恶性肿瘤与静脉血栓栓塞的研究进展

静脉血栓栓塞（VTE）是恶性肿瘤患者常见并发症,是仅次于肿瘤本身引起患者死亡的第二位原因。血栓有时可作为隐匿性癌的初始表现。血栓形成参与了肿瘤的进展、血管生成和转移等机制。恶性肿瘤患者合并血栓栓塞不仅增加治疗难度,而且降低患者的生存质量并缩短生存时间。抗凝治疗不仅能有效的治疗血栓,而且具有一定的抗肿瘤作用。低分子肝素（LMWH）作为预防和治疗静脉血栓栓塞有效的和安全的首选药物,其优点包括延长生存时间和改善生活质量,减少静脉血栓栓塞的发生率。推荐在院的及接受手术治疗的肿瘤患者预防性使用LMWH。LMWH应作为已确诊的和存在再发可能的VTE的肿瘤患者的一线治疗。     

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。     

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。     

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。      

低分子肝素治疗Trousseau′s综合征

1865年,Trousseau首次报告肿瘤与血栓栓塞性疾病的关系,游走性静脉血栓形成首次被描述。而且,目前在肿瘤病人中,各种静脉和动脉其他的血栓栓塞性疾病被称为Trousseau′s综合征。尽管有争论,血栓栓塞现象一直被认为是潜隐性肿瘤,尤其是未有血栓形成的其他危险因素的癌症病人的先兆。血栓形成常可提示恶性肿瘤的诊断。 本文报告4例病人患有广泛的静脉血栓栓塞性疾病,随之诊断又患有恶性肿瘤。所有病人最后均应用enoxaparin(一种低分子肝素,low-Molecular-weight heparin,LMWH)皮下给药治疗,理想地控制了血栓栓塞。     

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。     

肿瘤相关静脉血栓栓塞症的预防与治疗中国专家指南（2015版）

《中国肿瘤临床》2015年第20期刊登由中国临床肿瘤学会（CSCO）肿瘤与血栓专家共识委员会的多位权威专家撰写的《肿瘤相关静脉血栓栓塞症的预防与治疗中国专家指南（2015年版）》，该指南对肿瘤患者静脉血栓栓塞症（venous thromboembolism，VTE）的发生率、危险因素、预防方法与治疗原则进行了系统总结，供肿瘤临床医师参考，以期降低肿瘤患者VTE率，提高生存质量。欢迎登陆本刊网站浏览与下载该文。     

晚期恶性肿瘤患者合并静脉血栓栓塞症18例临床分析

静脉血栓栓塞症(venous thromboembolism,VTE)是指堵塞静脉血管的血凝块(血栓)形成,血栓形成在不同部位、不同阶段会出现不同表现,包括深静脉血栓(deep venous thrombosis,DVT)和肺血栓栓塞症(pulmonary thromboembolism,PTE),是目前医学界公认的具潜在致命性的常见疾病之一,是恶性肿瘤患者,尤其是长期卧床患者的主要合并症.2003至2007年我科共收治恶性肿瘤并发静脉血栓栓塞患者18例,现报告如下.     

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。     

淋巴瘤患者静脉血栓栓塞症的研究进展

血液恶性肿瘤患者易发生出凝血障碍，以急性白血病为代表，其中淋巴瘤出凝血障碍发生率也较高，凝血异常所致静脉血栓栓塞（VTE）是其死亡主要原因之一。淋巴瘤血栓栓塞症在非霍奇金淋巴瘤中发生率明显高于霍奇金淋巴瘤，VTE的发生可形成凝血瀑布从而促进肿瘤生长，提示患者疾病进展及病情恶化。淋巴瘤VTE发生的危险因素及相关特点可作为临床早期用药干预的依据从而改善患者预后，极大提高患者的生活质量。     

Cancer and thrombosis: implications of published guidelines for clinical practice

Cancer is a frequent finding in patients with thrombosis, and thrombosis is much more prevalent in patients with cancer, with important clinical consequences. Thrombosis is the second most common cause of death in cancer patients. Venous thromboembolism (VTE) in cancer is also associated with a high rate of recurrence, bleeding, a requirement for long-term anticoagulation, and worsened quality of life. Risk factors for cancer-associated VTE include particular cancer types, chemotherapy (with or without antiangiogenic agents), the use of erythropoietin-stimulating agents, the presence of central venous catheters, and surgery. Novel risk factors include platelet and leukocyte counts and tissue factor. A risk model for identifying cancer patients at highest risk for VTE has recently been developed. Anticoagulant therapy is safe and efficacious for prophylaxis and treatment of VTE in patients with cancer. Available anticoagulants include warfarin, heparin, and low-molecular weight heparins (LMWHs). LMWHs represent the preferred therapeutic option for VTE prophylaxis and treatment. Their use may be associated with improved survival in cancer, although this issue requires further study. Despite the significant burden imposed by VTE and the availability of effective anticoagulant therapies, many oncology patients do not receive appropriate VTE prophylaxis as recommended by practice guidelines. Improved adherence to guidelines could substantially reduce morbidity, decrease resource use, enhance quality of life, and improve survival in these patients.     

