Intravenous immunoglobulin G and anti-D as therapeutic interventions in immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is a disorder caused by accelerated destruction of antibody-coated platelets in the reticuloendothelial system (RES), especially the spleen. Inhibition of RES function following intravenous administration of high-dose immunoglobulin G (IVIG) or intravenous anti-D leads to rapid, albeit usually temporary, reversal of thrombocytopenia in the majority of children and adults with ITP. In emergency situations high-dose IVIG is preferred over anti-D because of the more rapid rate of platelet response; for maintenance therapy in Rh positive ITP patients (e.g. children with chronic ITP pre-splenectomy) anti-D is preferred because of its comparable efficacy to IVIG plus ease of administration and lower cost. In children with typical acute ITP and platelet counts < 20 x 10(9)/L IVIG is preferred over anti-D; however other approaches in this patient cohort should be considered before high-dose IVIG, specifically careful observation alone with therapy given only to children with clinically significant haemorrhage or short course oral prednisone at a starting dose of approximately 4 mg/kg/day. Studies are required to define the short and longer term effects of both IVIG and anti-D on the immune system in order to plan more rational use of these immunomodulatory therapies in this model autoimmune disorder.     

An evaluation of intravenous immunoglobulin in the treatment of human immunodeficiency virus-associated thrombocytopenia

BACKGROUND: Anecdotal evidence suggests that high-dose intravenous immunoglobulin (IVIG) is useful in the management of human immunodeficiency virus (HIV)-associated thrombocytopenia. STUDY DESIGN AND METHODS: To rigorously evaluate this therapy, a crossover study was designed to compare IVIG, given at 1 g per kg per day for 2 consecutive days each week for 4 weeks, with intravenous saline placebo administered according to the same schedule. Subjects were randomly assigned to receive either IVIG or saline during the first 4 weeks; if IVIG was given, there was a 4-week period of no therapy before beginning placebo administration. Criteria for eligibility were platelet count of less than 50,000 per microL (50 × 10(9)/L), elevated platelet-associated IgG levels, increased megakaryocytes in the bone marrow, and positive HIV antibody test. Twelve patients (11 men, 1 woman) were studied. Seven patients completed the full protocol. Four dropped out: after 2, 5 (2 patients), and 8 weeks that included at least 2 weeks of IVIG. RESULTS: All patients sustained an increase in platelet count in response to IVIG, with increments ranging from 15,000 to 358,000 per microL (15 to 350 × 10(9)/L) (mean, 180,000/microL [180 × 10(9)/L]; median, 174,000/microL [174 × 10(9)/L]). No patient had an increase after placebo infusions. There were no adverse effects of treatment, and weekly chemical analyses showed no new abnormalities except for mild elevations in the serum protein. The duration of responses ranged from 2 to 10 weeks. No patient demonstrated refractoriness to IVIG. CONCLUSION: IVIG consistently raises platelet counts in patients with HIV-associated thrombocytopenia.     

原发免疫性血小板减少症的规范化诊治

原发免疫性血小板减少症(primary immune thrombocytopenia, ITP)是一种获得性免疫介导的血小板减少性疾病,其发病机制为免疫失耐受导致的血小板破坏过多及巨核细胞产生血小板不足。临床表现主要为血小板减少性的出血及疲劳等症状。ITP的诊断无特异性指标,需排除其他的血小板减少性疾病。治疗目的为维持血小板在安全水平,预防出血,并提高患者生活质量。治疗指征为血小板≤30×10⁹/L和(或)有出血表现,对于老年患者、重体力劳动者、有高血压等出血风险较高的合并症患者以及需抗血小板、抗凝治疗患者等,可适当放宽治疗指征。一线治疗为糖皮质激素及静脉注射人免疫球蛋白;二线治疗包括促血小板生成药物、利妥昔单抗及脾切除等治疗;对于难治性ITP患者,可考虑维A酸等三线治疗。     

