免疫性中性粒细胞减少症

当中性粒细胞数在成人低于2.0×109/L,10～14岁儿童低于1.8×109/L,<10岁的儿童及婴幼儿低于1.5×109/L,称为粒细胞减少症;当中性粒细胞数低于0.5×109/L,称为粒细胞缺乏症(agraulocytosis)。免疫性粒细胞减少症包括同种免疫新生儿中性粒细胞减少症、自身免疫性中性粒细胞减少症(autoimmuneneutropenia,AIN)和自身免疫性疾患相关性中性粒细胞减少症[1]。同种免疫新生儿中性粒细胞减少症是由于胎儿携带母亲体内不存在的父源性粒细胞抗原,引发母体产生针对粒细胞的同种抗体,通过胎盘进入胎儿体内诱发粒细胞的减少。1病因和发病机制AIN的发…     

中性粒细胞减少症的诊断步骤

中性粒细胞减少症(Neutropenia,Np)是临床常见的一组综合征,逐年增多,引人关注。为了能在临床上探究其病因和发病机理,须按照以下之诊断步骤:首先确定有无中性粒细胞减少,其次明确 NP 的病因和机理,最后探索其功能缺陷类型.     

免疫性血细胞减少症的分类及治疗原则

血细胞减少多为造血系统重症。愈来愈多的证据表明,许多“原发性”血细胞减少源于免疫系统异常,故称之为“免疫性血细胞减少症”。明晰免疫性血细胞减少症的分类及治疗原则,具有重要理论意义和临床价值。1免疫性血细胞减少症的分类根据引起血细胞减少的异常免疫机制和血细胞减少情况不同,免疫性血细胞减少症可分为以下几种类型。1·1自身抗体介导的血细胞减少症(1)自身免疫性溶血性贫血(AIHA):这是人们认识最早的一种免疫性血细胞减少症,主要发病机制是机体产生了针对成熟红细胞的自身抗体,通过诱导巨噬细胞吞噬(不完全温抗体型)或直接激…     

粒细胞减少症

近年来各种病因所引起的粒细胞减少状态较多,引起了人们的注意。同时由于血液细胞的亚显微形态结构、细胞生理、生化以及免疫机制研究的发展,对粒细胞减少症的了解有了新的进展。兹将有关文献综述如下。     

免疫性血小板减少症的治疗进展

正原发免疫性血小板减少症(immune thrombocytopenia,ITP)是一种复杂的多种机制共同参与的获得性自身免疫性疾病。虽然原发性ITP是一种良性疾病,但目前尚无法根治,也不能改变其自然病程,其死亡率与正常人群无明显差异,患者多死于感染而非出血。因此,ITP的治疗目的是使患者血小板计数(PLT)提高到安全水平,降低出血风险,改善患者的生活质量。原则上,对于原发性ITP,如果其PLT高于30×109/L,无出血,血小板功能及凝     

结缔组织病伴免疫性血小板减少症的诊断治疗进展

摘要 免疫性血小板减少症 (ITP) 为免疫介导的疾病,分为原发性ITP和继发性ITP。结缔组织病(CTD)是一组主要侵犯全身结缔组织的系统性自身免疫性疾病,容易合并继发性ITP的疾病包括系统性红斑狼疮、原发性干燥综合征、抗心磷脂抗体综合征等。CTD-ITP患者出血倾向增加,严重者可致内脏出血,病死率高,是影响CTD患者预后的重要因素。近年来有关CTD-ITP的发病机制、临床表现、治疗方法的研究取得了较大进展,新型生物制剂和促血小板生成药物的使用让更多患者获益。早期诊断、出血程度分级、风险判断以及个性化达标治疗是获得良好预后的关键。     

原发免疫性血小板减少症治疗进展

<正>原发免疫性血小板减少症(primary immune thrombocytopenia,ITP),既往称特发性血小板减少性紫癜(idiopathic thrombocytopenia purpura),是一种以体液免疫和细胞免疫介导的血小板过度破坏和巨核细胞成熟障碍为特征的获得性出血性疾病。ITP常见的临床表现为皮肤黏膜出血、月经过多,甚至内脏或颅内出血,可危及生命。近年来,     

