恶性血液病患者抗心磷脂抗体与凝血、纤溶、免疫机制相关性研究
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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、C_3、C_4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(F_(1+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；F_(1+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、C_3、C_4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
Purpose: The malignant hematologic disease is a kind of malignant tumour and
disease 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 in
malignant 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 with
malignant 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 for
twenty 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
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、C_3、C_4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(F_(1+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；F_(1+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、C_3、C_4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
Purpose: The malignant hematologic disease is a kind of malignant tumour and
disease 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 in
malignant 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 with
malignant 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 for
twenty 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
引文
1. pierangeli SS, Gharavi AE, Harris EN. Testing for antiphospholipid antibodies; proble ms and solutions. Clin Obstet Gynecol, 2001, 44: 48-57.
2. Horkko S, Miller E, Branch DW, et al.proc Natl Acad Sci USA, 1997; 94(19): 10356-10361
3. Koike T, Matsuura E.Lupus, 1996; 5(5): 378-380
4. Matsuura E, Lgarashi Y, Fujimoto M, et al. Lancet, 1990; 336(8708): 177-178
5. Merkel PA, Chang Y, Pierangeli SS, et al. Am J Med, 1996; 101(6): 576-583
6. Lillicrap DP, Pinto M, Benford K, et al. Am J Clin Pathol, 1990; 93(6): 771-775
7. leko, M. Antiphospholipid antibodies and thrombosis: the putative mechanis ms of hypercoagulable state in patients with anticardiolipin antibody[J]. Rinsho Byori, 2000, 48(4): 293.
8. Love PE, Santoro SA. Ann Intern Med, 1990; 112(9): 682-698
9. Levine SR, Salowich PL, Sawaya KL, et al. Stroke, 1997; 28(9): 1660-1665
10. Sammaritano LR. Lupus, 1996; 5(5): 436-439
11. Bick RL. Baker WF. Hematol Oncol Clin North Am, 1992; 6(6): 1287-1299
12．丁磊，凌晓斌，胡翊群等。中华血液学杂志，2001：9 (9)：492-493
13．叶晓芬，胡洁，沈伊臬等。中国实验临床免疫学杂志，1997，3：23
14. Wilson WA, Gharavi AE, Koike T, et al. International consensus statement on prelimiary classification criteria for definite antiphospholipid syndrome: report of an internation workshop. Arthritis Rheum, 1999, 42:1309-1311.
15．王振义，李家增，阮长耿，等。血栓与止血与止血基础理论与临床，第2版，上海：上海科学技术出版社，1995：298-301。
16. Blann AD, Lip GYH, Beevers BG, et al. Soluble P-selectin in atherosclerosis: A comparson with endothelial cell and platelet markers. Thormb haemost, 1997, 77: 1077
17. Sadler JE. Thrombomodulin structure and function.1 Thromb Hae most, 1997, 78(1): 392-395.
18. Leo R, Pratico D, Iuliano L, et al. Platelet activation by superoxide anion and hydroxyl radicals intrinsically generated by platelets that had undergone anoxia and than reoxygenated. Circulation, 1997, 95:885
19．关彩霞，血液病患者血浆凝血因子X活性测定的临床意义。临床血液学杂志，1994，7(1)：29-29。
20．乔颖，朱媛媛，丛雅琴，等。急性白血病血浆Ⅶ和Ⅸ凝血因子活性测定意义。血栓与止血学杂志，1997，4(4)：158-159。
21．丛玉隆，伍平，殷宗健，等。血浆凝血因子测定的影响因素探讨。中华医学检验杂志。1995，18(2)：75-77。
22．王中和、吴直江、陆顺娟等。头颈部癌患者手术及放疗前后T细胞亚群变化及其预后价值[J]。实用口腔医学杂志，1994，10(4)：235．
23. Ohovada S. Peripheral blood T cell subsets as a prognostic factor in gastric cancer[J]. 上海免疫学杂志，1998，18(4)：238。
24．陈伟强、张世能。肝癌忠者治闻前后T细胞亚群和SIL2R水平的变化[J]。上海免疫学杂志，1998，18(4)：238。
25．陆紫敏，顾凤英，申远等。恶性血液病治疗前后T细胞亚群和NK细胞活性测定分析。[J]中国肿瘤临床与康复，2002，(9)2：14-16。
26．朱理玮、李克敏、薛承销售部、乳腺癌患者T细胞亚群变化的定量检测及其临床意义[J]。中国肿瘤临床，1994，21(3)：209。
27. Goldstein AL. Clinical applications of thymsin alpha-1[J].Cancer Invest, 1994, 12(5): 545.
28．尹浩然、朱正纲、陈雪华等。进展期胃癌忠者手术前后自然杀伤细胞活性及T细胞亚群变化的研究[J]。中华消化杂志，1992，12(5)：276。
29. John GF, Susan FC, Jolm L, et al. Anticardiolipin antibodies in patients with rheumatic diseases, Arth Rheumat, 1987, 30(7): 752-760.
