甲氨蝶呤治疗难治或复发性特发性血小板减少性紫癜的临床研究

目的探求难治或复发性特发性血小板减少性紫癜(ITP)高效、低毒、经济实用的治疗手段.方法49例ITP患者采用泼尼松治疗难治或复发的ITP患者分为3组治疗泼尼松组11例甲基泼尼松龙1 g/d,静脉滴注,共3～5 d,然后泼尼松1 mg·kg-1·d-1,口服;其他随机分为2组,即长春新碱组19例泼尼松1 mg·kg-1·d-1,口服,长春新碱1 mg静脉滴注,每周1次;甲氨蝶呤组19例泼尼松1 mg·kg-1·d-1,口服,甲氨蝶呤10 mg静脉滴注(或口服),每周1次.分别观察治疗前后总体疗效、血象、血小板相关抗体(PA-IgG)变化及不良反应.结果3组治疗完全反应率依次为27%、67%和79%,总反应率分别为55%、84%和89%,而长期反应率分别为18%、42%和52%.后2组完全反应率、总反应率及长期反应率均显著高于泼尼松组(P均＜0.01),并且甲氨蝶呤组较长春新碱组亦有更高的趋势.PA-IgG变化各组治疗前后PA-IgG均下降(P＜0.01);长春新碱、甲氨蝶呤治疗后均比泼尼松组治疗后分别下降更显著(均P＜0.01);甲氨蝶呤治疗后比长春新碱治疗后水平更低(P＜0.05).长春新碱治疗组主要不良反应是神经末梢损害,占45.5%,而甲氨蝶呤治疗组仅有8.7%出现了口腔黏膜溃疡.结论加用甲氨蝶呤或长春新碱治疗难治或复发性ITP均可提高疗效,甲氨蝶呤有效率更高、激素减量快、远期效果好、安全性高.     

小剂量利妥昔单抗治疗难治性免疫性血小板减少性紫癜的疗效观察

免疫性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)是临床常见的出血性疾病,约有11％的患者对常规治疗无反应或疗效难以维持[1],自2010年以来我们应用利妥昔单抗治疗10例难治性ITP,取得了一定疗效,报道如下. 临床资料 2010年1月～ 2012年10月我科收治难治性ITP患者10例(男4,女6),中位年龄35(17～60)岁,病程1～7年.所有患者均应用标准剂量泼尼松无效,3例行脾切除手术,7例曾接受过长春新碱或环磷酰胺、大剂量免疫球蛋白、环孢素A、达那唑等多种方法治疗无效或复发.10例均符合难治性ITP诊断标准[3].     

环胞菌素A治疗难治性免疫性血小板减少性紫癜15例疗效观察

免疫性血小板减少性紫癜（ITP）是因免疫机制导致血小板破坏增多的临床上常见的出血性疾病。难治性的ITP是经过足量的正规糖皮质激素、脾切除,或一般的免疫抑制剂如环磷酰胺、长春新碱等治疗无效或继发失效的患者。2003年1月～2008年3月,我们应用环孢素A治疗15例难治性ITP,取得较好效果。现报告如下。     

特发性血小板减少性紫癜103例患者的临床分析

目的 探讨特发性血小板减少性紫癜(ITP)患者发病的年龄分布、治疗反应及影响因素等.方法 回顾性总结我院1992年7月-2006年12月收治的ITP患者的住院及门诊资料.结果 ITP 103例中,随访时间为2个月～15年,男∶女=35∶68;≥60岁发病患者34.0%(35/103);所有患者中,激素敏感型为57.3%(59/103),多以完全或部分反应健康存活;脾切除6例,栓塞1例,栓塞者无效,随访到的5例切脾者4例血小板一直正常;免疫抑制剂中,环孢素A效果较好,联合激素时其有效率为81.3%(26/32).发展为干燥综合征2例,红斑狼疮1例,淋巴瘤1例.103例中死亡7例,仅1例为脑出血(30岁),其余2例死于脑血栓/梗死,2例死于非血液肿瘤,1例死于肾病,1例死于淋巴瘤.ITP患者中难治率为17.2%(10/58).结论 ITP发病有随年龄增长而升高的趋势,临床表现各异,致命性出血少,联合免疫治疗宜个体化.     