免疫性血小板减少症脾切除治疗

目的:探讨免疫性血小板减少症(ITP)患者脾切除术后预后的影响因素。方法:回顾性分析31例行脾切除术治疗的ITP患者,统计分析患者的疗效,包括显效、良效、进步、无效,并对性别、年龄、脾脏大小、对激素治疗的反应、术前病程时长、术前血小板计数、手术方式等相关因素进行分析。结果:31例患者中,25例采用腹腔镜术式,6例采用开腹手术;中位随访时间29个月,显效21例(67.7%),良效5例(16.1%),进步3例(9.7%),无效2例(6.5%),无一例死亡。年龄≤30岁的患者显效率明显高于年龄30岁的患者(P=0.046),术前血小板计数≥20×10~9/L的患者显效率明显高于术前血小板计数20×10~9/L的患者(P=0.018)。结论:脾切除术是一种治疗ITP安全、有效的治疗方法。年龄小于30岁和术前血小板计数高于20×10~9/L是对ITP脾切除术疗效有利的影响因素。     

A morphologic and immunologic study of the large granular lymphocyte in neutropenia with T lymphocytosis

We report four patients with expansion of a unique population of lymphocytes that is consistently associated with neutropenia. Two patients also had rheumatoid arthritis and autoantibodies. The lymphocytes contained many cytoplasmic azurophilic granules, which possessed strong acid phosphatase activity. Multiple cytoplasmic parallel tubular arrays were observed ultrastructurally. These granular lymphocytes showed the T suppressor/cytotoxic cell phenotype (E+, OKT3+, OKT8+, OKT4-, OKM1-, OKI1-) and exhibited antibody-dependent cell-mediated cytotoxic activity but little or no natural killer cytotoxicity. They did not respond to recall antigens, concanavalin A, or pokeweed mitogen, but the cells from one patient did respond to phytohemagglutinin. No in vitro suppressor cell activity on mitogenic responses of allogeneic cells and on mixed lymphocyte cultures could be demonstrated. There was no evidence of suppression of immunoglobulin synthesis in vivo. It is uncertain that the expansion of this subset of lymphocytes represents a leukemic process. Their constant association with neutropenia, however, raises the possibility that the increase in large granular lymphocytes and neutropenia might be pathogenetically related.     

Pathophysiology and treatment of severe chronic neutropenia

 Severe chronic neutropenia (SCN) include a heterogeneous group of diseases characterized by blood neutrophil counts chronically less than 0.5×10⁹/L. In phase I–III studies in SCN patients, treatment with recombinant human granulocyte colony stimulating factor (r-metHuG-CSF; Filgrastim) resulted in a rise in the absolute neutrophil counts (ANC) to above 1.0×10⁹/L associated with a reduction in bacterial infections. Long-term treatment with filgrastim up to 8 years demonstrate a sustained ANC response, a significant reduction of the need for intravenous antibiotics and a dramatic improvement in the quality of life. In 1994 an international registry for severe chronic neutropenia (SCNIR) was established to improve care for chronic neutropenia and for further understanding the pathophysiology of this rare disease. Three-hundred and ten patients have been enrolled to this registry so far. Worldwide phase I–III studies with filgrastim and SCNIR provide information on 424 patients with severe chronic neutropenia. Adverse events include the development of acute myeloid leukemia in approximately 7% of the patients within the cohort of patients with congenital neutropenia (Kostmann's syndrome) suggesting that congenital neutropenia is a preleukemic syndrome. None of the patients with cyclic of idiopathic neutropenia developed leukemia suggesting that filgrastim is not involved in the development of leukemia. Received: 19 December 1995 / Accepted: 21 December 1995     

Thalidomide-induced severe neutropenia during treatment of multiple myeloma

Recent reports have shown that thalidomide has antiangiogenic activity and is effective for the treatment of refractory multiple myeloma. Unlike other antineoplastic drugs, thalidomide is reported to rarely cause severe hematologic toxicity. In Keio University Hospital, 44 patients with refractory multiple myeloma, including 18 who had relapsed after hematopoietic stem cell transplantation, were treated with this drug as a single agent. Severe grade 3 or 4 neutropenia during thalidomide treatment was observed in 10 patients. This phenomenon was not noted in previous reports. Neutropenia usually occurred in the first or second week of treatment. Concomitant progression of thrombocytopenia occurred in 5 cases, and bone marrow hypoplasia without a significant increase in myeloma cell numbers was also observed in 5 cases. Neutropenia was not correlated with anti-tumor response or the plasma concentration of thalidomide but was more frequently observed in patients with a low neutrophil and platelet count, anemia, or a high plasma cell percentage in the bone marrow before thalidomide treatment. Thus, this drug should be used carefully for patients with pretreatment cytopenia or a high tumor burden in the bone marrow.     

