儿童过敏性紫癜合并肾损害40例临床分析

目的：探讨儿童过敏性紫癜合并肾损害的发病相关因素。方法将102例过敏性紫癜患儿按照是否有肾损害分为紫癜组（n=62）和肾损害组（n=40）2组,对2组临床资料进行回顾性分析。结果肾损害组年龄7岁以上占85.0%（34/40）,有明确诱因者77.5%（31/40）,皮疹反复发作次数超过3次者72.5%（29/40）,和紫癜组比较差异均有统计学意义（P<0.05）。在首发症状方面,肾损害组患儿表现为单一紫癜者比例较低（5.0%,2/40）,伴腹痛或多系统病变者比例高,和紫癜组比较差异均有统计学意义（P<0.05）。结论对于年龄大于7岁,皮疹反复发作,首发症状合并腹痛或多系统病变的过敏性紫癜患儿要及时行肾功能检查,防止肾损害被误诊或漏诊。     

Treatment with short-term,high-dose cyclosporin A in children with refractory chronic idiopathic thrombocytopenic purpura

We report on 14 children (seven boys, seven girls) with chronic idiopathic thrombocytopenic purpura (ITP) refractory to multiple treatments, who were given a short-term therapy (range between 6 and 10 weeks) with high doses of cyclosporin A (CyA) (median, 10 mg/kg/d). Six patients experienced adverse events and one developed severe systemic mycosis during therapy. A complete response (CR) was observed in four patients and a partial response (PR) in three patients. Only the four CR patients, who were all girls, had a sustained response. These data suggest that CyA may be effective in some children with chronic symptomatic ITP.     

Ten years of prophylactic treatment with fresh-frozen plasma in a child with chronic relapsing thrombotic thrombocytopenic purpura as a result of a congenital deficiency of von Willebrand factor-cleaving protease

We report the results of 10 years of prophylactic fresh-frozen plasma (FFP) infusion therapy in a 14-year-old girl with chronic relapsing thrombotic thrombocytopenic purpura (TTP), in whom a severe congenital von Willebrand factor (VWF)-cleaving protease deficiency has been documented. Severe haemolytic crises triggered by infections were prevented and her present renal and neurological functions have been preserved. Sequential measurements of protease activity and platelet count after FFP infusion led us to conclude tentatively that 5% may be sufficient to degrade very large and adhesive VWF multimers.     

CD4^＋CD25^＋调节性T细胞在特发性血小板减少性紫癜患者中的变化及意义

目的:通过检测特发性血小板减少性紫癜(ITP)患者治疗前后外周血CD4 CD25 调节性T细胞(regulatory T cell,Treg)的比例及变化规律,探讨Treg细胞在ITP发病中的可能作用。方法:采集30例急、慢性ITP患者治疗前、后和20例正常对照者的外周血标本,流式细胞仪检测Treg细胞的比例及变化,并评价其与血小板计数的相关性。结果:30例ITP患者治疗前Treg细胞的比例为(1.59±0.86)%,明显低于正常对照组(3.87±1.73)%(P<0.01),治疗后其比例显著升高,为(2.51±1.17)%,明显高于治疗前(P<0.01),但仍低于正常对照组(P<0.01);Treg细胞在治疗显效和良效组显著高于进步和无效组(P<0.01),进步组与无效组比较差异无统计学意义(P>0.05);此外治疗前后Treg细胞比例与血小板计数呈显著正相关(P<0.05)。结论:ITP患者外周血Treg细胞比例降低,但随免疫抑制治疗的疗效逐渐升高,提示CD4 CD25 调节性T细胞可能参与了ITP的发病机制。     

A case report of transfusion-related acute lung injury during plasma exchange therapy for thrombotic thrombocytopenia purpura

