Risk assessment models for cancer-associated venous thromboembolism

Venous thromboembolism (VTE) is common in cancer patients, and is associated with significant morbidity and mortality. Several factors, including procoagulant agents secreted by tumor cells, immobilization, surgery, indwelling catheters, and systemic treatment (including chemotherapy), contribute to an increased risk of VTE in cancer patients. There is growing interest in instituting primary prophylaxis in high-risk patients to prevent incident (first-time) VTE events. The identification of patients at sufficiently high risk of VTE to warrant primary thromboprophylaxis is essential, as anticoagulation may be associated with a higher risk of bleeding. Current guidelines recommend the use of pharmacological thromboprophylaxis in postoperative and hospitalized cancer patients, as well as ambulatory cancer patients receiving thalidomide or lenalidomide in combination with high-dose dexamethasone or chemotherapy, in the absence of contraindications to anticoagulation. However, the majority of cancer patients are ambulatory, and currently primary thromboprophylaxis is not recommended for these patients, even those considered at very high risk. In this concise review, the authors discuss risk stratification models that have been specifically developed to identify cancer patients at high risk for VTE, and thus might be useful in future studies designed to determine the potential benefit of primary thromboprophylaxis.     

Thromboprophylaxis with low‐molecular‐weight heparin in medical patients with cancer

Venous thromboembolism (VTE) is a frequent complication of cancer and cancer treatment and is associated with multiple clinical consequences, including recurrent VTE, bleeding, and an increase in the risk of death. Although the risks associated with VTE have been well recognized in surgical cancer patients, there is also considerable and increasing risk in medical cancer patients. VTE risk factors in medical cancer patients include the type and stage of cancer, major comorbid illnesses, current hospitalization, active chemotherapy, hormone therapy, and antiangiogenic agents. Low‐molecular‐weight heparins (LMWHs) are recommended commonly for the prevention of VTE in hospitalized cancer patients and in higher risk ambulatory cancer patients because of their favorable risk‐to‐benefit profile. These agents have demonstrated effectiveness in both the primary and secondary prevention of VTE in medical cancer patients. Extended‐duration anticoagulant therapy is often recommended to reduce the risk of VTE recurrence in patients with cancer. LMWHs are often used for long‐term prophylaxis because of a reduced need for coagulation monitoring, few major bleeding episodes, and once‐daily dosing. Despite clinical and practical benefits, a substantial proportion of medical cancer patients do not receive VTE prophylaxis. To improve the appropriate prevention and treatment of VTE in cancer patients, guidelines have been published recently by the American Society of Clinical Oncology and the National Comprehensive Cancer Network. Widespread dissemination and application of these guidelines are encouraged to improve the appropriate use of these agents and to improve clinical outcomes in medical cancer patients at risk for VTE and its complications. Cancer 2009. © 2009 American Cancer Society.     

Prediction and Prevention of Cancer‐Associated Thromboembolism

Venous and arterial thromboembolism are prevalent, highly burdensome, and associated with risk of worse outcomes for patients with cancer. Risk for venous thromboembolism (VTE) varies widely across specific cancer subpopulations. The ability to predict risk of cancer‐associated VTE is critical because an optimal thromboprophylaxis strategy is best achieved by targeting high‐risk patients with cancer and avoiding prophylaxis in patients with cancer at low risk for VTE. A validated risk tool for solid tumors has been available for a decade. Newer tools have focused on specific populations, such as patients with multiple myeloma. Emerging studies continue to optimize risk prediction approaches in patients with cancer. Recent randomized trials have specifically addressed risk‐adapted thromboprophylaxis using direct oral anticoagulants, and revised guidelines have included these new data to formulate recommendations for outpatient thromboprophylaxis. Implementation science approaches to enhance use of outpatient prophylaxis in the context of these guideline changes are under way. However, major knowledge gaps remain, including a lack of data for inpatient thromboprophylaxis in the cancer setting and a lack of formal tools for identifying risk of bleeding. This review describes optimal approaches to risk prediction and patient selection for primary pharmacologic thromboprophylaxis of cancer‐associated VTE, addresses barriers to implementing these practices, and highlights strategies to overcome them.Implications for PracticeRisk for venous thromboembolism (VTE) varies widely among patients with cancer. Individual risk can be determined using validated approaches. Inpatient and postsurgical thromboprophylaxis is more widely accepted. However, most patients with cancer develop VTE in the outpatient setting. Recent randomized trials have demonstrated benefit to risk‐adapted outpatient thromboprophylaxis. High‐risk patients may therefore be considered for outpatient thromboprophylaxis as recommended by recently updated guidelines. System‐wide implementation approaches are necessary to improve compliance with prophylaxis.     