VATP方案治疗难治性慢性特发性血小板减少性紫癜23例分析

我们于 1 996年 1月采用长春新碱、达那唑、胸腺肽、泼尼松 ( VATP)方案治疗难治性慢性特发性血小板减少性紫癜 ( ITP) 2 3例 ,现将结果报告如下。1　资料与方法1 .1　临床资料本组 2 3例 ,男 9例 ,女 1 4例 ,年龄 1 4～ 62岁(中位年龄 2 9岁 )。中位病程 2 2个月 ( 7～ 68个月 )。所有患者均接受过正规糖皮质激素治疗无效 ,正规用药时间 4～ 1 0个月。 5例曾应用丙种球蛋白 ,2例为脾切除后复发 ,1例曾用硫唑嘌呤。所有患者均有皮肤和粘膜出血 ,8例有月经过多 ,6例有牙龈出血。治疗前平均血小板计数为 ( 1 9.2± 8.9)× 1 0 9/L。1 .2　…     

干扰素治疗老年特发性血小板减少性紫癜9例报告

特发性血小板减少性紫癜 (ｉｄｉｏｐａｔｈｉｃｔｈｒｏｍｂｏｃｙｔｏｐｅｎｉｃｐｕｒｐｕｒａ ,ＩＴＰ)是临床常见的一种出血性疾病。老年人ＩＴＰ常反复发作 ,泼尼松治疗的完全缓解率仅 10 %～ 15 %[1] ,其他替代疗法如长春新碱、硫唑嘌呤、环磷酰胺、达那唑等副作用大 ,应用于老年患者病死率高[2 ] 。 1996年 2月至 2 0 0 0年 10月 ,我院用α 干扰素治疗老年ＩＴＰ患者 9例 ,取得一定疗效 ,现报道如下。1　 对象和方法1 1　病例　全部病例均为住院患者 ,符合 1986年 12月首届中华血液学学会全国血栓与止血会议拟定的ＩＴＰ诊断标准[3 …     

用血小板长春花碱复合物治疗1例难治性特发性血小板减小性紫癜

1例慢性特发性血小板减少性紫癜应用肾上腺皮质激素、脾切除治疗,未达到效果而存在致命性血小板减少时,可采用免疫抑制剂长春新碱、硫唑嘌呤或环磷酰胺来治疗。1年前 Ahn 等(Ahn Y S 等:N Engl J Med 298:1101,1978)报道过输注血小板-长春花复合物的另一种治疗方法。     

GIP方案治疗难治性或复发性非霍奇金淋巴瘤的临床观察

随着化疗的进展,非霍奇金淋巴瘤(NHL)的化疗效果不断提高.对NHL患者,目前常规采用以联合化疗方案(环磷酰胺 阿霉素 长春新碱 泼尼松,CHOP)为主的综合治疗,但一部分NHL患者起始治疗时即对化疗耐药,或经过治疗达到完全缓解后很快复发.     

大剂量丙种球蛋白联合甲基强的松龙短程冲击治疗免疫性血小板减少性紫癜

皮质激素、免疫抑制剂或脾切除等方法治疗无效的免疫性血小板减少性紫癜(ITP),是ITP治疗过程中的一个难题.由于常规治疗无效,过低的血小板常常是引发出血危象(内脏、颅内出血及明显的粘膜出血)的主要原因,也成为ITP死亡的主要类型.为促使这类病人血小板的增加并快速渡过危险阶段,我们采用大剂量丙种球蛋白(HD-IVIG)联合甲基强的松龙(HDMP)短程冲击,治疗13例此类免疫性血小板减少性紫癜,效果满意,现报道如下.     

重组人白介素-11联合肾上腺皮质激素治疗特发性血小板减少性紫癜的临床观察

目的:探讨重组人白细胞介素-11(rhIL11)联合肾上腺皮质激素治疗特发性血小板减少性紫癜(ITP)的疗效。方法:分观察组及对照组,观察组给予rhIL1125～50μg·kg-1·d-1皮下注射连用5～7d,血小板上升正常后用泼尼松1～2mg·kg-1·d-1口服,2周后逐渐减量;对照组单用泼尼松治疗,用法同上。结果:观察组在血小板开始上升时间、血小板达峰值时间、控制出血症状时间均少于单用泼尼松组(P<0.01),观察组总有效率95%高于单用泼尼松组的66.7%(P<0.05)。结论:rhIL-11可以有效促进ITP患者外周血小板的恢复,迅速控制ITP患者的出血症状。     

Life-threatening bleeding episodes in primary immune thrombocytopenia: a single-center retrospective study of 169 inpatients

