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。     

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。      

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。      

肿瘤与静脉血栓栓塞症

 肿瘤患者有较高的静脉血栓发生率。研究发现,静脉血栓栓塞症（VTE）可增加肿瘤患者的死亡风险。VTE的发生机制与组织因子（TF）及癌促凝物质（CP）等因素密切相关。患者相关性因素、肿瘤相关性因素及治疗相关性因素均可导致患者VTE发生率增加。应重视对患者危险因素进行评估,对高危患者及早进行预防性抗凝治疗,在诊断VTE后应立即进行急性期治疗及慢性期维持治疗。     

肿瘤患者VTE风险评估模型的研究进展

静脉血栓栓塞（venous thromboembolism,VTE）已经成为肿瘤患者最常见的并发症,且成为除肿瘤患者外第二大死因。肿瘤本身是一种存在血栓和出血双风险并存的状态,对患者能够进行有效风险评估筛查的模型显得尤为关键。只有能在对肿瘤患者进行精准的风险分层,低风险患者能够不进行血栓预防或仅进行机械预防降低治疗成本和出血风险,高风险患者预防血栓中获益。本文对目前肿瘤并发相关VTE的情况、当前VTE风险评估模型的对比、风险模型的建立及未来发展方向进行探讨,旨在提高对相关VTE风险评估模型的的认识,并对风险模型的建立和发展提出理论支持。      

肺癌静脉血栓栓塞的危险因素及生物标志物的研究进展

癌症是引起静脉血栓栓塞(venous thromboembolism,VTE)的重要危险因素,而VTE是引起肿瘤患者死亡的重要原因。肺癌患者VTE的发生率在不同的研究中结果有所差别,发生率从7%~13%不等,其中还包括大量可疑肺栓塞病例。肺癌患者VTE发生的危险因素可以分为三类:患者自身特征、肿瘤相关因素以及治疗相关的因素。此外,许多生物标志物也被发现可以作为VTE发生的危险因素(例如D-二聚体)。了解肺癌VTE发生的危险因素对于预防血栓并发症的发生、改善肺癌患者的治疗方面具有重要的意义。本文就VTE危险因素及生物标志物进行综述。     

恶性肿瘤与静脉血栓形成关系的研究进展

恶性肿瘤与静脉血栓栓塞（venous thromboembolism，VTE）关系密切。恶性肿瘤患者发生VTE，不仅增加治疗难度，而且降低患者生存质量及减少生存预期，因此越来越受到，临床医生重视，成为近期肿瘤研究的热点问题之一。肿瘤细胞可以直接分泌癌促凝物质，或通过激活单核细胞和巨噬细胞释放细胞因子。这些蛋白质因子诱导凝血反应，增加发生VTE的风险。某些特定类型的肿瘤，如原发性脑肿瘤、胰腺癌、卵巢癌、乳腺癌、结直肠癌及非小细胞肺癌发生VTE的风险较高。此外，多种原因所致静脉血液淤滞、抗肿瘤药物及孕激素类药物治疗也是VTE发生的危险因素。通过详细的病史询问、体格检查及相关实验室检查可以诊断大部分自发性VTE患者的隐匿性恶性肿瘤。进一步的检查手段能否增加患者生存受益，有待于进一步的临床试验研究。肿瘤患者外科术前予普通肝素、低分子量肝素（low molecular weighthepann，LMWH）及戊聚糖预防治疗可以有效降低发生VTE的风险，且三类药物具有相似效果。此类患者术后继续行LMWH抗凝治疗亦可以减少VTE的发病率。低剂量抗凝治疗并未降低行中心静脉插管的肿瘤患者发生导管相关血栓形成（catheter—related thrombosis，CRT）的风险。对肿瘤内科患者行抗凝预防治疗的必要性及有效性尚未明确。要制定预防血栓形成的最佳策略，仍有待于临床继续深入研究。     

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。     

国内肿瘤患者的营养风险及营养不良研究现状分析

我国关于肿瘤患者营养风险及营养不良的研究逐年增多,肿瘤患者营养风险及营养不良的研究在国内外已经引 起越来越多的重视。研究显示,我国肿瘤患者营养风险和营养不良的发生率极高,患病率可高达 40%~80%,晚期恶性肿瘤 患者的营养不良和营养风险发生率则更高。营养风险和营养不良的发生严重影响肿瘤患者的预后,降低患者对手术、放疗 和化疗的耐受性和敏感性,降低患者的生活质量,减少生存时间。合理的营养治疗可以缩短住院时间,降低并发症发生 率和住院费用,改善患者生活质量,降低总死亡率,同时增加患者总生存期。由此看出,肿瘤患者的临床营养治疗日 趋重要,对恶性肿瘤患者采取积极有效的早期干预治疗具有重要意义。因此,本文总结了近年来国内肿瘤患者临床营 养研究的进展,就国内关于肿瘤患者的临床营养研究现状进行综述,提出了肿瘤营养治疗和营养研究的新思路,即在恶性 肿瘤发生、发展中尽早使用合适的营养筛查工具如营养风险筛查量表、主观全面评定量表对患者进行营养筛查及营养评估, 在有营养风险和营养不良的患者中给予合理、有效的营养治疗,这对于改善患者生活质量及疾病转归具有积极的临床价值。     

