肿瘤患者静脉血栓栓塞症的风险评估模型及其应用

静脉血栓栓塞症（VTE）是肿瘤患者常见的并发症和死亡原因。多项研究显示，有效的VTE风险评估模型和恰当的预防性抗凝治疗可以降低肿瘤患者的血栓发生风险。但哪些肿瘤患者需要进行预防性抗凝治疗，需要有效的VTE风险评估模型，对肿瘤患者进行VTE风险分层。对血栓高危人群，在排除抗凝禁忌证后进行预防性抗凝。但肿瘤疾病存在复杂性，不同的病理类型和分期，VTE风险和特点不同，而目前专门针对肿瘤患者的VTE风险评估模型仍然有限，本文将对肿瘤患者的VTE风险评估模型的现状及其应用进行综述。     

恶性淋巴瘤血栓形成的研究进展

静脉血栓栓塞（venous thrombolism,VTE）是恶性肿瘤患者第二致死原因,并且癌症患者是血栓栓塞的高发人群,其预防和治疗是非常重要的。肿瘤患者发生VTE的风险较非肿瘤患者至少增加7倍,而血液系统肿瘤并发VTE的概率则较非肿瘤患者增加28倍,严重影响了恶性淋巴瘤患者的预后和生活质量。恶性淋巴瘤患者并发VTE的机制和危险因素尚未明确,VTE的发生与组织因子、微粒以及基因的单核苷酸多态性相关。为了降低VTE发生率,预测可能发生VTE的高危患者是非常重要的,这些患者将会从血栓预防中受益,因此临床上急需一种简单有效的VTE风险评估模型,联合检测外周血中生物标记物可提高VTE诊断率。由于淋巴瘤患者发生出血的风险较高,导致血栓的治疗更加复杂。本文就恶性淋巴瘤患者发生VTE的流行病学、发病机制、预防和治疗的最新研究做一综述。      

肿瘤患者静脉血栓栓塞抗凝出血与复发风险研究进展

肿瘤相关静脉血栓栓塞症(cancer-associated venous thromboembolism, CAVTE)为肿瘤患者在疾病进程中的常见并发症和死亡原因。其静脉血栓栓塞症(venous thromboembolism, VTE)复发和抗凝后严重出血的高风险可能会导致治疗延误和死亡率增加。目前, 国内外指南并未推荐对所有门诊患者直接进行一级预防, 但建议在化疗前评估发生静脉血栓栓塞的个体风险。本文对目前肿瘤患者静脉血栓栓塞抗凝出血与复发研究进展以及现行VTE防治指南和VTE风险评估模型进行综述。      

基因突变状态与肿瘤相关性静脉血栓关系的研究进展

肿瘤相关性静脉血栓栓塞疾病（venous thromboembolic disease，VTE）已成为当下肿瘤患者的第二大死因，诸多学者提出多种血栓风险模型，从而筛选出血栓发生风险可能较高的患者进行药物及物理干预措施，减少肿瘤相关性VTE的发生。随着精准医学的不断发展，现有结论已不能满足医务人员探索肿瘤相关性VTE相关问题的要求。基因检测已经成为肿瘤患者的“基线”检查，检测常见的驱动基因如表皮生长因子受体（epidermal growth factor receptor，EGFR）、间变性淋巴瘤激酶（anaplastic lymphoma kinase，ALK）、v-ros UR2肉瘤病毒癌基因同源物1（v-ros UR2 sarcoma virus oncogene homolog 1，ROS1）和鼠类肉瘤病毒致癌基因（kirsten ras sarcoma，KRAS）等已成为常态且被指南推荐应用于临床，基因突变状态在影响临床预后和治疗决策方面的地位日益凸显。基因突变状态与肿瘤相关性VTE之间是否存在关联，可否根据基因状态筛选出具有较高血栓风险的癌症人群，从而为更好地实施预防管理策略提供理论基础。本文旨在对基因突变状态与肿瘤相关性VTE之间关系的研究进展及其潜在机制进行综述。      