Autoimmune thrombocytopenia

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which platelets coated with mainly antibodies against platelet GPIIb/IIIa and GPIb/IX are destroyed in the spleen. Recent evidence suggests that platelets are also destroyed by cytotoxic T cells. The diagnosis is made by exclusion for other causes of thrombocytopenia. As routine blood counts are becoming more available, many mild cases of ITP (platelets >30 x 10(9) L(-1)) are being diagnosed and they usually do not require treatment. In patients with platelet counts persistently <30 x 10(9) L(-1), treatment with corticosteroids, and/or intravenous immunoglobulin (IVIG) or anti-D may be required. The primary goal of treatment is to maintain the platelet count at a safe level with minimal side effects. After 3-6 months, if spontaneous remission has not occurred and if the side effects are significant, splenectomy is recommended. This is the single most effective treatment of ITP. The refractory patients who fails splenectomy and subsequently first- and second-line therapies, is a management dilemma. Therapeutic options are limited, available treatments potentially toxic and the chances of sustained response low. Observation with no active treatment is a reasonable option. With the increased availability of the thrombopoietic agents in the future, there may be a good prospect of keeping the platelet counts of these refractory patients at a safe long-term level with one of these drugs.     

联合使用免疫抑制剂治疗难治性原发免疫性血小板减少症的疗效及其对血小板相关抗体水平影响的研究

目的观察联合使用免疫抑制剂治疗难治性原发免疫性血小板减少症（ITP）的疗效,研究联合使用免疫抑制剂对难治性ITP患者血小板相关抗体（PAIG）水平的影响。方法2009年2月-2013年2月,将22例难治性ITP患者按入院号顺序随机分为联合治疗组和单药治疗组。联合治疗组先予甲泼尼龙及静脉免疫球蛋白滴注,血小板值迅速上升后联合使用2～3种不同组合的免疫抑制剂;单药组先予甲泼尼龙及静脉免疫球蛋白滴注,血小板上升后接受1种免疫抑制剂治疗。维持治疗3～6个月,结束治疗后随访6～24个月。运用流式细胞术检测治疗前后患者血清PAIG水平。结果联合治疗组显效6例,良效2例,进步1例,无效2例,对照组显效0例,良效2例,进步1例,无效7例,两组治疗反应差异有统计学意义（Z=-2．796,P=0．005）。两组对象治疗后PAIG水平均明显降低,联合治疗组治疗后PAIG水平明显低于单药治疗组,差异有统计学意义（P〈0．05）。结论联合使用免疫抑制剂治疗治疗难治性ITP疗效较好,且能明显降低患者的PAIG水平。     

小剂量利妥昔单抗治疗慢性特发性血小板减少性紫癜疗效分析

目的 探讨小剂量利妥昔单抗(抗CD20单抗)治疗慢性特发性血小板减少性紫癜(ITP)临床疗效、安全性及患者免疫学改变.方法 采用小剂量利妥昔单抗(100 mg,每周1次,共4次)治疗26例对糖皮质激素和免疫球蛋白治疗无效的慢性ITP患者,检测治疗前后血常规,免疫球蛋白和血小板相关抗体及淋巴细胞亚群CD3~+、CD3~+CD4~+、CD3~+CD8~+、CD3~- CD56~+、CD4~+ CD25~+、CD4~+ CD25~+ FOXP3~-、CD4~+ CD25~+ FOXP3~+和CD19~+CD20~+细胞.结果 26例患者,完全缓解(CR)6例(23.1%),有效(R)10例(38.5%),其中l例复发,无效(NR)10例(38.5%).中位随访时间5.5(0.8-8)个月,起效和达CR中位时间分别为27(1-104)d和41(4-109)d.治疗前后免疫球蛋白定量和CD3~+、CD3~+CD4~+、CD3~+CD8~+、CD3~- CD56~+、CD4~+CD25~+、CD4~+ CD25~+ FOXP3~+细胞计数差异无统计学意义.治疗后的CD4~+CD25~+FOXP3~-细胞计数比治疗前降低(P<0.05).治疗后的CD19~+CD20~+细胞计数与治疗前相比明显减少(P<0.01).治疗后血小板相关抗体PAIgG比治疗前减低(P<0.05).26例患者均无明显的不良反应.结论 小剂量利妥昔单抗可能是一种高效、安全治疗ITP的药物,但其最佳用药方案、长期疗效以及不良反应仍有待临床进一步观察.     

