获得性低巨核细胞血小板减少性紫癜29例回顾性分析
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摘要
前言
获得性低巨核细胞血小板减少性紫癜是一组临床表现为皮肤、粘膜出血,实验室检查血小板减少、骨髓巨核细胞减少甚至缺如而红、白系细胞大致正常的疾病。它的临床表现跟特发性血小板减少性紫癜相似,所以它常被当作特发性血小板减少性紫癜的一个特殊类型,也有报道它可转化其他疾病,主要是血液系统疾病,因此它也被认为可能是其他疾病的前期表现,也有人认为它是一个独立的疾病,本质是各种因素引起的巨核细胞生成障碍,治疗效果不同于特发性血小板减少性紫癜,也不向其他疾病转化。获得性低巨核细胞血小板减少性紫癜其实是一组疾病的共同表现,它的预后和转归也不尽相同。因其在临床较少见,相关研究少,目前AATP的机制尚不清楚,治疗上大多数医生仍采用传统的治疗特发性血小板减少性紫癜的方法,但多数治疗效果差。
目的
进一步了解获得性低巨核细胞血小板减少性紫癜的临床特点并探索影响获得性低巨核细胞血小板减少性紫癜治疗效果的因素。可使我们在疾病早期做出正确的判断,以选择适合的治疗方案。
方法
回顾性分析汕头大学第一附属医院2002年至2008年的29例获得性低巨核细胞性血小板减少性紫癜的临床资料,分析该病的临床特点以及性别、年龄、初诊时外周血的血小板计数、淋巴细胞比例、骨髓巨核细胞数、合并免疫相关性疾病等因素与获得性低巨核细胞性血小板减少性紫癜治疗效果的关系。
结果
AATP患者中男性治疗有效率0%,女性有效率65.21%,差异有统计学意义(P<0.05);不同年龄阶段的患者治疗有效率有无明显的统计学差异(P>0.1);初诊时血小板计数的不同跟患者治疗有效率亦有明显关系(P<0.05);而外周血淋巴细胞比例的变化跟患者疗效差别无明显统计学意义(P>0.1);初诊时骨髓巨核细胞数是否缺如能够影响治疗效果(P<0.05);是否合并免疫相关疾病对患者治疗效果无明显影响(P>0.1)。
结论
男性患者、初诊时血小板计数低于10×109/L、巨核细胞完全缺如可能是AATP的高危因素,治疗效果差。
Foreword
Acquired amegakaryocytic thrombocytopenic purpura(AATP), is a group of disorders,of which the clinical presentation are burising、bleeding, and its laboratory examination are thrombocytopenia、marked decrease or total absence of megakaryocytes with the other cell lines preserved in the bone marrow. The clinical presentation of AATP is similar to Idopathic thrombocytopenic purpura(ITP), so it is usually cosidered as a special type of ITP. Some studies indicated that it may be a primary disorder of other disease, most of them are hematologic diseases. Otherwise, some people just think it’s a independent disease,of which the essense is the suppression of megakaryocytic differentiation caused by a variety of factors. Its therapeutic effect dissimilar to ITP, and it also not progress to other diseases. AATP is a manifestation of groups of diseases, it has a variety of prognosis. AATP is a rare disorder, which is lack of studies, so its pathogenetic mechanisms are not very well understood. Many doctors still adopt the common therapy of ITP for AATP, but majority of patients didn’t response.
Objective
The thesis is to get more knowledge of AATP, and try to find out some factors that can predict the prognosis of AATP, it may help doctors to make a correct diagnosis and choose a more effective therapy.
Methods
We make a retrospective analysis of 29 cases of AATP form the first affiliated hospital of Shantou university medical college. We analyse list the characteristic of AATP, and try to find out the relationship amount sex、age、first platelet count in periphery blood、proportion of lymphocyte、megakaryocyte count in bone marrow、undergo a autoimmune disease and reaction of teatment.