肿瘤细胞减灭加腹腔热灌注化疗术后静脉血栓栓塞症的预防

  目的  评估行肿瘤细胞减灭术（cytoreductive surgery，CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy，HIPEC）治疗的腹膜癌患者静脉血栓栓塞症（venous thromboembolism，VTE）发生风险，研究术后早期主/被动活动联合间歇充气加压按摩对VTE的预防效果。  方法  对2015年5月至2016年8月武汉大学中南医院肿瘤科收治的120例胃肠道及妇科肿瘤等来源的腹膜癌患者行CRS+HIPEC治疗，使用Caprini血栓风险评估模型评价VTE风险，所有患者采取早期肢体主/被动活动及间歇充气加压按摩治疗，记录分析VTE相关事件。  结果  患者中位Carprini评分为12（10~16）分，均为VTE极高危组，在3个月的随访中仅1例患者发生深静脉血栓，经药物治疗后痊愈。  结论  腹膜癌患者VTE风险极高，术后早期足背曲/跖曲及扩胸等主/被动运动联合间歇充气加压按摩，可有效预防VTE。      

Caprini和Rogers血栓风险评估模型在胸外科肺癌患者围手术期应用的验证研究

目的：对Caprini和Rogers血栓风险评估模型在胸外科肺癌患者围术期筛查静脉血栓栓塞症（Venous Thromboembolism, VTE）高风险的适用性进行分析,以验证其有效性。方法：根据入排标准纳入2015年3月至2017年3月在四川省肿瘤医院胸外科接受手术治疗的肺癌患者,术后未预防性抗凝处理。所有患者围术期行双下肢血管彩超检查,怀疑肺血管栓塞者行胸CT检查,前瞻性收集临床和实验室相关指标。以Caprini和Rogers血栓风险评估量表对所有患者进行血栓风险评分。分别分析Caprini和Rogers评分不同层级组之间术后VTE发生率、危险因素、实验室指标的差异。结果：152例肺癌患者入选本研究,术后深静脉血栓（Deep Vein Thrombosis, DVT）发生率25%（38/152）,无肺栓塞发生。全组患者Caprini评分为8～15分,均至少为VTE高风险层级,其中高危组（5-8分）66例,极高危组（＞9分）86例;两组DVT发生率为26.6% vs.21.3%（P=0.46）,差异无统计学意义。全组Rogers评分9-18分,其中低危组（7-10分）67例,中高危组（＞10分）85例;低危组与中高危组DVT发生率为25.4% vs.22.1%（p=0.64）,差异无统计学意义。Caprini评分高危组与极高危组之间和Rogers评分低危组与中高危组之间在DVT危险因素吸烟指数、血型构成、合并COPD病史、组织学类型、VATS、手术时间、术后卧床时间、病理学分期的差异均无统计学意义（p＞0.05）;在围术期各时点的凝血指标及NLR（中性-淋巴细胞比值）的差异亦无统计学意义。结论：Caprini血栓风险评估模型评价胸外科肺癌手术患者易评为VTE高风险人群,对预防VTE具有积极的指导意义,但Caprini和Rogers血栓风险评估模型对胸外科肺癌患者围术期VTE风险层级评估的有效性尚不确切,应探索建立符合我国肺癌人群特质的胸外科血栓风险评估量表体系。     

恶性肿瘤抗凝治疗后肝素诱导血小板减少症的诊断与治疗进展

恶性肿瘤患者多伴有凝血机制的异常,如血小板增多、血小板聚集功能亢进等,从而导致血栓发生,是恶性肿瘤最常见的并发症之一。根据发生血栓的流行病学调查显示,恶性肿瘤患者发生静脉血栓栓塞症（VTE）的风险约为非恶性肿瘤患者的4～7倍。目前有关发生恶性肿瘤相关血栓的危险因素包括患者、恶性肿瘤及治疗相关因素,可根据恶性肿瘤相关血栓的生物学标志物及其危险模型进行评估,并对其进行预防及治疗。恶性肿瘤患者发生VTE一般采用肝素或低分子肝素治疗,但经肝素抗凝治疗后又常常发生血小板减少,导致患者的皮肤黏膜广泛出血及器官出血。因此,本文就恶性肿瘤相关血栓发生的原因、抗凝治疗后肝素诱导血小板减少症的临床和实验室诊断及其临床治疗进展作一综述,供血液肿瘤科的临床医师讨论和参考。     