Cancer-associated thrombosis: focus on extended therapy with dalteparin

The increased risk of thrombosis-related morbidity and mortality in patients with cancer remains, even in the face of anticoagulant therapy. Moreover, recurrent venous thromboembolism (VTE) complicates the management of cancer and adversely affects quality of life and survival. Until recently, initial therapy with unfractionated heparin or low-molecular-weight heparin (LMWH) followed by long-term therapy with an oral anticoagulant was the standard of care for the secondary prevention of acute thromboembolism in most patients. However, according to the results of the CLOT trial (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent VTE in Patients With Cancer), extended LMWH therapy with dalteparin represents an alternative to standard oral anticoagulation. In terms of efficacy, the incidence of recurrent VTE in patients receiving dalteparin was half that of those receiving warfarin (27 of 336 patients vs 53 of 336 patients, respectively), for a 52% relative risk reduction. The incidence of major bleeding in this trial was not significantly different in the two arms. Although this LMWH regimen is supported by the latest practice guidelines of the American College of Chest Physicians, the question of whether long-term treatment with LMWH in cancer patients actually affects survival apart from the benefits of thromboprophylaxis remains to be answered.     

Thromboprophylaxis in major abdominal surgery for cancer.

AIMS: To review the epidemiology and pathogenesis of venous thromboembolism (VTE) in surgical cancer patients, in addition to the use of thromboprophylaxis in major abdominal surgery, such as low-molecular-weight heparin (LMWH) and fondaparinux. METHODS: Systematic review of the literature, focussing on risk factors for VTE, parenteral methods of thromboprophylaxis, approaches to prolonged prophylaxis, and effects on patient survival. FINDINGS: Patients with cancer undergoing abdominal surgery are at substantially higher risk for VTE than patients without cancer. Furthermore, prolonged thromboprophylaxis for up to 4 weeks is more effective than short-term administration in these high-risk patients. The concurrent use of graduated compression stockings has a synergistic effect on the reduction in VTE risk. CONCLUSIONS: Thromboprophylaxis with LMWH has been shown to minimise the incidence of thromboembolic events, and is a well-established therapy worldwide. The American College of Chest Physicians recommends the routine use of thromboprophylaxis, with LMWH or unfractionated heparin, in patients with cancer who are undergoing surgical procedures, and the appropriate use of these thromboprophylactic agents has significant implications for the clinical care and quality of life of surgical patients with cancer.     

Low molecular weight heparins as extended prophylaxis against recurrent thrombosis in cancer patients

Cancer has been shown to be an independent risk factor for the development of venous thromboembolism (VTE; deep vein thrombosis and pulmonary embolism). Thromboprophylaxis reduces the incidence of VTE in patients with cancer; however, active cancer places patients at high risk for recurrent VTE, necessitating extended prophylactic regimens. Extended prophylaxis in patients with cancer can be problematic because of increased risk for bleeding. Oral anticoagulants, such as warfarin, have been the standard of care for extended prophylaxis, but maintaining a clinically effective level of anticoagulation can be difficult because of a wide range of drug interactions, a narrow therapeutic window, and an increased risk of bleeding complications, particularly in patients with cancer. Recent evidence indicates that long-term prophylaxis with low-molecular-weight heparins (LMWHs) is an effective and safe alternative to oral anticoagulation in patients with VTE and cancer, reducing the risk for recurrent VTE by up to 52%. LMWHs can also be seen as cost-effective for long-term prophylaxis, because higher drug acquisition costs are offset by the potential for reduced hospital stays, reduced need for coagulation monitoring, and fewer bleeding complications. Some studies suggest that LMWHs may also have direct antitumor effects and improve survival rates, most notably in patients with non-metastatic disease. Further clinical research is needed to evaluate the potential survival benefits of LMWH therapy in patients with cancer.     

FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragm in?a dded to standard t herapy i n patients with lung c ancer

Background  

Venous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer.     

Managing thromboembolic disease in the cancer patient: efficacy and safety of antithrombotic treatment options in patients with cancer

Management of thromboembolic disease in patients with cancer can be challenging. Patients with cancer who have established thrombosis are at increased risk of recurrent VTE and of anticoagulant-associated bleeding compared to patients with no cancer. The optimal treatment of VTE in patients with cancer should lower the risk of recurrent VTE without increasing the risk of bleeding and ideally improve a patient's quality of life. Initial treatment of VTE in patients with cancer should be with LMWH, which may be administered, subcutaneously, at home. The current standard of care for long-term treatment of VTE remains oral anticoagulant, which should be administered for as long as the cancer is active. However, the use of oral anticoagulants can be problematic in these patients due to possible anorexia and vomiting. The efficacy and safety of long-term treatment of VTE in cancer patients with LMWH is currently under investigation.