低分子肝素治疗恶性肿瘤并发深静脉血栓剂量及疗效的初步研究(附27例分析)

目的探讨应用低分子肝素治疗恶性肿瘤合并深静脉血栓形成的剂量及效果,分析联合其他常规抗肿瘤治疗手段对生存期以及疗效有影响的相关因素。方法回顾性分析本院2007年1月至2011年1月收治的27例恶性肿瘤合并深静脉血栓患者的临床资料。抗凝治疗方法:每天低分子肝素0.1 U/kg皮下注射,体质量>60 kg者,每天低分子肝素0.6 mL皮下注射,体质量<60 kg者,每天低分子肝素0.3 mL皮下注射,中位治疗时间21天(0-180.0天)。结果 27例恶性肿瘤合并深静脉血栓患者应用低分子肝素抗凝治疗的短期疗效客观有效率66.7%,疾病控制率85.2%。不良反应少。中位生存期8.5月(0-33.2月)。根据患者体质量调整应用低分子肝素抗凝治疗相对安全,抗肿瘤治疗疗效与低分子肝素短期疗效相关(P=0.000)。结论恶性肿瘤患者合并血栓患者应用低分子肝素抗凝治疗安全,疗效较好,耐受性好,其抗肿瘤治疗疗效与低分子肝素治疗血栓短期疗效相关。     

肿瘤与血栓形成研究进展

血栓形成与肿瘤形成关系密切,其机制与肿瘤本身及释放的因子和治疗相关.大部分肿瘤血栓患者可通过初步筛查检测出来.美国胸科协会已发布抗凝指南,其中低分子肝素抗凝同时亦抗肿瘤.     

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。     

肝素及其类似物抗乳腺癌作用研究进展

肿瘤是深静脉血栓形成的高危因素之一,因而很多肿瘤患者会伴发静脉血栓形成,这使得抗凝治疗必不可少。近期很多临床研究及Meta分析表明,肿瘤患者在接受抗凝治疗后,生存期得到明显改善。肝素是一种广泛应用于静脉血栓的抗凝剂,据此,研究人员提出猜想:肝素是否具有抗肿瘤活性?大量实验性研究就此全面开展,结果证实:普通肝素、低分子肝素、肝素各种化学衍生物与多种肿瘤的发生、发展进程相关。该文主要概述了肝素及其类似物抗乳腺癌的作用及其可能的内在机制。     

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。      

超声监测胸外科肿瘤术后低分子肝素预防深静脉血栓的临床研究

目的探讨应用超声监测胸外科肿瘤术后给予低分子肝素预防深静脉血栓的临床效果。方法将2010年1月至2010年12月间80例行胸外科恶性肿瘤手术治疗的患者随机分为两组,每组各40例。观察组患者术后给予低分子肝素治疗,对照组患者术后未给予低分子肝素治疗,对两组患者进行超声检查,观察深静脉血栓发生的情况。结果两组患者手术时间、胸腔引流量、拔管时间比较差异无统计学意义（P〉0．05）;观察组患者静脉血栓形成率显著低于对照组,差异有统计学意义（P〈0．05）;两组患者D-二聚体、血小板计数（PLIT）和纤维蛋白原（FIB）治疗后均有不同程度的改善,差异有统计学意义（P〈0．05）。治疗1d后两组患者的观察指标比较无显著性差异（P〉0．05）,但治疗3天后,FIB和D-二聚体比较,差异有统计学意义（P〈0．05）。结论临床上胸外科肿瘤手术后给予低分子肝素能够有效预防深静脉血栓的形成,超声能够作为早期监测患者下肢深静脉血栓形成的重要方法。     

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。     

恶性肿瘤患者与血栓症

血栓症是恶性肿瘤患者的一种常见并发症,直接影响患者的预后。恶性肿瘤可通过多种机制导致血栓形成,而血栓形成又促进了恶性肿瘤的生长和转移。这类血栓症的表现随血栓形成部位的不同而不同,多同时伴有恶性肿瘤的原发表现。90%以上的恶性肿瘤患者可出现凝血系统相关指标异常。恶性肿瘤患者凝血功能正常时,不必进行预防性抗血栓治疗。当凝血功能异常时,预防性治疗的必要性尚无定论,但对于接受手术的恶性肿瘤患者,预防性治疗能显著降低静脉血栓发病率。抗血栓形成药物,如低分子肝素,可控制血液的高凝状态,减少恶性肿瘤患者血栓症的发病率。恶性肿瘤患者一旦确诊有血栓形成就必须进行抗凝治疗,皮下应用低分子肝素已经成为急性血栓症的一线治疗药物。低分子肝素和丙酮苄羟香豆素还可以抑制肿瘤生长和转移,延长肿瘤患者的生存时间。     