Results
65.21% of female patients reacted to the therapy while 0% male patients did, the difference is obvious(P<0.05). Patients of different years old didn’t have obvious reaction to therapy(P>0.1). Patient whose first platelet count is less than 10×109/L had a bad reaction to therapy too(P<0.05). The proportion of lymphocyte didn’t affect the reaction to therpy( P>0.1). Totally defect of megakaryocyte in bone marrow induce a poor reaction to therpy(P<0.05).Whether accompany with a atuoimmune disease didn’t affect the reaction to therpy( P>0.1).
Conclusions
Male、platelet count less than 10×109/L、have a total absence of megakaryocytes in bone marrow may be the risk factors of AATP, patients with them have a poor reaction to therapy.
获得性低巨核细胞血小板减少性紫癜是一组临床表现为皮肤、粘膜出血,实验室检查血小板减少、骨髓巨核细胞减少甚至缺如而红、白系细胞大致正常的疾病。它的临床表现跟特发性血小板减少性紫癜相似,所以它常被当作特发性血小板减少性紫癜的一个特殊类型,也有报道它可转化其他疾病,主要是血液系统疾病,因此它也被认为可能是其他疾病的前期表现,也有人认为它是一个独立的疾病,本质是各种因素引起的巨核细胞生成障碍,治疗效果不同于特发性血小板减少性紫癜,也不向其他疾病转化。获得性低巨核细胞血小板减少性紫癜其实是一组疾病的共同表现,它的预后和转归也不尽相同。因其在临床较少见,相关研究少,目前AATP的机制尚不清楚,治疗上大多数医生仍采用传统的治疗特发性血小板减少性紫癜的方法,但多数治疗效果差。
目的
进一步了解获得性低巨核细胞血小板减少性紫癜的临床特点并探索影响获得性低巨核细胞血小板减少性紫癜治疗效果的因素。可使我们在疾病早期做出正确的判断,以选择适合的治疗方案。
方法
回顾性分析汕头大学第一附属医院2002年至2008年的29例获得性低巨核细胞性血小板减少性紫癜的临床资料,分析该病的临床特点以及性别、年龄、初诊时外周血的血小板计数、淋巴细胞比例、骨髓巨核细胞数、合并免疫相关性疾病等因素与获得性低巨核细胞性血小板减少性紫癜治疗效果的关系。
结果
AATP患者中男性治疗有效率0%,女性有效率65.21%,差异有统计学意义(P<0.05);不同年龄阶段的患者治疗有效率有无明显的统计学差异(P>0.1);初诊时血小板计数的不同跟患者治疗有效率亦有明显关系(P<0.05);而外周血淋巴细胞比例的变化跟患者疗效差别无明显统计学意义(P>0.1);初诊时骨髓巨核细胞数是否缺如能够影响治疗效果(P<0.05);是否合并免疫相关疾病对患者治疗效果无明显影响(P>0.1)。
结论
男性患者、初诊时血小板计数低于10×109/L、巨核细胞完全缺如可能是AATP的高危因素,治疗效果差。
Foreword
Acquired amegakaryocytic thrombocytopenic purpura(AATP), is a group of disorders,of which the clinical presentation are burising、bleeding, and its laboratory examination are thrombocytopenia、marked decrease or total absence of megakaryocytes with the other cell lines preserved in the bone marrow. The clinical presentation of AATP is similar to Idopathic thrombocytopenic purpura(ITP), so it is usually cosidered as a special type of ITP. Some studies indicated that it may be a primary disorder of other disease, most of them are hematologic diseases. Otherwise, some people just think it’s a independent disease,of which the essense is the suppression of megakaryocytic differentiation caused by a variety of factors. Its therapeutic effect dissimilar to ITP, and it also not progress to other diseases. AATP is a manifestation of groups of diseases, it has a variety of prognosis. AATP is a rare disorder, which is lack of studies, so its pathogenetic mechanisms are not very well understood. Many doctors still adopt the common therapy of ITP for AATP, but majority of patients didn’t response.
Objective
The thesis is to get more knowledge of AATP, and try to find out some factors that can predict the prognosis of AATP, it may help doctors to make a correct diagnosis and choose a more effective therapy.
Methods
We make a retrospective analysis of 29 cases of AATP form the first affiliated hospital of Shantou university medical college. We analyse list the characteristic of AATP, and try to find out the relationship amount sex、age、first platelet count in periphery blood、proportion of lymphocyte、megakaryocyte count in bone marrow、undergo a autoimmune disease and reaction of teatment.
