恶性肿瘤中医证候与血栓弹力图检测相关性分析及其临床实践

【作者】 黄佳琴；

【导师】 李忠；

【作者基本信息】 北京中医药大学 ， 中西医结合临床， 2014， 博士

【摘要】 [研究背景]据报道,约15%的肿瘤患者在疾病的发展过程中有临床显性的静脉血栓栓塞症,血栓栓塞性疾病是目前癌症患者最常见的并发症和第二位死亡原因。采取积极的措施进行预防和治疗高凝状态,对改善恶性肿瘤患者的整体生活质量具有重要的积极意义。目前针对肿瘤高凝状态的西医抗凝药物主要有低分子肝素、维生素K拮抗剂、抗血小板药物等,但均具有出血风险大,且需反复抽血监测血凝,目前临床使用并未达成共识。如何防治恶性肿瘤血液高凝状态是目前研究热点之一,中医药在改善血凝状况、减轻临床症状,进而预防肿瘤转移与复发等方面均显示出一定的疗效,中药改善恶性肿瘤患者血液高凝状态的作用已得到越来越多的认可。但是目前关于恶性肿瘤高凝状态的中医临床研究相对较少,主观干预因素多,均限制了中医药治疗恶性肿瘤高凝状态的临床应用。凝血是一个非常复杂的过程,其中涉及到许多因子的相互作用,传统的实验室血凝检查只能反应凝血过程的某个孤立的部分,无法了解患者凝血功能全貌。血栓弹力图能以图形的方式,动态、完整地监测从凝血开始至血凝块形成及纤维蛋白溶解的全过程,对凝血因子、血小板功能、纤维蛋白原和纤维蛋白溶解等情况进行全面的检测和评估,其结果快速而准确,能更好的为临床服务。在此基础上,我们以血栓弹力图检测值作为判断高凝状态的探索性指标,开展了恶性肿瘤中医证候与血栓弹力图检测相关性探讨及其临床实践的研究。[研究目的]通过调查性临床研究,分析恶性肿瘤高凝状态与瘤种、分期、KPS评分、既往西医治疗等之间的相关性,分析恶性肿瘤患者中医常见证候分布,探索恶性肿瘤高凝状态与中医证候之间的关系,并通过临床实践,进一步探讨中医温阳益气、活血化痰法对改善恶性肿瘤高凝状态的临床疗效,为临床治疗提供参考。[研究方法]第一部分：恶性肿瘤中医证候与血栓弹力图检测相关性分析。以2013年9月至2014年1月在东直门医院血液肿瘤科就诊的门诊恶性肿瘤患者为研究对象,制定调查表,收集病例。采用描述性分析了解患者一般资料、病情信息、血栓弹力图指标分布情况、中医证型分布情况；了解高凝组患者在各瘤种、临床分期、KPS评分、既往西医治疗中的构成比；并分析高凝组患者与中医各证型之间的关系；分析中医各证型与血栓弹力图指标R值、K值、Angle角值、MA值、CI值之间的关系。第二部分：益气温阳、活血化痰法对血栓弹力图的影响。以2013年10月至2014年1月期间在北京中医药大学东直门医院血液肿瘤科就诊的门诊或病房的符合纳入标准的恶性肿瘤高凝状态患者为研究对象,对治疗前后的血栓弹力图指标、KPS评分以及安全性指标进行分析。观察中医温阳益气、活血化痰法对血栓弹力图的影响及安全性。[结果]①在所收集的215例恶性肿瘤患者中,气虚、血瘀、气滞、痰湿、阳虚均是临床常见的证候,其构成比分别为83.26%、66.05%、64.19%、52.09%和50.70%；②在恶性肿瘤患者中高凝状态与化疗、放疗无明显相关性(P>0.05),而与瘤种、临床分期、KPS评分、手术治疗具有一定关系(P<0.05)；③在各中医证型中,阳虚寒凝证与高凝状态关系密切(P<0.05),阳虚寒凝证患者中血液高凝状态的发生率较非阳虚寒凝证患者升高；④不同的中医证型(复合),血栓弹力图指标K值、Angle角值、CI值具有一定差异(P<0.05),阳虚寒凝组具有较高的Angle角值和CI值；⑤恶性肿瘤患者血液发生高凝的危险因素有：瘤种、肿瘤分期、阳虚寒凝证和Angle角值。⑥经益气温阳、活血化痰法治疗后,血栓弹力图指标Angle角值、MA值、CI值均较治疗前下降,K值较治疗前上升(P<0.05)；⑦益气温阳、活血化痰法能改善恶性肿瘤高凝状态患者生活质量(P<0.05)；⑧治疗前后生化指标比较无明显变化(P>0.05),未发生不良反应。[结论]1.阳虚寒凝证与恶性肿瘤高凝状态具有密切关联度。2.瘤种、临床分期、KPS评分、手术治疗均与恶性肿瘤高凝状态具有一定的关联性。3.气虚、血瘀、气滞、痰湿、阳虚均是恶性肿瘤患者临床常见证候,温阳益气、活血化痰理气法可作为恶性肿瘤的基本治疗策略。4.益气温阳、活血化痰法能够改善恶性肿瘤患者血液高凝状态。5.益气温阳、活血化痰法能够改善恶性肿瘤高凝状态患者生活质量。6.益气温阳、活血化痰基本方具有较好的临床安全性。更多还原

