自身免疫性溶血性贫血和Evans综合征复发及其相关因素分析

目的　了解自身免疫性溶血性贫血 (AIHA)和Evans综合征复发率及其相关因素。方法　对治疗后完全缓解的 5 2例AIHA和Evans综合征患者随访 1～ 14年 ,了解其复发率 ,并采用同期病例对照法 ,比较不同因素与复发的相关性。结果　总复发率为 5 7.7% ;首次复发中位时间为缓解后 9个月 ;Coombs试验阴性型复发率为 30 .8% (13例中 4例复发 ) ,温抗体型复发率为 5 4 .0 % (2 4例中 13例复发 ) ,冷温双抗体及冷抗体型复发率为 86 .7% (15例中 13例复发 ) ,合并冷抗体患者复发率明显高于其他两型 (P <0 .0 5 ) ;抗体效价和≥ 10 0的患者复发率为 92 .9% (14例中 13例复发 ) ,抗体效价和 <10 0者复发率为 5 9.1% (2 2例中 13例复发 ) ,随着抗体效价升高 ,复发率明显增高 (P <0 .0 5 ) ;反复感染者易复发 ;加入环孢菌素A(CsA)的治疗方案较传统单用激素方案复发率明显降低 (P <0 .0 1) ;复发与激素、CsA的疗程密切相关 (P <0 .0 1)。结论　AIHA和Evans综合征复发率较高 ;分型施治、减少感染、加用CsA、延长疗程可减少复发。     

环孢菌素A治疗自身免疫性溶血性贫血和Evans综合征疗效观察

目的 探讨环孢菌素A（CsA)在自身免疫性溶血性贫血（AIHA）和Evans综合征的综合免疫抑制治疗中所起的作用。方法 前瞻性研究CsA合并传统方案（泼尼松 达那唑（18例）和单用传统方案（26例）治疗Coombs试验阳性的AIHA和Evans综合征的疗效。结果 CsA组3个月有效率为94.4%,平均起效时间为19.9d,完全缓解率为88.9%,其中进行长期随访的12例患者1年内仅1例复发（复发率3.3%）,2年内2例复发（复发率（16.7%),3年复发率仍为16.7%;而传统方案3个月有效率为92%,平均起效时间为23.2d,完全缓解率为100%。两组治疗有效率、平均起效时间差异无显著性,而完全缓解率CsA组显著高于传统方案组,3年内复发率CsA组明显低于传统方案组。结论 使用含CsA的综合免疫抑制方案治疗AIHA和Evans综合征可提高并巩因疗效。     

Management of immune thrombocytopenic purpura in adults

Primary immune thrombocytopenic purpura (ITP), also referred to as idiopathic thrombocytopenic purpura, is an organ-specific autoimmune disorder in which antibody-coated or immune complex-coated platelets are destroyed prematurely by the reticuloendothelial system, resulting in peripheral blood thrombocytopenia. The disease is heterogeneous with regard to its severity and clinical course and is unpredictable in its response to therapy. Although the basic underlying pathophysiology of ITP has been known for more than 50 years, current treatment guidelines are based on expert opinion rather than on evidence because of a lack of high-quality clinical trials and research. The only patients for whom treatment is clearly required are those with severe bleeding and/or extremely low platelet counts (< 10 x 10(9)/L). Treatment of patients with ITP refractory to corticosteroids and splenectomy requires careful evaluation of disease severity, patient characteristics related to risk of bleeding, and adverse effects associated with treatment. Clinical trials with numerous new agents are under way, which we hope will add more effective and targeted strategies to our therapeutic armamentarium. We describe a logical and structured approach to the clinical management of ITP in adults, based on a literature review and our personal experience.     

