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This chapter examines the challenge for and the changing role of palliative care, particularly with respect to venous thromboembolism (VTE). There are several factors that have driven the expansion of palliative care beyond just the provision of terminal care for cancer patients. These include the advances in the management of metastatic diseases which means that patients with incurable diseases may live longer and receive palliative therapies for several years. This chapter suggests that the challenge for palliative care in VTE is to ensure that patients receive appropriate management that maximizes their quality of life and is in accordance with their wishes.

This chapter looks at the epidemiology or health-event patterns associated with venous thromboembolism (VTE). It explains that VTE, comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a multifactorial disease, involving interactions between environmental exposures and genetic predispositions. It investigates the disease burden or incidence, outcomes, and risk factors of VTE in the community, the elderly population, and in individuals with advanced diseases.

This chapter examines the pathogenesis of venous thromboembolism (VTE) in patients with cancer. It explains that patients with cancer are more likely to develop VTE than those without. This is because the coagulation cascade is activated by factors related both directly and indirectly to the tumour, and all parts of Virchow's triad may be involved with the development of thrombosis. Despite the progress in thrombosis research, many questions remain unanswered including the role of primary thromboprophylaxis and the possibility of adjuvant anticoagulation as an anticancer therapy.

This chapter aims to review the pharmacology and use of both the established and the newer anticoagulants used in venous thromboembolism (VTE). These include unfractionated heparin, low molecular weight heparins (LMWH), danaparoid, coumarins, idraparinux, and hirudin. This chapter discusses the history, composition, mechanism of action, dosage, monitoring, reversal, indications and contraindications, and adverse effects of these anticoagulants.

This chapter discusses the treatment and secondary prevention measures for venous thromboembolism (VTE) in advanced cancer. It evaluates the general approach to treating cancer patients with acute deep vein thrombosis (DVT) or pulmonary embolism and discusses some controversial areas of management. It provides several reports to illustrate management options and considerations that are unique to patients with advanced disease.

This chapter reviews the current published evidence available that may guide the clinician in the appropriate use of primary thromboprophylaxis and in the application of this evidence in the care of advanced cancer patients. It provides recommendations for the prevention of venous thromboembolism (VTE) in the real world palliative care setting and discusses some relevant clinical cases. It suggests that thromboprophylaxis is inappropriate in the terminal phases since symptoms attributable to VTE can be managed with end-of-life drugs.

This chapter examines the specific issues connected to clinical decision-making concerning whether or not to treat a venous thromboembolism (VTE) patient with advanced cancer in the palliative care setting. It discusses how strategies from the broader literature on decision-making in healthcare could be applied to the palliative care setting. It recommends the use of a tool called clinical decision analysis which can integrate both research evidence and measures of patient preferences in order to suggest what the optimum option may be for that patient.

This chapter provides an overview of existing evidence in relation to the management of venous thromboembolism (VTE) in non-malignant diseases or noncancer diagnoses. Diagnosis of VTE in non-malignant disease can be challenging as the clinical features of the condition, such as chronic obstructive pulmonary disease (COPD) or stroke with concurrent pneumonia, may mimic or obscure symptoms of pulmonary embolism. Many non-malignant conditions including heart failure and renal failure are associated with an increased risk of bleeding with anticoagulation.

Blood clotting within the venous circulatory system, in contrast to arterial thrombosis, occurs at a relatively slow pace in response to stagnation of flow (stasis) and activation of coagulation. As with arterial thrombosis, vascular injury, either direct in the setting of trauma or indirect as a diffuse, systemic inflammatory response (that ultimately causes endothelial cell damage), represents an important stimulus. Venous thrombi are intravascular deposits composed predominantly of erythrocytes and fibrin, with a variable contribution of platelets and leukocytes. In a majority of cases, thrombosis begins in areas of slow flow within the venous sinuses of valve cusp pockets either in the deep veins of the calf or upper thigh or at sites of direct injury following trauma (Kakkar et al., 1969; Nicolaides et al., 1971). Stasis predisposes to thrombosis most profoundly in the setting of inflammatory states and activated coagulation factors. Slowed blood flow impairs the clearance of coagulation proteases, which through bioamplification increases the local concentration of thrombin substrate. If local thromboresistance is impaired, as may be the case with inherited or acquired thrombophilias (see Chapter 24), thrombosis occurs. Blood flow velocity is reduced by indwelling catheters, which also causes focal endothelial injury, peripheral edema, pregnancy, and valve cusp damage from prior venous thrombosis and/or chronic venous insufficiency (Trottier et al., 1995). Although venous thrombosis can occur in a variety of sites, the most common encountered in clinical practice is within the deep veins of the lower extremity. Thrombi developing within the veins of the calf or thigh can serve as a nidus for growth (propagation), which may cause complete venous obstruction, or embolize to the lungs (pulmonary embolism).

Venous thromboembolism represents a true worldwide medical problem that is encountered within all realms of practice. Venous thromboembolism (VTE) occurs in approximately 100 patients per 100,000 population yearly in the United States and increases exponentially with each decade of life (White, 2003). Approximately one-third of patients with symptomatic deep vein thrombosis (DVT) experience a pulmonary embolism (PE). Death occurs within 1 month in 6% of patients with DVT and 12% of those with PE. Early mortality is associated strongly with presentation as PE, advanced age, malignancy, and underlying cardiovascular disease. An experience dating back several decades has provided a better understanding of disease states and conditions associated with VTE (Anderson and Spencer, 2003). Given the potential morbidity and mortality associated with VTE, it is apparent that prophylaxis represents an important goal in clinical practice. A variety of anticoagulants including unfractionated heparin, low-molecular-weight heparin (LMWH), and warfarin have been studied. More recently, two new agents have been developed that warrant discussion. Fondaparinux underwent a worldwide development program in orthopedic surgery for the prophylaxis of VTE. The program consisted mainly of four large, randomized, double-blind phase II studies comparing fondaparinux (SC), at a dose of 2.5 mg starting 6 hours postoperatively, with the two enoxaparin regimens approved for VTE prophylaxis—40 mg qd or 30 mg twice daily beginning 12 hours postoperatively. The results support a greater protective effect with fondaparinux, yielding a 55.2% relative risk reduction of VTE (Bauer et al., 2001; Eriksson et al., 2001; Lassen et al., 2002; Turpie et al., 2001, 2002; ). A European program of three large-scale clinical trials (MElagatran for THRombin inhibition in Orthopedic surgery [METHRO] I, II, and III, and EXpanded PRophylaxis Evaluation Surgery Study [EXPRESS]) (Eriksson et al., 2002a, b, 2003a, b) evaluated the safety and efficacy of subcutaneous melagatran followed by oral ximelagatran compared with LMWH for thromboprophylaxis following total hip replacement (THR) and total knee replacement (TKR) surgery.