Prediction of Anticoagulant-Related Bleeding Risk in Patients with Cancer

项目摘要 在癌症患者中，抗凝剂相关大出血的风险是 没有癌症的病人。这些出血的致死率为7%。目前的指南建议无限期 在许多癌症和静脉血栓栓塞（VTE）患者中， 评估出血风险。然而，没有基于证据的模型来量化患者的出血风险 癌症患者服用抗凝剂此外，最近的试验表明，直接口服 抗凝剂作为预防癌症患者初始VTE的一级预防。因此，有一个 强烈需要平衡患者中VTE和抗凝剂相关出血的竞争风险， 癌虽然有一些模型可以量化非癌症人群（即房颤、非癌症人群）的出血风险， 癌症相关性VTE）服用抗凝剂，但尚未在癌症患者中得到验证。 量化癌症和静脉血栓栓塞患者的出血风险将允许采用循证方法， 通过尽量减少出血高危患者的抗凝治疗来预防和治疗VTE， 允许在低出血风险的患者中司法使用。本研究的总体目标是制定一个 癌症合并静脉血栓栓塞患者抗凝治疗相关出血的预测模型 并在考虑进行原发性VTE的高风险癌症患者中校准该模型， 抗凝治疗的血栓预防。我们将通过以下方式实现我们的总体目标 具体目的：（1）在7489例癌症患者队列中验证8种现有出血预测模型 和VTE接受抗凝治疗，（2）完善和验证癌症特异性预测模型，以量化 接受VTE抗凝治疗的癌症患者中抗凝剂相关出血的风险，以及（3） 在接受原发性肝癌治疗的癌症患者队列中校准精确的出血预测模型， 两项随机试验（AVERT和CASSINI）中纳入了抗凝剂血栓预防。这些目标将是 在出血、静脉血栓栓塞（特别是癌症患者）和 开发和实施风险预测模型。这一建议是创新的，因为它解决了一个 通过预测，目前在管理伴有或处于VTE高风险的癌症患者方面存在差距 该模型用于量化干预（抗凝治疗）的风险，以告知和指导患者护理。这 研究将是重要的，因为它有可能减少抗凝剂相关的出血， 癌症患者的出血相关发病率和死亡率。

Project Summary Among patients with cancer, the risk of anticoagulant-related major bleeding is more than double that of patients without cancer. These bleeds have a fatality rate of 7%. Current guidelines recommend indefinite anticoagulant therapy in many patients with cancer and venous thromboembolism (VTE) with periodic assessments of bleeding risk. However, no evidence-based models exist to quantify bleeding risk in patients with cancer taking anticoagulants. In addition, recent trials have demonstrated effectiveness of direct oral anticoagulants as primary prophylaxis for prevention of initial VTE in patients with cancer. Thus, there is a strong need to balance the competing risks of VTE and anticoagulant-related bleeding in patients with cancer. While there are models that quantify bleeding risk in non-cancer populations (i.e. atrial fibrillation, non- cancer associated VTE) taking anticoagulants, they have not been validated in patients with cancer. Quantification of bleeding risk in patients with cancer and VTE would allow for an evidence-based approach to preventing and treating VTE by minimizing anticoagulant therapy in patients at high-risk of bleeding and allowing for judicial use in patients at low-risk of bleeding. The overall objective of this study is to develop a prediction model for anticoagulant-related bleeding in patients with cancer and VTE on anticoagulant therapy and to calibrate that model in cancer patients at high-risk of VTE being considered for primary thromboprophylaxis with anticoagulant therapy. We will accomplish our overall objective through the following specific aims: (1) validate eight existing bleeding prediction models in a cohort of 7489 patients with cancer and VTE receiving anticoagulant therapy, (2) refine and validate a cancer-specific prediction model to quantify risk of anticoagulant-associated bleeding in patients with cancer on anticoagulant therapy for VTE, and (3) calibrate the refined bleeding prediction model in a cohort of patients with cancer receiving primary anticoagulant thromboprophylaxis enrolled in two randomized trials (AVERT and CASSINI). These aims will be addressed with an expert research team in the areas of bleeding, VTE (especially in patients with cancer) and development and implementation of risk prediction models. This proposal is innovative as it addresses a current gap in the management of patients with cancer with or at high-risk of VTE by developing a prediction model to quantify the risk of the intervention (anticoagulant therapy) to inform and guide patient care. This research will be significant because it has the potential to decrease anticoagulant-related bleeding and thus bleeding related morbidity and mortality in patients with cancer.