【作者】 刘金宏；

【导师】 赵洪国；

【作者基本信息】 青岛大学 ， 内科学， 2004， 硕士

【摘要】 目的：恶性血液病是造血系统的一种恶性肿瘤性疾病，在青少年恶性肿瘤中发病率占首位，严重威胁人类的健康，其特征是在骨髓及其它组织中恶性细胞的异常增生及浸润，可导致正常造血功能受抑与机体凝血、纤溶、免疫机制受损。机体的免疫功能与肿瘤的发生和发展有密切关系，当宿主免疫功能与肿瘤的发生和发展有密切关系，当宿主免疫功能低下或受抑制时，肿瘤发病率增高，而在肿瘤进行性生长时，患者的免疫功能进一步受到抑制。恶性血液病患者的免疫功能异常与预后密切相关，抗心磷脂抗体（ACA）是与心磷脂分子中带负电荷的磷酸二酯基团结合的一种自身抗体，在监控机体的免疫功能 上有重要意义。 ACA是以血小板和内皮细胞膜上带负电荷的心磷脂作为靶抗原，在参与凝血过程时，影响多种依赖的反应体系，可引起凝血、纤溶功能的紊乱。另外，ACA与血小板内膜的磷脂结合，增加了单核巨噬细胞对血小板的吞噬和破坏，导致血小板减少，同时ACA促使血小板激活，从而易于形成血栓，使血小板进一步消耗性减少，造成极大多数恶性血液病患者临床表现有出血。 为了研究ACA与恶性血液病患者的凝血、纤溶、免疫机制的相关性，通过检测恶性血液病患者ACA发生率，检测血浆纤维蛋白原、D二聚体、凝血酶原片段1+2，纤溶酶原等凝血、纤溶指标，检测血清IgG、IgA、IgM、C₃、C₄及循环免疫复合物的含量等免疫指标，经统计学处理控讨其相关性，评估恶性血液病患者临床出血险度与免疫状态，从而降低恶性血液病患者的化疗相关死亡率以提高总体生存率，具有很高的临床实际应用价值。 方法：研究对象，选自菏泽医专附属医院及青岛大学医学院附属医院血液科门诊与住院恶性血液病患者。对照组，选自菏泽医专100名健康查体的学生。实验室检测。血浆制备，抽取静脉血以0.13mol／L拘椽酸钠抗凝，2500×g离心20分钟取上层血浆-30℃冻存，1月内待检。血清制备，抽取静脉血经37℃温育后，2500×g离心20分钟，吸取血清置-30℃保存待测。ACA检测。采用ELISA法分虽检测血清IgG、IgA、IgM型ACA。每例标本均检测2次，之间相隔1个月。阳性结果判断以ACA结合指数上限X标准品A值的数为依据。试剂购于福建太阳生物技术公司。凝血、纤溶指标检测。血浆纤维蛋白（Fg）、D二聚体（DD）、凝血酶原片段1+2(F₁₊₂)、纤溶酶原（PLG）使用Sysmex CAI500仪器检测。Fg定量用clauss法；DD检测用免疫比浊法；F₁₊₂检测用ELISA法；PLG检测用发色底物法。试剂购于Dade Behring公司。免疫指标的检定。采用免疫比浊法测定血清IgG、IgA、IgM、C₃、C₄的含量，循环免疫复合物 摘要CIC以聚乙二醇浊度法测定。统计学处理八（:A的三种免疫球蛋自与凝1111.、纤溶和免疫功能检测结果之间相关性分析，各组间阳性率比较XZ检验。结果:l、AcA的分布。恶性血液病患者AcA阳性率为39.7%，正常对照组AcA阳性率为8%，两组相比有显著性意义（、P<0.01）。2、ACA与急性白血病缓解的关系。治疗前测定ACA的患者有随访结果的之1心例，比中化疗后已取得完全缓解者:拍例，A（姚阳性!魂例，!魂例末能取得缓解随即死l’_，A以阳性者6例，二者间无显著性差异（P）（）.（）5）。3、ACA免疫类型（IgG、IgM、lgA）与凝血和纤溶指标的相关性。AC八一lgG和ACALgM与恶性血液病患者的!）一二聚体、凝血.酶原片段1+2、纤溶酶原之间有显示著相关性。4、lf0栓取!（或）DIC与ACA一IgG、ACA一坛M之间具有相关性（P<0.05）.5、ACA与免疫指标的关系，ACA结合指数与血清免疫球蛋白，循环免疫复.合物高度相关性（}〕<0.01），ACA一工gG与C;呈负相关性（P<0.05）。结论:在恶性血.液病患者体内，抗心磷!}旨抗体与凝血、纤溶、免疫机制具有相关性更多还原

