肺癌前血栓状态的研究进展

前血栓状态是由多种病理因素引起的凝血与抗凝血系统、纤溶系统平衡失调,血液黏滞性增高,有利于血栓形成的一种病理生理状态。前血栓状态形成机制复杂,临床上与肺癌关系密切,是血栓事件相关的原因,同时与肿瘤复发、转移相关。抗凝治疗可能成为抗肿瘤治疗的途径之一,可以减少血栓事件的发生率,影响肿瘤的复发、转移,提高病人的生活质量。     

恶性肿瘤患者血栓前状态的检测

目的　对恶性肿瘤患者的血小板活化状态抗凝及纤溶部分指标进行检测 ,探讨其血栓前状态生物指标的变化。方法　采用酶联免疫法和发色底物法检测肿瘤患者 5 0例 ,正常人 30例的活化血小板α颗粒膜蛋白 (GMP 14 0 )及血浆蛋白 (PC) ,组织型纤溶酶原激活物 (t PA)及其抑制物 (PAI)含量。结果　肿瘤患者GMP 14 0、PC、t PA量显著增高 (P <0 .0 5 )PAI与正常人相近 ,(P >0 .0 5 )。结论　提示恶性肿瘤患者存在着血小板活化功能、凝血和纤溶活性增强。     

恶性肿瘤血栓前状态测定

 本文对95例恶性肿瘤患者测定血浆血栓烷B₈（TXB₂）、6-酮-前列腺素F1a（6-酮-PGF1a）、VWF、抗凝血酶-Ⅲ：C（AT-Ⅲ：C）等、对肿瘤易致血栓形成并发症病理变化进行探讨，结果认为TXB₂等水平变化与肿瘤血栓前状态有关，化疗亦能诱发或加重血栓前状态。     

恶性肿瘤患者血栓前状态的诊断与治疗

目的总结国内外近年来恶性肿瘤患者血栓前状态诊断及防治研究进展。方法应用PubMed和CBM（中国生物医学文献数据库）及CNKI（中国知网）期刊全文数据库检索系统,以＂恶性肿瘤、血栓前状态、静脉血栓栓塞、诊断、治疗＂为关键词,检索从2005-2010年的国内外相关文献。纳入标准：（1）恶性肿瘤患者血栓前状态的发生机制和后果;（2）恶性肿瘤患者血栓前状态的诊断程序及指标;（3）恶性肿瘤患者血栓前状态的防治策略。根据纳入标准,符合条件的文献八十余篇。结果多数肿瘤患者存在血栓前状态,各种因素综合作用导致肿瘤患者的血栓前状态并促进肿瘤的转移复发,血栓前状态的有效防治可使患者受益。但目前对肿瘤患者血栓前状态的筛查及诊断尚无统一标准。结论科学的诊断程序及实验室指标可以帮助筛查恶性肿瘤患者的血栓前状态,期待针对肿瘤患者血栓前状态的进一步临床及实验研究,以明确诊断思路并进行有效干预。     

血液肿瘤血栓前状态测定临床意义

本文对80例血液恶性肿瘤患者观察了血拴前状态表现。发现急性白血病化疗前临床出血症状明显,除血小板生成受肿瘤细胞干扰外,血管内皮细胞 PGI_2异常释放亦参与形成急性白血病的出血因素,故6—酮—前列腺素(6—酮—PGF_(1a))增高为主。慢性白血病及其它血液恶性肿瘤对血小板、血管内皮细胞及肝功能的作用,导致血拴烷 B_2(TXB_2)、VWF 升高,6—酮—PGF_(1a)、抗凝血酶—Ⅲ(AT—Ⅲ:C)降低,形成肿瘤患者血拴前状态的另一个特点。     

肺癌患者血栓前状态的研究

背景与目的 晚期肺癌患者存在血栓前状态.本研究旨在探讨肺癌患者凝血及纤溶指标与肺癌临床病理特征关系及与预后的相关性.方法 对60例肺癌患者及20例健康人的血浆凝血及纤溶指标分别进行测定.结果 肺癌组中血浆纤维蛋白原(FIB)、D-二聚体、纤维蛋白降解产物(FDP)值明显高于对照组,抗凝血酶Ⅲ(AT-Ⅲ)值明显低于对照组,肺癌组各指标与患者的年龄、性别、病理类型、肿瘤大小、TNM分期、有无远处转移等临床病理特征之间无明显关系.肺癌患者血浆FIB值、D-二聚体值与生存期之间有显著负相关(FIB相关系数r=-0.32,P<0.05;D-二聚体相关系数r=-0.41,P<0.01).结论 肺癌患者存在凝血及纤溶功能的异常,可导致血液的高凝状态,有利于血栓的形成,血浆FIB值、D-二聚体值与患者的预后密切相关.抗凝及活血化瘀治疗对肺癌的发生、发展及预后可能有重要的临床意义.     