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are multisystemic disorders that are characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic manifestations, resulting from platelet agglutination in the arterial microvasculature. Until the introduction of plasma-based therapy, TTP was associated with a mortality rate greater than 90%. Current outcomes of TTP and HUS have improved dramatically with the use of plasma exchange, which should be initiated promptly at diagnosis. Recent evidence suggests that deficiency of a specific plasma protease responsible for the physiologic degradation of von Willebrand factor plays a pathogenic role in a substantial proportion of familial and acute idiopathic cases of TTP. Although multiple triggers, such as infection, drugs, cancer, chemotherapy, bone marrow transplantation, and pregnancy, are recognized, knowledge of the pathogenesis of TTP and HUS in relationship to these disorders remains incompletely understood and continues to evolve. While uncommon, TTP and HUS are of considerable clinical importance because of their abrupt onset, fulminant clinical course, and high morbidity and mortality in the absence of early recognition and treatment.     

Cellular immune mechanisms in autoimmune thrombocytopenic purpura: An update

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disorder in which autoantibodies are directed against an individual's own platelets, leading to enhanced clearance through Fc receptor (R)-mediated phagocytosis by macrophages residing in the reticuloendothelial system (RES), particularly in the spleen. The production of IgG autoantibodies is critically dependent on cellular immune mechanisms particularly relating to T cells. We review the recent literature of the cell-mediated immunology of AITP focusing on platelet phenotype, genetics, T-cell reactivities, and cytokine profiles in patients with AITP. Understanding the interaction between these cell-mediated mechanisms is vital for developing antigen specific immunotherapies to treat this autoimmune disease.     

Pathophysiology of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Summary

Thrombotic microangiopathies are rare disorders characterized by the concomitant occurrence of severe thrombocytopenia, microangiopathic hemolytic anemia, and a variable degree of ischemic end‐organ damage. The latter particularly affects the brain, the heart, and the kidneys. The primary forms, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), although their clinical presentations often overlap, have distinctive pathophysiologies. TTP is the consequence of a severe ADAMTS‐13 deficiency, either immune‐mediated as a result of circulating autoantibodies, or caused by mutations in ADAMTS‐13. HUS develops following an infection with Shiga‐toxin producing bacteria, or as the result of excessive activation of the alternative pathway of the complement system because of mutations in genes encoding complement system proteins.

     

Four patients with both thrombotic thrombocytopenic purpura and autoimmune thrombocytopenic purpura: the concept of a mixed immune thrombocytopenia syndrome and indications for plasma exchange

Autoimmune thrombocytopenic purpura (ATP) and thrombotic thrombocytopenic purpura (TTP) are each well recognized clinical syndromes which may appear as single episodes or may have chronic relapsing courses. We present four patients negative for human immunodeficiency virus (HIV) infection who appear to have both diagnoses with either concomitant or intermingled episodes, and we review seven additional patients reported in the literature with similar features. All four of our patients are female, two have underlying connective tissue disorders, and their ATP processes came to our attention because of incomplete response of the platelet count to plasma exchange therapy (PEX) during a TTP phase (Cases 1 and 2) or development of thrombocytopenia in the absence of microangiopathy on the background of prior typical TTP episodes (Cases 3 and 4). Recognition of the ATP diagnosis in each case resulted in discontinuation of PEX (Cases 1 and 2) or not instituting PEX (Cases 3 and 4). In each instance, a satisfactory rise in platelet count followed treatment for ATP. Based upon this experience, we conclude that some individuals may have a mixed immune thrombocytopenia syndrome; careful analysis of the mechanism of thrombocytopenia, especially in recurrent episodes and in patients who respond incompletely to PEX for TTP, is important when deciding whether to initiate or continue PEX, or to consider therapies appropriate for other mechanisms of thrombocytopenia.     

Treatment of idiopathic thrombocytopenic purpura in adults: efficacy of domestic intravenous immunoglobulin in immune thrombocytopenia]