30. Aguirre V, Cuchacovich R, Barria L, et al. Prevalence and isotype distribution of antiphospholipid antibodies in Childean patients with syste mic lupus erythematosus (SLE). Lupus, 2001, 10(2): 75-80.
31. Pope JE, Thompson A. The frequency and significance of anticardiolipin antibodies in seleroderma. J Rheumatol, 2000, 27(6): 1450-1452.
32. Roussel V. Prevalence and clinical significance of antiphospholipid antibodies in multiple sclerosis: a study of 89 patients. J Autoimmun, 2000, 14(3): 259-265.
33. Ordi-Ros J, Villarreal J, Monegal F, et al. Asnticardiolipin antibodies in patients with chronic hedpatitis C vires infection characterization in relation to antiphospholipid syndrome. Clin Diagn Lab Immunol, 2000, 7(2): 241-244.
34. Lossos IS, Bogomolski Yahalom V, Matzner Y. Anticardiolipin antibodies in acute myeloid leuke mia: prevalence and clinical significance. Am J Hematol, 1998, 57(2): 139-143.
35．王振义。血栓与止血基础理论与临床[M]。上海：上海科学出版社，1995，507-513。
36．汪钟。现代血栓病学[M】。北京：北京医科大家联合出版社，1997，1。
37．王霄霞，王明山。肾病综合征患者血浆D二聚体检测的临床意义[J]。实用医学杂志，1998，12：25。
38. Chamley LW, Pattison NS, McKay EJ. Anomalous anticardiolipin antibody results may be due to cofactor variability[J]. Am J Hematol, 1991, 37(4): 289.
39．邓宇斌，陈顺乐，鲍春德，等。抗磷脂抗体作用的抗原组成成分分析研究[J]。中国免疫学杂志，1997，13(3)：167-169。
40．邓水泉，高丽玲，张盛洪，等。高血压病患者抗心磷脂抗体测定的临床意义[J]。中国循环杂志，1997，12(4)：270-271。
41．汪芳，孙福成，胡锦章，等。300例冠状动脉造影狭窄程度与血浆纤维蛋白原水平关系[J]。中国循环杂志，1998，13(2：)78-79。
42. Lossos, -I-S; Anticardiolipin antibodies in acute myeloid leukemia: prevalence and clinical significance. Am-J-Hematol. 1998 Feb: 57(2): 139-143.
43．顾静，陈唤青；杨锦嫒：(南通医学院附属医院血液研究室)白血病患者抗心磷脂抗体的研究。南通医学院学报。1995V15N_2：187-188。
44. Fabrizi F, Sangiorgio R,Pontoricro G, et al ,Antiphospholipid (apl) antiodies in eng-stage renl disease [J].J Nephorl. 1999.12(2):89.
45. Vaidys S ,Sellers R ,Kimball P ,et al ,Frquency,potentialrisk and therapeutic in end-stage renal disease patrents with antiphospholipid antibody syndrome:a multicenter study[J].Transplantaation.2000.69(7): 1348.
46. Shah NM,Khamashta MA,Atsumi T ,et al.Oucome of patients with anticardiolipim antibodies:a 10 year follow-rp of 52 patients[J].Lupus. 1998.7:3.
47. Myones BL,McCurdy D.The amtiphospholipid syndrime:im munologic and climical aspects,climical spectrun and tratmant[J]. J Rheumatol,2000,27(Suppl 58) :20.
48. Sherer Y, Levy Y, Shoenfeld Y. Intravenous immunoglobulin therapy of antiphospholipid syndrome[J]. Rheumatology,2000, 39(4):421.
49. Aoki K, Antiphospholipid antibody syndrome in adverse pregnancy[J]. Rinsho Byori, 2000, 48(4): 323.
50. Lima F, Khamashta MA, Buchanan NMM, et al. Astudy of sixty pregnancies in patients with the antiphospholipid syndrome[J]. Clin Exp Rheumatol, 1996, 14:131.
