癌症相关的静脉血栓栓塞症 概述 NCCN2016v1

Cancer-Associated Venous Thromboembolic Disease癌症相关的静脉血栓栓塞症

NCCN Guidelines Version 1.2016 NCCN指南2016年第1版山东省肿瘤医院呼吸肿瘤内科张品良

Overview 概述

Venous thromboembolism (VTE) is a common and life-threatening condition in cancer patients. Results from a retrospective study of hospitalized adult cancer patients with neutropenia (n=66,106) showed that approximately 3% to 12% of these patients, depending on the type of malignancy, experienced VTE during their first hospitalization. In a recent health claims database analysis of patients undergoing chemotherapy for solid tumors in the ambulatory setting (n=17,284), VTE occurred in 12.6% of patients during the 12-month period from initiation of chemotherapy. The incidence ranged from 8% to 19% depending on the tumor type. VTE incidence was 1.4% among age- and gender-matched control cohort without cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for VTE specifically outline strategies to prevent and treat VTE in adult patients with either a diagnosis of cancer or for whom cancer is clinically suspected. These guidelines are characterized by iterative evaluations of the therapeutic advantages of implementing pharmacologic anticoagulation measures based on both the perceived risk of bleeding (ie, contraindications to anticoagulation) and the cancer status of the patient. 在癌症患者中静脉血栓栓塞(VTE)是一种常见且致命性状况。来自住院的中性粒细胞减少症成年癌症患者(n=66，106)的一项回顾性研究结果显示大约这些患者中3%-12%，取决于恶性肿瘤的类型，在其首次住院期间出现静脉血栓栓塞。在最近一项健康索赔数据库正在接受化疗的实体瘤患者的研究中在不卧床的情况下(n=17，284),在从化疗开始的12个月期间12.6%的患者发生静脉血栓栓塞。发生率范围从8%至19%依赖于肿瘤类型。在年龄与性别匹配的无癌对照组当中静脉血栓栓塞发生率是1.4%。NCCN肿瘤临床实践指南(NCCN指南)关于静脉血栓栓塞特别提出在诊断癌症或临床怀疑癌症的成年患者中防治静脉血栓栓塞的策略。这些指南的特点在于根据出血风险的认知(即，抗凝禁忌证)和患者的恶性肿瘤情况反复评估实现药理抗凝措施的治疗优势。

In the NCCN Guidelines for VTE, we define VTE broadly to include deep venous thrombosis (DVT), pulmonary embolism (PE), superficial vein thrombosis (SVT), and thrombosis in other vascular territories (eg, portal vein, mesenteric vein, inferior vena cava [IVC] and superior vena cava [SVC], pelvis). DVT management is divided into categories that include the upper extremity and the SVC; the lower extremity including the IVC, pelvis, iliac, femoral, and popliteal veins; the distal lower extremity (eg, calf); the splanchnic vasculature; and catheter-related DVT.在NCCN关于静脉血栓栓塞指南中，我们明确静脉血栓栓塞广泛至包括深静脉血栓形成(DVT)、肺栓塞(PE)、浅静脉血栓形成(SVT)和其它区域血管(例如门静脉、肠系膜静脉、下腔静脉[IVC]和上腔静脉[SVC]、骨盆)的血栓形成。DVT的治疗分类包括上肢和SVC；下肢包括下腔静脉、骨盆、髂、股和腘静脉；下肢远端（如小腿）；内脏血管；以及导管相关性DVT。

The association of VTE with underlying malignancy was first reported by Armand Trousseau in 1865 and is supported by the results of more recent studies. Pathophysiologic explanations of the etiology of VTE in cancer include known hypercoagulability (eg, pro-coagulants such as tissue factor expressed by cancer cells), vessel wall damage, and vessel stasis from direct compression. The incidence of cancer- associated VTE is further increased by the presence of additional risk factors, such as acquired or congenital thrombophilia (eg, antiphospholipid syndrome, factor V Leiden), prolonged immobilization, surgical procedures, and chemotherapeutic regimens. Armand Trousseau 1865年首次报道并被最近的研究结果证实静脉血栓栓塞与潜在恶性肿瘤相关。恶性肿瘤静脉血栓栓塞的病因学病理生理解释包括已知的高凝状态(例如前促凝物质象癌细胞表达的组织因子)、血管壁损伤和直接压迫引起的瘀血。其他危险因素的存在如获得性或先天性易栓症(例如抗磷脂综合征、莱登Ⅴ因子)、长期制动、手术方式以及化疗方案进一步增加癌症相关的静脉血栓栓塞发生率。

The occurrence of VTE has been reported to increase the likelihood of death for cancer patients by 2- to 6-fold. For example, gynecologic cancer patients with PE were found to have a 6-fold increased risk for death at 2 years compared with similar patients without PE. Furthermore, VTE has been reported to be the most common cause of death at 30-day follow-up among cancer patients undergoing surgery. 已报道发生静脉血栓栓塞的肿瘤患者死亡的可能性增加2-6倍。例如，发现有肺栓塞的妇科癌症患者与相似的无肺栓塞患者相比在2年时死亡风险增加6倍。此外，已报道在接受手术的肿瘤患者当中静脉血栓栓塞是随访30日时最常见的死因。

The critical need for the development of clinical practice guidelines focusing specifically on VTE in cancer patients is further underscored by the results of practice surveys of VTE prophylaxis. The Fundamental Research in Oncology and Thrombosis (FRONTLINE) survey noted that only 50% of surgical oncologists and 5% of medical oncologists routinely used VTE prophylaxis in their cancer patients. Similar results were documented in the multinational IMPROVE and ENDORSE registries of hospitalized medically ill patients in which only 45% of cancer patients received any form of VTE prophylaxis. These results are of particular concern when juxtaposed with a recent review of postmortem reports that showed that approximately 80% of cases of fatal PE occur in nonsurgical patients. 根据静脉血栓栓塞预防的实际调查结果进一步强调急需发展特别聚焦于癌症患者静脉血栓栓塞的临床实践指南。肿瘤与血栓形成基础研究(FRONTLINE)调查指出只有50%的外科肿瘤学家与5%的内科肿瘤学家在其肿瘤患者中常规应用静脉血栓栓塞预防。在住院的内科疾病患者改善与支持多国登记中也证明相似的结果，其中只有45%的肿瘤患者接受了任意一种形式的静脉血栓栓塞预防。当时并列的特别关注这些结果的一项最新尸检报告综述显示大约80%的致命肺栓塞病例发生在非手术的患者中。