Results
65.21% of female patients reacted to the therapy while 0% male patients did, the difference is obvious(P<0.05). Patients of different years old didn’t have obvious reaction to therapy(P>0.1). Patient whose first platelet count is less than 10×109/L had a bad reaction to therapy too(P<0.05). The proportion of lymphocyte didn’t affect the reaction to therpy( P>0.1). Totally defect of megakaryocyte in bone marrow induce a poor reaction to therpy(P<0.05).Whether accompany with a atuoimmune disease didn’t affect the reaction to therpy( P>0.1).
Conclusions
Male、platelet count less than 10×109/L、have a total absence of megakaryocytes in bone marrow may be the risk factors of AATP, patients with them have a poor reaction to therapy.
引文
1. Hoffman R, Bruno E, Elwell J, et al. Acquired amegakaryocytic thrombocytopenic purpura: a syndrome of diverse etiologies. Blood, 1982, 60:1173–8.
2. Y Xue, R Zhang. Acquired amegakaryocytic thrombocytopenic purpura with a Philadelphia chromosome. Cancer Genet Cytogenet, August 1, 1993, 69(1): 51-6.
3. G Lugassy. Non-Hodgkin's lymphoma presenting with amegakaryocytic thrombocytopenic purpura. Ann Hematol, July 1, 1996, 73(1): 41-2.
4. PA Kouides and JM Rowe. Large granular lymphocyte leukemia presenting with both amegakaryocytic thrombocytopenic purpura and pure red cell aplasia: clinical course and response to immunosuppressive therapy. Am J Hematol, July 1, 1995, 49(3): 232-6.
5. Dominic W. Lai a, Thomas P. Loughran Jr,et al. Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia associated with an occult large granular lymphocyte leukemia. Leukemia Research,2008, 32:823–827.
6. Ergas D, Tsimanis A, et al. T-gamma large granular lymphocyte leukemia associated with amegakaryocytic thrombocytopenic purpura, Sjogren’s syndrome, and polyglandular autoimmune syndrome type II, with subsequent development of pure red cell aplasia. Am J Hematol,2002, 69:132-134.
7. Wesley H. Witteles,et al. Lung Cancer Presenting With Amegakaryocytic Thrombocytopenia. JOURNAL OF CLINICAL ONCOLOGY , 2008 Mar 1, 26(7):1171-4.
8. I. Maslovsky,D. Gefel ,et al. Malignant thymoma complicated by amegakaryocytic thrombocytopenic purpura , European Journal of Internal Medicine. 2005, 16:523-524.
9. JA King, MY Elkhalifa, LF Latour ,et al. Rapid progression of acquired amegakaryocytic thrombocytopenia to aplastic anemia. South Med J, January 1, 1997, 90(1): 91.
10.石慧文。获得性低巨核细胞性血小板减少性紫癜。国外医学输血及血液学分册,2001,24(6)。
11.Domingo Luciani, Caracas, Venezuela. Acquired amegakaryocytic thrombocytopenic purpura:Review of a not very well-defined disorder. Eur J Intern Med, November 1, 2005, 16(7): 477-81.
12.李四强,宫超,等。获得性低巨核细胞减少性紫癜骨髓活检的临床意义。中国误诊学杂志,2005,5(5):921-922。
13.李栋。获得性低巨核细胞性血小板减少性紫癜20例临床分析。中华血液学杂志,1996,17(3),148-149。
14.陆德炎陈义平,等。获得性单纯无巨核细胞性血小板减少性紫癜发病机制的研究。中华血液学杂志,1999,22(3):124-126。
15. M Katai, T Aizawa, N Ohara , et al. Acquired amegakaryocytic thrombocytopenic purpura with humoral inhibitory factor for megakaryocyte colony formation. Intern Med, March 1, 1994, 33(3): 147-9.