51．瞿文，吕琳，黄达永，等。血小板减少下腔及左肾静脉血栓抗心磷脂抗体阳性[J]。中华医学杂志，2001，81(17)：1027。
52. Reshetnyak TM, Kalashnikova LA, Alexandrova EN, et al. Outcome of 280 patients with systemic lupus erythematosus and 74 patients with primary antiphospholipid
syndrome: 8 year follows-up[J]. J Autoimmun, 2000, 15: 93.
53. Mary Carmen Amigo MD. Prognosis in antiphospholipid syndrome[J]. Rheu Dis Clin, 2001, 27(3): 661.
54. Matsuura E, Igarashi Y, Fujimoto M, et al. Anticardiolpin cofactor(s and differntial diagnosis of autoimmune disease. Lancet, 1990, 336:177-178.
55. Greaves M, Cohen H, MacHin SJ, et al. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol, 2000, 109:704-715.
56. Horkko S, Olee T, Mo L, et al. Anticardiolpin antibodies from patients with the antiphospholipid antibody syndrome recognize epitopes in both beta(2)- glycoprotein 1 and oxidized low-density lipoprotein., Circulation, 2001, 103:941-946.
57. Reber G, Arvieux J, Comby E, et al. Multicenterf evaluation of nine commercial kits for the quantitation of anticardiolipin antiboidies, the working group on methodologies in hae mostasis form the GEHT(Grouped) Etudes surl Hemostase et al Thrombose). Thromb Haemost, 1995, 73: 444-452.
58. Tincani A, Balestrieri G, Allegri F, et al. Overview on anticardiolipin ELISA standardization, J Autoimmun, 2000, 15: 195-197.
59. Pierangeli SS, Stewart M, Silva LK, et al. An antiphospholipid wet workshop: 7_(th) intermational symposium on antiphospholipid antibodies J Rheumatol, 1998, 25: 156-160.
60. Merkel PA, Chang Y, Pierangeli SS, et al. Comparison between the standard anticardiolipin antibody test and a new phospholipid test inpatients with connective tissue diseases. J Rheumatol, 1999, 26: 591-596.
61. Abreu I, Pierangeli SS, Harris EN. Comparison of three assays for the detection of antiphospholipid and anti-β 2-glycoprote in 1 antibodies. Lupus, 1998, 7:S211.
62. Harris EN, Pierangeli SS. 'Equivocal' antiphopholipid syndrome. J Autoimmun, 2000, 15: 81-85.
2. Horkko S, Miller E, Branch DW, et al.proc Natl Acad Sci USA, 1997; 94(19): 10356-10361
3. Koike T, Matsuura E.Lupus, 1996; 5(5): 378-380
4. Matsuura E, Lgarashi Y, Fujimoto M, et al. Lancet, 1990; 336(8708): 177-178
5. Merkel PA, Chang Y, Pierangeli SS, et al. Am J Med, 1996; 101(6): 576-583
6. Lillicrap DP, Pinto M, Benford K, et al. Am J Clin Pathol, 1990; 93(6): 771-775
7. leko, M. Antiphospholipid antibodies and thrombosis: the putative mechanis ms of hypercoagulable state in patients with anticardiolipin antibody[J]. Rinsho Byori, 2000, 48(4): 293.
8. Love PE, Santoro SA. Ann Intern Med, 1990; 112(9): 682-698
9. Levine SR, Salowich PL, Sawaya KL, et al. Stroke, 1997; 28(9): 1660-1665
10. Sammaritano LR. Lupus, 1996; 5(5): 436-439
11. Bick RL. Baker WF. Hematol Oncol Clin North Am, 1992; 6(6): 1287-1299
12．丁磊，凌晓斌，胡翊群等。中华血液学杂志，2001：9 (9)：492-493
13．叶晓芬，胡洁，沈伊臬等。中国实验临床免疫学杂志，1997，3：23
14. Wilson WA, Gharavi AE, Koike T, et al. International consensus statement on prelimiary classification criteria for definite antiphospholipid syndrome: report of an internation workshop. Arthritis Rheum, 1999, 42:1309-1311.
