Prognostic significance of splenic follicle size in splenectomized idiopathic thrombocytopenic purpura patients

Summary The prognostic significance of splenic follicle (B-lymphocyte compartment) size was studied in 62 patients splenectomized for idiopathic thrombocytopenic purpura (ITP). Patients with hyperplasia of splenic follicles (mean follicle diameter >500 m) were more likely to relapse or to develop additional autoimmune disorders than patients without hyperplastic splenic follicles (mean follicle diameter <500 m) (p<0.01). The enlargement of splenic follicles had a positive predictive value of 27% and a negative predictive value of 100% for a poor outcome of splenectomy. Thus, the histological examination of spleens surgically removed for ITP seems to be an appropriate method to obtain the first indication of the possible long-term effect of splenectomy almost immediately after the operation.     

Risk factors for neonatal thrombocytopenia in pregnancy complicated by idiopathic thrombocytopenic purpura

 The aim of this study was to evaluate risk factors for the occurrence of fetal/neonatal passive immune thrombocytopenia (PIT) in pregnancy complicated with ITP. We studied 52 pregnancies with ITP and the 54 neonates retrospectively. Neonatal platelet counts were compared with maternal platelet counts, platelet-associated IgG (PAIgG) values and the presence of antiplatelet antibody in maternal circulation, history of previous PIT, maternal treatments for ITP, and other maternal/neonatal factors including gestational age and birth weight. Logistic regression analysis for multivariables was performed. PIT (platelet counts <100×10³/μl) without neonatal mortality or any morbidity was observed in eight (15.4%) of 52 pregnancies. The presence of circulating antiplatelet antibodies in maternal blood, splenectomy prior to pregnancy, and a history of previous PIT were observed more frequently with statistical significance in women giving birth to neonates who developed PIT. By logistic regression analysis, splenectomy prior to pregnancy was found to be the single significant variable (p=0.017, odds ratio 9.33) among the risk factors for PIT. Thus, splenectomy prior to pregnancy is related to increased risk for PIT in ITP-complicated pregnancy. Received: July 11, 1997 / Accepted: March 10, 1998     

Perinatal management of idiopathic thrombocytopenic purpura in pregnancy: risk factors for passive immune thrombocytopenia

Summary Thirty-nine pregnant women with idiopathic thrombocytopenic purpura (ITP) were studied in order to evaluate the influence of therapies for maternal ITP on fetal passive immune thrombocytopenia (PIT). Neonatal platelet counts were also compared with platelet counts, amount of PAIgG, and presence of circulating antiplatelet antibody in maternal blood. Eight of 41 neonates (19.5%) presented PIT without neonatal mortality. A higher incidence of PIT was observed in women with prior splenectomy than in women without splenectomy (66.7% vs 11.4%). Neither a therapeutic effect nor an increased risk of PIT was observed with steroids or gammaglobulin administration. No correlation was found between neonatal platelet counts and maternal platelet counts or maternal PAIgG, while positive cases for circulating antiplatelet antibody assay presented a higher incidence of PIT than negative cases. Additionally, a higher incidence of PIT was observed in women with a history of previous PIT than in women with a history of normal delivery. Prior splenectomy, presence of antiplatelet antibody in maternal blood, and a history of previous PIT seem to be risk factors for fetal PIT.     

Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori

The relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been investigated in several studies. We investigated the prevalence of H. pylori infection and the clinical effects of eradication in 22 Japanese patients with chronic ITP. H. pylori infection was found in 14 (63.6%) of the patients by histologic and culture examinations of biopsy samples obtained by gastrointestinal endoscopy. H. pylori was eradicated by proton pump inhibitors and 2 kinds of antibiotics in 13 (92.9%) of the 14 patients in whom the results of treatment could be evaluated. Five (38.4%) of those 13 patients had platelet recovery (platelet count of more than 100 x 10(9)/L and an increase of more than 30 x 10(9)/L with respect to the baseline value) after eradication. The median follow-up period was 15 months. One patient who had a complete response had a partial relapse after cessation of prednisolone treatment without any evidence of H. pylori reinfection. Another patient, in whom H. pylori was not eradicated even after 2 treatment sessions, had a partial response after treatment. A screening examination for H. pylori infection may be necessary for Japanese patients with newly diagnosed ITP. Although the exact mechanism underlying platelet recovery after H. pylori eradication is not clear, the results of this study indicated that H. pylori eradication treatment is a good option for some patients with chronic ITP.     

