特发性血小板减少性紫癜的病因及疗效探讨

目的 :探讨特发性血小板减少性紫癜 (ITP)的病因与疗效的关系。方法 :对 16 0例ITP患者的临床及实验室资料进行回顾分析 ,分 4组采取 4种治疗方法 :A组 :抗幽门螺旋杆菌 (HP)加地塞米松冲击继之泼尼松治疗 ;B组 :泼尼松加大剂量丙种球蛋白冲击治疗 ;C组 :泼尼松加达那唑治疗 ;D组 :难治性的给以睥切除治疗。按显效、良效、有效、无效评价治疗效果。结果 :急性ITP 90例 ,慢性ITP 70例 ,男 5 5例 ,女 10 5例 ,男女之比为 1∶2 ,就诊时中位年龄 39岁 ,均有出血表现 ,中位PLT数 15× 10 9/L。有HP感染 75例 ,血小板表面抗体 (PAIGg)阳性 90例 ;血小板自身抗体阳性 30例 ;骨髓巨核细胞增多 114例 ,正常 35例 ,减少 10例 ,巨核细胞均以颗粒巨核细胞为主。T细胞亚群分布以CD4 /CD8降低为主。 4种治疗效果以抗HP加地塞米松冲击继之泼尼松治疗和泼尼松加大剂量丙种球蛋白冲击治疗为好 ,泼尼松加达那唑治疗次之。前两种治疗与后两种之间差异有统计学意义 ,均 P <0 .0 1。结论 :HP感染及自身免疫因素的异常是ITP发病的直接病因。抗HP、激素、大剂量丙种球蛋白是较理想的治疗选择     

血液病血小板无效输注的原因探讨

目的:探讨输注血小板无效的原因。方法:观察131例血液病患者的659例次单采血小板输注情况及效果并讨论其影响因素。结果:①急性白血病组(AL)、再生障碍性贫血组(AA)、特发性血小板减少性紫癜(ITP)组输注有效率分别为66.49%、71.19%、51.39%(P<0.05);②AL、AA发热组输注有效率低于未发热组(P<0.05);③AL脾脏肿大与无肿大组及弥散性血管内凝血(DIC)组与无DIC组输注有效率差异在统计学有显著差异(P<0.05);④外周造血干细胞移植组、骨髓移植组输注有效率分别为52.54%、38.22%(P<0.05),造血干细胞移植死亡组与未死亡组输注有效率分别为23.21%、52.91%(P<0.05)。结论:引起血小板输注无效的病因复杂。血小板输注应视患者一般状况、血小板计数及出血情况作出综合判断,避免或减少血小板输注无效,提高血小板输注的有效率。     

急性白血病患者血小板无效输注的原因分析

目的：探讨急性白血病（AL）血小板输注无效的原因。方法：观察106例AL患者的263例次单采血小板输注效果并检测血小板抗体,分析讨论血小板无效输注的影响因素。结果：①AL血小板无效输注率为43．35％;②血小板抗体阳性检出率为32．32％;③血小板输注有效组与无效组的抗体阳性检出率的差异有统计学意义（P〈0．01）。④AL发热组输注无效率高于未发热组（P〈0．01）;脾脏肿大与无肿大组无效输注率差异有统计学意义（P〈0．01）。结论：引起血小板输注无效的病因复杂。血小板输注前应进行血小板抗体的筛选,避免或减少造成血小板输注无效的原因,提高血小板输注的有效率。     