Prospective evaluation of the immunobead assay for the diagnosis of adult chronic immune thrombocytopenic purpura (ITP)

Summary.  Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by antibody-induced platelet destruction. To better define the role of antigen-specific assays in adult chronic ITP, we prospectively measured platelet-associated autoantibody against either glycoprotein (GP) IIb/IIIa or GPIb/IX in 282 patients with chronic ITP and 289 patients with thrombocytopenia of other causes. We divided chronic ITP into four subgroups: presplenectomy, mild (platelet count >30 000 µL⁻¹ requiring no therapy), presplenectomy, severe (platelet count <30 000 µL⁻¹ requiring therapy but not splenectomy), postsplenectomy, remission (postsplenectomy partial or complete remission without further therapy) and postsplenectomy refractory (required therapy after splenectomy failure). Positive results: total ITP group, 55.4%; presplenectomy, mild, 31.1%; presplenectomy, severe, 42.6%; postsplenectomy, remission, 50.0%; and postsplenectomy, refractory, 87.8%. In addition, the degree of positivity increased with the severity of the patient's disease. The assay had a minimum specificity of 84.4% if clinical factors, consistent with immune thrombocytopenia, were not considered in patients with thrombocytopenia associated with other diseases. However, if clinical factors consistent with immune thrombocytopenia were considered and only patients with questionable immune thrombocytopenia and patients 'lost to follow-up' were included in the false-positive group the specificity was 93.1%. We conclude that the presence of immune thrombocytopenia is highly probable if the immunobead assay is positive and that antigen-specific assays are diagnostically useful in adult chronic ITP.     

Platelet Kinetics in Idiopathic Thrombocytopenic Purpura Patients Treated with Thrombopoietin Receptor Agonists

Aim

Thrombopoietin receptor agonists (Tpo RA) increase platelet counts in the majority of chronic autoimmune thrombocytopenia (idiopathic thrombocytopenic purpura; ITP) patients. It is unknown whether this treatment may also improve platelet survival (PS) in these patients.

Methods

In order to determine platelet survival (PS), autologous platelets were labeled with ¹¹¹In oxine and retransfused in six patients under treatment with Tpo RA (romiplostim n = 3; eltrombopag n = 3).

Results

Stable platelet counts of greater than 100 × 10³/μl were observed in all 6 patients. Platelet survival was decreased in all cases (mean 2.10 days; range 0.13–3.73 days). No correlation was found between platelet count and PS. Similarly, there was no significant relationship between platelet turnover and platelet count. However, a high platelet turnover, exceeding 25 or three times the norm was observed in 2 patients who presented the lowest PS (0.13 or 0.83 days). Two patients had a moderately shortened PS (1.91 or 2.42 days), and, correspondingly, a moderately increased platelet turnover rate (63,072 or 72,872 platelets/μl/day).

Conclusion

These results indicate that Tpo RA may not only overcompensate platelet destruction in ITP, but may interfere with other mechanisms, which, in some cases, results in a reduced platelet destruction rate.     