Myelofibrosis and idiopathic thrombocytopenic purpura

 A case of idiopathic myelofibrosis (IMF) with concomitant autoimmune thrombocytopenic purpura (AITP) is reported. The literature on platelet antibodies in IMF is reviewed. Received: 25 March 1997 / Accepted: 11 July 1997     

特发性血小板减少性紫癜患者外周血单个核细胞中糖皮质激素诱导的亮氨酸拉链蛋白mRNA表达的研究

目的探讨特发性血小板减少性紫癜（ITP）患者使用糖皮质激素治疗前后外周血单个核细胞中GILZmRNA的表达及作用。方法选择未使用糖皮质激素治疗的ITP患者23例（病例对照组）、使用糖皮质激素治疗后的患者22例（治疗组）及健康体检者22例（正常对照组）作为研究对象,采用RT—PCR法检测其外周血单个核细胞中GILZmRNA的表达,同时采用ELISA法检测其血清中IFN-γ、IL-10的表达。结果与正常对照组相比,病例对照组GILZmRNA表达明显降低（P〈0．01）,IFN-γ表达明显升高（P〈0．01）,IL-10表达明显降低（P〈0．01）,而治疗组GILZmRNA、IFN-γ、IL-10表达差异则无明显统计学意义（P均〉0．05）。结论糖皮质激素可以上调TP患者外周血单个核细胞中GILZmRNA表达;GILZmRNA表达上调可明显抑制Th1细胞因子分泌,增强Th2细胞因子分泌,纠正ITP患者血清中Th1／Th2的失衡。     

抗幽门螺杆菌治疗对慢性特发性血小板减少性紫癜患者疗效观察

目的通过对特发性血小板减少性紫癜(ITP)患者行抗幽门螺杆菌(HP)感染的临床研究,观察ITP与HP感染之间的关系以及抗HP在ITP患者治疗中的作用。方法2003-07~2003-12对解放军301医院17例慢性ITP患者采用14C尿素呼气试验进行HP检测,女11例,男6例,病程4个月至8年,并对阳性患者行奥美拉唑、克拉霉素及阿莫西林三联根除HP治疗,观察血小板情况。结果本组17例患者中HP阳性13例,阴性4例,抗HP后转阴11例,其中8例血小板水平较前有所提高。结论抗HP治疗确实可提高部分慢性ITP患者的血小板数。     

High-dose dexamethasone as a first- and second-line treatment of idiopathic thrombocytopenic purpura in adults

The current first-line choice of treatment of idiopathic thrombocytopenic purpura (ITP) in adults, prednisone, is effective but has many side effects. Furthermore, reduction of the dose leads to a relapse of ITP in a majority of cases. Courses of high-dose dexamethasone (HD) aim to avoid these problems. We treated 36 patients with newly diagnosed or recurrent ITP with an 8-day course of HD, with a peak dose of 40 mg/day. The courses were repeated up to a maximum of six courses, with a 28-day interval. Acute and chronic effects of HD on platelet counts were observed, as well as side effects. HD led to an acute response (rise of platelet count to a level above 50×10⁹/l) in 83%. When HD was given as a first-line treatment, 59% of patients were still in remission after 31 months. When HD was given as a second-line treatment, 50% of patients were in remission after 5 months, declining to 25% after 54 months. Side effects were frequent but rarely dangerous. In conclusion, acute effects of HD were excellent. Long-term effects of HD as a first-line therapy of ITP were good, but its long-term effects as a second-line therapy were much poorer.     

Treatment advances in adult immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by autoantibody-mediated destruction of platelets. The disease generally runs a mild clinical course, though significant morbidity and mortality can occur. Steroids and/or splenectomy are effective in treating the disease in approximately 70% of patients. These treatments have been well established with approximately 50 years of clinical experience. While open splenectomy is the traditional surgical procedure, laparoscopic splenectomy, splenic artery embolization, and splenic irradiation are viable alternatives. For patients who relapse after the above therapies, treatment is more difficult and seldom results in a cure. The goals of therapy involve maintaining a safe platelet count while minimizing toxicities from the treatment. Multiple treatment options exist including corticosteroids, androgens, immunomodulatory drugs, cytotoxic chemotherapy, immunoglobulin preparations, bone marrow transplantation, Helicobacter pylori eradication, and others. While the standard treatment of steroids and splenectomy has changed little over the past decades, a number of promising new therapies on the horizon may soon join the armamentarium upon which the clinician can draw to fight the disease. In this review, we will examine treatment for chronic ITP in adults in the pre-splenectomy, splenectomy, and post-splenectomy settings.     