CMV和EBV感染与儿童ITP的关系

目的 :探讨巨细胞病毒 (CMV)和Epstein Barr病毒 (EBV)感染与儿童特发性血小板减少性紫癜 (ITP)的关系。方法 :采用基础PCR方法检测了 44例ITP患儿外周血白细胞中CMV和EBV的感染情况 ,并结合实验室及临床特征进行分析。结果 :①ITP患儿CMV感染阳性率较高 ,达 6 1.4% ;在慢性反复发作的患儿中 ,CMV阳性率更高 (71.9% ) ,显著高于急性ITP患儿 (33.3% ) (χ2 =5 .47,P <0 .0 5 )。CMV阳性患儿血小板自身抗体阳性率较高 ,血小板及巨核细胞数均较低 ,出血症状明显 ,激素治疗效果较差。② 5 0 %的ITP患儿外周血EBVDNA阳性 ,急性患儿较多见 ,但与慢性患儿比差异无显著性意义。EBV阳性患儿血小板自身抗体阳性率也较高 ,以抗GPⅡb/Ⅲa升高最明显 ,显著高于EBV阴性患儿 (χ2 =4.96 ,P <0 .0 5 )。与CMV阳性患儿相比 ,EBV阳性患儿血小板减少多为轻、中度 ,骨髓中巨核细胞数正常或增多 ,出血症状少见 ,预后较好。结论 :CMV和EBV感染与部分儿童ITP的发病有关 ,不同的病毒感染有不同的发病机制和临床特征。     

免疫抑制治疗无效的特发性血小板减少性紫癜患者血小板相关免疫球蛋白的亚型分析

目的分析糖皮质激素、环孢菌素A治疗无效的特发性血小板减少性紫癜(ITP)患者血小板相关免疫球蛋白(PAIg)的亚型。方法采用酶联免疫法(ELISA)对19992004年绵阳市中心医院收治的17例激素治疗无效、4例激素 环孢菌素A治疗无效以及30例激素治疗有效ITP患者的PAIg亚型进行检测。结果17例激素治疗无效的患者PAIg各亚型抗体较之激素治疗有效ITP患者差异有显著性(P<0·01),激素治疗无效组PAIg各亚型水平均明显增高;激素 环孢菌素A治疗无效组PAIgM较之激素治疗有效ITP患者有所增高(P<0·05)。结论激素治疗无效的ITP患者PAIg各亚型均显著增高,提示PAIg在介导ITP患者异常免疫反应过程中起重要作用,PAIg各亚型水平的增高可能有助于预测ITP患者对激素治疗的敏感性。     

122例特发性血小板减少性紫癜血小板输注疗效观察

目的:探讨特发性血小板减少性紫癜(ITP)患者临床血小板输注的指征.方法:比较122例ITP患者输注血小板和未输注血小板的临床转归;比较血小板输注前及输注24 h后血小板计数.参照PAIg,分析抗体与血小板输注疗效的相关性.结果:67例未输注血小板的患者中,有2例PLT＜10×109/L的患者发生严重出血危及生命,55例输注血小板的惠者,有17例(31%)PLT较输注前降低,其中7例输注后PLT＜10×109/L,未发生严重出血;ITP患者血小板输注无效率86%,PAIg升高患者血小板输注无效率升高,有统计学差异.结论:如无明显的出血症状,ITP血小板输注指征建议PLT＜10×109/L,应输注少白细胞同型单采血小板制荆.     

特发性血小板减少性紫癜患者血小板相关抗体水平与预后的关系

目的:探讨特发性血小板减少性紫癜(ITP)与血小板相关抗体之间的相互关系,为临床诊断和治疗提供帮助。方法:回顾性分析了2000年1月～2007年4月应用流式细胞术检测140例临床确诊的ITP患者初诊时及治疗前后不同血小板相关抗体——血小板膜糖蛋白抗体(PAIg)的表达。结果:ITP患者初诊时PAIgG、PAIgA及PAIgM抗体表达水平均高于正常对照组;PAIgG、PAIgM、PAIgA表达水平与血小板数之间均呈负相关,相关系数分别为γ=-0.72、γ=-0.83和γ=-0.67。在确诊ITP后予激素等免疫治疗无效转变为慢性ITP的患者时,PAIgM抗体水平要明显高于激素治疗有效的急性ITP患者,并且PAIgM异常增高或联合PAIgG增高的比例要显著多于急性ITP患者(均P<0.05)。35例PAIgG和PAIgM同时升高的ITP患者,经治疗血小板升至正常后,PAIgG、PAIgM抗体表达水平均有显著下降。结论:ITP的发生与血小板抗体密切相关,初诊ITP患者PAIgM单独或联合PAIgG异常增高常提示预后不良,易转变为慢性ITP。     

