肿瘤患者同型半胱氨酸与静脉血栓及凝血功能的相关性研究

目的:研究血浆同型半胱氨酸(Hcy)水平与肿瘤患者静脉血栓(VTE)及凝血功能的相关性,同时探讨肿瘤患者发生静脉血栓的相关危险因素,为临床治疗提供参考。方法:检测182例发生VTE的肿瘤患者和200名普通肿瘤患者及200名健康体检者（对照组）血浆Hcy、D-二聚体(D-Dimer,D-D)、纤维蛋白原(FIB)、凝血因子VIII(FVIII)、组织纤维溶酶原激活物(t-PA)等指标。结果:VTE患者Hcy、D-D、FVIII、FIB及t-PA检测水平均高于普通肿瘤患者及健康体检者（P＜0.05）;而普通肿瘤患者组D-D、FIB水平高于健康体检者（P＜0.05）;Hcy、D-D检测VTE的ROC曲线下面积分别为0.72（95%CI:0.68~0.79）和0.77（95%CI:0.72~0.83）;VTE肿瘤患者组中,Hcy、D-D血液含量存在明显的相关性（P=0.003 3,r=0.622）;高Hcy水平、D-D高水平以及t-PA血浆含量高是肿瘤患者发生VTE的危险因素。结论:Hcy水平能有效反映治疗患者的凝血状态,监测Hcy及D-D水平可以提高VTE的诊断效率,对肿瘤患者的预后有重要的临床参考价值。     

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。     

99例晚期恶性肿瘤患者静脉血栓栓塞症的诊治情况分析

目的:了解晚期恶性肿瘤患者合并静脉血栓栓塞症（venous thromboembolism,VTE)的诊治及预防情况,加强肿瘤相关性VTE的认知,提高患者生活质量及改善预后。方法:收集2012年1月至2016年10月住院确诊为VTE的肿瘤患者（VTE组）的病历资料,与同时期入院的非VTE的肿瘤患者对照（对照组）,对两组资料进行Logistic回归分析,寻找可能的VTE高危因素。结果:VTE组及对照组各99例患者。VTE组中,年龄>60岁64例,ZPS评分>2分57例,IV期65例;以彩超确诊者84例,以CT诊断者15例;发生在下肢深静脉者71例。VTE组:49例应用低分子肝素抗凝,出院后应用华法林后续治疗10例,大多数VTE组患者未应用预防性抗凝。在多因素Logistic回归分析中,血红蛋白下降、凝血酶时间延长以及中心静脉置管的应用在统计学上存在显著的差异。结论:恶性肿瘤合并VTE多发生在60岁以上、IV期和活动不良的患者,其后续抗凝治疗不足,临床上缺乏主动预防的措施及意识。     

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。      

恶性肿瘤相关静脉血栓栓塞症的研究进展

静脉血栓栓塞症（VTE）是恶性肿瘤的常见并发症之一,发生率为4％～20％,也是导致肿瘤患者死亡的主要原因之一。住院和接受积极治疗的肿瘤患者是VTE的高发人群。VTE将增加肿瘤患者的致残率和致死率,影响抗肿瘤的疗效,加重医疗资源及患者的负担。国际上采用风险预测模型可以有效评估VTE的风险因素,以便有针对性地实施预防性抗凝治疗策略。近年来越来越多的临床研究显示,在肿瘤患者中积极防治VET有较多的益处。     

恶性肿瘤与静脉血栓形成若干研究进展

静脉血栓栓塞症（VTE）在恶性肿瘤患者的发生率显著高于一般人群，已日益受到肿瘤临床各科的广泛关注。恶性肿瘤患者易并发VTE，溶栓后易复发，根据恶性肿瘤并发VTE的特点进行抗凝和溶栓治疗，手术和化疗中常规预防VTE非常重要。本文简要介绍恶性肿瘤患者中VTE的发生情况、危险因素、病理机制、诊断及辅助检查的若干进展，为临床治疗和预防提供依据和参考。     