The efficacy of rituximab in patients with splenectomized refractory chronic idiopathic thrombocythopenic purpura

The most difficult problem a physician encounters is the management of patients with idiopathic thrombocytopenic purpura (ITP), who has persistent severe thrombocytopenia after failure of initial treatment with glucocorticoids and splenectomy. Most of the patients refractory to corticosteroids and splenectomy will become refractory to other available agents, such as intravenous immunoglobulin (IVIg), danazol or chemotherapy. In this study, we investigated the effect of rituximab on 17 splenectomized refractory chronic ITP patients. Here, we showed that the anti-CD20 antibody, rituximab, induces a clinically significant response in severe chronic ITP patients, who are unresponsive to other therapeutic options. After sixth month, 10 out of 14 responders were still maintaining their durable and significant platelet responses (platelet counts >50 × 10⁹/l), without requirement to any other ITP medication. Therefore, we suggest that, rituximab is an effective treatment option in splenectomized refractory or relapsed ITP patients. Rituximab was well tolerated without severe side effects.     

特发性血小板减少性紫癜无效输注原因分析

目的:探讨特发性血小板减少性紫癜(ITP)患者血小板无效输注的原因.方法:90例确诊的ITP患者中对输注血小板的48例计算血小板计数增高指数(CCI),评价输注的效果并分析与感染、脾脏肿大、血小板抗体、骨髓巨核细胞数和免疫指标等因素的关系.结果:18例应用血小板和激素治疗的患者,44.4%有效输注,30例应用血小板、激素和丙种球蛋白患者,53.3%有效输注.24例无效输注患者中在感染组与非感染组、脾脏肿大组与正常组、血小板相关抗体升高组与正常组,有效输注率有显著性差异.骨髓巨核细胞数升高组与正常组、调节性T细胞低表达组与正常组,有效输注率差异无统计学意义.结论:ITP患者输注血小板50%存在无效输注,其原因可能与感染、脾脏肿大、血小板相关抗体有关.因此控制感染和抑制免疫应作为首选治疗,而血小板的输注应严格把握指征.     

幽门螺杆菌与特发性血小板减少性紫癜发病关系的研究进展

幽门螺杆菌(Hp)感染与特发性血小板减少性紫癜(ITP)的发病有关。约50%Hp阳性ITP患者根除Hp后血小板减少症得以完全或部分缓解。目前Hp相关ITP的发病机制尚不完全清楚,此文就其发病机制研究进展作一综述。     

Clinical effect of intravenous immunoglobulin on chronic idiopathic thrombocytopenic purpura

Summary High dose immunoglobulin infusions showed a marked effect on platelet counts in eight out of nine chronic ITP patients and in one SLE patient. In the comparison of different IgG-preparations, the pepsin treated IgG F (ab′)₂ showed no platelet elevation while the sulfonated did. The elevated platelet count could not be maintained after discontinuation of IgG infusions, but in six out of ten patients the platelet level remained above the pretreatment values. This new treatment seems to be safe and effective in adulthood ITP.     

特发性血小板减少性紫癜患者B淋巴细胞凋亡研究

目的探讨B淋巴细胞在特发性血小板减少性紫癜(ITP)发病机制中的作用。方法用流式细胞术检测ITP患者外周血B淋巴细胞表面Fas蛋白、FasL蛋白以及胞浆内抗凋亡蛋白bcl2的表达水平。结果ITP患者外周血中B淋巴细胞表面Fas和FasL蛋白表达与对照组相比无统计学意义,B淋巴细胞胞浆内bcl2的表达水平高于正常人(P<0.05)。结论B淋巴细胞凋亡受抑可能参与ITP自身免疫的发病机制。     

慢性特发性血小板减少性紫癜患者血清转化生长因子-β1测定的意义

目的探讨血清转化生长因子-β1（TGF-β1）在慢性特发性血小板减少性紫癜（ITP）中的临床意义。方法采用双抗体夹心酶联免疫吸附法（ELISA）检测38例初治慢性ITP患者治疗前后血清中TGF-β1水平。结果慢性ITP患者治疗前TGF-β1水平明显高于对照组（P〈0．01）。经治疗缓解后血清TGF-β1水平与治疗前比较明显下降（P〈0．01）。未缓解者TGF-β1水平与初诊患者比较差异无统计学意义（P〉0．05）。TGF-β1水平与血小板数呈负相关（r=-0．342,P〈0．05）,与巨核细胞数呈正相关（r=0．409,P〈0．01）。结论TGF-β1参与了慢性ITP的发病,检测TGF-β1水平变化有助于对慢性特发性血小板减少性紫癜患者病情的判断,可作为疗效观察的辅助指标。     