16. Podolak-Dawidziak M,et al. Acquired amegakaryocytic thrombocytopenic purpura (AATP): a study of autologous megakaryocyte progenitors and the effect of patients plasma on normal marrow megakaryocyte colony formation. Folia Haematol Int Mag Klin Morphol Blutforsch,1990, 117(2):347-51。
17. Kuwaki T, Hagiwara T, Yuki C, et al. Quantitative analysis of thrombopoietin receptors on human megakaryocytes. FEBS Lett,1998, 427: 46250.
18. Kaushansky K, et al. Thrombopoietin: the primary regulator of platelet production. Blood, 1995, 86:419–31.
19. Wendling F, Maraskovsky E, Debili N, Florindo C, Teepe M,Titeux M, et al. cMpl ligand is a humoral regulator of megakaryocytopoiesis.Nature, 1994, Jun 16, 369(6481):519-20.
20.David J. Kuter. New thrombopoietic growth factors. Blood,2007, 109: 4607-4616.
21.Hiroko Shiozaki,Shuichi Miyawaki,et al. Autoantibodies neutralizing thrombopoietin in a patient with amegakaryocytic thrombocytopenic purpura. Blood, 2000,95(6):2187-2188.
22.Mukai HY,et al. Serum thrombopoietin (TPO) levels in patients with amegakaryocytic thrombocytopenia are much higher than those with immune thrombocytopenic purpura. Thromb Haemost, 1996, Nov, 76(5):675-8.
23. Masataka Kuwana, Yuka Okazaki, et al. Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: relationship to thrombocytopenia with megakaryocytic hypoplasia. Arthritis and Rheumatism,2002, Aug, 46(8):2148-59.
24. M. Kuwana, J. Kaburaki,et al. Two types of autoantibody-mediated thrombocytopenia in patients with systemic lupus erythematosus. Rheumatology,2006, 45:851-854.
25.T Fukushima,L Dong,et al. Successful treatment of amegakaryocytic thrombocytopenia with anti-CD20 antibody (rituximab) in a patient with systemic lupus erythematosus. Lupus, 2008,17(3), 210-214.
26.F Benedetti, D de Sabata and G Perona,et al. T suppressor activated lymphocytes (CD8+/DR+) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura. Stem Cells, 1994,vol 12, 205-213.
27. Colovic M, Pavlovic S, et al. Acquired amegakaryocytic thrombocytopenia associated with proliferation of gamma/delta TCR T-lymphocytes and a BCR-ABL (p210) fusion transcript. Eur J Haematol, 2004, 73:372-375.
28.Michael Doubek, Zdenek Koristek,et al. Megakaryocyte Colony-Forming Units (CFU-Meg) Growth Is Enhanced by Alemtuzumab Mediated LymphocyteDepletion: In Vitro Experiments and a Case Report of Acquired Amegakaryocytic Thrombocytopenic Purpura. Blood ,2005,106: 1246.
29. Institut za hematologiju, et al. Acquired amegakaryocytic thrombocytopenia: three case reports and a literature review. Med Pregl, 2004 , May-Jun, 57(5-6):292-7.
30.M Podolak-Dawidziak,et al. Acquired amegakaryocytic thrombocytopenic purpura (AATP): a study of autologous megakaryocyte progenitors and the effect of patients plasma on normal marrow megakaryocyte colony formation. Folia Haematol Int Mag Klin Morphol Blutforsch, January 1, 1990, 117(2): 347-51.
31.刘斌,刘文君,郭渠莲,等。人巨细胞病毒感染对脐血巨核系祖细胞体外增殖的影响。实用儿科杂志,2004,19(1):75。
32.江丽琴。获得性低巨核细胞性血小板减少性紫癜10例报告。临床儿科杂志,1998,16(2):119-120。
33. Quintas-Cardama A, et al. Acquired amegakaryocytic thrombocytopenic purpura successfully treated with limited cyclosporin A therapy. Eur J Haematol, 2002, 69(3):185–186.
34.Yoichi Azuno,et al. Successful Cyclosporin A therapy for acquired amegakaryocytic thrombocytopenic pruprua. American Journal of Hematology,2002, 69:296–299.
35. N Agarwal, JE Spahr, et al. Acquired amegakaryocytic thrombocytopenic purpura. Am J Hematol, February 1, 2006, 81(2): 132-5.