ITP患者血清血小板生成素水平与临床治疗效果的关系

目的 探讨血小板生成素（TPO）对特发性血小板减少性紫癜（ITP）临床治疗效果的影响。方法 将25例初治ITP患者按治疗效果分为有效组和无效组,另设正常对照组22例。采用ELISA法和放免法分别检测治疗前后血清TPO水平,取治疗前骨髓涂片计数巨核细胞数量。结果 无效组TPO水平明显高于有效者及对照组（P均〈0．05）,有效者与对照组间无显著性差异;无效者巨核细胞计数则显著低于有效者（P〈0．01）。结论 血清高水平TPO可能预示ITP治疗困难;TPO治疗有效与无效者的发病机理可能存在差异。     

特发性血小板减少性紫癜患者免疫相关指标的检测及其临床意义

目的 检测特发性血小板减少性紫癜(ITP)患者免疫相关指标的变化,探讨其在ITP发病机制中的作用及其临床意义.方法 应用酶联免疫斑点技术(ELISPOT)、改良血小板抗原单克隆抗体固相化检测技术(MAIPA)、流式细胞术及夹心法ELISA分别检测64例1TP患者及31例正常对照者分泌GPⅡb/Ⅲa抗体B细胞、血小板特异性抗体(抗GPⅡb/Ⅲa抗体、抗GP I b/Ⅸ抗体)、T淋巴细胞亚群、网织血小板(RP)及血小板生成素(TPO)的变化.结果 ITP患者分泌GPⅡb/Ⅲa抗体B细胞频数[急性ITP组患者为7.6±4.6/105个外周血单个核细胞(PBMC),慢性ITP组患者为5.3±3.0/105个PBMC]、血小板特异性抗体(抗GPⅡb/Ⅲa抗体、抗GPI b/Ⅸ抗体)的吸光度值(急性ITP组患者为0.51±0.11、0.48±0.06,慢性ITP组患者为0.49±0.10、0.46±0.09)、CD8+T淋巴细胞百分比[(27.09±9.86)%]、RP百分比[巨核细胞增多组为(24.85±19.18)%,巨核细胞正常组为(23.89±18.90)%]明显高于正常对照组[1.3±0.5/105个PBMC,0.33±0.06,0.41±0.03,(22.08±4 54)%,(8.19±2.46)%,P值均＜0.05],其中急性ITP患者分泌GPⅡb/Ⅲa抗体B细胞高于慢性ITP患者(P＜0.05).ITP组CD3+T淋巴细胞百分比、CD4+T淋巴细胞百分比及CD4+/CD8+比值[(60.88±14.59)%、(28.41±10.55)%、1.18±0.59]均低于正常对照组[(69.89±6.43)%、(35.38±5.05)%、1.64±0.29,P值均＜0.05].ITP患者巨核细胞增多组TPO水平(72.09±41.64)明显低于ITP患者巨核细胞正常组(118.60±70.72,P＜0.05),与正常对照组(75.37±26.32)之间差异无统计学意义(P＞0.05).结论 分泌GPⅡb/Ⅲa抗体B细胞、血小板特异性抗体、T淋巴细胞亚群、RP%及TPO在ITP诊断及指导定向干预治疗中有一定的意义.     