The NCCN Clinical Practice Guidelines on Venous Thromboembolic Disease: strategies for improving VTE prophylaxis in hospitalized cancer patients

The risk for venous thromboembolism (VTE) is high in hospitalized cancer patients, and is associated with an elevated risk for recurrent thrombosis, bleeding complications, and use of health care resources. Thromboembolism is the second leading cause of death in hospitalized cancer patients. Thromboprophylaxis with unfractionated heparin or low-molecular-weight heparins has been clinically proven to reduce the risk for VTE and improve outcomes. However, VTE prophylaxis continues to be underprescribed in cancer patients. Recognizing the clinical burden of VTE in cancer patients, the National Comprehensive Cancer Network (NCCN) recently released guidelines for VTE prevention and management. These NCCN guidelines recommend evidence-based prophylactic anticoagulant therapy for all patients admitted to hospital with a diagnosis of cancer who do not have contraindications to anticoagulant use. However, there continue to be barriers to the implementation of clinical practice guidelines and appropriate use of VTE prophylaxis. Multifaceted active educational and electronic interventions are necessary to raise awareness and reduce the burden of cancer-associated thrombosis and its attendant consequences.     

Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWIss Venous ThromboEmbolism Registry (SWIVTER)

Background: Venous thromboembolism (VTE) prophylaxis remains underutilized, particularly in cancer patients. We explored clinical predictors of prophylaxis in hospitalized cancer patients before the onset of acute VTE.Methods: In the SWiss Venous ThromboEmbolism Registry, 257 cancer patients (61 ± 15 years) with acute VTE and prior hospitalization for acute medical illness or surgery within 30 days (91% were at high risk with Geneva VTE risk score ≥3) were enrolled.Results: Overall, 153 (60%) patients received prophylaxis (49% pharmacological and 21% mechanical) before the onset of acute VTE. Outpatient status at the time of VTE diagnosis [odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18–0.53], ongoing chemotherapy (OR 0.51, 95% CI 0.31–0.85), and recent chemotherapy (OR 0.53, 95% CI 0.32–0.88) were univariately associated with the absence of VTE prophylaxis. In multivariate analysis, intensive care unit admission within 30 days (OR 7.02, 95% CI 2.38–20.64), prior deep vein thrombosis (OR 3.48, 95% CI 2.14–5.64), surgery within 30 days (OR 2.43, 95% CI 1.19–4.99), bed rest >3 days (OR 2.02, 95% CI 1.08–3.78), and outpatient status (OR 0.38, 95% CI 0.19–0.76) remained the only independent predictors of thromboprophylaxis.Conclusions: Although most hospitalized cancer patients were at high risk, 40% did not receive any prophylaxis before the onset of acute VTE. There is a need to improve thromboprophylaxis in cancer patients, particularly in the presence of recent or ongoing chemotherapy.     

Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with cancer. The risk of VTE varies over the natural history of cancer, with the highest risk occurring during hospitalization and after disease recurrence. Patient and disease characteristics are associated with further increased risk of VTE in this setting. Specific factors include cancer type (eg, pancreatic cancer, brain cancer, lymphoma) and the presence of metastatic disease at the time of diagnosis. VTE is a significant predictor of increased mortality during the first year among all types and stages of cancer, with metastatic disease reported to be the strongest predictor of mortality. VTE is also associated with early death in ambulatory patients with cancer. These data highlight the need for close monitoring, prompt treatment, and appropriate preventive strategies for VTE in patients with cancer. The American Society of Clinical Oncology and the National Comprehensive Cancer Network have issued guidelines regarding the prophylaxis and treatment of patients with cancer. This review summarizes the impact of VTE on patients with cancer, the effects of VTE on clinical outcomes, the importance of thromboprophylaxis in this population, relevant ongoing clinical trials examining the prevention of VTE, and new pharmacologic treatment options.     

