Venous Thrombosis in Cancer Outpatients: Prevention and Role of Tissue Factor

描述(由申请人提供)： 静脉血栓栓塞症(VTE)是癌症患者的主要问题，会导致死亡率和发病率，干扰最佳治疗，并导致高昂的费用。一级预防是静脉血栓栓塞术最有效的管理策略，通常推荐给高危住院患者。然而，癌症治疗和静脉血栓栓塞术的负担越来越多地转移到门诊护理环境中，但关于癌症门诊患者的预防措施的信息很少。成功的预防依赖于它在高危患者中的应用，我们最近开发、验证并发表了一种预测VTE的风险评估模型，该模型适用于接受化疗的癌症门诊患者。在这项拟议的研究中，我们将在此模型的基础上检验动态癌症患者静脉血栓栓塞术预防的安全性和有效性，并表征组织因子对静脉血栓栓塞术的贡献。该提案聚焦于两个具体目标。目的1是进行一项前瞻性随机临床试验，比较达肝素预防与不治疗在开始化疗的高危非卧床型癌症患者减少静脉血栓形成方面的安全性。患者将被随机分为两组，一组每天接受达肝素5000U皮下注射，另一组在12周内不进行预防治疗。他们将被跟踪以发展有症状的VTE，并将接受无症状DVT的系列超声筛查和无症状PE的胸部CT扫描。所有血栓和出血事件将由盲人评审员进行评估。目的2确定组织因子(TF)作为预测接受化疗的癌症门诊患者VTE的标志物的价值。将使用参加目标1所述临床试验的患者的血液和样本，以及同时开始化疗的低风险患者队列。我们将确定高危患者的基线Tf是否高于低风险或中等风险的VTE患者。此外，我们将在临床试验中确定基线血浆组织因子水平是否可以预测VTE。我们将确定化疗期间升高的转铁蛋白水平是否预示着VTE的发展。最后，我们将确定升高的转铁蛋白水平是否与止血激活的其他标志物相关。公共卫生相关性：接受化疗的癌症患者经常出现腿部静脉血栓，导致疼痛和肿胀，并可能扩散到肺部，导致呼吸问题或死亡。我们将进行一项临床试验，以确定低剂量的血液稀释剂预防性治疗是否会减少这些血栓的发生。我们还将进行研究，以确定凝血系统中的某些异常是否有助于预测这一问题。

DESCRIPTION (provided by applicant): Venous thromboembolism (VTE) is a major problem in patients with cancer, contributing to mortality and morbidity, interfering with optimum treatment and resulting in high costs. Primary prophylaxis is the most effective management strategy for VTE and is generally recommended for high-risk hospitalized patients. However, cancer treatment and the burden of VTE is shifted increasingly to the ambulatory care setting, but little information is available regarding prophylaxis in cancer outpatients. Successful prophylaxis depends on its application in patients at highest risk, and we have recently developed, validated and published a predictive risk assessment model for VTE in a population of cancer outpatients receiving chemotherapy. In the proposed study, we will build on this model to examine the safety and efficacy of VTE prophylaxis in ambulatory cancer patients and also characterize the contribution of tissue factor to VTE. The proposal is focused on two specific aims. Aim 1 will be to conduct a prospective, randomized clinical trial comparing the safety efficacy of prophylaxis with dalteparin to no treatment in reducing VTE in high-risk ambulatory cancer patients initiating chemotherapy. Patients will be randomized to receive either dalteparin 5000U subcutaneously daily or no prophylaxis for 12 weeks. They will be followed for the development of symptomatic VTE and will undergo screening with serial ultrasonography for asymptomatic DVT and chest CT scan for asymptomatic PE. All thrombotic and bleeding events will be evaluated by blinded adjudicators. Aim 2 will be to establish the value of tissue factor (TF) as a predictive marker for VTE in cancer outpatients receiving chemotherapy. Blood and samples from patients enrolled in the clinical trial described in Aim 1 and from a cohort of concurrent low-risk patients also initiating chemotherapy will be used. We will determine if baseline TF is higher in patients at high-risk compared to those at low or intermediate risk of VTE. Further, we will determine if baseline plasma tissue factor levels are predictive of VTE in the clinical trial. We will determine if increasing TF levels during chemotherapy are predictive of the development of VTE. Finally, we will determine if elevated TF levels correlate with other markers of hemostatic activation. Public Health Relevance: Patients with cancer who are receiving chemotherapy often develop blood clots in the leg veins that cause pain and swelling and can travel to the lungs causing breathing problems or death. We will conduct a clinical trial to determine if preventive treatment with a low dose of a blood thinning drug will reduce the frequency of these clots. We will also do studies to determine if certain abnormalities in the blood clotting system can help predict this problem.