15．王振义，李家增，阮长耿，等。血栓与止血与止血基础理论与临床，第2版，上海：上海科学技术出版社，1995：298-301。
16. Blann AD, Lip GYH, Beevers BG, et al. Soluble P-selectin in atherosclerosis: A comparson with endothelial cell and platelet markers. Thormb haemost, 1997, 77: 1077
17. Sadler JE. Thrombomodulin structure and function.1 Thromb Hae most, 1997, 78(1): 392-395.
18. Leo R, Pratico D, Iuliano L, et al. Platelet activation by superoxide anion and hydroxyl radicals intrinsically generated by platelets that had undergone anoxia and than reoxygenated. Circulation, 1997, 95:885
19．关彩霞，血液病患者血浆凝血因子X活性测定的临床意义。临床血液学杂志，1994，7(1)：29-29。
20．乔颖，朱媛媛，丛雅琴，等。急性白血病血浆Ⅶ和Ⅸ凝血因子活性测定意义。血栓与止血学杂志，1997，4(4)：158-159。
21．丛玉隆，伍平，殷宗健，等。血浆凝血因子测定的影响因素探讨。中华医学检验杂志。1995，18(2)：75-77。
22．王中和、吴直江、陆顺娟等。头颈部癌患者手术及放疗前后T细胞亚群变化及其预后价值[J]。实用口腔医学杂志，1994，10(4)：235．
23. Ohovada S. Peripheral blood T cell subsets as a prognostic factor in gastric cancer[J]. 上海免疫学杂志，1998，18(4)：238。
24．陈伟强、张世能。肝癌忠者治闻前后T细胞亚群和SIL2R水平的变化[J]。上海免疫学杂志，1998，18(4)：238。
25．陆紫敏，顾凤英，申远等。恶性血液病治疗前后T细胞亚群和NK细胞活性测定分析。[J]中国肿瘤临床与康复，2002，(9)2：14-16。
26．朱理玮、李克敏、薛承销售部、乳腺癌患者T细胞亚群变化的定量检测及其临床意义[J]。中国肿瘤临床，1994，21(3)：209。
27. Goldstein AL. Clinical applications of thymsin alpha-1[J].Cancer Invest, 1994, 12(5): 545.
28．尹浩然、朱正纲、陈雪华等。进展期胃癌忠者手术前后自然杀伤细胞活性及T细胞亚群变化的研究[J]。中华消化杂志，1992，12(5)：276。
29. John GF, Susan FC, Jolm L, et al. Anticardiolipin antibodies in patients with rheumatic diseases, Arth Rheumat, 1987, 30(7): 752-760.
30. Aguirre V, Cuchacovich R, Barria L, et al. Prevalence and isotype distribution of antiphospholipid antibodies in Childean patients with syste mic lupus erythematosus (SLE). Lupus, 2001, 10(2): 75-80.
31. Pope JE, Thompson A. The frequency and significance of anticardiolipin antibodies in seleroderma. J Rheumatol, 2000, 27(6): 1450-1452.
32. Roussel V. Prevalence and clinical significance of antiphospholipid antibodies in multiple sclerosis: a study of 89 patients. J Autoimmun, 2000, 14(3): 259-265.
33. Ordi-Ros J, Villarreal J, Monegal F, et al. Asnticardiolipin antibodies in patients with chronic hedpatitis C vires infection characterization in relation to antiphospholipid syndrome. Clin Diagn Lab Immunol, 2000, 7(2): 241-244.
34. Lossos IS, Bogomolski Yahalom V, Matzner Y. Anticardiolipin antibodies in acute myeloid leuke mia: prevalence and clinical significance. Am J Hematol, 1998, 57(2): 139-143.
35．王振义。血栓与止血基础理论与临床[M]。上海：上海科学出版社，1995，507-513。
36．汪钟。现代血栓病学[M】。北京：北京医科大家联合出版社，1997，1。
37．王霄霞，王明山。肾病综合征患者血浆D二聚体检测的临床意义[J]。实用医学杂志，1998，12：25。
38. Chamley LW, Pattison NS, McKay EJ. Anomalous anticardiolipin antibody results may be due to cofactor variability[J]. Am J Hematol, 1991, 37(4): 289.
39．邓宇斌，陈顺乐，鲍春德，等。抗磷脂抗体作用的抗原组成成分分析研究[J]。中国免疫学杂志，1997，13(3)：167-169。
40．邓水泉，高丽玲，张盛洪，等。高血压病患者抗心磷脂抗体测定的临床意义[J]。中国循环杂志，1997，12(4)：270-271。
41．汪芳，孙福成，胡锦章，等。300例冠状动脉造影狭窄程度与血浆纤维蛋白原水平关系[J]。中国循环杂志，1998，13(2：)78-79。
42. Lossos, -I-S; Anticardiolipin antibodies in acute myeloid leukemia: prevalence and clinical significance. Am-J-Hematol. 1998 Feb: 57(2): 139-143.
