation in reducing the risk of thrombosis. Conclusion: Awareness of patients and care professionals regarding the high risk of thrombosis among cancer population represent an urgent need. Risk assessment tools to predict patients at increased risk of thrombosis would be of value and help target education and reduce the risk of diagnostic overshadowing. i Table of Contents Chapter 1 Theses introduction ................................................................................. 1 1.1 Introduction .................................................................................................... 1 1.2 Background ..................................................................................................... 1 1.2.1 Incidental pulmonary embolism .............................................................. 1 1.3 Statement of the problem .............................................................................. 2 1.4 Aims................................................................................................................. 4 1.5 Research questions ......................................................................................... 4 1.6 Research design .............................................................................................. 4 1.7 Definition of Terms ......................................................................................... 5 1.7.1 Symptom burden ..................................................................................... 5 1.7.2 Quality of life ............................................................................................ 6 1.7.3 Performance status .................................................................................. 6 1.8 Theses contents .............................................................................................. 6 Chapter 2 Literature review ...................................................................................... 9 2.1 Introduction .................................................................................................... 9 2.2 Epidemiology of i-PE ....................................................................................... 9 2.3 Clinical characteristics of patients with i-PE ................................................. 10 2.4 Symptomology .............................................................................................. 12 2.5 Radiology ....................................................................................................... 14 2.6 Natural course and outcome of cancer associated i-PE ............................... 16 2.7 Embolic burden ............................................................................................. 17 2.8 Management of i-PE ..................................................................................... 18 2.9 Stratification and Prognostic assessment; can we predict the patient at risk?22 2.9.1 Risk stratification tools in cancer associated thrombosis ...................... 23 2.9.2 Risk stratification tools in cancer patients with PE ................................ 24 2.9.3 Hull Score ............................................................................................... 25 2.10 Quality of life of cancer patients with i-PE.................................................. 27 2.11 Thrombogenic biomarkers .......................................................................... 29 2.11.1 Tissue factor and TF positive microvesicles ......................................... 31 2.11.2 Proteinase-activated receptor 2 (F2RL1) and Thrombosis .................. 39 2.11.3 Factor Xa .............................................................................................. 41 2.11.4 C-reactive protein (CRP) ....................................................................... 42 2.11.5 Factor VII .............................................................................................. 42 2.11.6 D-dimer ................................................................................................ 43 ii 2.12 Endothelial cells .......................................................................................... 44 2.13 Summary ..................................................................................................... 45 Chapter 3 Methodology .......................................................................................... 46 3.1 Introduction .................................................................................................. 46 3.2 Methodological approach for the theses...................................................... 46 3.2.1 Experience of people living with cancer associated thrombosis ........... 47 3.2.2 The impact of i-PE on patients’ clinical outcome and experience ......... 50 3.2.3 Qualitative methodology used in this theses ........................................ 61 3.2.4 Mixed methods research ....................................................................... 65 3.2.5 Theses synthesis ..................................................................................... 70 3.3 Summary of the methodology chapter ......................................................... 71 Chapter 4 Systematic literature review and qualitative analysis of cancer patients’ experience of living with cancer associated thrombosis ........................................................... 72 4.1 Introduction .................................................................................................. 72 4.2 Aim of Systematic review:............................................................................. 73 4.3 Review objective ........................................................................................... 73 4.4 Systematic literature review methods .......................................................... 73 4.4.1 Search strategy....................................................................................... 73 4.4.2 Inclusion criteria ..................................................................................... 73 4.4.3 Study selection ....................................................................................... 74 4.5 Data extraction.............................................................................................. 74 4.6 Quality Appraisal ........................................................................................... 74 4.7 Analysis ......................................................................................................... 74 4.8 Results ........................................................................................................... 75 4.8.1 Overview of articles ............................................................................... 75 4.8.2 Study populations .................................................................................. 76 4.9 Findings synthesis ......................................................................................... 76 4.9.1 Knowledge deficit .................................................................................. 76 4.9.2 Effects of cancer associate thrombosis .................................................. 79 4.9.3 Effects of cancer associated thrombosis treatments ............................ 84 4.9.4 Employment of coping mechanisms ...................................................... 90 4.10 Discussion.................................................................................................... 92 4.10.1 Lack of information .............................................................................. 92 4.10.2 Effects of cancer associated
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