Cancer and thrombosis: implications of published guidelines for clinical practice

Cancer is a frequent finding in patients with thrombosis, and thrombosis is much more prevalent in patients with cancer, with important clinical consequences. Thrombosis is the second most common cause of death in cancer patients. Venous thromboembolism (VTE) in cancer is also associated with a high rate of recurrence, bleeding, a requirement for long-term anticoagulation, and worsened quality of life. Risk factors for cancer-associated VTE include particular cancer types, chemotherapy (with or without antiangiogenic agents), the use of erythropoietin-stimulating agents, the presence of central venous catheters, and surgery. Novel risk factors include platelet and leukocyte counts and tissue factor. A risk model for identifying cancer patients at highest risk for VTE has recently been developed. Anticoagulant therapy is safe and efficacious for prophylaxis and treatment of VTE in patients with cancer. Available anticoagulants include warfarin, heparin, and low-molecular weight heparins (LMWHs). LMWHs represent the preferred therapeutic option for VTE prophylaxis and treatment. Their use may be associated with improved survival in cancer, although this issue requires further study. Despite the significant burden imposed by VTE and the availability of effective anticoagulant therapies, many oncology patients do not receive appropriate VTE prophylaxis as recommended by practice guidelines. Improved adherence to guidelines could substantially reduce morbidity, decrease resource use, enhance quality of life, and improve survival in these patients.     

Anticoagulation therapy for prevention and treatment of venous thromboembolic events in cancer patients: A review of current guidelines

Cancer patients in general have a high risk of venous thromboembolic events (VTE) driven not only by patient-related risk factors, but also risk factors related to the disease and anti-cancer therapies. Cancer patients with documented VTE have a notably worse outcome than non-cancer VTE patients. Since VTE is a highly preventable condition, it is striking that large surveys have shown significant underuse of VTE prophylaxis in surgical cancer patients and in medical cancer patients in particular. Recently, guidelines have been issued from European and American medical oncology societies and organizations for identification of cancer patients at risk, and the guidelines give recommendations for treatment of individual groups of cancer patients.     

肿瘤患者静脉血栓栓塞抗凝出血与复发风险研究进展

肿瘤相关静脉血栓栓塞症(cancer-associated venous thromboembolism, CAVTE)为肿瘤患者在疾病进程中的常见并发症和死亡原因。其静脉血栓栓塞症(venous thromboembolism, VTE)复发和抗凝后严重出血的高风险可能会导致治疗延误和死亡率增加。目前, 国内外指南并未推荐对所有门诊患者直接进行一级预防, 但建议在化疗前评估发生静脉血栓栓塞的个体风险。本文对目前肿瘤患者静脉血栓栓塞抗凝出血与复发研究进展以及现行VTE防治指南和VTE风险评估模型进行综述。      

Risk of venous thromboembolism in patients undergoing cancer surgery and options for thromboprophylaxis

Patients with cancer have an increased risk of developing venous thromboembolism (VTE) due to a hypercoagulable state associated with malignancy. This risk is further complicated in patients undergoing cancer-related surgery due to immobility, other cancer treatments, and biologic changes associated with surgery. Despite this relatively high risk of VTE, many patients are not prescribed adequate prophylaxis in the pre- or post-operative periods. This article reviews available measures for thromboprophylaxis in light of current guidelines.     

Thromboprophylaxis in major abdominal surgery for cancer.

AIMS: To review the epidemiology and pathogenesis of venous thromboembolism (VTE) in surgical cancer patients, in addition to the use of thromboprophylaxis in major abdominal surgery, such as low-molecular-weight heparin (LMWH) and fondaparinux. METHODS: Systematic review of the literature, focussing on risk factors for VTE, parenteral methods of thromboprophylaxis, approaches to prolonged prophylaxis, and effects on patient survival. FINDINGS: Patients with cancer undergoing abdominal surgery are at substantially higher risk for VTE than patients without cancer. Furthermore, prolonged thromboprophylaxis for up to 4 weeks is more effective than short-term administration in these high-risk patients. The concurrent use of graduated compression stockings has a synergistic effect on the reduction in VTE risk. CONCLUSIONS: Thromboprophylaxis with LMWH has been shown to minimise the incidence of thromboembolic events, and is a well-established therapy worldwide. The American College of Chest Physicians recommends the routine use of thromboprophylaxis, with LMWH or unfractionated heparin, in patients with cancer who are undergoing surgical procedures, and the appropriate use of these thromboprophylactic agents has significant implications for the clinical care and quality of life of surgical patients with cancer.     

