抗凝对非小细胞肺癌治疗的机制研究

近年来越来越多的研究开始关注恶性肿瘤患者并发的凝血功能异常,不仅导致血栓形成,还与肿瘤的生长、浸润侵袭、转移等密切相关,从而直接影响预后。肝素作为传统抗凝剂已众所周知,且抗凝药物已出现在恶性肿瘤治疗指南中。美国临床肿瘤学会（ASCO）、欧洲肿瘤内科学会（ESMO）以及美国临床药学学会（ACCP）等机构推荐低分子肝素作为治疗癌症相关血栓的首选,然而预防性应用抗凝药物对控制恶性肿瘤、延长PFS 及OS的机制仍不明确。本文将从多方面介绍抗凝药物对控制恶性肿瘤的复发转移及延长生存的病理生理学机制。      

肿瘤与凝血

在恶性肿瘤患者中,常伴有凝血、纤溶、血小板及血管功能异常导致的出血或血栓形成。这些异常也参与肿瘤转移。本文介绍近年来肿瘤与凝血方面的临床及基础研究进展,以有助于对肿瘤治疗及肿瘤患者凝血机制异常的了解。恶性肿瘤的临床出血与血栓形成 90%肿瘤转移患者和50%恶性肿瘤患者存在着止血功能异常。 10%恶性肿瘤患者有出血症状,主要原因是化疗导致的血小板减少症,而肿瘤细胞的组织侵袭及播散性血管内凝血[DIC]也是原因之一。急性白血病的出血发生率达18～60%,占急性白血病死因10%。     

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。     

恶性肿瘤患者血液高凝状态形成机制及防治

大多数恶性肿瘤患者存在血液高凝状态,易导致血栓形成,并与肿瘤转移复发密切相关。高凝状态形成机制与肿瘤、肿瘤相关治疗、合并症等相关。诊断指标主要有血小板、凝血与纤溶、P-选择素和溶酶体蛋白、血液流变学等。肿瘤高危血栓患者应使用低分子肝素,卧床肿瘤患者及肿瘤相关手术应预防血栓栓塞,肿瘤并发静脉血栓栓塞应用溶栓,伴有高凝状态的肿瘤患者应予化疗联合抗凝治疗。     

恶性肿瘤患者凝血功能异常的研究进展

近年来研究发现恶性肿瘤患者普遍存在凝血异常,高凝状态易并发血栓的形成,而血栓形成是恶性肿瘤患者常见的并发症,是仅次于恶性肿瘤本身引起患者死亡的第二位原因。不同的抗肿瘤治疗对机体凝血功能产生不同的影响,通过对凝血功能相关指标的检测,可以初步诊断恶性肿瘤患者的高凝状态。因此,通过对恶性肿瘤患者凝血功能异常的诊断及不同抗肿瘤治疗对恶性肿瘤患者机体凝血功能的影响进行综述。     

恶性肿瘤患者的止血异常

恶性肿瘤患者的凝血及纤溶异常较常见,其发生率根据肿瘤的类型及程度而异,肿瘤患者中其异常的发生率约50%,而在转移性肿瘤则超过90%。这些异常一般并不引起明显症状,但15%以上患者在临床上有出血及血栓形成。患者在急性阶段后期常有严重的复发性血栓形成,应立即作抗凝治疗。英国推荐作3～4天的短程治疗,北美常用7～10天,一般用口服华法令来治疗。对危险性很高患者主张做持续性肝素皮下注射,使部分凝血激酶时间至少保持在对照值的1.5倍。如可能也应积极治疗恶性肿瘤。     

低分子肝素在恶性肿瘤患者中的应用进展

低分子肝素(LMWH)应用于恶性肿瘤患者的辅助治疗是近年来临床研究的热点.现有研究表明, LMWH可能在抑制血液高凝状态、血栓形成、肿瘤的生长和转移等方面具有潜在的优势.LMWH的部分抗肿瘤作用依赖于抗凝途径得以发挥,在某种程度上又独立于抗凝作用.本文通过研究和分析现有的文献与资料,介绍LMWH在恶性肿瘤患者中的抗血栓形成及抗肿瘤作用,主要从LMWH阻断恶性肿瘤诱导的血液高凝状态、抑制恶性肿瘤组织血管生成、恶性肿瘤细胞的增殖及肿瘤的进展和转移等方面进行分析,同时对LMWH的应用安全性及降低恶性肿瘤患者的病死率、延长患者的生存期等方面进行综合评价.     

药物调节凝血机制在抗癌治疗中的意义

肿瘤病人凝血机制异常和血栓栓塞性疾病的发病率增高,提示凝血系统参与了肿瘤的生长与转移过程。药物调节凝血机制能提高肿瘤的治疗效果,检测凝血机制的某些指标对肿瘤诊断、疗效评价以及预后估计均有一定价值。     

低分子肝素抗凝治疗延长肿瘤患者生存机制的研究进展

肿瘤患者凝血系统常被激活而处于高凝状态,易于形成血栓.静脉血栓事件的防治是目前肿瘤研究中的热点.近年来有研究表明低分子肝素在治疗肿瘤患者深静脉血栓形成的同时能延长患者的生存.本文简要综述有关低分子肝素抗凝治疗延长肿瘤患者生存及其分子机制的研究进展.     