血浆D-二聚体水平与恶性肿瘤患者发生静脉血栓的相关性

目的:观察血浆D-二聚体（D-dimer,D-D）水平对恶性肿瘤患者相关静脉血栓栓塞症（venous thromboembolism,VTE）发生的风险评估效果。方法:回顾性分析2016年1月至2017年1月本院新收住并经病理组织学证实的171例恶性肿瘤患者的临床资料,以初诊3个月内是否发生静脉血栓栓塞症（VTE）分为VTE组（32例）和非VTE组（139例）,比较两组患者、不同临床分期患者、不同治疗方式患者、不同静脉血栓风险分层患者的血浆D-D值水平,采用Logistic多因素回归分析血浆D-D水平对恶性肿瘤患者相关VTE发生的风险评估效果。结果:VTE组的血浆D-D值水平显著高于非VTE组（P＜0.05）,且随着恶性肿瘤临床分期的增加和静脉血栓风险分层的增高,该现象更加显著。Logistic多因素回归分析结果表明,化疗、手术、静脉血栓风险评估和血浆D-D水平是患者发生VTE的独立危险因素（P＜0.05）。结论:恶性肿瘤患者血浆D-D值水平明显升高,且与恶性肿瘤的临床分期和血栓风险分层相关;对恶性肿瘤患者进行血浆D-D值水平的检测,对预防恶性肿瘤患者初诊3个月内VTE的发生具有十分重要的参考意义。     

肺癌围术期患者静脉血栓栓塞症的预防与护理现状调查分析

背景与目的 了解我国医院肺癌围术期患者静脉血栓栓塞症(venous thromboembolism, VTE)的预防与护理现状.方法 采用自行设计的调查问卷,在第一届胸科加速康复外科(enhanced recovery after surgery, ERAS)华西论坛上,对全国108名胸外科护士长进行调查.结果 ①评估工具与预防规范:97.22%的医院已采用不同评估工具对肺癌围术期患者进行VTE风险分级,其中67.59%的医院已形成VTE预防护理规范.②筛查、预防与随访:56.48%的医院对肺癌患者进行了VTE术前筛查,90.74%的医院对住院患者进行了VTE预防,52.78%的医院对出院患者继续进行了VTE预防,仅有17.59%医院对出院患者VTE的发生情况进行了随访.③不同类型医院肺癌围术期患者VTE预防现状相比,差异无统计学意义(P>0.05),但在VTE风险评估、住院患者VTE预防方面专科医院所有患者已全面实现(100.00%).结论 肺癌围术期VTE预防工作已受到广泛重视,但尚缺乏有效的VTE风险评估工具和标准化的VTE预防护理指南.     