AIM: The study of effectiveness of intravenous immunoglobulin (IVIG) in therapy of idiopathic thrombocytopenic purpura (ITP) in adults. MATERIALS AND METHODS: High doses of IVIG (0.2-0.4 g/kg b.w. for 4-6 days) were given to 6 female patients aged 20 to 59 years (median--39 years) with immune thrombocytopenia. 4 patients had primary ITP resistant to glucocorticosteroids (GCS) and 1 female had chronic ITP treated by splenectomy without effect. 1 patient with rheumatoid arthritis developed severe thrombocytopenia combined with agranulocytosis when treated with nonsteroid antiinflammatory drugs. RESULTS: The response was observed in 5 of 6 patients (in 4 patients resistant to GCS and 1 RA patient). In 3 of them the effect was rated as excellent (platelets level > 150,000 per cubic millimeter), in 2 patients it was good (platelets count from 50,000 to 150,000 per cubic millimeter). Splenectomy was performed in 4 cases with ITP on day 8-14 after IVIG therapy. The 2- and 6-month follow-up evidenced for good results of the surgical treatment. The RA patient showed a stable rise of the blood count. Serious side effects of IVIG therapy were not registered. CONCLUSION: IVIG of Russian produce is effective in the treatment of drug-induced thrombocytopenia and ITP resistant to GCS.     

Life-threatening autoimmune hemolytic anemia in a patient with the acquired immune deficiency syndrome

Increasing numbers of patients are being seen with the acquired immune deficiency syndrome (AIDS). An abnormal serology with a positive direct antiglobulin test has been observed in these patients and is usually not thought to contribute to significant clinical morbidity. We describe a patient with AIDS who presented with a severe hemolytic anemia which was not distinguishable clinically and serologically from the idiopathic form of autoimmune hemolytic anemia.     

特发性血小板减少性紫癜患者免疫状态分析

目的 探讨特发性血小板减少性紫癜(ITP)患者免疫状态的异常改变.方法 以52例ITP确诊患者为观察组,其中慢性ITP(CITP)组27例、急性ITP(AITP)组25例;以52例体检健康者为对照组.检测各组受试对象外周血T淋巴细胞亚群、血清免疫球蛋白及补体、红细胞免疫功能,并对结果 进行统计学分析.结果 观察组CD3+、CD4+、CD4+/CD8+、红细胞C3b受体花环检出率均低于对照组,CD8+、IgA、IgG、IgM、C3、C4、免疫复合物花环检出率高于对照组(P＜0.05);CITP组变化幅度大于AITP组(P＜0.05).结论 ITP患者免疫状态呈异常状态,且与疾病严重程度等有较大的相关性.     

Rituximab: an anti-CD20 antibody for the treatment of chronic refractory immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by antibody-mediated platelet destruction. Despite initial response to corticosteroids, most adults relapse during steroid taper, and splenectomy is the treatment of choice for these patients. Those whom splenectomy fails to cure present a therapeutic challenge. Subsequent management usually involves some form of chronic immune suppression, which has serious side effects and long-term morbidity. Rituximab, a recently-approved anti-CD20 chimeric monoclonal antibody, has shown efficacy in preliminary studies. We report the cases of 3 patients with refractory ITP who achieved acceptable platelet counts after treatment with rituximab.     

Nomifensine-induced immune hemolytic anemia and posttransfusion purpura in the same patient

A 53-year-old white woman had severe hemolytic anemia while taking nomifensine. A drop of hemoglobin to 61 g per I prompted the transfusion of two units of packed red cells. Nine days later, severe thrombocytopenia with multiple petechiae ensued. Both hemolysis and thrombocytopenia resolved promptly upon withdrawal of the drug and short-term prednisolone treatment. Serologic studies showed nomifensine-dependent, metabolite-specific red cell antibodies as the cause of immune-mediated hemolysis and, in serum samples obtained after purpura, strong platelet-specific PlA1 and weak HLA antibodies suggested a diagnosis of posttransfusion purpura.     

Cocaine‐induced microangiopathic hemolytic anemia mimicking idiopathic thrombotic thrombocytopenic purpura: A case report and review of the literature

Our understanding of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura (TTP) has increased, but remains incomplete, particularly with respect to cases of suspected TTP that are either unresponsive to therapeutic plasma exchange (TPE) or have normal ADAMTS13 (a d isintegrin‐like a nd m etalloprotease with t hrombos pondin type 1 motif 13 ) activity. A 53‐year‐old woman presented with severe anemia (hemoglobin 1.8 g/dL) and clinical and laboratory findings consistent with TTP in conjunction with acute cocaine use. The patient was treated with TPE until the pre‐treatment ADAMTS13 activity was reported as normal without evidence of an inhibitor. TPE was stopped and the patient continued to improve without treatment. This patient's microangiopathic hemolytic anemia (MAHA) appeared to be secondary to cocaine use. The proposed pathogenesis is likely a combination of cocaine‐induced vasoconstriction, vascular damage, platelet activation, and procoagulation. This is the fifth published report of cocaine‐induced MAHA and to our knowledge the first with ADAMTS13 testing. J. Clin. Apheresis 29:284–289, 2014. © 2014 Wiley Periodicals, Inc.     