低分子量肝素预防胸部肿瘤开胸术后血栓性疾病的临床研究

目的观察低分子量肝素预防胸部肿瘤开胸术后血栓性疾病的效果。方法将2004年1月至2005年8月住我科的食管癌、贲门癌、肺癌患者随机分为治疗组和对照组,每组320例,治疗组于术后第1天开始皮下注射低分子量肝素,每日1次,连用5d,观察术后胸液量并统计血栓性疾病发生率。结果两组患者胸液量差异无显著性(P>0.05),治疗组血栓性疾病发生率明显低于对照组(P<0.01)。结论低分子量肝素预防胸部肿瘤开胸术后血栓性疾病有明显效果,较为安全可靠。     

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。     

Pylethrombosis associated with gastric cancer in Moschcowitz's disease: successful management with anticoagulant. Report of a case

Portal vein thrombosis secondary to gastric cancer has been rarely reported. The main difficulty is represented by the correct differential diagnosis between benign and malignant thrombus and therefore by its treatment. In this report we describe a 62-year-old woman with Moschcowitz's disease who developed pylethrombosis and gastric cancer. Preoperative examination confirmed the relationship between the portal vein thrombosis and Moschcowitz's disease. She underwent an aggressive surgical procedure for the gastric cancer and conservative treatment of the thrombosis with subcutaneus administration of 8000 IU/day of low molecular weight heparin (LMWH) at the time of diagnosis, interrupted eight hours before surgery and resumed eight hours after with 4000 IU/day. At discharge LMWH treatment was replaced with oral sodium warfarin home treatment to keep the international normalized ratio range between 2 and 3. Regression of the thrombosis with low molecular weight heparin was confirmed by computed tomography. The patient survived more than two years. We believe that patients with gastric cancer complicated by benign partial portal vein thrombosis could gain particular benefit from adjuvant anticoagulant treatment, so that the surgical approach can be limited to gastric cancer.     

Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial

Recent studies suggest that low molecular weight heparin (LMW heparin) therapy in malignancy may improve cancer survival following surgical resection. We studied prospectively whether cancer mortality during follow-up in women with previously untreated breast, and pelvic cancer is reduced in those who randomly received LMW heparin (Certoparin) compared to patients given unfractionated heparin (UF heparin) for thrombosis prophylaxis during primary surgery. In a prospective, randomized, double-blind clinical trial, 160 patients received Certoparin and 164 UF heparin until post-operatively day 7. Survival estimations are based on the outcome data from a subset of 140 LMW heparin - and 147 UF heparin recipients. Long-term survival in the Certoparin group compared to the UF heparin group was significantly improved after 650 days (P=0. 0066) but not thereafter when analysis was performed on all cancer cell types combined. In the probability estimates survival benefit within this time was restricted to patients with pelvic cancer but was not observed in breast cancer. However, in breast cancer patients who received LMW heparin the impact of classical tumor prognostic markers was statistically significant after 1,050 days but not after 650 days. Thus, breast cancer patients with unfavorable prognosis seem to benefit in terms of survival advantage from LMW heparin within the 650 days after surgery. These results suggest that improvement in cancer survival can be achieved after even a short course of treatment with LMWH (compared to UFH) given for DVT prophylaxis in the post-operative period. An effect of UFH on disease outcome is not excluded. Further definitive trials of LMWH vs. placebo for cancer outcome (rather then DVT) using doses and schedules that may be more optimal are indicated.     

Cancer, coagulation, and anticoagulation

Thromboembolic disease affects about 15% of cancer patients and presents a challenge to the oncologist for both prophylaxis and treatment. Although long known to be associated with malignancy, the underlying biochemical mechanisms are poorly understood. Both low-dose warfarin and low molecular weight heparin are effective strategies for prophylaxis of venous thromboembolism, including those involving venous access devices. Current treatment options for venous thromboembolism include heparin (unfractionated and low molecular weight), warfarin, and internal vena cava filters. The appropriate use of these therapeutic options in cancer patients is reviewed herein. There is suggestive evidence that heparin may be superior to warfarin in the long-term treatment of venous thromboembolism. Whether anticoagulants might also improve cancer survival rates independent of their effect on thromboembolism deserves further investigation.     