肿瘤并发静脉血栓形成196例临床分析

背景与目的：静脉血栓形成(venous thromboembolism,VTE)是恶性肿瘤患者的第二常见死亡原因。通过了解复旦大学附属肿瘤医院5年间收治的患者VTE的发病情况,分析VTE的相关特点,以提高肿瘤合并VTE的诊断和防治意识,改善患者预后。方法：对复旦大学附属肿瘤医院2009年7月-2014年6月收治的196例肿瘤并发VTE的患者的临床资料进行回顾性分析。分析肿瘤并发VTE的临床特点及发病情况,了解相关因素对VTE发病的影响,了解VTE首发情况。结果：复旦大学附属肿瘤医院5年间共收治肿瘤患者207 514例,其中VTE患者196例,肿瘤并发VTE发生率为0.94‰。腺癌在妇科肿瘤(56.5%)、胃肠道肿瘤(91.7%)、肺癌(71.4%)和胰腺癌(80%)中所占比例较高。单变量Logistic回归分析显示,腺癌为肿瘤患者并发肺栓塞(pulmonary embolism,PE)的高危险因素(OR=0.36,95%CI：0.146~0.885,P=0.026)。化疗大于2次者明显比化疗小于等于2次者VTE的发生率更高(χ²=10.976,P=0.001)。手术组VTE发生率高于非手术组。妇科肿瘤中有大量腹水者的非手术患者并发VTE者(>2 000 mL)更多(34.1% vs 10.7%,P=0.015)。术后和放化疗期间78%~88%的患者因出现深静脉血栓(deep vein thrombosis,DVT)症状发现VTE,而术前检查期间主要是在下肢静脉加压超声(compression venous ultrasonography,CUS)检查发现(59.1%)。复旦大学附属肿瘤医院术后进行物理性预防血栓措施者为15例(13.9%)。结论：复旦大学附属肿瘤医院的肿瘤相关性VTE发生率较其他流行病学调查发生率低。肿瘤患者术后并发VTE的风险明显高于非手术者。腺癌更易并发PE。对于临床无VTE症状的肿瘤患者和大量腹水的妇科肿瘤患者应积极进行VTE的相关检查,术后应更积极采取物理抗栓措施。     

Primary prevention and treatment of venous thromboembolic events in patients with gastrointestinal cancers - Review

Venous thromboembolism event (VTE) is a common and morbid complication in cancer patients. Patients with gastrointestinal cancers often suffer from symptomatic or incidental splanchnic vein thrombosis, impaired liver function and/or thrombocytopenia. These characteristics require a thorough risk/benefit evaluation for individual patients. Considering the risk factors for the development of VTE and bleeding events in addition to recent study results may be helpful for correct initiation of primary pharmacological prevention and treatment of cancer-associated thrombosis (CAT), preferably with low molecular weight heparins (LMWH). Whereas thromboprophylaxis is most often recommended in hospitalized surgical and non-surgical patients with malignancy, there is less agreement as to its duration. With regard to ambulatory cancer patients, the lack of robust data results in low grade recommendations against routine use of anticoagulant drugs. Anticoagulation with LMWH for the first months is the evidence-based treatment for acute CAT, but duration of secondary prevention and the drug of choice are unclear. Based on published guidelines and literature, this review will focus on prevention and treatment strategies of VTE in patients with gastrointestinal cancers.     

The NCCN Clinical Practice Guidelines on Venous Thromboembolic Disease: strategies for improving VTE prophylaxis in hospitalized cancer patients

The risk for venous thromboembolism (VTE) is high in hospitalized cancer patients, and is associated with an elevated risk for recurrent thrombosis, bleeding complications, and use of health care resources. Thromboembolism is the second leading cause of death in hospitalized cancer patients. Thromboprophylaxis with unfractionated heparin or low-molecular-weight heparins has been clinically proven to reduce the risk for VTE and improve outcomes. However, VTE prophylaxis continues to be underprescribed in cancer patients. Recognizing the clinical burden of VTE in cancer patients, the National Comprehensive Cancer Network (NCCN) recently released guidelines for VTE prevention and management. These NCCN guidelines recommend evidence-based prophylactic anticoagulant therapy for all patients admitted to hospital with a diagnosis of cancer who do not have contraindications to anticoagulant use. However, there continue to be barriers to the implementation of clinical practice guidelines and appropriate use of VTE prophylaxis. Multifaceted active educational and electronic interventions are necessary to raise awareness and reduce the burden of cancer-associated thrombosis and its attendant consequences.     