Guidelines of the National Comprehensive Cancer Network on the use of myeloid growth factors with cancer chemotherapy: a review of the evidence

The prophylactic use of myeloid growth factors reduces the risk of chemotherapy-induced neutropenia and its complications, including febrile neutropenia and infection-related mortality. Perhaps most importantly, the prophylactic use of colony-stimulating factors (CSFs) has been shown to reduce the need for chemotherapy dose reductions and delays that may limit chemotherapy dose intensity, thereby increasing the potential for prolonged disease-free and overall survival in the curative setting. National surveys have shown that the majority of patients with potentially curable breast cancer or non-Hodgkin's lymphoma (NHL) do not receive prophylactic CSF support. In this issue, the National Comprehensive Cancer Network presents guidelines for the use of myeloid growth factors in patients with cancer. These guidelines recommend a balanced clinical evaluation of the potential benefits and harms associated with chemotherapy to define the treatment intention, followed by a careful assessment of the individual patient's risk for febrile neutropenia and its complications. The decision to use prophylactic CSFs is then based on the patient's risk and potential benefit from such treatment. The routine prophylactic use of CSFs in patients receiving systemic chemotherapy is recommended in patients at high risk (>20%) of developing febrile neutropenia or related complications that may compromise treatment. Where compelling clinical indications are absent, the potential for CSF prophylaxis to reduce or offset costs by preventing hospitalization for FN should be considered. The clinical, economic, and quality of life data in support of these recommendations are reviewed, and important areas of ongoing research are highlighted.     

Safety and efficacy of primary thromboprophylaxis in cancer patients

Cancer is often complicated by venous thromboembolism (VTE), a common and potentially fatal complication associated with poor prognosis in these patients. An increased incidence of VTE is being observed due to the advanced age of cancer patients, the thrombogenic effect of novel drugs and advances in the diagnosis of related complications. In this review, we look at five different risk groups of cancer patients with an increased probability of developing VTE, including hospitalized patients undergoing chemotherapy, patients undergoing a surgical procedure, ambulatory patients undergoing chemotherapy, patients with a central venous access and patients receiving antiangiogenic drugs or anticoagulant therapy due to previous chronic diseases. The aim of this review is to summarize the most important clinical evidence reported to date on the suitability of primary thromboprophylaxis to cancer patients. Recommendations have drawn up for each group based on current evidence and guidelines to facilitate decision-making in clinical practice.     

Risk assessment and prophylaxis for VTE in cancer patients

The frequency of venous thromboembolism (VTE) is rising in patients with cancer. VTE contributes to mortality and morbidity, but the risk for VTE can vary widely between individual patients. Clinical risk factors for VTE in cancer include primary site of cancer, use of systemic therapy, surgery, and hospitalization. Biomarkers predictive of VTE include platelet and leukocyte counts, hemoglobin, D-dimer, and tissue factor. A recently validated risk model incorporates 5 easily available variables and can be used clinically to identify patients at increased risk of VTE. In high-risk settings, including surgery and hospitalization, thromboprophylaxis with either unfractionated heparin or low-molecular-weight heparins has been shown to be safe and effective. Recent studies have also suggested a potential benefit for thromboprophylaxis in the ambulatory setting, although criteria for selecting patients for prophylaxis are not currently well defined. This article focuses on recent and ongoing studies of risk assessment and prophylaxis in patients with cancer.     

VTE as a quality indicator

Venous thromboembolism (VTE) is still the most common preventable cause of hospital death, with cancer a known significant risk factor for its development. Prophylaxis to prevent VTE in hospitalized surgical and medical patients has been suboptimal, and efforts for improvement have been unsuccessful. Recent practice guidelines on VTE in oncology from the National Comprehensive Cancer Network and American Society of Clinical Oncologists have further highlighted this relationship and could bridge performance measures and outcomes that can affect the strategies for preventing deep venous thrombosis and pulmonary embolism in oncology patients. Hospitals and physicians with poor performance data will have problems with payment from the Centers for Medicare & Medicaid Services and contracting the best rates from other payors. Hospital accreditation from The Joint Commission could be an issue for poorly performing institutions, as could consumer acceptance. The authors believe that specific oncology VTE measures should be developed to help decrease the current poor rates of VTE prophylaxis and also improve hospital and physician compliance.     