Pathophysiologic mechanisms, clinical features and treatment of idiopathic neutropenia

The term idiopathic neutropenia describes a benign disorder of granulopoiesis characterized by the unexplained reduction in the absolute neutrophil count below the lower limit of the normal range for a prolonged period. Recent studies have provided evidence that this neutropenic condition comprises two distinct disease entities on the basis of the underlying pathogenetic mechanisms: first, the primary autoimmune neutropenia mediated by autoantibodies against mature neutrophils and/or their bone marrow progenitor/precursor cells; and second, the previously named chronic idiopathic neutropenia, that might now be called chronic immunologic neutropenia, characterized by T-cell- and cytokine-mediated suppression of granulopoiesis. Despite the differences in the bone marrow granulocytic progenitor cell reserves that actually reflect the differences in the implicated pathophysiologic mechanisms, both disease entities usually display an uncomplicated clinical course with minimal symptoms. Treatment decisions should be individualized on the basis of patients' clinical course and the indicated therapies are analyzed in this review. The clinical and laboratory data characterizing these neutropenic conditions and the available in vitro data that have led to remarkable progress in the understanding of the pathophysiology of both disorders are also summarized.     

Haematological effects of lithium and its use in treatment of neutropenia

Conclusion Lithium is a safe drug to use and results so far fully justify continued experimentation with this agent in a variety of haematological disorders. The major haematological effect of lithium in man is stimulation of granulopoiesis, the most likely mode of action being an enhancement of CSA production. Consistent with this view is the observation that neutropenic states most likely to benefit from lithium treatment are those where impaired CSA activity is demonstrable. While the physiological importance of CSA is still not completely understood experience with lithium would support a major role for CSA in the regulation of granulopoiesis. Colony-stimulating factors are produced by monocyte-macrophages, lymphocytes, and endothelial cells. Further work will be required to define the physiological significance and effect of lithium on CSA production by each of these cell types.The success of lithium in protecting granulopoiesis following cancer chemotherapy suggests that CSA production is suboptimal in this situation. Defective CSA production may be an important and hitherto unrecognised effect of cancer chemotherapeutic agents and further studies are indicated.There is little evidence that lithium directly affects pluripotent stem cells in man, and it is clearly without effect in most cases of severe aplastic anaemia where stem-cell failure is almost total. However, the inhibitory action of lithium on suppressor lymphocytes might be put to therapeutic use in pure red cell aplasia or in cases of aplastic anaemia where inhibition of erythroid or granulocyte precursor cells can be unequivocally demonstrated in co-culture.     

Late-onset neutropenia following rituximab treatment for rheumatologic conditions

Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of normal and malignant B lymphocytes. Its use in autoimmune conditions is rapidly expanding. Late-onset neutropenia (LON) is a well-recognized side effect of rituximab therapy in lymphoma patients. Only a small number of cases of LON have been reported in patients with autoimmune disorders. The aim of this work is to review cases in Israel and to compare them to published cases in the literature thus adding to the body of knowledge regarding this unusual phenomenon. Members of the Israeli Rheumatology Association were encountered by e-mail, requesting reports of cases of LON after therapy with rituximab. Submitted cases were reviewed, with demographics and clinical data collated and tabled. Current cases were compared to previously published rheumatology cases. Twelve episodes of LON following rituximab therapy were reported. All patients were female with an average age of 50 years (range 22–78). LON occurred at an average of 155 days after therapy (range 71–330). The average leukocyte count was1,456 white cells, with an average of 413 neutrophils (range 0–1,170 neutrophils). Three of the patients underwent bone marrow biopsies which showed white cell line maturation arrest with an increased number of lymphocytes. No blasts were seen. Our results add support to the growing evidence that this adverse event usually follows a benign course and is not an absolute contraindication for repeat treatment if required in the future. However, vigilance is recommended with routine periodic blood counts, especially 5 months following rituximab administration when the risk is expected to be the highest.