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 (VTE) 是癌症患者的一个主要问题，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 VTE 最有效的管理策略，通常建议高危住院患者使用。然而，癌症治疗和静脉血栓栓塞的负担越来越多地转移到门诊护理机构，但有关癌症门诊患者预防的信息很少。成功的预防取决于其在最高风险患者中的应用，我们最近在接受化疗的癌症门诊患者群体中开发、验证并发布了 VTE 预测风险评估模型。在拟议的研究中，我们将在此模型的基础上检查动态癌症患者 VTE 预防的安全性和有效性，并描述组织因子对 VTE 的贡献。该提案侧重于两个具体目标。目标 1 是开展一项前瞻性、随机临床试验，比较达肝素预防治疗与不治疗在开始化疗的高危动态癌症患者中降低 VTE 的安全性效果。患者将被随机分配接受每日皮下注射达肝素 5000U 或不接受预防治疗 12 周。他们将跟踪有症状 VTE 的发展情况，并接受系列超声检查以发现无症状 DVT，并接受胸部 CT 扫描以发现无症状 PE。所有血栓和出血事件都将由盲审员进行评估。目标 2 是确定组织因子 (TF) 作为接受化疗的癌症门诊患者 VTE 预测标志物的价值。将使用来自参与目标 1 中描述的临床试验的患者以及同时开始化疗的一组低风险患者的血液和样本。我们将确定高风险患者的基线 TF 是否高于 VTE 低风险或中风险患者。此外，我们将确定临床试验中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 TF 水平升高是否可以预测 VTE 的发生。最后，我们将确定升高的 TF 水平是否与其他止血激活标志物相关。公共健康相关性：接受化疗的癌症患者通常会在腿部静脉中形成血栓，导致疼痛和肿胀，并可能转移到肺部，导致呼吸问题或死亡。我们将进行一项临床试验，以确定使用低剂量血液稀释药物进行预防性治疗是否会减少这些血栓的发生频率。我们还将进行研究，以确定凝血系统中的某些异常是否可以帮助预测这个问题。

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.