Primary prevention and treatment of venous thromboembolic events in patients with gastrointestinal cancers - Review

Venous thromboembolism event (VTE) is a common and morbid complication in cancer patients. Patients with gastrointestinal cancers often suffer from symptomatic or incidental splanchnic vein thrombosis, impaired liver function and/or thrombocytopenia. These characteristics require a thorough risk/benefit evaluation for individual patients. Considering the risk factors for the development of VTE and bleeding events in addition to recent study results may be helpful for correct initiation of primary pharmacological prevention and treatment of cancer-associated thrombosis (CAT), preferably with low molecular weight heparins (LMWH). Whereas thromboprophylaxis is most often recommended in hospitalized surgical and non-surgical patients with malignancy, there is less agreement as to its duration. With regard to ambulatory cancer patients, the lack of robust data results in low grade recommendations against routine use of anticoagulant drugs. Anticoagulation with LMWH for the first months is the evidence-based treatment for acute CAT, but duration of secondary prevention and the drug of choice are unclear. Based on published guidelines and literature, this review will focus on prevention and treatment strategies of VTE in patients with gastrointestinal cancers.     

Thrombosis and cancer

Venous thromboembolism (VTE) is a potentially life-threatening condition that can be associated with significant morbidity. Thrombosis and cancer are linked by numerous pathophysiological mechanisms; the frequency of VTE and the recurrence rate are increased in the cancer population in comparison with other patient groups. VTE is the second most common cause of death in patients with cancer, but can also be the initial presenting complaint in patients with an occult malignancy. Risk factors for cancer-related VTE include tumour type, surgery, chemotherapy and the use of central venous catheters; predictors of VTE for individuals are only now beginning to emerge. Patients with cancer who develop symptomatic VTE during chemotherapy are at a greater risk of early mortality than those without VTE. The apparent impact of VTE on early mortality in patients with cancer raises the question of whether anticoagulation might improve long-term survival in this population, by direct tumour biology-modifying mechanisms. There are widely published guidelines that highlight the benefits of effective VTE strategies in patients with cancer. In partnership with the patient and their carers, the clinical team can improve patient outcomes with optimal risk assessment and concordance with national and international guidelines in the prophylaxis and treatment of VTE.     

Preventing thromboembolic complications in cancer patients after surgery: a role for prolonged thromboprophylaxis

Patients undergoing major abdominal surgery for malignancy are at particularly high risk of developing VTE. Extra protection against this can be given to patients with cancer by using a higher dose of LMWH than normally used for prophylaxis, with no increase in bleeding complications. Despite thromboprophylaxis with high-dose LMWH for the first postoperative week, the rate of late VTE is estimated to be between 10% and 20%. A meta-analysis of two studies using dalteparin or enoxaparin has shown that prolonging thromboprophylaxis for a further 3 weeks significantly reduces the risk of late occurring VTE by 62%. Thromboprophylaxis with LMWH for at least one month should be considered in patients undergoing surgery for malignant disease.     

How to improve the implementation of guidelines on cancer-related thrombosis

Venous thromboembolism (VTE; defined by deep-vein thrombosis, central venous catheter-related thrombosis or pulmonary embolism) is a major therapeutic issue in cancer patients. VTE is reported in 15-20% of patients with cancer and is an independent prognostic factor and a leading cause of death. In this population, low-molecular-weight heparins have been shown to be superior to vitamin K antagonists. The Italian Association of Medical Oncology, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, the French 'Institut National du Cancer', the European Society of Medical Oncology and the American College of Chest Physicians have all published specific guidelines, but their implementation is still low in clinical practice. Methodological assessment of these guidelines was performed using the Appraisal of Guidelines Research & Evaluation Instrument. None of the guidelines on thrombosis and cancer have sought for patients' preferences, nor were they tested among target users. VTE in cancer patients requires a multidisciplinary approach but downstream of the guidelines publication, the potential organisational barriers in applying the recommendations have not been discussed. Tolerance and cost-effectiveness of long-term use of low-molecular-weight heparin may account for the large heterogeneity seen in daily clinical practice. Homogenization of guidelines in international consensus working groups followed by educational and active implementation strategies would be very valuable in order to improve the care of VTE in cancer patients.     

The prophylaxis of venous thrombosis in patients with cancer undergoing major abdominal surgery: emerging options

Cancer is a risk factor for venous thromboembolism (VTE). This risk is amplified by treatment with chemotherapy, radiation, or surgery. Thus, patients with cancer undergoing major surgery should receive appropriate prophylaxis. Available agents include low-dose unfractionated heparin (LDUH), low-molecular-weight heparin (LMWH), and Factor Xa inhibitors. Recent data suggest that Factor Xa inhibitors are safe and effective for VTE prevention in patients with cancer undergoing abdominal surgery. Further study in this patient population is warranted.