乳腺癌术后静脉血栓栓塞的发生及预防

静脉血栓栓塞（venous thromboembolism,VTE）包括深静脉血栓形成（deep venous thrombosis,DVT）和肺栓塞（pulmonary embolism,PE）,是肿瘤患者的常见并发症和死亡原因。癌症患者VTE的年发生率约为0．48％,是普通人群的4倍。这一方面可能与肿瘤导致的血液高凝状态有关,另一方面则与患者接受的治疗（包括手术、化疗、激素治疗、放射治疗及留置中心静脉导管）有关。     

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.     

Estimated Glomerular Filtration Rate Is an Easy Predictor of Venous Thromboembolism in Cancer Patients Undergoing Platinum‐Based Chemotherapy

Background.

Reduced estimated glomerular filtration rate (eGFR) has been associated with increased venous thromboembolism (VTE) risk in the general population. VTE incidence significantly increases in cancer patients, especially those undergoing chemotherapy. Despite the evidence that a substantial number of cancer patients have unrecognized renal impairment, as indicated by reduced eGFR in the presence of serum creatinine levels within the reference value, chemotherapy dosage is routinely adjusted for serum creatinine values. Among chemotherapies, platinum-based regimens are associated with the highest rates of VTE. A cohort study was designed to assess the value of pretreatment eGFR in the risk prediction of a first VTE episode in cancer outpatients without previous history of VTE who were scheduled for platinum-based chemotherapy.

Methods.

Serum creatinine and eGFR were evaluated before the start of standard platinum-based chemotherapy in a cohort of 322 consecutive patients with primary or relapsing/recurrent solid cancers, representative of a general practice population.

Results.

Patients who experienced a first VTE episode in the course of chemotherapy had lower mean eGFR values compared with patients who remained VTE free. Multivariate Cox analysis demonstrated that eGFR had an independent value for risk prediction of a first VTE episode during treatment, with a 3.15 hazard ratio. Indeed, 14% of patients with reduced eGFR had VTE over 1-year follow-up compared with 6% of patients with normal eGFR values.

Conclusion.

The results suggest that reductions in eGFR, even in the presence of normal serum creatinine, are associated with an increased VTE risk in cancer outpatients undergoing platinum-based chemotherapy regimens. Determining eGFR before chemotherapy could represent a simple predictor of VTE, at no additional cost to health care systems.     

Association Between Decreased Serum Albumin With Risk of Venous Thromboembolism and Mortality in Cancer Patients

Background.

In cancer patients, reduced serum albumin has been described as a marker for global declining health and poor prognosis. Our aim was to investigate the association of albumin concentrations with the occurrence of venous thromboembolism (VTE) and mortality in patients with cancer.

Methods.

This investigation was performed in the framework of the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study. We included 1,070 patients with active cancer and assayed serum albumin from venous blood taken at study inclusion. Risk for occurrence of VTE was calculated in a proportional subdistribution hazard regression model with respect to competing risk of death and adjusted for cancer site, leukocyte count, estimated glomerular filtration rate, and cholinesterase.

Results.

Patients (630 males [58.9%] and 440 females [41.1%]) were observed for a median of 723 days. During follow-up, 90 VTE events (8.4%) and 396 deaths (37.0%) occurred. The median albumin was 41.3 g/L (25th–75th percentile, 37.6–44.2). Patients with albumin levels below the 75th percentile had a 2.2-fold increased risk of VTE (95% confidence interval [CI] 1.09–4.32), as well as a 2.3-fold increased risk of death (95% CI 1.68–3.20) compared with patients with albumin above the 75th percentile.

Conclusion.

Decreased serum albumin levels in cancer patients were significantly associated with increased risk of VTE and mortality. Serum albumin, a marker of a cancer patient’s overall prognosis, could be considered for risk assessment of important clinical outcomes such as VTE and mortality.