小剂量肝素治疗肺癌患者血栓前状态的临床研究

报道７５例中、晚期肺癌血栓前状态Ｄ－二聚体在治疗过程中的变化情况。小剂量肝素加化疗加／或放疗治疗组４０例，Ｄ－二聚体转正常３２例、有效率（８０％）。化疗加／或放射治疗（无肝素组）３５例，Ｄ－二聚体转正常６例，有效率１７．１％（Ｐ＜０．０１）。观察结果表明：小剂量肝素治疗中、晚期肺癌血栓前状态是一种有效、安全的方法。     

以静脉血栓为首发表现的恶性肿瘤23例

目的 分析以静脉血栓为首发表现的恶性肿瘤患者的临床特点,进一步探讨深静脉血栓与恶性肿瘤的关系.方法 分析23例以深、浅静脉血栓形成为首发表现的恶性肿瘤患者的临床表现、栓塞部位、是否合并肺栓塞、凝血功能检测指标、血小板计数、原发肿瘤类型、转移与否以及抗凝治疗效果,分析肿瘤与深静脉血栓形成的关系.结果 深静脉血栓形成16例（上肢3例,下肢13例）,游走性血栓性浅静脉炎7例（上肢2例,下肢4例,胸壁1例）,凝血功能检查示血浆纤维蛋白原含量、血小板计数均不同程度升高或降低,抗凝血酶活性不同程度下降,D-二聚体水平增高,5例合并远处脏器转移.抗凝治疗及腔静脉滤器降低血栓复发、大出血及致死性肺栓塞.结论 不明原因的静脉血栓患者应高度警惕肿瘤的存在,抗凝治疗及腔静脉滤器是降低并发症的重要保证.     

血栓弹力图在恶性肿瘤中的临床应用价值

血栓弹力图（thromboela-stogram,TEG）是根据凝血过程中凝血块的粘弹性变化所绘制出的图像,能够全面、快速、准确地反映凝血功能。因此TEG被广泛应用于凝血功能监测、预防血栓、指导术中输血、指导治疗以及多种疾病过程中凝血和纤溶功能的监测。本文就TEG在恶性肿瘤中的临床应用价值作一综述。     

血液肿瘤血栓前状态测定临床意义

本文对80例血液恶性肿瘤患者观察了血挂前状态表现。发现急性白血病化疗前临床出血症状明显，除血小扳生成受肿瘤细胞干扰外，血管内皮细胞PGI2异常释放亦参与形成急性白血病的出血因素，故6-酮-前列臃素(6-酮-PG1a)增高为主。慢性白血病及其它血液恶性肿瘤对血小扳、血管内皮细胞及肝功能的作用，导致血栓烷B2(TXB2)、VWF升高，6-酮-PGF1a，抗凝血酶-Ⅲ(AT-Ⅲ，C)降低，形成肿瘤患者血拴前状态的另一个特点。     

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。     

Anticoagulation prophylaxis for central venous catheter-associated thrombosis in cancer patients: An Australian perspective

Background: The use of indwelling central venous catheters (CVC) for chemotherapy delivery is essential for people receiving therapies by protracted venous infusion and for patients with difficult venous access. Complications include infection and catheter‐related thrombosis. Strategies have been suggested to prevent catheter‐related thrombosis, however, there is no clear consensus on how to proceed. Guidelines recommend against the use of prophylactic anticoagulation in adult patients with solid organ malignancies and an indwelling CVC. We investigated the practice of Australian medical oncologists. Methods: A written questionnaire was mailed to all members of the Medical Oncology Group of Australia assessing practices of prophylactic anticoagulation in adult patients with solid organ malignancies and CVC. Results: Responses were obtained from 141 (55%) medical oncologists and from 40 advanced trainees. Ten percent (n = 4) of oncology trainees and 18.4% (n = 26) of medical oncologists routinely administered anticoagulants to patients with a CVC without a previous history of line‐related thrombus. The most common strategy employed (73% of those using anticoagulation) was to recommend 1 mg of warfarin. Conclusions: The results demonstrate that a significant number of patients in Australia receive routine anticoagulation, the most popular strategy being the use of low‐dose warfarin. Based on our results there is a clear need for further education regarding the lack of supporting data and the potential harm that may ensue.     

恶性肿瘤与肺栓塞关系及介入治疗

肺栓塞死亡率较高,临床发现肿瘤患者肺栓塞发生率显著高于一般人群,对此类患者进行必要的干预和治疗有助于提高患者生存质量,延长生存期。介入放射学技术在肺栓塞预防和治疗方面积累了一定的经验。本文就肺栓塞与恶性肿瘤关系以及介入技术在肺栓塞防治中的作用进行综述,以期为临床治疗提供一定的选择参考。     

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.     

癌症相关性孤立下肢远端深静脉血栓形成的临床研究进展

静脉血栓栓塞症(venous thromboembolism,VTE)在癌症患者中发病率较高,是导致癌症患者疾病进展或死亡的重要因素.下肢深静脉血栓(deep vein thrombosis,DVT)形成在VTE中占比多、危害大,可分为近端DVT形成(proximal deep vein thrombosis,PDVT...     

Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer: a systematic review

BACKGROUND.