升血小板胶囊对小鼠免疫性血小板减少症的治疗作用及其机制

目的 探讨升血小板胶囊对小鼠免疫性血小板减少症（ITP）的治疗作用及免疫调控机制。方法 将40只小鼠随机分为对照组、模型组、强的松组、胶囊组各10只。除对照组外，其余三组均用抗血小板抗体于小鼠腹腔内注射，诱导持续性血小板减少成功建立ITP模型。对照组、模型组给予生理盐水灌胃，强的松组、胶囊组分别给予相同体积的强的松溶液、升血小板胶囊溶液灌胃，每日1次，连续8 d。模型维持4周处死动物，计数小鼠外周血小板、骨髓涂片产板巨核细胞，检测小鼠脾脏Tregs细胞构成比、Tregs/CD4值以及小鼠脾脏Tregs细胞Foxp3mRNA表达、Teff细胞IL-2 mRNA表达。结果 对照组、模型组、强的松组、胶囊组小鼠外周血小板计数分别为（600.35±145.39）、（123.33±16.24）、（327.66±73.20）、（577.35±76.94）×109/L，骨髓产板巨核细胞计数分别为（55.05±5.83）、（26.90±2.49）、（66.27±3.58）、（63.45±3.44）个；与模型组比较，胶囊组、强的松组ITP小鼠外周血小板水平升高、产板巨核细胞数增加（P均<0.05）...     

Factors influencing platelet transfusion refractoriness in patients undergoing allogeneic hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation has been considered a risk factor for development of platelet transfusion refractoriness. The objective of this study was to assess the platelet transfusion refractoriness rate in patients undergoing allogeneic hematopoietic stem cell transplantation from different sources. We retrospectively reviewed the charts and transfusion records of patients who underwent allogeneic stem cell transplantation at our institution between 2013 and 2015. The evaluation of post-transfusion platelet count was assessed for each transfusion given, from day of progenitor infusion to day 30 after transplantation. Of 167 patients included in this study, 101 received peripheral blood stem cell transplantation (PBSCT) and 66 received umbilical cord blood transplantation (UCBT). Overall, the percentage of platelet transfusions with a 14-h CCI lower than 5000 was 59.3%, being these data significantly higher for UCBT (67.6%) than for PBSCT (31.0%). Seventy-eight percent of patients underwent UCBT become refractory, while 38.6% of patients who received PBSCT were refractory. Factors associated to platelet refractoriness were lower CD34+ cell dose infused, higher number of antibiotics used, presence of anti-HLA I antibodies, and reduced-intensity conditioning regimen. Platelet refractoriness is a frequent and complex adverse event and remains a therapeutic challenge in the management of patients undergoing HSCT. There is a higher rate of platelet refractoriness in patients who received UCBT as compared to patients who received PBSCT.     

Refractoriness to Platelet Transfusion Following Double Valve Replacement in an ITP Patient Who Had Undergone Splenectomy

Abstract Reports of patients with idiopathic thrombocytopenic purpura (ITP) undergoing cardiac surgery are rare, and almost all of the reported cases required platelet transfusion. ITP patients, especially those having a history of splenectomy or a history of heavy bleeding, may have to undergo multiple platelet transfusions. Such transfusions may induce al-loimmunization against the human leukocyte antigen (HLA) and result in refractoriness to subsequent platelet transfusions. We report a case of a 63-year-old female with ITP, with a history of splenectomy and multiple platelet transfusions, who underwent aortic and mitral valve replacement. Although corticosteroid administration, high-dose immunoglobulin therapy, and repeated platelet transfusion led to a temporary increase in platelet count and successful hemostasis, refractoriness to platelet transfusion occurred postoperatively because of the presence of the anti-HLA antibody. In addition, the patient showed complications of pyothorax. Corticosteroids might have exerted an inhibitory influence on the occurrence of pyothorax.     

微柱凝胶免疫技术检测血小板同种抗体及配型的临床应用

目的：观察多次输血患者血小板抗体的产生对血小板输注效果的影响。方法：采用微柱凝胶免疫技术（MGIA），对108名反复多次输血而又需要输注血小板的患者检测血小板同种抗体。对抗体阳性且输注无效的患者采用MGIA进行交叉配合性试验。结果：反复多次输血患者，血小板同种抗体阳性率为26．85％（29／108）；29例血小板同种抗体阳性患者中，再次输注血小板时，26例发生输注无效；血小板同种抗体阳性组与阴性组比较血小板校正增加指数（CCI）差异有统计学意义（P〈0．01）；并且血小板抗体阳性率随输血次数增加而增加。结论：反复多次输血患者，易发生同种免疫反应，产生血小板相关抗体，导致血小板输注无效；MGIA检测血小板抗体方法稳定，操作简便，用于血小板配型，能较好的解决因血小板抗体阳性引起的输注无效问题，提高血小板输注效果。     