选择性脾切除治疗儿童特发性血小板减少性紫癜

目的总结脾切除对内科治疗无效或反复复发的儿童特发性血小板减少性紫癜（ITP）的治疗效果。方法对1996年1月至2006年12月36例儿童特发性血小板减少性紫癜行选择性脾切除术的疗效和术后早期并发症的临床资料作回顾性分析。结果所有患儿在转入外科前均在内科接受正规治疗。32例（88．89％）患儿脾切除后效果明显，4例（11．11％）部分显效，全组无重大并发症。结论选择性脾切除是治疗儿童特发性血小板减少性紫癜的一种安全和有效的治疗手段。     

成人特发性血小板减少性紫癜与幽门螺杆菌CagA蛋白的关系

目的了解成人特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)与幽门螺杆菌(helicobacter pylori,Hp)CagA蛋白的关系。方法采用14C尿素呼吸试验对正常成人和ITP患者进行Hp检测后,对Hp阳性的ITP患者进行CagA蛋白抗体检测。依据急性ITP,慢性ITP,难治性ITP对ITP患者进行分类。结果 223例正常患者中123例Hp阳性,感染率为55.2%,而CagA蛋白抗体阳性为42例,占34.1%。278例ITP患者中Hp阳性176例,感染率63.3%,其中CagA蛋白抗体阳性83例,占47.2%,ITP患者的Hp感染率与正常人相似,但CagA蛋白抗体阳性率显著高于正常人(P<0.05)。Hp感染率及CagA蛋白抗体阳性率在急性ITP患者中分别为62.2%和46.4%,慢性ITP为63.2%和47.0%,难治性ITP为64.7%和48.5%,比较显示不同类型的ITP患者Hp感染率及CagA抗体阳性率差异无统计学意义(P>0.05)。结论纳入研究的ITP患者的Hp感染率与正常人相似,但CagA蛋白抗体阳性率明显高于正常人,提示CagA蛋白在成人ITP的发生发展中具有一定作用。进一步分析也显示不同类型的ITP患者Hp感染率及CagA蛋白阳性率差异无统计学意义。     

Management of chronic autoimmune thrombocytopenic purpura (ITP) in adults.

The management of thrombocytopenia in adults is a therapeutic challenge requiring not only the science but the art of medicine. The disease is usually chronic and a third of those affected will have significant thrombocytopenia despite attempts at presently accepted forms of management. Adults tolerate moderate degrees of thrombocytopenia and treatment of asymptomatic patients with platelet counts greater than 30 x 10(9)/L is usually not required. Steroids, splenectomy, and the use of steroid-sparing immunosuppressive drugs remain the mainstay of treatment, although short-term responses to intravenous immunoglobulin (IVIg) and anti-D may be beneficial. The multitude of therapies with anecdotal reports of responses attests to the frustration felt by hematologists in the management of this disease when conventional treatments fail.     

Clinical effects of high-dose immunoglobulin therapy in adults with idiopathic thrombocytopenic purpura

15 patients suffering from idiopathic thrombocytopenic purpura were treated in our department with high-dosage immunoglobulins. The daily dosage amounted to between 0.13 and 0.4 g/kg body weight, administered for 4 to 15 days consecutively. The platelet count in 10 patients increased within the first week of treatment, but this increase was maintained for more than 4 weeks in only 3 patients. The average age of these 10 patients amounted to 41.2 years and was significantly lower than that of the remaining 5 patients (66.6 years), who failed to respond. Only one of 4 splenectomized patients responded with an increase in platelet count. Two different immunoglobulin preparations were used. No difference in efficacy was found and both preparations were well tolerated.