Transfusion-related acute lung injury (TRALI) is a transfusion reaction that is often under recognized and underreported. Implications for diagnosis not only influence treatment considerations but also extend to donor selection, donor deferral and ultimately the safety of the final blood product. We report a case of a previously well 19-year-old female who presented a one week history of flu-like symptoms and mucosal bleeding. Laboratory results confirmed the diagnosis of thrombotic thrombocytopaenia purpura (TTP) and she was commenced on plasma exchange. During her second day of plasma exchange, she developed dyspnoea and rigors. Examination and investigation findings were consistent with a clinical diagnosis of TRALI. Granulocytes immunofluorescent test (GIFT - flow cytometry) was performed and cross reactivity was demonstrated between the patient's granulocytes and plasma from one of the nine donor fresh frozen plasma (FFP) packs. She made a full recovery. TRALIa accounts for 7% of all adverse events reported in the Serious Hazards of Transfusion (SHOT) database and has a mortality rate between 5-25%. Apheresis patients are a particularly vulnerable group of patients where clinical recognition and rapid laboratory confirmation of TRALI is imperative to minimize the risk of further patient exposure to donor granulocyte or human leukocyte antigen (HLA) antibodies. The provision of plasma from male donors may additionally reduce exposure. On a wider scale, rapid donor identification and deferral maintains the safety of the national blood supply.     

Plasma-soluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpura

We investigated the levels of various cytokines and soluble factors in ITP patients, in order to determine the influence of these factors on the pathogenesis of ITP. We found increases in IL-2, IL-6, IFN-gamma, and M-CSF levels in ITP patients compared with those in healthy individuals. On lymphocyte phenotype analysis, we found no clear difference in total T cell population (CD2+ CD19- cells) or cytotoxic T cell frequency (CD8+ CD11b- cells) between these two groups. The frequency of helper/inducer T cells (CD4+ CD8- cells) was decreased in ITP patients. There was a significant increase in activated T cells (CD3+ HLA-DR+ cells) in ITP patients. Furthermore, frequencies of NK cells of potent activity (CD16+ CD56+ cells) were significantly elevated in ITP patients. Seventeen of the 54 ITP patients (31.5%) had elevated levels of sFas, and 11 of the 54 patients (20.4%) of sFasL. In addition, a significant increase of sFasL was observed in sFas-positive ITP patients, and in these patients the sFasL level was correlated with that of sFas (r = 0.687, p < 0.01). We found significant increases in IL-2 and sIL-2R levels in sFas-positive ITP patients. For other factors examined, however, there were no differences in level between sFas-positive and -negative ITP patients. Percentages of activated T cells (CD3+ and HLA-DR+ cells) and NK cells (CD16+ and CD56+ cells) were significantly higher in sFas-positive ITP patients than in sFas-negative ITP patients. These findings suggests that the pathogenesis of ITP includes alteration of the Fas/FasL pathway.     

The Role of Autoreactive T-cells in the Pathogenesis of Idiopathic Thrombocytopenic Purpura

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease mediated by antiplatelet autoantibodies. The major target of these autoantibodies is a platelet membrane glycoprotein, GPIIb-IIIa, which is a receptor for fibrinogen and other ligands. We recently identified CD4+ T-cells autoreactive to GPIIb-IIIa in ITP patients. These T-cells are considered pathogenic because they help B-cells produce antibodies that bind to normal platelet surfaces. GPIIb-IIIa-reactive T-cells respond to chemically reduced and tryptic peptides of GPIIb-IIIa but not to native GPIIb-IIIa, indicating that the epitopes they recognize are "cryptic" determinants generated at a subthreshold level by the processing of native GPIIb-IIIa under normal circumstances. Although GPIIb-IIIa-reactive T-cells are also detected in healthy individuals, they are activated in vivo only in ITP patients. Activation of GPIIb-IIIa-specific T-cells and the subsequent production of pathogenic anti-GPIIb-IIIa antibodies can be induced by functional antigen-presenting cells in the spleen that present cryptic GPIIb-IIIa peptides to these T-cells. The pathogenic process of ITP can be explained as a continuous loop in which B-cells produce antiplatelet autoantibodies, splenic macrophages phagocytose antibody-coated platelets and present GPIIb-IIIa-derived cryptic peptides, and GPIIb-IIIa-reactive CD4+ T-cells exert their helper activity. Further studies examining the mechanisms that induce the processing and presentation of cryptic peptides derived from the platelet antigen at disease onset will clarify how the pathogenic autoantibody response in ITP is initiated.     