The effect of anticoagulants on cancer risk and survival: systematic review

OBJECTIVES: Several in vitro and in vivo studies have shown that low molecular weight heparin and warfarin may directly inhibit tumour cell growth and prevent metastatic spread. However, the clinical evidence in support of an anti-cancer effect is less conclusive. We summarize the evidence from clinical studies that examine the effect of these anticoagulants on cancer development and briefly describe the current understanding of the potential mechanisms by which anticoagulants may exert an anti-cancer effect. METHODS: English-language articles reporting on warfarin, coumarin or low molecular weight heparin for the treatment or prevention of cancer were selected from PUBMED. All randomized clinical trials, case-control studies, cohort studies, and meta-analyses were retrieved. Detailed data review and abstraction was performed according to pre-specified criteria. RESULTS: Of ninety-nine articles retrieved, 12 warfarin and 17 low molecular weight heparin articles were included in the review. We found no consistent evidence that warfarin may improve cancer survival, though there is indirect evidence that prolonged warfarin use may decrease the risk of urogenital cancer. Low molecular weight heparin may improve survival of patients with small cell lung cancer and those with advanced malignancy who have more favorable prognoses. CONCLUSION: Clinical evidence exists in support of an anti-neoplastic effect of anticoagulants. However, more research is needed to further define which cancer type and stage would most benefit from low molecular weight heparin, as well as to explore the role of warfarin in urogenital tumour development.     

乳腺癌术后肺栓塞27例临床特征分析

目的探讨乳腺癌外科术后肺栓塞的临床特征。 方法选取2008年1月1日至2020年1月1日在北京大学肿瘤医院行乳腺癌手术后出现肺栓塞的患者27例，收集并分析其临床资料、诊断结果、治疗及预后等。 结果入组的27例肺栓塞患者的临床表现无特异性，均通过肺动脉CT血管造影（CTPA）显示动脉充盈缺损确诊，其中双侧肺栓塞18例，单侧肺栓塞9例。超声检查显示伴下肢深静脉血栓14例，伴上肢深静脉血栓4例。18例早期予以足量低分子肝素（0.1 ml/10 kg，2次/d）抗凝治疗，9例予以减量低分子肝素（0.05 ml/10 kg，2次/d）抗凝治疗，患者均好转。在治疗过程中出现大出血1例，抗凝减量并予以输血治疗后好转。随访3个月无失访及死亡患者。 结论乳腺癌术后肺栓塞的临床表现无特异性，早期诊断和治疗可降低病死率。     

Anticoagulants in thrombosis and cancer: the missing link

Many cancer patients reportedly have hypercoaguable state, with recurrent thrombosis due to the impact of cancer cells and chemotherapy on the coagulation cascade. A number of retrospective studies showed that cancer patients are at higher risk of developing venous thromboembolism. In addition to the pathological mechanisms associated with tumor-mediated increase in thrombotic events, cancer therapies including chemotherapy, immobilization, cancer surgery and the use of central venous catheters contribute toward a hypercoaguable state and are therefore independent risk factors of venous thromboembolism in cancer patients. Studies have demonstrated that unfractionated heparin or low molecular weight heparin (LMWH) interferes with various processes involved in tumor growth and metastasis. These processes might include fibrin formation, binding of heparin to angiogenic growth factors – such as basic fibroblast growth factor and VEGF – modulation of tissue factor, release of tissue factor pathway inhibitor and other mechanisms. Clinical trials have suggested an improved efficacy of LMWH, as compared with UFH on the survival of cancer patients with deep vein thrombosis. Similarly, the impact of warfarin on the survival of cancer patients with thromboembolic disorders was demonstrated. Recent studies from our laboratory defined the role of the LMWH (tinzaparin), warfarin, antifactor VIIa and recombinant tissue factor pathway inhibitor in the modulation of angiogenesis, tumor growth and tumor metastasis.     

Anticoagulants in thrombosis and cancer: the missing link

Many cancer patients reportedly have hypercoaguable state, with recurrent thrombosis due to the impact of cancer cells and chemotherapy on the coagulation cascade. A number of retrospective studies showed that cancer patients are at higher risk of developing venous thromboembolism. In addition to the pathological mechanisms associated with tumor-mediated increase in thrombotic events, cancer therapies including chemotherapy, immobilization, cancer surgery and the use of central venous catheters contribute toward a hypercoaguable state and are therefore independent risk factors of venous thromboembolism in cancer patients. Studies have demonstrated that unfractionated heparin or low molecular weight heparin (LMWH) interferes with various processes involved in tumor growth and metastasis. These processes might include fibrin formation, binding of heparin to angiogenic growth factors--such as basic fibroblast growth factor and VEGF--modulation of tissue factor, release of tissue factor pathway inhibitor and other mechanisms. Clinical trials have suggested an improved efficacy of LMWH, as compared with UFH on the survival of cancer patients with deep vein thrombosis. Similarly, the impact of warfarin on the survival of cancer patients with thromboembolic disorders was demonstrated. Recent studies from our laboratory defined the role of the LMWH (tinzaparin), warfarin, antifactor VIIa and recombinant tissue factor pathway inhibitor in the modulation of angiogenesis, tumor growth and tumor metastasis.