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。     

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。      

宫颈癌合并深静脉血栓30例临床分析

目的：静脉血栓栓塞症（VTE）是恶性肿瘤患者常见并发症。本文结合文献分析我院住院病人宫颈癌患者静脉血栓的临床特征,分析VTE形成机制及诱发因素,探索最佳治疗方法。方法：对近5年我科收治的宫颈癌合并深静脉血栓30例患者的临床资料进行分析。结果：30例患者中17例VTE的发生和介入手术化疗有关。2例（6.7%）血栓栓塞发生在宫颈癌确诊之前,28例（93.3%）发生在宫颈癌确诊之后,单纯并发下肢深静脉血栓形成（DVT）27例,合并肺栓塞（PTE）2例,DVT合并PTE 1例。22例在栓塞前有化疗史。结论：血栓可能为肿瘤病人的首发表现,病人出现不能解释的血栓栓塞性疾病应考虑有肿瘤的可能。抗凝治疗对于血栓栓塞症疗效确切。及时诊断和治疗可以延长患者的生存期,降低患者的死亡率。口服避孕药、口服甲地孕酮、介入手术与VTE的发生几率可能有关。分期晚,远地转移的肿瘤患者易出现血栓栓塞。     

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。     

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。     

Anticoagulation therapy for prevention and treatment of venous thromboembolic events in cancer patients: A review of current guidelines

Cancer patients in general have a high risk of venous thromboembolic events (VTE) driven not only by patient-related risk factors, but also risk factors related to the disease and anti-cancer therapies. Cancer patients with documented VTE have a notably worse outcome than non-cancer VTE patients. Since VTE is a highly preventable condition, it is striking that large surveys have shown significant underuse of VTE prophylaxis in surgical cancer patients and in medical cancer patients in particular. Recently, guidelines have been issued from European and American medical oncology societies and organizations for identification of cancer patients at risk, and the guidelines give recommendations for treatment of individual groups of cancer patients.     

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。     

Risk assessment and prophylaxis for VTE in cancer patients

The frequency of venous thromboembolism (VTE) is rising in patients with cancer. VTE contributes to mortality and morbidity, but the risk for VTE can vary widely between individual patients. Clinical risk factors for VTE in cancer include primary site of cancer, use of systemic therapy, surgery, and hospitalization. Biomarkers predictive of VTE include platelet and leukocyte counts, hemoglobin, D-dimer, and tissue factor. A recently validated risk model incorporates 5 easily available variables and can be used clinically to identify patients at increased risk of VTE. In high-risk settings, including surgery and hospitalization, thromboprophylaxis with either unfractionated heparin or low-molecular-weight heparins has been shown to be safe and effective. Recent studies have also suggested a potential benefit for thromboprophylaxis in the ambulatory setting, although criteria for selecting patients for prophylaxis are not currently well defined. This article focuses on recent and ongoing studies of risk assessment and prophylaxis in patients with cancer.     

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors

Venous thromboembolism (VTE) often occurs after surgery and can even occur before surgery in patients with gynaecological malignancies. We investigated the incidence of VTE before treatment of endometrial cancer and associated risk factors. Plasma D-dimer (DD) levels before initial treatment were examined in 171 consecutive patients with endometrial cancer. Venous ultrasound imaging (VUI) of the lower extremities was performed in patients with DD >or=1.5 microg ml(-1), as the negative predictive value of DD for VTE is extremely high. For patients with deep vein thrombosis (DVT), pulmonary scintigraphy was performed to ascertain the presence of pulmonary thromboembolism (PTE). Risk factors for VTE were analysed using univariate and multivariate analyses for 171 patients. Of these, 37 patients (21.6%) showed DD >or=1.5 microg ml(-1), 17 (9.9%) displayed DVT by VUI and 8 (4.7%) showed PTE on pulmonary scintigraphy. All patients with VTE were asymptomatic. Univariate analysis for various risk factors revealed older age, non-endometrioid histology and several variables of advanced disease as significantly associated with VTE before treatment. Obesity, smoking and diabetes mellitus were not risk factors. Multivariate analysis confirmed extrauterine spread and non-endometrioid histology as independently and significantly associated with risk of VTE. These data suggest that silent or subclinical VTE occurs before treatment in at least around 10% of patients with endometrial cancer. Risk factors for VTE before treatment might not be identical to those after starting treatment.     