【Abstract】 Purpose: The malignant hematologic disease is a kind of malignant tumour anddisease of the hemopoiesis system, the incidence of the disease takes the first place in teenagers’ malignant tumour, and it threatens the human health seriously. It is characterized by malignant unusual hyperplasia and soading of cells in medulla ossium and other tissues, which can damage the normal hemopoiesis function and the mechanism of blood coagulation fibrinolysis and immunology. The immune function of the organism has close relations with emergence and development of the rumour. When host’s immune function is low or restrained, the incidence of tumour increases, and in the growth of the tumour, the patient’s immune function is suppressed further. The malignant blood disease patient’s immnue function is closely related to prognosis., ACA is an autoantibody, which is united in two ester base with negative electrics at phosphatide molecule phosphoric acid. It is significant in monitoring the body’s immune function. ACA’s target antigen is the negative cardiolipin in the blood platelets and the membrane of endothelium. It influences various reaction systems depending on cardiiolipin in the course of blood coagulation, disruptiung the function of blood coagulation and fibrinolysis. In addition, ACA’s combination with the phosphatide of the membrane in the blood platelet increases the phagocytosis and destruction of the blood platelets by monocytes, reducing the blood platelets. At the same time ACA impels the blood platelet to be activated, and thus the thrombus forms easily, reducing the blood platelets further and causing the clinical manifestation of bleeding in the majority of malignant blood diesease patients. In order manifestation of bleeding in the majority of malignant blood disease patients. In order to study ACA’s relation with the machanism of blood coaugulation fibrinolysis and immunology malignant blood disease patients, we measure the incidence of ACA, coagulation and fibrinolysis indexes, such as plasma fibrinogen, Ddimer , serozyme fragment 1+2, plasminogen, etc, and immune indexes, such as serum IgG,IgM,C3,C4,circulating immune complex,etc.through statistic analysis we investigate their relations and thus assess the dangerous degree of hemorrhage and immune state inmalignant blood disease patients, which can reduce patients’ mortality associated with chemotherapy and improve overall survival rate. So ACA has great clinic practical application value.Methods: 1 Research object, selected from the outpatients and inpatients withmalignant blood diseases of the affiliated hospitals of Heze medical college and Qingdao university medical college. 2 control, selected from 100 healthy students of Heze medical college. 3 The laboratory measurement. 3.1 The plasma preparing, collect the vein blood, anticoagulated with the sodium citrate of 0.13mol/L. after centrifugation at 2500*g fortwenty minutes, collect upper plasma and place it in -30癈 environment. Measure it in one month. 3.2 The scrum preparing, collect vein blood after cultivated in 37癈 environment,centrafugating at 2500*g for twenty minutes. Draw serum and put it in -30 癈environment for measuring. 3.3 ACA measurement, measure serum IgG,IgA,IgM Mode ACA separately by ELISA. Each sample is measured for 2times. The second time is underwent one month after the first. Positive results are judged by ACA combination index upper limit * standard product A value. The reagent is purchased in the sun biotech company of Fujian. 3.4 The measurement of blood coagulation and fibrinolysis indexes. The plasma fibrinogen (Fg), Ddimer(DD), serozymel+2(f1+2) and plasminogen are measured by Sysmex CAI500, Fg is measured by clauss, DD by immunonephelometry, f1+2 by ELISA. The reagent is purchased in Dade Behring Company. 3.5 Determine the immune index. Adopt the immunonephelometry to determine serum IgG, IgA, IgM, C3, C4. Immune complex is measured. 3.6 Statistic analysis. Three immunoglobulin (Ig) of ACA and blood coagulation, fibrinolysis and result of immune funct更多还原