Bleeding is the most important clinical outcome in patients with immune thrombocytopenia (ITP), and the goal of therapy in such cases is to treat or prevent bleeding. The frequency of and risk factors for bleeding events in ITP have only recently been identified in several large-scale studies. However, there is little published information about severe life-threatening bleeding in ITP. To clarify the clinical features of life-threatening bleeding in patients with primary ITP, we systematically reviewed the medical records of all ITP patients that were admitted to our hospital between January 1, 1992, and December 31, 2015. Of 169 consecutive inpatients with primary ITP, 8 suffered life-threatening bleeding (10 episodes: gastrointestinal, 4 cases; pulmonary, 1 case; and intracranial, 5 cases). All of these patients were ≥?60 years of age and had platelet counts of <?20 × 10⁹/L. The highest incidence of such bleeding was found among elderly patients in their 80s with platelet counts of <?5 × 10⁹/L. Among the patients aged ≥?60 years with platelet counts of <?20 × 10⁹/L, the background data of the patients with and without life-threatening bleeding episodes were compared. It was shown that the patients in the bleeding group were older than those in the non-bleeding group (80.13 ± 2.31 vs. 73.39 ± 2.51 years, p = 0.0266). Hypertension, diabetes mellitus, anticoagulant use, ITP phase, and sex were not identified as strong risk factors for life-threatening bleeding. Combining age and the platelet count might be a useful way of identifying ITP patients that are at risk of life-threatening bleeding. Most intracranial hemorrhaging (4/5) was spontaneous and multifocal, suggesting that these might be characteristics of ITP-related bleeding in elderly patients.     

Immune thrombocytopenia in the elderly: clinical course in 525 patients from a single center in China

Immune thrombocytopenia (ITP), often diagnosed in the elderly, is a hematologic disorder induced by autoimmune mechanism. In this retrospective study, we evaluated the clinical features, the risk of bleeding, and the response to treatment in 525 elderly ITP patients (age ≥60 years) diagnosed at our center from 1980 to 2009. There were more females at 60–74 years of age (P?=?0.044). The median duration of follow-up was 27 months (range 1–253 months). Ten patients developed thrombosis during treatment of ITP. At diagnosis, 461 patients (87.8 %) had signs of bleeding. The risk of severe bleeding was associated with both platelet count (P?<?0.001; odds ratio (OR), 0.973) and age (P?=?0.025; OR, 1.039). The cutoff points in the platelet count at which bleeding and severe bleeding would begin to appear were 29.5?×?10⁹ and 21.5?×?10⁹/L, respectively. Sixteen of 144 patients (11.1 %) who did not receive any treatment achieved remission spontaneously. The total response rate to treatment was 62.4 % (166/266). The median time to remission was 7 days, and combined use of intravenous immunoglobulin and steroids took effect faster than use of steroids alone (P?=?0.001). Fifty-two patients (31.3 %) relapsed during follow-up. Of the 27 patients who died during follow-up, seven deaths were directly attributed to ITP. In conclusion, the response rate has been improved since the last 10 years. ITP is also a self-limited disease to some extent in the elderly, but easy to relapse. This review represents the largest collection of elderly ITP patients in China in a single center.     

Long-term follow-up of idiopathic thrombocytopenic purpura in 310 patients.

BACKGROUND AND OBJECTIVES. Idiopathic thrombocytopenic purpura (ITP) induces thrombocytopenia by means of an autoimmune mechanism. Despite the available therapies a subset of patients develop chronic refractory severe thrombocytopenia (i.e. a platelet count consistently lower than 20 to 30x10(9)/L), and life-threatening bleeding can occasionally occur. It has been suggested that the risk of major bleeding is higher in elderly patients and in patients with bleeding at diagnosis. However, since clear data on the influence of clinical and/or laboratory parameters on outcome are lacking, some patients may be receiving unnecessary treatment. DESIGN AND METHODS. We made a retrospective analysis of a series of 310 patients with chronic ITP (108 males and 202 females), with a median age at diagnosis of 40 years (range 8-87 years). The median follow-up time was 121 months, (range 7-434 months). Therapy was most often started in the presence of hemorrhagic complications and/or a platelet count <30x10(9)/L either at diagnosis or during follow-up. RESULTS. Our findings confirmed that patients who were symptomatic at diagnosis were more likely to have bleeding during their follow-up. Moreover, all the patients who suffered major bleeding during their follow-up had median platelet counts of 10x10(9)/L (range 1-20) at that time. Only one patient, aged 43 years, died of hemorrhage following prolonged severe thrombocytopenia. Age >60 years was not associated with any significant differences in incidence of bleeding at diagnosis or during follow-up. INTERPRETATION AND CONCLUSIONS. We conclude that prospective studies are required to evaluate whether it may be reasonable to treat only symptomatic patients, independently of age.     