Mechanisms for linezolid-induced anemia and thrombocytopenia

BACKGROUND: Linezolid has been associated with anemia and thrombocytopenia. Mechanisms for neither have been elucidated. OBJECTIVE: To propose mechanisms for linezolid-induced anemia and thrombocytopenia. CASE SUMMARY: A 78-year-old white woman with Staphylococcus epidermidis endocarditis was treated with linezolid after developing resistance to multiple antibiotic regimens. After 7 days of linezolid therapy, she developed thrombocytopenia, while an anemia present since admission remained unchanged. A bone marrow biopsy was performed, primarily looking for a mechanism for the thrombocytopenia. Histopathology revealed adequate megakaryocytes, ringed sideroblasts, and vacuolated pronormoblasts. A course of immune globulin (IVIG) was administered, with slowing in the rate of decline in platelets. She died 24 hours after her last dose of IVIG of congestive heart failure. DISCUSSION: The presence of ringed sideroblasts and vacuolated pronormoblasts suggests that linezolid-induced anemia is secondary to a chloramphenicol-like suppression of erythropoiesis. The presence of adequate, normal-appearing megakaryocytes suggests immune-mediated thrombocytopenia, not marrow suppression. Although the response to IVIG is difficult to interpret because of the patient's death, there was a slowing in the rate of decline of the platelet count, further supporting immune-mediated thrombocytopenia. An objective causality assessment indicated that the adverse drug event was probably due to linezolid. CONCLUSIONS: There appear to be 2 distinct mechanisms for linezolid-induced cytopenias. While anemia is reversible and manageable with transfusions, thrombocytopenia can be a treatment-limiting toxicity. The ability to treat through an immune-mediated cytopenia with IVIG may be beneficial for critically ill patients with few therapeutic options.     

Contemporary management of primary immune thrombocytopenia in adults

Summary. Immune thrombocytopenia (ITP) comprises a syndrome of diverse disorders that have in common immune‐mediated thrombocytopenia, but that differ with respect to pathogenesis, natural history and response to therapy. ITP may occur in the absence of an evident predisposing etiology (primary ITP) or as a sequela of a growing list of associated conditions (secondary ITP). Primary ITP remains a diagnosis of exclusion and must be differentiated from non‐autoimmune etiologies of thrombocytopenia and secondary causes of ITP. The traditional objective of management is to provide a hemostatic platelet count (> 20–30 × 10⁹ L^?1 in most cases) while minimizing treatment‐related toxicity, although treatment goals should be tailored to the individual patient and clinical setting. Corticosteroids, supplemented with either intravenous immune globulin G or anti‐Rh(D) as needed, are used as upfront therapy to stop bleeding and raise the platelet count acutely in patients with newly diagnosed or newly relapsed disease. Although most adults with primary ITP respond to first‐line therapy, the majority relapse after treatment is tapered and require a second‐line approach to maintain a hemostatic platelet count. Standard second‐line options include splenectomy, rituximab and the thrombopoietin receptor agonists, romiplostim and eltrombopag. Studies that directly compare the efficacy, safety and cost‐effectiveness of these approaches are lacking. In the absence of such data, we do not favor a single second‐line approach for all patients. Rather, we consider the pros and cons of each option with our patients and engage them in the decision‐making process.     

Autoimmune thrombocytopenia due to chronic lymphocytic leukemia treated with fludarabine

OBJECTIVE: To report a case of autoimmune thrombocytopenia due to chronic lymphocytic leukemia (CLL) treated with fludarabine. CASE SUMMARY: A 68-year-old white woman with CLL was treated with oral chlorambucil. She subsequently presented with severe autoimmune thrombocytopenia purpura (ITP). Intravenous gammaglobulin was administered without response, and a therapeutic splenectomy produced only a temporary response, with platelets reaching 65 x 10(3)/mm(3). Four weeks later, the platelet level was below 10 x 10(3)/mm(3). At that time, the woman was treated with fludarabine. The platelet count 4 weeks later was normal (270 x 10(3)/mm(3)) and has been sustained for over 22 months. DISCUSSION: Fludarabine has been reported to be causative in the onset of autoimmune cytopenias with CLL. Our case cautiously suggests fludarabine as a potential treatment for cases of CLL-associated ITP refractory to standard therapy. CONCLUSIONS: Fludarabine could be considered as treatment of ITP in CLL refractory to standard treatment.     