High-dose intravenous IgG for chronic idiopathic thrombocytopenic purpura in adults

Summary Sixteen adult patients of mean age 48 years with chronic ITP were studied for platelet response to high-dose (0.4 g/kg body weight per day for five consecutive days) intravenous polyvalent intact IgG in the absence of any concurrent treatment. The platelet count returned to normal values in nine patients, a partial response (rise in the platelet count between 50 and 150 ×10⁹/l) was observed in three cases. One patient refractory to any other treatment went into a sustained remission. In the other responsive patients the response was only transient. Among seven splenectomised patients only three responded to IgG infusions versus nine in the non-splenectomised group. The length of ITP history appeared as a more critical factor for the response to IgG than previous splenectomy.     

The role of apoptosis in childhood Henoch–Schonlein purpura

The pathogenesis of vasculitis is complex and is yet to be fully elucidated, although it is known that inflammatory cells play a major role. Dysregulation of apoptosis and defective clearance of inflammatory cells could lead to the persistence of inflammation and excessive tissue injury. In this study we aimed to investigate Fas (CD95) and apoptosis on peripheral blood (PB) neutrophil and lymphocytes in Henoch–Schonlein purpura, both in the acute phase and after resolution to determine the role of apoptosis in this self-limited vasculitis. Leukocytoclastic vasculitis presenting with Henoch–Schonlein purpura (HSP) was diagnosed according to ACR 1990 criteria and confirmed by skin biopsy. Thirty-seven patients (22 boys, 15 girls) aged 2.5–17 years (9 ± 3.3) were enrolled in the study. Expression of CD95 and apoptosis were investigated by the annexin/PI method on peripheral blood neutrophils and lymphocytes in both the acute and the resolution phases of the disease. The mean neutrophil and lymphocyte CD95 expression was 65.4 ± 37.6% and 33.3 ± 7.3%, respectively, in the acute stage and 62.8 ± 44.2% and 41 ± 20%, respectively, in the resolution (P > 0.05). The percentage of apoptotic peripheral blood neutrophils and lymphocytes as determined by annexin positivity was 13.3 ± 11.31% and 8.6 ± 9.5%, respectively, during the acute phase and 4.6 ± 3.4% and 3.1 ± 3.1%, respectively, in the resolution (P = 0.002, P = 0.008). These results suggest that increased apoptotic process in the immune effector cells in the acute phase of the disease may play an important role in the early control of inflammatory response and repair in leukocytoclastic vasculitis, thereby contributing to the self-limited nature of the disease.     

Investigation of megakaryocyte apoptosis in children with acute and chronic idiopathic thrombocytopenic purpura

OBJECTIVE: Although the platelet destruction shows a primary role in the thrombocytopenia of idiopathic thrombocytopenic purpura (ITP), it has been demonstrated that impaired platelet production may also contribute to the severity of thrombocytopenia in ITP. The present study examined megakaryocyte apoptosis in bone marrow aspirates of children with acute and chronic ITP and investigated the role of megakaryocyte apoptosis in ITP pathophysiology. METHODS: Thirteen children diagnosed with acute ITP and eight children diagnosed with chronic ITP comprised the study group. Ten children, who were hospitalized for scoliosis operation but healthy otherwise, comprised the control group. In all children, megakaryocytes were isolated from the same amount of bone marrow aspirate samples using MACS CD61 MicroBeads (Miltenyl Biotec, Auburn, CA, USA). Megakaryocyte apoptosis was studied with transferase-mediated d-UTP-bitin nick end-labeling method. RESULTS: Isolated megakaryocyte counts did not differ significantly between acute ITP, chronic ITP and control groups. The percentage of apoptotic megakaryocytes did not differ significantly between acute ITP group and control group and between chronic ITP group and control group. The percentage of apoptotic megakaryocytes in patients with chronic ITP was significantly lower than the patients with acute ITP. There was no correlation between the percentage of apoptotic megakaryocytes and platelet counts of the cases. CONCLUSIONS: Increased megakaryocytic apoptosis does not play a role in the pathogenesis of dysmegakaryopoiesis and impaired platelet production in children with ITP. Decreased megakaryocyte apoptosis in cases with chronic ITP may be due to suppression of megakaryocyte maturation, as the terminal phase of the megakaryocyte lifespan is characterized by the onset of apoptosis.