【Abstract】 Background:According to the report, about15%of the cancer patients had clinically overt venous thromboembolism, which is the most common complication in these patients and as the second cause of death. Taken active measures to prevent and treat hypercoagulable state has important positive significance in improve the overall quality of life of patients with malignant tumor. A lot of basic and clinical studies have proved that traditional Chinese medicine can effectively improve the hypercoagulable states of cancer patients, and have no significant adverse reactions. Traditional Chinese medicine has a large advantage in prevention and treatment of hypercoagulable state. However, current clinical research of traditional Chinese medicine on cancerous hypercoagulable state is relatively small, the differential treatment is confusion, and has lots of subjective intervention factors. That’s greatly limitied the TCM treatment in clinical application for cancer patients with highcoagulation state. Coagulation is a very complex process, which involves the interaction of many factors. The traditional laboratory coagulation check only isolated parts of the clotting process, and can not understand the whole picture. Thrombelastogram can graphically dynamic, full monitoring the whole process of blood coagulation, from start to clot formation and fibrinolysis, comprehensive testing and evaluate coagulation factors, platelet function, fibrinogen and fibrin dissolution conduct and the results are fast and accurate, can better for clinical services. On this basis, we use thrombelastograph detection value as judged by a hypercoagulable state exploration targets, carried out a study to explore the relationship of cancer patients between TCM syndromes and thrombelastograph testing and its relevance to clinical practice.Objectiver:Throughout the clinical research, study the correlation between cancer hypercoagulable state and tumor stage, KPS score and prior treatment. Analysis of the common syndrome distribution in cancer patients. Explore the relationship between cancer hypercoagulable state and TCM syndromes, and through clinical trials to further evaluate the clinical efficacy of improving cancer patients with hypercoagulable states by the therapeutic methods of Warming Yang and Invigorating Qi, promoting blood circulation and resolving phlegm.Methods:Part one:We took the outpatients with cancer form Dongzhimen hospital during September2013and2014January as study cases, developed investigation table and collected case. Use descriptive research method to recognize the patient’s general information, disease information, thrombelastograph index distribution and TCM syndromes. Then learn the ratio of tumor lesion site, clinical stage, KPS score and prior treatment in the hypercoagulable group. Third, analyze the relationship between cancerous hypercoagulable state and TCM syndromes. Forth, analyze the relationship between the syndromes and thrombelastograph index as R, K, Angle, MA and CI. Part two:We took the out and hospitalized patients with hypercoagulable state form Dongzhimen hospital during October2013and2014January for the study. Analyze thrombelastograph indicators and safety targets before and after the treatment. Observe the clinical efficacy and safety by the therapeutic methods of Warming Yang and Invigorating Qi, promoting blood circulation and resolving phlegm. Results:①In the collected215cases, qi deficiency, blood stasis, qi stagnation, phlegm, yang deficiency were common clinical syndromes, and its constituent ratio was83.26%,66.05%,64.19%,52.09%and50.70%respecily.②In the cancer patients the relationship between hypercoagulable states and chemotherapy, radiation therapy was not show (P>0.05), while the tumor lesion site, clinical stage, KPS score, surgical treatment has a certain relationship (P<0.05).③In various syndromes, the yang deficiency and coagulated cold syndrome closely related with hypercoagulable state (P<0.05), and has higher hypercoagulable states incidence compared with non-yang deficiency and coagulated cold syndrome patients.④The different syndromes (type two combination) have some differences with TEG index K value, Angle values and CI values (P<0.05), yang deficiency and coagulated cold syndrome group has a higher angle value and CI values.⑤Independent risk factor for the occurrence of cancer patients with blood hypercoagulable are:tumor stage, tumor location, yang deficiency and coagulated cold syndrome and Angle value.⑥After taking the Chinese medicine, the patients’ thrombelastograph index angle value, MA value, CI values were all decreased, K values was rised (P<0.05).⑦The therapeutic methods of Warming Yang and Invigorating Qi, promoting blood circulation and resolving phlegm can improve the quality of life of cancer patients with hypercoagulable state (P<0.05).⑧Biochemical parameters before and after treatment showed no significant change (P>0.05), and adverse reactions did not occur. Conclusion:①Yang deficiency and coagulated cold syndrome is closely related to hypercoagulable state.②Tumor lesion site, clinical stage, KPS score, surgery and cancer treatment are have a certain relevance with hypercoagulable state.③Qi deficiency, blood stasis, qi stagnation, phlegm, Yang deficiency are common clinical syndromes in cancer patients, and yang qi, blood and Warming Yang and Invigorating Qi, promoting blood circulation and resolving phlegm and Qi method can be used as one of a basic treatment strategies in malignancies.④The rapeutic method of Warming Yang and Invigorating Qi, promoting blood circulation and resolving phlegm can improve the hypercoagulable state in patients with malignant tumors.⑤Warming Yang and Invigorating Qi, promoting blood circulation and resolving phlegm method can improve the quality of life of malignancy hypercoagulable state.⑥The rapeutic method of Warming Yang and Invigorating Qi, promoting blood circulation and resolving phlegm has a good clinical safety.更多还原