Preliminary laboratory based diagnostic criteria for immune thrombocytopenic purpura: evaluation by multi-center prospective study

BACKGROUND: We proposed diagnostic criteria for immune thrombocytopenic purpura (ITP) by modifying the existing guidelines for diagnosis of ITP and by incorporating laboratory tests found useful for predicting its diagnosis, for example erythrocyte count, leukocyte count, anti-GPIIb/IIIa antibody-producing B cells, platelet-associated anti-GPIIb/IIIa antibodies, percentage of reticulated platelets, and plasma thrombopoietin. OBJECTIVE AND METHODS: To validate our criteria, we conducted a multi-center prospective study involving 112 patients with thrombocytopenia and a morphologically normal peripheral blood film at the first visit. Each patient underwent a physical examination, routine laboratory tests, and specialized tests for the anti-GPIIb/IIIa antibody response and platelet turnover. RESULTS: Ninety-one patients (81%) satisfied the proposed criteria at first visit. Clinical diagnosis was made by skilled hematologists > 6 months after the first visit; ITP was diagnosed in 88 patients and non-ITP disorders in 24. The proposed criteria had 98% sensitivity, 79% specificity, a 95% positive predictive value, and a 90% negative predictive value. A relatively low specificity appears to be attributed to a few patients who had both ITP and aplastic anemia or myelodysplastic syndrome. CONCLUSIONS: Our preliminary diagnostic criteria based on ITP-associated laboratory findings were useful for the differential diagnosis of ITP, but additional evaluations and modifications will be necessary to develop criteria that can be used routinely.     

巨核细胞与血小板参数在血小板减少性疾病中的应用

目的探讨巨核细胞与血小板(PLT)参数在血小板减少性疾病中的应用价值。方法对72例血小板减少症患者分组进行巨核细胞数及血小板4项参数[PLT、血小板体积(PCT)、血小板平均体积(MPV)、血小板体积分布宽度(PDW)]检测,并做比较。结果与正常对照组相比,PLT值特发性血小板减少性紫癫(ITP)组最低(P<0.01),脾亢组次之(P<0.01),PCT与PLT变化一致,各组PDW均增高(P<0.01),MPV以ITP组与免疫组显著增高(P<0.05);其他各组与ITP组相比,巨核细胞数、PLT值、PCT均有显著性差异(P<0.01),免疫组与ITP组相比MPV、PDW有显著性差异(P<0.05)。4组病例骨髓均表现为巨核细胞成熟障碍,ITP组巨核细胞总数及颗粒巨明显增多,巨幼细胞性贫血(MgA)组巨核细胞呈病态改变。结论观察血小板参数及巨核细胞的形态特征,对血小板减少性疾病诊断及鉴别诊断具有重要意义。     

Plasma thrombospondin in immune thrombocytopenic purpura

Patients with immune thrombocytopenic purpura (ITP) rarely suffer life-threatening haemorrhages despite significant thrombocytopenia, probably because large numbers of hyperfunctioning platelets are present. Thrombospondin is a platelet alpha-granule protein and its plasma level may reflect platelet activation. We assessed circulating thrombospondin levels in 12 newly diagnosed ITP patients (one man; 11 women, aged 36 +/- 16 years) before they were treated for ITP. Twelve healthy people (four men; eight women, aged 31 +/- 11 years) acted as controls. Plasma thrombospondin concentrations were measured using enzyme-linked immunoassays. Thrombospondin concentrations tended to be higher, despite thrombocytopenia, in ITP patients (158.8 +/- 28.2 ng/ml) compared with controls (120.7 +/- 18.2 ng/ml). The difference was not statistically significant, but the relatively high circulating thrombospondin concentrations we observed suggest that residual platelets could be activated in ITP, thus indicating a more benign clinical course compared with aplastic thrombocytopenia.     

