Cancer, blood clots and bleeding Treatment and prevention of cancer-associated thrombosis

People with cancer have a very high risk of venous thrombo-embolism (VTE), comprising deep vein thrombosis and pulmonary embolism, compared to people without cancer. Treatment of VTE in people with cancer is complicated since both the bleeding risk and recurrent VTE risk are higher than in people without cancer. In this thesis several studies on the treatment, prevention and etiology of cancer-associated VTE are presented. In part 1 (chapters 2 to 5) studies on the treatment of cancer-associated VTE are discussed. Chapter 2 presents a study in the drug-drug interaction between edoxaban and tamoxifen in women with breast cancer. Chapter 3 is a systematic review and meta-analysis of randomized controlled trials on direct oral anticoagulants (DOAC) versus low-molecular-weight heparin (LMWH) for the treatment of cancer-associated VTE. Chapter 4 discusses risk factors on gastro-intestinal bleeding in patients with VTE and gastro-intestinal cancer on edoxaban. In Chapter 5 the risk of cancer in patients with factor Xa inhibitors is studied in a Danish population cohort study. In part 2 (chapters 6 to 8) studies on the prevention of cancer-associated VTE are discussed. Chapter 6 is a narrative review on primary thromboprophylaxis in ambulatory cancer patients. Chapter 7 is a systematic review and meta-analysis on primary thromboprophylaxis in ambulatory cancer patients with a high risk of VTE. In Chapter 8 we discuss the predictive value of the biomarker GDF-15 for bleeding in patients with thromboprophylaxis in the AVERT trial. In part 3 (chapters 9 to 11) studies on aetiology and epidemiology of cancer-associated VTE are presented. In chapter 9 results of a study on intrinsic pathway activation in patients with pancreatic cancer are reported. Chapter 10 shows a study in tumor gene expression and VTE risk in patients with pancreatic cancer. Chapter 11 is a study on the prevalence of pulmonary embolism in cancer patients on whom autopsy is performed.