The authors compared the relative efficacy and safety of low‐ molecular‐weight heparin (LMWH) and unfractionated heparin (UFH) for the initial treatment of venous thromboembolism (VTE) between patients with and without cancer.

METHODS.

By using Cochrane methodology for systematic reviews, separate meta‐analyses were conducted for subgroups of patients with and without cancer, and relative risks (RRs) were compared for statistical significance. The methodologic quality for each outcome was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.

RESULTS.

LMWH reduced mortality significantly compared with UFH in patients with cancer (RR of 0.71; 95% confidence interval [95% CI], 0.52‐0.98 [moderate‐quality evidence]) but not in patients without cancer (RR of 0.97; 95% CI, 0.65‐1.46 [low‐quality evidence]). However, the difference in the RR for the 2 subgroups did not reach statistical significance (P = .113). The difference between LMWH and UFH in the effect on recurrent VTE was not statistically significant in the subgroup with cancer (RR of 0.78; 95% CI, 0.29‐2.08 [low‐quality evidence]), in the subgroup without cancer (RR of 0.94; 95% CI, 0.60‐1.46 [low‐quality evidence]), or between the 2 subgroups (P = .367). No data were available for bleeding outcomes, thrombocytopenia, or postphlebitic syndrome.

CONCLUSIONS.

The current results indicated that LMWH most likely is superior to UFH in reducing mortality in the initial treatment of VTE for patients with cancer. There is a need for more and better designed trials to confirm these findings. Cancer 2008. © 2008 American Cancer Society.     

Venous thromboembolism is a relevant and underestimated adverse event in cancer patients treated in phase I studies

Background:

To investigate, retrospectively, the role of tumour histotype and antiangiogenic drugs for venous thromboembolism (VTE) development in advanced cancer patients treated in phase I studies.

Methods:

Patients enrolled and treated in phase I studies conducted by SENDO (Southern Europe New Drugs Organisation) were considered.

Results:

Data of 1415 patients were included in the analysis: 526 (37.2%) patients were males, median age was 57.3 years (range: 13–85). Fifty-six (3.96%) patients developed a VTE. At multivariate analysis gynaecologic (hazard ratio (HR): 2.8, 95% confidence interval (CI): 1.29–6.23, P=0.009) and gastrointestinal tumours (HR: 3.23, 95% CI: 1.18–8.87, P=0.023) as well as combination regimens of cytotoxic and antiangiogenic agents (HR: 2.6, 95% CI: 1.11–6.30, P=0.028), white blood cell >11 000 μl⁻¹ (HR: 2.59, 95% CI: 1.10–6.09, P=0.028) and haemoglobin<10 g dl⁻¹ (HR: 3.1, 95% CI: 1.07–8.94, P=0.037) were statistically correlated with VTE development. Venous thromboembolism was the fourth most common cause of drug discontinuation. The median time from first drug administration to discontinuation was 1.4 for VTE and 2.3 months for the other adverse events (P=0.02).

Conclusion:

Venous thromboembolism is a relatively common complication among patients treated in the context of phase I studies, and may lead to early drug discontinuation. A greater risk of developing VTE is associated with the diagnosis of gynaecologic and gastrointestinal tumours and the combined use of chemotherapy and antiangiogenic drugs.     

Incidence and predictors of venous thromboembolism (VTE) among ambulatory high‐risk cancer patients undergoing chemotherapy in the United States

BACKGROUND:

Recent studies suggest that thromboprophylaxis is beneficial in preventing venous thromboembolism (VTE) in cancer outpatients, but this is not widely adopted because of incomplete understanding of the contemporary incidence of VTE and concerns about bleeding. Therefore, the authors examined the incidence and predictors of VTE in ambulatory patients with bladder, colorectal, lung, ovary, pancreas, or gastric cancers.

METHODS:

Data were extracted from a large health care claims database of commercially insured patients in the United States between 2004 and 2009. Demographic and clinical characteristics of the cancer cohort (N = 17,284) and an age/sex‐matched, noncancer control cohort were evaluated. VTE incidence was recorded during a 3‐month to 12‐month follow‐up period after the initiation of chemotherapy. Multivariate analyses were conducted to identify independent predictors of VTE and bleeding.

RESULTS:

The mean age of the study population was 64 years, and 51% of patients were women. VTE occurred in 12.6% of the cancer cohort (n = 2170) over 12 months after the initiation of chemotherapy versus 1.4% of controls (n = 237; P < .0001); incidence ranged by cancer type from 19.2% (pancreatic cancer) to 8.2% (bladder cancer). Predictors of VTE included type of cancer, comorbidities (Charlson Comorbidity Index score or obesity), and commonly used specific antineoplastic or supportive care agents (cisplatin, bevacizumab, and erythropoietin).

CONCLUSIONS:

This large, contemporary, real‐world analysis confirmed high rates of VTE in select patients with solid tumors and suggested that the incidence of VTE is high in the real‐world setting. Awareness of the benefits of targeted thromboprophylaxis may result in a clinically significant reduction in the burden of VTE in this population. Cancer 2013. © 2012 American Cancer Society.