Immunoglobulin G dimers and immune complexes are dispensable for the therapeutic efficacy of intravenous immune globulin in murine immune thrombocytopenia

BACKGROUND: Several mechanisms have been proposed to explain the therapeutic effects of intravenous immunoglobulin (IVIG) in immune thrombocytopenia (ITP). Noteworthy, a major role has been attributed to immunoglobulin (Ig)G dimers present in IVIG. It has also been suggested that immune complexes formed between IVIG and the patient's proteins after infusion could contribute to the therapeutic effect of IVIG in several autoimmune disorders. We recently observed that in‐house preparations of polyclonal human IgG derived from small pools of plasma and devoid of IgG dimers were as efficient as IVIG in a mouse model of thrombocytopenia. In this work, we revisited the role of IgG dimers in the therapeutic effects of IVIG in ITP. STUDY DESIGN AND METHODS: We used the passive mouse model of ITP to determine the therapeutic efficacy of human IgG preparations devoid of IgG dimers and of dimer‐enriched and ‐depleted commercial IVIG. Immune complex formation between IVIG and mouse plasma proteins was evaluated using a combination of chromatography and immunoprecipitation procedures. RESULTS: All preparations tested showed the same efficacy to alleviate ITP, regardless of their dimer contents. Significant amounts of immune complexes formed between IVIG and mouse plasma proteins were detected. However, the amount of immune complexes detected using the in‐house preparation of human polyclonal IgG and mouse plasma was significantly lower, although the in‐house preparation exhibited the same therapeutic efficacy as commercial IVIG. CONCLUSION: IgG dimers and immune complexes are dispensable to prevent thrombocytopenia in a mouse model of the disease.     

免疫性血小板减少症老年患者个体化治疗的研究进展

免疫性血小板减少症(ITP)是一种由体液免疫及细胞免疫异常共同介导的自身免疫性疾病,血小板破坏增多及生成减少共同参与其发病.既往普遍认为儿童及育龄期妇女为ITP的高发人群,但近年来相关文献报道,随着年龄的增长,ITP的发病率不断增高,年龄≥60岁的老年人已经成为新的ITP高发人群.由于ITP老年患者合并症多,对治疗反应及耐受性较年轻患者差,更易发生严重的出血症状,病死率增高.目前,针对ITP老年患者的经典治疗方法包括:糖皮质激素、静注人免疫球蛋白(IVIG)、脾切除术、免疫抑制剂等,但是约1/3的ITP老年患者接受治疗后,疾病仍迁延不愈.随着相关研究的深入,利妥昔单抗、血小板生成素受体激动剂(TPORA)罗米司亭与艾曲波帕、新型免疫抑制剂霉酚酸酯(MMF)等新药在治疗ITP老年患者中均显示出较好的疗效,然而根据ITP老年患者的具体情况对其实施个体化治疗变得越来越重要.笔者拟对ITP的个体化治疗方法及其最新研究进展,结合ITP老年患者这一特殊群体的具体情况进行综述.     

Reacting appropriately to thrombocytopenia in pregnancy

The lower limit of normal for the platelet count is considered to be 150,000/cu mm in both pregnant and nonpregnant normal adults. In the absence of preeclampsia, sepsis, drugs, or other apparent causes, the finding of asymptomatic mild thrombocytopenia in pregnant women is compatible with previously unrecognized immune thrombocytopenic purpura (ITP). Because of the risk of fetal/neonatal thrombocytopenia and the subsequent risk of neonatal intracranial hemorrhage in infants born of mothers with ITP, the optimal mode of delivery for an asymptomatic but thrombocytopenic mother is problematic. Conceivably, those gravidas with mild previously unrecognized thrombocytopenia may not have ITP and thus could be spared cesarean section. From the platelet counts of 730 antepartum patients, we found a mean value of 263,900/cu mm with a standard deviation of 66,000/cu mm, yielding 95% confidence limits of 134,500 to 393,300/cu mm. The distribution is statistically indistinguishable from a normal distribution. Of 26 asymptomatic thrombocytopenic patients with no hematologic history, none had infants with hemorrhage or platelet counts less than 100,000/cu mm. Only one patient subsequently had severe glucocorticoid-resistant thrombocytopenia requiring splenectomy several months after delivery. The remaining patients continue to be asymptomatic to date, with platelet counts greater than 100,000/cu mm. We suggest a plan for managing less than normal platelet counts in asymptomatic gravidas without a history of hematologic abnormality.     