Treatment of cancer-associated venous thromboembolism in the age of direct oral anticoagulants

Anticoagulation for cancer-associated venous thromboembolism (VTE) can be challenging due to complications—including bleeding and potential drug–drug interactions with chemotherapy—associated with vitamin K antagonists and inconvenience of low-molecular-weight heparin (LMWH). Direct oral anticoagulants (DOACs) could partially overcome these issues, but until recently there were no large clinical trials assessing their efficacy and safety in cancer patients. This review summarizes clinical treatment guidelines, prior clinical and real-world evidence for anticoagulant choice, recent clinical trials assessing DOACs for cancer-associated VTE (i.e. Hokusai-VTE Cancer, SELECT-D, CARAVAGGIO, and ADAM VTE), and special considerations for DOAC use. Based on established data, clinical guidelines recommend patients with cancer-associated VTE receive LMWH treatment of at least 3–6 months. Nevertheless, LMWH is underused and associated with poor compliance and persistence in these patients relative to oral anticoagulants. Clinical data supporting DOAC use in cancer patients are becoming available. In Hokusai-VTE Cancer, edoxaban was noninferior to dalteparin for the composite of recurrent VTE and major bleeding (12.8% versus 13.5%), with numerically lower recurrent VTE (7.9% versus 11.3%) and significantly higher major bleeding (6.9% versus 4.0%); only patients with gastrointestinal cancer had significantly higher risk of bleeding with edoxaban. In SELECT-D, rivaroxaban had numerically lower VTE recurrence (4% versus 11%), comparable major bleeding (6% versus 4%), and numerically higher clinically relevant nonmajor bleeding (13% versus 4%) versus dalteparin. Most bleeding events were gastrointestinal or urologic; patients with esophageal/gastroesophageal cancer had higher rates of major bleeding with rivaroxaban (36% versus 11%). For comparison of apixaban versus dalteparin, CARAVAGGIO is ongoing, and preliminary results from ADAM VTE are favorable. This review concludes that DOACs appear to be reasonable alternatives to LMWH for treatment of cancer-associated VTE. In patients with gastrointestinal cancer, DOAC use should be considered on a case-by-case basis with consideration of the relative risks and benefits.     

Cancer and thrombosis: managing the risks and approaches to thromboprophylaxis

Patients with cancer are at increased risk of venous thromboembolism (VTE) compared with patients without cancer. This results from both the prothrombotic effects of the cancer itself and iatrogenic factors, such as chemotherapy, radiotherapy, indwelling central venous devices and surgery, that further increase the risk of VTE. Although cancer-associated thrombosis remains an important cause of morbidity and mortality, it is often underdiagnosed and undertreated. However, evidence is accumulating to support the use of low-molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients with cancer. Not only have LMWHs been shown to be at least as effective as coumarin derivatives in this setting, but they have a lower incidence of complications, including bleeding, and are not associated with the practical problems of warfarin therapy. Furthermore, a growing number of studies indicate that LMWHs may improve survival among patients with cancer due to a possible antitumor effect. Current evidence suggests that LMWHs should increasingly be considered for the longterm management of VTE in patients with cancer.     

Les biomarqueurs de la maladie thromboembolique veineuse chez le patient atteint de cancer

Today, the thrombosis associated with cancer is clearly established. The risk of venous thromboembolism (VTE) in cancer is dependent on clinical parameters of cancer patients and the type of tumor. Thus, the relationship between VTE and the type of cancer is complex, caused by the tumor progression, the inflammatory state, and the hemostasis. Several biomarkers had been identified to detect VTE in cancer patients. This review summarizes usual biomarkers, assessed regularly in laboratory and included in risk assessment score, and discusses new biomarkers for prediction of VTE.     

恶性肿瘤合并静脉血栓栓塞症1例诊治分析

静脉血栓栓塞症（VTE）在肿瘤患者中的发病率是非肿瘤患者的6~7倍，并且是肿瘤患者第二常见的致死原因，同时其发病率呈逐年上升趋势。因此，肿瘤患者合并VTE的早期诊断、早期治疗尤为重要。现介绍1例天津医科大学肿瘤医院介入治疗肿瘤科收治的胰腺癌合并下肢深静脉血栓形成患者的诊治经验及多学科讨论，以提高临床工作中对肿瘤患者合并VTE的重视，并注重多学科间的协作治疗。