Idiopathic thrombocytopenic purpura in elderly patients: a study of 47 cases from a single reference center

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is often diagnosed in the elderly, but no specific guidelines exist for such patients. We describe our experience with ITP management in elderly patients and analyze the therapeutic response. METHODS: We retrospectively reviewed a cohort of 47 consecutive elderly ITP patients (> or =60 years old) followed in a single reference center. We specifically analyzed the clinical characteristics, therapies used, patient response rates, and side effects. RESULTS: The mean age of the 47 patients was 66 (range 60-82) years; 31 patients were female. Their initial presentation included bleeding limited to the skin (n=10, 21%) and bleeding at one or more other sites (n=26, 56%); 11 patients (23%) were asymptomatic. The mean platelet count was 52 x 10(9)/L (range 1-120 x 10(9)/L). After 1 and 6 months, the overall response rate was: 61% and 33% with corticosteroids (n=43), 80% and 50% with splenectomy (n=10), and 14% and 60% with danazol (n=15), respectively. Side effects of these therapies were reported in 100% of these elderly ITP patients, 60% and 50% with these drugs, respectively. No response was reported using IVIg. One case of fatal sepsis was noted after splenectomy. CONCLUSIONS: The results confirm (1) that age influences the hemorrhagic pattern of ITP expression, response, and adverse effects of conventional ITP therapies, and (2) that danazol has the potential to be an effective therapeutic alternative to splenectomy in elderly ITP patients.     

Refractory idiopathic thrombocytopenic purpura which responded to protein A column

Currently, there is no satisfactory therapy available for patients with chronic idiopathic thrombocytopenic purpura (ITP) who are unresponsive to conventional therapeutic modalities. In this report, we describe a patient with chronic refractory ITP treated with immobilized protein A in an extracorporeal system. The patient was a 74 years old male diagnosed as ITP in 1980. Despite steroid therapy, the disease progressed and the patient exhibited ecchymosis and gum bleeding which was unresponsive to intravenous gammaglobulin therapy. Severe gastrointestinal bleeding was evident and administration of danazol was discontinued due to liver dysfunction. The patient was treated with extracorporeal protein A immunoabsorption. The patient's whole blood (200-300 ml per treatment) was separated into plasma and cellular components and the plasma was passed through an immunoabsorption column containing 200 mg of covalently bound protein A. The treated plasma and cellular components were returned to the patient. After 4 immunoabsorption treatments, the platelet counts elevated and there was evidence of improvement in gastrointestinal bleeding. This report indicates that protein A immunoabsorption therapy should be considered in patients with chronic refractory ITP.     

Dental procedures in 24 patients with chronic immune thrombocytopenia in prospective clinical studies of eltrombopag

Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by chronically low peripheral blood platelet counts. Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that increases platelet production. This report examines peri-procedural platelet counts and bleeding complications among chronic ITP patients requiring dental procedures while participating in clinical studies with eltrombopag. A total of 494 patients participated in five clinical studies of eltrombopag in chronic ITP. Information about dental procedures was collected prospectively in four studies and retrospectively in one study. Twenty-four patients (22 eltrombopag, 2 placebo) underwent 32 dental procedures (dental cleaning, tooth repair, artificial crown, dental prosthesis, tooth extraction, dental or wisdom teeth extraction, dental root extraction, and endodontic procedures, among others) during study treatment or up to 10 days later. Supplemental ITP therapy (e.g., corticosteroids, platelet transfusions) was given before the dental procedure to increase platelet counts in three eltrombopag-treated patients and both placebo-treated patients. The mean pre-procedure platelet count?±?standard deviation for all procedures in the overall population of patients, eltrombopag group, and placebo group prior to undergoing dental procedures was 96?000?±?81?069/µl,103?517?±?81?522/µl, and 23?333?±?9291/µl, respectively. Two patients in each group had platelet counts below 30?000/µl before the procedure. No patient who had a dental procedure experienced a bleeding adverse event. Among patients with chronic ITP who required a dental procedure during clinical studies of eltrombopag, supplemental ITP treatment was required for both patients who received placebo but was not required for most patients who received eltrombopag. No bleeding complications were reported. These data imply that patients with chronic ITP who receive eltrombopag and experience increases in platelet counts fulfill current pre-procedural platelet count recommendations to undergo invasive dental procedures, and may have a lower risk of bleeding complications and a reduced need for supplemental ITP treatment.     