Antiplatelet autoantibody-related microparticles in patients with idiopathic (autoimmune) thrombocytopenic purpura

Summary We used flow cytometry to detect antiplatelet antibody-related microparticles (MP) in 56 patients with idiopathic thrombocytopenic purpura (ITP). We measured MP in platelets following various types of stimulation in two experimental systems. In one system washed platelets were incubated with normal serum which included the complement system, and in the other, washed platelets were incubated with Tyrode's buffer. There were no differences between the two measurement systems in the degree of increase in MP using various agonists. An increase in MP using ITP plasma was found in 12 out of 56 patients. In particular, four patients showed a significant increase in MP in washed platelets (WP) plus serum. Furthermore, the increase in platelet-associated IgM (PAIgM) was significant in these patients. There was also a definite positive correlation between PAIgM and the percentage of MP of WP plus serum. On the other hand, no specificity for MP formation with anti-GPIIb/IIIa or anti-GPIb autoantibodies was observed. IgM antibody-related MP appear to exist in some patients with ITP.     

评价血小板相关抗体定量测定法对特发性血小板减少性紫癜的诊断价值

目的 :评价血小板相关抗体 (PAIg)定量测定法对诊断特发性血小板减少性紫癜 (ITP)的价值。 方法 :应用酶联免疫竞争抑制试验 (ELISA)定量测定血小板相关抗体 ,计算试验的灵敏度、特异度、准确度、阳性预测值 ,绘制受试者ROC曲线进行诊断价值的评价。结果 :根据常用判断PAIg阳性的临界值 ,血小板相关抗体试验诊断ITP的灵敏度较高 (95 % ) ,但特异度低 (48.8% ) ,准确度低 (5 7.5 % ) ,阳性预测值低 (30 .2 % )。用ROC曲线寻找诊断ITP的最佳临界值 ,用新的临界值 (PAIgG >16 0ng/10 7血小板或PAIgA >2 5ng/10 7或PAIgM >35ng/10 7)时 ,可提高诊断试验的特异度 ,从 4 8.8%提高到 6 2 .8% ,可确诊更多的患者 ;但准确度和阳性预测值仍低 ,分别为 6 7.9%和 36 .0 %。结论 :PAIg试验诊断ITP的特异度、准确度、阳性预测值较低 ,帮助诊断ITP的临床价值有限 ,即使用新的临界值提高了试验的特异度 ,但诊断ITP的价值仍不大。     

特发性血小板减少性紫癜患者T淋巴细胞周期和细胞周期调节蛋白cyclinA表达的变化

目的探讨特发性血小板减少性紫癜(ITP)患者外周血T淋巴细胞的细胞周期及细胞周期调节蛋白cyc linA的表达及其在发病机制中的作用。方法用流式细胞仪检测38例初发ITP患者T淋巴细胞的细胞周期的分布比例,细胞周期调节蛋白cyc linA的表达水平。结果初发ITP患者外周血S期和S G2/M期的T淋巴细胞比例显著高于对照组(P<0.05);G0/G1的T淋巴细胞比例显著低于对照组(P<0.05);初发ITP患者外周血T淋巴细胞cyc linA的表达率明显高于对照组(P<0.05)。结论在ITP患者中存在T淋巴细胞过度增殖,细胞以S和G2期为主,这可能与ITP的发病有关。     

静脉输注丙种球蛋白治疗特发性血小板减少性紫癜

目的:分析静脉输注丙种球蛋白治疗特发性血小板减少性紫癜(ITP)的疗效。方法:静脉输注丙种球蛋白(IVIG)0.4g·kg-1·d-1,连用5d。结果:25例患者经治疗后,显效11例(44%),其中基本治愈5例(20%);良好效果6例(24%);进步4例(16%);无效4例(16%),总有效率为84%。结论:治疗重症、难治性ITP患者,IVIG是一种安全、有效、无不良反应的治疗方法。特别对≤14岁的患儿和初治病例疗效更佳。并可反复使用,复发患者用糖皮质激素治疗仍有效。