36.R Kashyap, VP Choudhry,et al. Danazol therapy in cyclic acquired amegakaryocytic thrombocytopenic purpura: a case report. Am J Hematol, March 1, 1999, 60(3): 225-8.
37.李德亮何长生,等。静脉丙种球蛋白治疗获得性低巨核细胞性血小板减少性紫癜4例临床观察。中原医刊,2002,29(1):31。
38. H El Omri, H Skouri, I Kraiem,et al. Acquired amegakaryocytic thrombocytopenic purpura treated with intravenous immunoglobulins. Ann Med Interne (Paris), May 1, 2000, 151(3): 223-6.
39.UB Chaudhary, SF Eberwine, et al. Acquired amegakaryocytic thrombocytopenia purpura and eosinophilic fasciitis: a long relapsing and remitting course. Am J Hematol, March 1, 2004, 75(3): 146-50.
40.Joseph W. Leach, Khader K. Hussein, et al. Acquired Pure Megakaryocytic Aplasia Report of Two Cases With Long-Term Responses to Antithymocyte Globulin and Cyclosporine. American Journal of Hematology,1999, 62:115–117.
41. Pimjai Niparuck,Vichai Atichartakarn,et al. Successful treatment of acquired amegakaryocytic thrombocytopenic purpura refractory to corticosteroids and intravenous immunoglobulin with antithymocyte globulin and cyclosporin. Int J Hematol,2008, 88:223–226.
42. S Lonial, PA Bilodeau, et al. Acquired amegakaryocytic thrombocytopenia treated with allogeneic BMT: a case report and review of the literature. Bone Marrow Transplantation, 1999, 24:1337–1341.
43.苏加云。巨核细胞定量计数及分类的临床应用。检验医学与临床,2007,12(4):1173-1174。
2. Y Xue, R Zhang. Acquired amegakaryocytic thrombocytopenic purpura with a Philadelphia chromosome. Cancer Genet Cytogenet, August 1, 1993, 69(1): 51-6.
3. G Lugassy. Non-Hodgkin's lymphoma presenting with amegakaryocytic thrombocytopenic purpura. Ann Hematol, July 1, 1996, 73(1): 41-2.
4. PA Kouides and JM Rowe. Large granular lymphocyte leukemia presenting with both amegakaryocytic thrombocytopenic purpura and pure red cell aplasia: clinical course and response to immunosuppressive therapy. Am J Hematol, July 1, 1995, 49(3): 232-6.
5. Dominic W. Lai a, Thomas P. Loughran Jr,et al. Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia associated with an occult large granular lymphocyte leukemia. Leukemia Research,2008, 32:823–827.
6. Ergas D, Tsimanis A, et al. T-gamma large granular lymphocyte leukemia associated with amegakaryocytic thrombocytopenic purpura, Sjogren’s syndrome, and polyglandular autoimmune syndrome type II, with subsequent development of pure red cell aplasia. Am J Hematol,2002, 69:132-134.
7. Wesley H. Witteles,et al. Lung Cancer Presenting With Amegakaryocytic Thrombocytopenia. JOURNAL OF CLINICAL ONCOLOGY , 2008 Mar 1, 26(7):1171-4.
8. I. Maslovsky,D. Gefel ,et al. Malignant thymoma complicated by amegakaryocytic thrombocytopenic purpura , European Journal of Internal Medicine. 2005, 16:523-524.
9. JA King, MY Elkhalifa, LF Latour ,et al. Rapid progression of acquired amegakaryocytic thrombocytopenia to aplastic anemia. South Med J, January 1, 1997, 90(1): 91.
10.石慧文。获得性低巨核细胞性血小板减少性紫癜。国外医学输血及血液学分册,2001,24(6)。
11.Domingo Luciani, Caracas, Venezuela. Acquired amegakaryocytic thrombocytopenic purpura:Review of a not very well-defined disorder. Eur J Intern Med, November 1, 2005, 16(7): 477-81.