肺癌患者术后抗凝药物的不同干预时间对凝血功能的影响

目的:研究肺癌患者术后应用低分子肝素钙抗凝不同的起始时间对患者凝血功能的影响。方法:分析2017年11月至2018年5月我科收治的肺癌手术患者,按照手术顺序采用SPSS 19.0随机分成A、B、C、D组。其中A、B、C组为抗凝组,分别于术后12 h、24 h、48 h给予低分子肝素钙4 100 IU,bid,皮下注射,连续应用7天;D组为空白对照组。抗凝组和空白对照组术后都给予基础的血栓预防措施。术前及术后连续5天查血常规和血栓弹力图（TEG）并监测术后胸引量及下肢静脉血栓形成情况。结果:4组肺癌术后患者的下肢血栓形成情况:A组0例,B组1例下肢肌间静脉血栓形成,C组2例下肢肌间静脉血栓形成,D组6例肌间静脉血栓形成。A组与D组之间比较有显著差异。所有肺癌患者术后没有出现临床症状的静脉血栓栓塞症。血栓弹力图指标术前均无显著差异,而R值在术后组间比较均有显著差异。4组肺癌患者术后胸引量和出血相关并发症组间比较无显著差异。结论:肺癌术后12 h应用低分子肝素钙预防性抗凝治疗能明显降低静脉血栓形成的风险,优于24 h、48 h开始抗凝治疗。     

An expanding role for antithrombotic therapy in cancer patients

Thromboembolic disease has a negative impact on outcome in the cancer patient. Venous thromboembolism appears to be a more aggressive disease in patients with cancer who present with both a greater thrombus burden and more pronounced derangements of coagulation parameters with non-cancer patients with thrombosis. Restrospective analyses suggest that treatment of venous thromboembolism in cancer patients with low-molecular-weight heparin is associated with additional benefits in terms of their survival. The mechanism for this effect is unclear but may be attributed to a reduced incidence of recurrent thrombosis and fatal pulmonary embolism in those patients with underlying thrombosis. To investigate and potential of low-molecular-weight heparin to prolong survival in cancer patients without underlying thrombosis, a prospective trial (FAMOUS) has evaluated the effect of treatment with the low-molecular-weight heparin dalteparin for 1 year terms of survival of patients with advanced cancer and no underlying thrombosis.     

低分子肝素改善胰腺癌患者预后及相关机制研究进展

胰腺癌是严重危害人类健康的恶性肿瘤之一,预后差、生存率低。肿瘤相关性血栓事件的发生是胰腺癌患者预后不良的主要因素。越来越多的数据表明低分子肝素（low-molecular-weightheparin, LMWH）等抗凝剂的使用可以显著降低肿瘤相关性血栓事件（cancer-associated thrombosis）的发生率,改善胰腺癌患者的生活质量甚至预后。本文就LMWH应用于胰腺癌的相关临床研究及抗肿瘤方面的机制作一综述。     

恶性肿瘤合并静脉血栓栓塞症21例临床分析

目的探讨恶性肿瘤合并静脉血栓栓塞症（VTE）高危因素、诊断、治疗以及预防。方法回顾性分析21例恶性肿瘤合并静脉血栓栓塞症的临床资料。结果 21例病例中1例深静脉血栓形成（DVT）患者因为活动性咯血而未进行抗凝治疗,随诊发现患者患肢肿胀加重,超声复查提示血栓较前增大。1例肺血栓栓塞症（PTE）患者因病情危重未来得及行抗凝治疗以及溶栓治疗已经死亡。另1例PTE患者经对症治疗病情稳定后接受低分子肝素、华法林抗凝治疗,复查超声提示静脉血栓较前缩小。其余18例DVT患者经过抗凝治疗后患肢肿胀,疼痛减轻、消失或（和）超声检查提示静脉血栓较前缩小、消失,血流恢复通畅。结论通过分析恶性肿瘤合并静脉血栓栓塞症高危因素、诊断、治疗以及预防,提高DVT诊疗水平,减少PTE的发生,对防治VTE有重要意义。     

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.     

Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?

The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed.     

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.     

低分子肝素预防直肠癌根治术后下肢深静脉血栓形成的研究

 目的　对比观察采用低分子肝素预防直肠癌术后下肢深静脉血栓形成 (DVT)的临床效果。方法　将 1999年 10月～ 2 0 0 2年 12月施行直肠癌根治术的患者随机分为对照组和用药组。对照组 37例未预防性使用低分子肝素抗凝 ,用药组共 33例围手术期给予低分子肝素 ,两组患者均于术后行下肢静脉彩色超声检查。结果　用药组DVT发生率为 9.1% ,对照组DVT发生率为 2 7.0 % ,两组相比差异有显著性意义 (P <0 .0 1)。用药组未发现术中及术后出血增多等现象和不良反应。结论　低分子肝素可显著降低直肠癌根治术后下肢深静脉血栓的发生率 ,且具有良好的安全性。