Management of antithrombotic therapy in adults with immune thrombocytopenia (ITP): a survey of ITP specialists and general hematologist–oncologists

While patients with immune thrombocytopenia (ITP) and low platelet counts are at risk for bleeding, they are not protected against arterial and venous thrombotic events. Frequently, hematologists are asked to consult on a patient with ITP requiring an antiplatelet (AP) agent or anticoagulant (AC). No direct evidence exists to guide hematologists in weighing the risk of thrombosis against the risk of bleeding in patients with ITP. Therefore, we performed a survey to determine the preferred management of AP/AC therapy in ITP patients. The survey described hypothetical patient scenarios and asked respondents to recommend a minimum platelet count for initiation of AP/AC therapy. We surveyed both hematologists with an international reputation in treatment of ITP (n?=?48) and also general hematologist–oncologists in Oklahoma (n?=?97). Response rates were 38/48 (79%) for the ITP specialists and 46/97 (47%) for general hematologist–oncologists. Overall, recommended platelet thresholds for antithrombotic therapy were similar between ITP specialists and general hematologist–oncologists. Although both groups recommended a minimum platelet count of 50?×?10⁹/L for AP and AC therapy in most scenarios, there was great variability in individual practice patterns among respondents. This study highlights the need for studies of patients with ITP who require AP/AC therapy to provide high-quality evidence for establishing optimal management strategies.     

Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program

Romiplostim, a thrombopoietic agent with demonstrated efficacy against immune thrombocytopenia (ITP) in prospective controlled studies, was recently licensed for adults with chronic ITP. Only France has allowed romiplostim compassionate use since January 2008. ITP patients could receive romiplostim when they failed to respond to successive corticosteroids, intravenous immunoglobulins, rituximab, and splenectomy, or when splenectomy was not indicated. We included the first 80 patients enrolled in this program with at least 2 years of follow-up. Primary platelet response (platelet count ≥ 50 × 10(9)/L and double baseline) was observed in 74% of all patients. Long-term responses (2 years) were observed in 47 (65%) patients, 37 (79%) had sustained platelet responses with a median platelet count of 106 × 10(9)/L (interquartile range, 75-167 × 10(9)/L), and 10 (21%) were still taking romiplostim, despite a median platelet count of 38 × 10(9)/L (interquartile range, 35-44 × 10(9)/L), but with clinical benefit (lower dose and/or fewer concomitant treatment(s) and/or diminished bleeding signs). A high bleeding score and use of concomitant ITP therapy were baseline factors predicting romiplostim failure. The most frequently reported adverse events were: arthralgias (26%), fatigue (13%), and nausea (7%). Our results confirmed that romiplostim use in clinical practice is effective and safe for severe chronic ITP. This trial was registered at www.clinicaltrials.gov as #NCT01013181.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection and Idiopathic Thrombocytopenic Purpura

A treatment strategy for idiopathic thrombocytopenic purpura (ITP) is considered with the aim of cure or management of the bleeding tendency. In 1998, Gasbarrini et al reported a high prevalence of Helicobacter pylori infection in patients with ITP and showed that platelet recovery occurred after eradication therapy in most cases. Since then, many studies were performed to evaluate eradication therapy. This article discusses the incidence of H pylori infection in ITP, characteristic clinical features in H pylori-positive ITP, the effectiveness of eradication on platelet count increase, and the mechanisms of development of ITP by H pylori infection. Overall, there was a positive association between H pylori infection and ITP, and eradication of bacterium was accompanied by a significant increase in platelet counts in more than 50% of H pylori-positive ITP cases. These findings suggest that H pylori infection is involved in the mechanisms of thrombocytopenia in most cases of ITP in middle-aged and older patients. This approach could be beneficial to some ITP patients, but there were some uncertainties raised. To confirm the effectiveness of eradication therapy in H pylori-positive ITP, prospective studies conducted in several countries with a new treatment protocol are required, with a large number of ITP cases and longer follow-up.