Implications for Practice:

Cancer patients are at increased risk of venous thromboembolism (VTE). In this prospective cohort study of 1,070 cancer patients, decreased serum albumin was a marker for risk of VTE and mortality, independent of kidney or liver function and inflammation markers. The study identified a group of patients with high risk of cancer-associated VTE and a reduced prognosis who may benefit from supportive therapy such as primary VTE prophylaxis.     

Prediction and Prevention of Cancer‐Associated Thromboembolism

Venous and arterial thromboembolism are prevalent, highly burdensome, and associated with risk of worse outcomes for patients with cancer. Risk for venous thromboembolism (VTE) varies widely across specific cancer subpopulations. The ability to predict risk of cancer‐associated VTE is critical because an optimal thromboprophylaxis strategy is best achieved by targeting high‐risk patients with cancer and avoiding prophylaxis in patients with cancer at low risk for VTE. A validated risk tool for solid tumors has been available for a decade. Newer tools have focused on specific populations, such as patients with multiple myeloma. Emerging studies continue to optimize risk prediction approaches in patients with cancer. Recent randomized trials have specifically addressed risk‐adapted thromboprophylaxis using direct oral anticoagulants, and revised guidelines have included these new data to formulate recommendations for outpatient thromboprophylaxis. Implementation science approaches to enhance use of outpatient prophylaxis in the context of these guideline changes are under way. However, major knowledge gaps remain, including a lack of data for inpatient thromboprophylaxis in the cancer setting and a lack of formal tools for identifying risk of bleeding. This review describes optimal approaches to risk prediction and patient selection for primary pharmacologic thromboprophylaxis of cancer‐associated VTE, addresses barriers to implementing these practices, and highlights strategies to overcome them.Implications for PracticeRisk for venous thromboembolism (VTE) varies widely among patients with cancer. Individual risk can be determined using validated approaches. Inpatient and postsurgical thromboprophylaxis is more widely accepted. However, most patients with cancer develop VTE in the outpatient setting. Recent randomized trials have demonstrated benefit to risk‐adapted outpatient thromboprophylaxis. High‐risk patients may therefore be considered for outpatient thromboprophylaxis as recommended by recently updated guidelines. System‐wide implementation approaches are necessary to improve compliance with prophylaxis.     

恶性肿瘤合并静脉血栓栓塞症患者的临床特点分析CSCD

目的分析恶性肿瘤合并静脉血栓栓塞症(VTE)患者的临床特点并探寻相关危险因素。方法采用回顾性病例对照研究,调查恶性肿瘤合并VTE患者的临床及生存结局信息。采用卡方检验、Log rank检验和比例风险回归模型(Cox模型)等方法进行统计分析,采用GraphPad Prism8.0绘制生存曲线,分析VTE相关影响因素。结果5年间共收治新发恶性肿瘤患者11620例,其中合并VTE患者385例(3.31%)。恶性淋巴瘤患者合并VTE的比例最大,达到4.78%,其次是结直肠癌和乳腺癌,分别为4.40%和4.08%;联合治疗的患者比单一治疗方式发生VTE的比例高;分期越晚的患者合并VTE的比例越高;随访结果显示合并VTE患者中位生存时间为17.90月(95%CI:10.21~25.59),1、3、5年生存率分别为51.89%、37.76%、18.88%;多因素分析结果显示年龄、性别、TNM分期是影响VTE患者预后的独立危险因素。结论恶性肿瘤患者容易并发VTE,临床上应对高危患者密切观察、提早预防。     

肺癌术后并发静脉血栓栓塞症的临床分析

目的:分析肺癌术后发生静脉血栓栓塞(venous thromboembolism,VTE)的高危因素及其预后.方法:对1001例有完整临床随访资料的肺癌手术患者进行回顾性分析.应用螺旋CT、肺动脉造影和彩色多普勒超声诊断VTE.寿命表法绘制血栓发生曲线,COX多因素分析VTE高危因素.Kaplan-Meier法及log-rank检验绘制并比较高危因素血栓发生曲线及生存曲线.结果:术后1、3、5、11和30个月的VTE累积发生率分别为2.0％、3.0％、4.0％、5.0％和5.3％.COX多因素回归分析显示,接受不完全切除术患者发生VTE的风险比(hazard ratio,HR)为9.867(95％可信区间为5.275～18.459),P=0.000;术后接受化疗联合重组人血管内皮抑制素治疗患者的HR为3.472 (95％可信区间为1.761～6.845),P=0.000;术后接受表皮生长因子受体酪氨酸激酶抑制剂治疗患者的HR为2.808 (95％可信区间为1.439～5.479),P=0.002;术前基线血浆D-二聚体水平升高者的HR为7.520(95％可信区间为3.968～14.250),P=0.000.肺癌术后伴VTE患者的生存时间明显短于无VTE的患者(P=0.000).结论:不完全切除术、术后化疗联合重组人血管内皮抑制素治疗、表皮生长因子受体酪氨酸激酶抑制剂治疗和术前基线血浆D-二聚体水平升高是肺癌手术患者术后并发VTE的高危因素.肺癌术后伴VTE患者的生存时间明显短于无VTE的患者.     