原发性肝癌术后发生静脉血栓栓塞症的危险因素及Caprini风险预测模型的应用

目的:研究原发性肝癌术后发生静脉血栓栓塞症（venous thromboembolism,VTE）的危险因素,并验证和改良Caprini模型对肝癌术后患者VTE发生的预测能力。方法:对我院收治的452例肝癌患者进行回顾性分析,根据术后1月内是否发生VTE而分为VTE组和非VTE组。采用多因素Logistic回归以用来筛选VTE发生的独立危险因素。采用受试者操作特征曲线（receiver operating characteristic,ROC）和曲线下面积（area under ROC curve,AUC）来描述和比较传统Caprini模型和改良Caprini模型对VTE发生预测的准确性。结果:共有41例原发性肝癌患者术后出现VTE,整体发生率为9.07%。单因素分析示BMI、糖尿病患病率、门静脉癌栓发生率、手术时间、二次手术率、以及Caprini评分可能与VTE的发生有关。多因素分析示BMI（OR=1.14,P=0.01）、手术时间（OR=10.91,P=0.001）、有门静脉癌栓（OR=4.98,P=0.001）、二次手术（OR=7.85,P=0.01）和Caprini评分（OR=2.63,P=0.001）是VTE发生的独立危险因素。改良后的Caprini模型和一般Caprini模型在预测VTE时的AUC分别为0.912和0.811;当取最大约登指数时,二者敏感度分别为85.37%和63.41%,特异度分别为85.64%和87.59%。结论:BMI、手术时间、门静脉癌栓、二次手术是原发性肝癌患者术后VTE发生的独立影响因素,联合上述四种指标可以显著提高Caprini模型对VTE的预测能力。     

Frequency, clinical pattern and outcome of thrombosis in cancer patients in Saudi Arabia

Objectives: Thrombotic risk is increased in patients with cancer and there are important implications forthose who suffer a venous thromboembolism (VTE). We undertook this study to determine the frequency, clinicalpatterns, and outcome of VTE in Saudi patients with cancer. Methods: Cancer (solid tumors and lymphoma)patients who developed VTE from January 2004 to January 2009 were studied retrospectively. Demographicsand clinical characteristics related to thrombosis and cancer were evaluated. Results: A total of 701 patientswith cancer were seen during the study period. VTE was diagnosed in 47 (6.7%) patients (median age 52, range18-80 years). Lower limb DVT was the most common type, seen in 47% patients, followed by PE in 19%, and19% patients had both DVT & PE. Thrombosis was symptomatic in 72% patients while it was an incidentalfinding on routine workup in 28% . Cancer and VTE were diagnosed at the same time in 38% of patients, and47% patients developed VTE during the course of disease after the cancer diagnosis. The majority of VTE postcancer diagnoses occurred during the first year (median 4 months, range 1-14). Additional risk factors for VTEwere present in 22 (47%) patients and 14 (30%) of these patients were receiving chemotherapy at the time ofthrombosis. Only 5 (10.6%) patients were receiving thrombo-prophylaxis at the time of VTE diagnosis. Mostcommon types of tumors associated with thrombosis were breast cancer, non-Hodgkin’s lymphoma and lungcancer. The majority of the affected patients (79%) had advanced stage of cancer. After a median follow-up of13 (range 0.5-60) months, 38 (81%) patients had died. There was no difference in the mortality of patients withsymptomatic or asymptomatic thrombosis (82% vs 78.6%). Conclusions: Thrombotic complications can developin a significant number of patients with cancer, and almost half of the patients have additional risk factors forVTE. Thrombosis is usually associated with advanced disease and can be asymptomatic in more than a quarterof cases. Thromboprophylaxis in cancer patients is under-utilized. Community based studies are needed toaccurately define the extent of this problem and to develop effective prophylactic strategies.     