One-year follow-up of plasma exchange therapy in 14 patients with idiopathic thrombocytopenic purpura

Fourteen patients with idiopathic thrombocytopenic purpura (ITP) have been followed for one year after plasma exchange therapy. Exchange was performed prior to splenectomy in eight of nine patients with acute ITP and following splenectomy in five patients with chronic ITP. None with chronic ITP showed a response in platelet count as a result of exchange therapy. Four of the nine with acute ITP had poor responses and required splenectomy because of persistent severe thrombocytopenia. Three of these have responded completely and are in remission. One patient with acute ITP had an equivocal response, with a most recent platelet count of 93,000/microliter. The remaining four patients with acute ITP had prompt and complete responses and now have platelet counts above 100,000/microliter without steroid treatment. Although the good responses were temporally associated with the use of plasma but not albumin, the data are not sufficient to conclude that a plasma factor must be infused to obtain a satisfactory result. The overall response after one year was about that expected for acute ITP patients treated with prednisone and early splenectomy. Exchange plasmapheresis may be of value in decreasing the number of patients who require splenectomy, but a randomized, prospective study is needed to adequately assess this possibility.     

Comparison of platelet immunity in patients with SLE and with ITP

Idiopathic thrombocytopenic purpura (ITP) is characterized by the development of a specific anti-platelet autoantibody immune response mediating the development of thrombocytopenia. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide variety of autoantibodies. In 15-20% of SLE cases, patients develop thrombocytopenia which appears to be autoimmune in nature (SLE-TP). To better understand the pathogenesis of the thrombocytopenia associated with SLE, we investigated the overlapping platelet and cellular immune features between SLE and ITP. Thirty-one patients with SLE, eight with SLE-TP, and 17 with ITP, were studied and compared to 60 healthy controls. We evaluated platelet-associated IgG, platelet microparticles, reticulated platelets, platelet HLA-DR expression, in vivo cytokine levels, lymphocyte proliferation, and the T lymphocyte anti-platelet immune response in these patients. Patients with SLE-TP and those with ITP had increased platelet-associated IgG, an increased percentage of platelet microparticles, a higher percentage of reticulated platelets and larger platelets, suggesting antibody-mediated platelet destruction and increased platelet production. More than 50% of patients with ITP had increased HLA-DR on their platelet surface whereas subjects with SLE-TP did not. Analysis of serum cytokines demonstrated increased levels of IL-10, IL-15 and TNF-alpha in patients with SLE, but in those with ITP, only increased levels of IL-15 were seen, no increases in any of these cytokines were observed in patients with in SLE-TP. The ability of lymphocytes to proliferate in response to phorbol myristate acetate (PMA) stimulation was increased in SLE-TP, but was normal in both SLE and ITP. Lymphocytes from subjects with ITP displayed an increased ability to proliferate on exposure to platelets, in contrast, those with SLE-TP did not. While the number of subjects evaluated with SLE-TP was small, these data reveal a number of differences in the immunopathogenesis between SLE-TP and ITP.     

Comparison between IV immune globulin (IVIG) and anti‐D globulin for treatment of immune thrombocytopenia: a randomized open‐label study

To compare the effect of IV immune globulin (IVIG) and anti‐D globulin (anti‐D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open‐label, single‐center clinical trial was carried out in Amir‐Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti‐D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti‐D caused a quicker response on the 3rd day of treatment (P < 0.001). Both drugs caused a significant rise in number of platelets on the 7th and the 14th day of treatment. Compared to IVIG, except a significant drop in hemoglobin concentration (P < 0.001), anti‐D had lower rate of side effects including fever (P < 0.05), allergy (P < 0.01), and headache (P < 0.001). Our results showed that anti‐D was associated with rapid rise of platelets compared to IVIG. In addition, anti‐D treatment had acceptable safety profile.