A Predictive Score for Thrombosis Associated with Breast,Colorectal, Lung,or Ovarian Cancer: The Prospective COMPASS–Cancer‐Associated Thrombosis Study

Background

The stratification of outpatients on chemotherapy for breast, colorectal, lung, and ovarian cancers at risk of venous thromboembolism (VTE) remains an unmet clinical need. The derivation of a risk assessment model (RAM) for VTE in these patients was the aim of the study “Prospective Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients–Cancer Associated Thrombosis” (COMPASS–CAT).

Patients and Methods

The derivation cohort consisted of 1,023 outpatients. Patients on low molecular weight heparin (LMWH) thromboprophylaxis were excluded. Documented symptomatic VTE was the endpoint of the study.

Results

Patients had breast (61%), colorectal (17%), lung (13%), or ovarian cancer (8.6%) at localized (30%) or advanced stage (70%). In 64% of patients, cancer was diagnosed within the last 6 months prior to inclusion. Most of them were on chemotherapy when assessed. Symptomatic VTE occurred in 8.5% of patients. The COMPASS–CAT RAM includes the following variables: (a) anthracycline or anti‐hormonal therapy, (b) time since cancer diagnosis, (c) central venous catheter, (d) stage of cancer, (e) presence of cardiovascular risk factors, (f) recent hospitalization for acute medical illness, (g) personal history of VTE, and (h) platelet count. At 6 months, patients stratified at low/intermediate and high‐risk groups had VTE rates of 1.7% and 13.3%, respectively. The area under the curve of receiver operating characteristics analysis was 0.85. The sensitivity and specificity of the RAM were 88% and 52%, respectively. The negative and positive predictive values of the RAM were 98% and 13%, respectively.

Conclusion

The COMPASS–CAT RAM includes reliable and easily collected VTE risk predictors and, in contrast to the Khorana score, it is applicable after the initiation of anticancer treatment in patients with common solid tumors. Its robustness for stratification of patients at high and low/intermediate VTE risk needs to be externally validated.

Implications for Practice

The Prospective Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients–Cancer Associated Thrombosis (COMPASS–CAT) study provides a new risk assessment model (RAM) for venous thromboembolism (VTE) applicable in outpatients with breast, colorectal, lung or ovarian cancer. The COMPASS–CAT RAM is robust, applicable during chemotherapy and determines the need for VTE prévention by including reliable and easily collected VTE predictors associated with cancer status, its treatment as well as with patients' characteristics and comorbidities. An independent external validation of the RAM is indicated before its use in clinical practice.     

Thromboprophylaxis with low‐molecular‐weight heparin in medical patients with cancer

Venous thromboembolism (VTE) is a frequent complication of cancer and cancer treatment and is associated with multiple clinical consequences, including recurrent VTE, bleeding, and an increase in the risk of death. Although the risks associated with VTE have been well recognized in surgical cancer patients, there is also considerable and increasing risk in medical cancer patients. VTE risk factors in medical cancer patients include the type and stage of cancer, major comorbid illnesses, current hospitalization, active chemotherapy, hormone therapy, and antiangiogenic agents. Low‐molecular‐weight heparins (LMWHs) are recommended commonly for the prevention of VTE in hospitalized cancer patients and in higher risk ambulatory cancer patients because of their favorable risk‐to‐benefit profile. These agents have demonstrated effectiveness in both the primary and secondary prevention of VTE in medical cancer patients. Extended‐duration anticoagulant therapy is often recommended to reduce the risk of VTE recurrence in patients with cancer. LMWHs are often used for long‐term prophylaxis because of a reduced need for coagulation monitoring, few major bleeding episodes, and once‐daily dosing. Despite clinical and practical benefits, a substantial proportion of medical cancer patients do not receive VTE prophylaxis. To improve the appropriate prevention and treatment of VTE in cancer patients, guidelines have been published recently by the American Society of Clinical Oncology and the National Comprehensive Cancer Network. Widespread dissemination and application of these guidelines are encouraged to improve the appropriate use of these agents and to improve clinical outcomes in medical cancer patients at risk for VTE and its complications. Cancer 2009. © 2009 American Cancer Society.