12.李四强,宫超,等。获得性低巨核细胞减少性紫癜骨髓活检的临床意义。中国误诊学杂志,2005,5(5):921-922。
13.李栋。获得性低巨核细胞性血小板减少性紫癜20例临床分析。中华血液学杂志,1996,17(3),148-149。
14.陆德炎陈义平,等。获得性单纯无巨核细胞性血小板减少性紫癜发病机制的研究。中华血液学杂志,1999,22(3):124-126。
15. M Katai, T Aizawa, N Ohara , et al. Acquired amegakaryocytic thrombocytopenic purpura with humoral inhibitory factor for megakaryocyte colony formation. Intern Med, March 1, 1994, 33(3): 147-9.
16. Podolak-Dawidziak M,et al. Acquired amegakaryocytic thrombocytopenic purpura (AATP): a study of autologous megakaryocyte progenitors and the effect of patients plasma on normal marrow megakaryocyte colony formation. Folia Haematol Int Mag Klin Morphol Blutforsch,1990, 117(2):347-51。
17. Kuwaki T, Hagiwara T, Yuki C, et al. Quantitative analysis of thrombopoietin receptors on human megakaryocytes. FEBS Lett,1998, 427: 46250.
18. Kaushansky K, et al. Thrombopoietin: the primary regulator of platelet production. Blood, 1995, 86:419–31.
19. Wendling F, Maraskovsky E, Debili N, Florindo C, Teepe M,Titeux M, et al. cMpl ligand is a humoral regulator of megakaryocytopoiesis.Nature, 1994, Jun 16, 369(6481):519-20.
20.David J. Kuter. New thrombopoietic growth factors. Blood,2007, 109: 4607-4616.
21.Hiroko Shiozaki,Shuichi Miyawaki,et al. Autoantibodies neutralizing thrombopoietin in a patient with amegakaryocytic thrombocytopenic purpura. Blood, 2000,95(6):2187-2188.
22.Mukai HY,et al. Serum thrombopoietin (TPO) levels in patients with amegakaryocytic thrombocytopenia are much higher than those with immune thrombocytopenic purpura. Thromb Haemost, 1996, Nov, 76(5):675-8.
23. Masataka Kuwana, Yuka Okazaki, et al. Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: relationship to thrombocytopenia with megakaryocytic hypoplasia. Arthritis and Rheumatism,2002, Aug, 46(8):2148-59.
24. M. Kuwana, J. Kaburaki,et al. Two types of autoantibody-mediated thrombocytopenia in patients with systemic lupus erythematosus. Rheumatology,2006, 45:851-854.
25.T Fukushima,L Dong,et al. Successful treatment of amegakaryocytic thrombocytopenia with anti-CD20 antibody (rituximab) in a patient with systemic lupus erythematosus. Lupus, 2008,17(3), 210-214.
26.F Benedetti, D de Sabata and G Perona,et al. T suppressor activated lymphocytes (CD8+/DR+) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura. Stem Cells, 1994,vol 12, 205-213.
27. Colovic M, Pavlovic S, et al. Acquired amegakaryocytic thrombocytopenia associated with proliferation of gamma/delta TCR T-lymphocytes and a BCR-ABL (p210) fusion transcript. Eur J Haematol, 2004, 73:372-375.
28.Michael Doubek, Zdenek Koristek,et al. Megakaryocyte Colony-Forming Units (CFU-Meg) Growth Is Enhanced by Alemtuzumab Mediated LymphocyteDepletion: In Vitro Experiments and a Case Report of Acquired Amegakaryocytic Thrombocytopenic Purpura. Blood ,2005,106: 1246.
29. Institut za hematologiju, et al. Acquired amegakaryocytic thrombocytopenia: three case reports and a literature review. Med Pregl, 2004 , May-Jun, 57(5-6):292-7.
30.M Podolak-Dawidziak,et al. Acquired amegakaryocytic thrombocytopenic purpura (AATP): a study of autologous megakaryocyte progenitors and the effect of patients plasma on normal marrow megakaryocyte colony formation. Folia Haematol Int Mag Klin Morphol Blutforsch, January 1, 1990, 117(2): 347-51.
31.刘斌,刘文君,郭渠莲,等。人巨细胞病毒感染对脐血巨核系祖细胞体外增殖的影响。实用儿科杂志,2004,19(1):75。
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