Thrombosis and cancer

Venous thromboembolism (VTE) is a potentially life-threatening condition that can be associated with significant morbidity. Thrombosis and cancer are linked by numerous pathophysiological mechanisms; the frequency of VTE and the recurrence rate are increased in the cancer population in comparison with other patient groups. VTE is the second most common cause of death in patients with cancer, but can also be the initial presenting complaint in patients with an occult malignancy. Risk factors for cancer-related VTE include tumour type, surgery, chemotherapy and the use of central venous catheters; predictors of VTE for individuals are only now beginning to emerge. Patients with cancer who develop symptomatic VTE during chemotherapy are at a greater risk of early mortality than those without VTE. The apparent impact of VTE on early mortality in patients with cancer raises the question of whether anticoagulation might improve long-term survival in this population, by direct tumour biology-modifying mechanisms. There are widely published guidelines that highlight the benefits of effective VTE strategies in patients with cancer. In partnership with the patient and their carers, the clinical team can improve patient outcomes with optimal risk assessment and concordance with national and international guidelines in the prophylaxis and treatment of VTE.     

Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with cancer. The risk of VTE varies over the natural history of cancer, with the highest risk occurring during hospitalization and after disease recurrence. Patient and disease characteristics are associated with further increased risk of VTE in this setting. Specific factors include cancer type (eg, pancreatic cancer, brain cancer, lymphoma) and the presence of metastatic disease at the time of diagnosis. VTE is a significant predictor of increased mortality during the first year among all types and stages of cancer, with metastatic disease reported to be the strongest predictor of mortality. VTE is also associated with early death in ambulatory patients with cancer. These data highlight the need for close monitoring, prompt treatment, and appropriate preventive strategies for VTE in patients with cancer. The American Society of Clinical Oncology and the National Comprehensive Cancer Network have issued guidelines regarding the prophylaxis and treatment of patients with cancer. This review summarizes the impact of VTE on patients with cancer, the effects of VTE on clinical outcomes, the importance of thromboprophylaxis in this population, relevant ongoing clinical trials examining the prevention of VTE, and new pharmacologic treatment options.     

Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study

BACKGROUND: The incidence of venous thromboembolism (VTE) is increased in cancer, but little information is available about risk factors in cancer patients on chemotherapy. METHODS: We analyzed data from a prospective, multicenter observational study to determine the frequency and risk factors for VTE in ambulatory cancer patients initiating a new chemotherapy regimen. The association of VTE with clinical variables was characterized using univariate and multivariate analysis. RESULTS: Among 3003 patients treated with at least one cycle of chemotherapy, VTE occurred in 58 (1.93%) over a median follow-up of 2.4 months (0.8%/mo). The incidence varied significantly by site of cancer (P = 0.01) with highest rates in upper gastrointestinal (2.3%/mo) and lung cancer (1.2%/mo), and lymphoma (1.1%/mo). An elevated prechemotherapy platelet count was significantly associated with an increased rate of VTE (P for trend = 0.005). The incidence of VTE was 3.98% (1.66%/mo) for patients with a prechemotherapy platelet count > or = 350,000, compared with 1.25% (0.52%/mo) for patients with platelet counts of < 200,000 (P for trend=0.0003). In multivariate analysis, a prechemotherapy platelet count of > or = 350,000/mm(3) (adjusted OR 2.81, 95% CI 1.63-4.93, P = 0.0002), site of cancer, hemoglobin < 10 g/dL or use of erythropoietin, and use of white cell growth factors in high-risk sites of cancer were significantly associated with VTE. CONCLUSIONS: Symptomatic VTE is a frequent complication of chemotherapy. The prechemotherapy platelet count is a unique risk factor and can help identify high-risk patients for future trials of thromboprophylaxis.