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癌症患者的两倍多。 没有癌症的病人。这些出血的致死率为7%。目前的指导方针建议无限期 肿瘤合并静脉血栓栓塞症(VTE)患者的抗凝治疗 出血风险评估。然而，目前尚无循证模型可以量化患者的出血风险。 癌症患者服用抗凝血剂。此外，最近的试验已经证明了直接口服的有效性。 抗凝剂作为预防癌症患者初始静脉血栓形成的主要预防措施。因此，有一个 迫切需要平衡静脉血栓栓塞术和抗凝剂相关出血的相互竞争的风险 癌症。虽然有模型量化非癌症人群的出血风险(即心房颤动、非癌症 癌症相关静脉血栓)，服用抗凝剂，它们尚未在癌症患者中得到验证。 量化癌症和静脉血栓栓塞术患者的出血风险将使循证方法能够 通过尽量减少高危出血患者的抗凝治疗来预防和治疗VTE 允许司法使用于出血风险较低的患者。这项研究的总体目标是开发一种 肿瘤患者抗凝相关出血与静脉血栓栓塞术抗凝治疗的预测模型 并在VTE高危癌症患者中对该模型进行校正 通过抗凝治疗预防血栓形成。我们将通过以下几个方面实现总体目标 具体目标：(1)在7489名癌症患者队列中验证现有的8个出血预测模型 和接受抗凝治疗的VTE，(2)提炼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发生抗凝剂相关性出血的风险，以及(3) 在一组接受原发肿瘤治疗的癌症患者中校准改进的出血预测模型 抗凝剂血栓预防在两个随机试验(AVERT和Cassini)中登记。这些目标将是 与专家研究小组在出血、静脉血栓栓塞术(特别是癌症患者)和 风险预测模型的开发和实施。这项提议是创新的，因为它解决了 通过发展一种预测来管理患有或处于VTE高危状态的癌症患者的现状差距 模型量化干预(抗凝治疗)的风险，以告知和指导患者护理。这 研究将具有重要意义，因为它有可能减少抗凝剂相关的出血，从而 癌症患者与出血相关的发病率和死亡率。

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.