43．顾静，陈唤青；杨锦嫒：(南通医学院附属医院血液研究室)白血病患者抗心磷脂抗体的研究。南通医学院学报。1995V15N_2：187-188。
44. Fabrizi F, Sangiorgio R,Pontoricro G, et al ,Antiphospholipid (apl) antiodies in eng-stage renl disease [J].J Nephorl. 1999.12(2):89.
45. Vaidys S ,Sellers R ,Kimball P ,et al ,Frquency,potentialrisk and therapeutic in end-stage renal disease patrents with antiphospholipid antibody syndrome:a multicenter study[J].Transplantaation.2000.69(7): 1348.
46. Shah NM,Khamashta MA,Atsumi T ,et al.Oucome of patients with anticardiolipim antibodies:a 10 year follow-rp of 52 patients[J].Lupus. 1998.7:3.
47. Myones BL,McCurdy D.The amtiphospholipid syndrime:im munologic and climical aspects,climical spectrun and tratmant[J]. J Rheumatol,2000,27(Suppl 58) :20.
48. Sherer Y, Levy Y, Shoenfeld Y. Intravenous immunoglobulin therapy of antiphospholipid syndrome[J]. Rheumatology,2000, 39(4):421.
49. Aoki K, Antiphospholipid antibody syndrome in adverse pregnancy[J]. Rinsho Byori, 2000, 48(4): 323.
50. Lima F, Khamashta MA, Buchanan NMM, et al. Astudy of sixty pregnancies in patients with the antiphospholipid syndrome[J]. Clin Exp Rheumatol, 1996, 14:131.
51．瞿文，吕琳，黄达永，等。血小板减少下腔及左肾静脉血栓抗心磷脂抗体阳性[J]。中华医学杂志，2001，81(17)：1027。
52. Reshetnyak TM, Kalashnikova LA, Alexandrova EN, et al. Outcome of 280 patients with systemic lupus erythematosus and 74 patients with primary antiphospholipid
syndrome: 8 year follows-up[J]. J Autoimmun, 2000, 15: 93.
53. Mary Carmen Amigo MD. Prognosis in antiphospholipid syndrome[J]. Rheu Dis Clin, 2001, 27(3): 661.
54. Matsuura E, Igarashi Y, Fujimoto M, et al. Anticardiolpin cofactor(s and differntial diagnosis of autoimmune disease. Lancet, 1990, 336:177-178.
55. Greaves M, Cohen H, MacHin SJ, et al. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol, 2000, 109:704-715.
56. Horkko S, Olee T, Mo L, et al. Anticardiolpin antibodies from patients with the antiphospholipid antibody syndrome recognize epitopes in both beta(2)- glycoprotein 1 and oxidized low-density lipoprotein., Circulation, 2001, 103:941-946.
57. Reber G, Arvieux J, Comby E, et al. Multicenterf evaluation of nine commercial kits for the quantitation of anticardiolipin antiboidies, the working group on methodologies in hae mostasis form the GEHT(Grouped) Etudes surl Hemostase et al Thrombose). Thromb Haemost, 1995, 73: 444-452.
58. Tincani A, Balestrieri G, Allegri F, et al. Overview on anticardiolipin ELISA standardization, J Autoimmun, 2000, 15: 195-197.
59. Pierangeli SS, Stewart M, Silva LK, et al. An antiphospholipid wet workshop: 7_(th) intermational symposium on antiphospholipid antibodies J Rheumatol, 1998, 25: 156-160.
60. Merkel PA, Chang Y, Pierangeli SS, et al. Comparison between the standard anticardiolipin antibody test and a new phospholipid test inpatients with connective tissue diseases. J Rheumatol, 1999, 26: 591-596.
61. Abreu I, Pierangeli SS, Harris EN. Comparison of three assays for the detection of antiphospholipid and anti-β 2-glycoprote in 1 antibodies. Lupus, 1998, 7:S211.
62. Harris EN, Pierangeli SS. 'Equivocal' antiphopholipid syndrome. J Autoimmun, 2000, 15: 81-85.