血小板输注中抗体检测和配合试验的应用

目的：提高血小板制剂对血小板减少、尤其是血小板输注无效症（PTR）患者的输注疗效,避免宝贵血源的浪费。方法：应用单抗固相微孔板（MASPAT）法检测患者血清中的血小板抗体,进行血小板供者与患者之间的配合试验。结果：2005年6月-2007年11月对109例患者进行了血小板抗体的检测,其中42例患者检出血小板抗体（阳性率38．5％）,对含有血小板抗体的患者经适合性血小板输注后,血小板计数有明显上升。结论：MASPAT法在特异性、敏感性、重复性方面良好,操作快速、简便,判断可靠;易做到规范化,程序化,标准化;据此建立的“适合性血小板输注”对含有血小板抗体的患者是有效的,可用于临床血小板抗体的检测和配合试验。     

Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA-matched haematopoietic cell transplant for sickle cell disease

The relevance of donor-specific human leukocyte antigen (HLA) antibodies in HLA-mismatched haematopoietic cell transplant (HCT) is known, but the importance of HLA antibodies in HLA-matched HCT is unclear. We hypothesized that HLA antibodies detected before HCT would cause platelet transfusion refractoriness during HCT and investigated this in a multi-centre study. Pre-HCT samples from 45 paediatric patients with sickle cell disease (SCD) undergoing HLA-matched HCT were tested for HLA class I antibodies. The number of platelet transfusions received before day +45 was compared between those with and without antibodies. Thirteen of 45 (29%) patients had a positive HLA class I antibody screen, and these patients received significantly more platelet transfusions than patients without antibodies (median 19 vs. 7·5, P = 0·028). This platelet transfusion association remained significant when controlling for conditioning regimen. Among alloimmunized patients, there was no association between the panel-reactive antibody and the number of platelet transfusions. Patients with HLA class I antibodies also had a higher incidence of acute graft-versus-host disease (GVHD): 6/13 (46%) vs. 3/32 (9%), P = 0·011. Pre-HCT HLA class I alloimmunization is associated with increased platelet transfusion support and acute GVHD in paediatric HLA-matched HCT for SCD. Further studies are needed to investigate the pathobiology of this association.     

Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients

A variety of patient and product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets (TRAP). Responses measured were platelet increments, interval between platelet transfusions, and platelet refractoriness. Patient factors that improved platelet responses were splenectomy and increasing patient age. In contrast, at least 2 prior pregnancies, male gender, splenomegaly, bleeding, fever, infection, disseminated intravascular coagulation, increasing height and weight, lymphocytotoxic antibody positivity, an increasing number of platelet transfusions, or receiving heparin or amphotericin were associated with decreased posttransfusion platelet responses. Platelet factors that were associated with improved platelet responses were giving ABO-compatible platelets, platelets stored for 48 hours or less, and giving large doses of platelets while ultraviolet B (UV-B) or gamma irradiation decreased platelet responses. However, in alloimmunized lymphocytoxic antibody-positive patients, the immediate increment to UV-B-irradiated platelets was well maintained, whereas all other products showed substantial reductions. Refractoriness to platelet transfusions developed in 27% of the patients. Platelet refractoriness was associated with lymphocytotoxic antibody positivity, heparin administration, fever, bleeding, increasing number of platelet transfusions, increasing weight, at least 2 pregnancies, and male gender. The only factors that reduced platelet refractoriness rates were increasing the dose of platelets transfused or transfusing filtered apheresis platelets.     

A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients

Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo-immunization resulting in platelet transfusion refractoriness and a high risk for life-threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo-antibodies may play a pathophysiologic role in platelet refractoriness. Here we conducted a pilot trial to investigate the use of eculizumab, a monoclonal antibody that binds and inhibits C5 complement, to treat platelet transfusion refractoriness in allo-immunized patients with severe thrombocytopenia. A single eculizumab infusion was administered to 10 eligible patients, with four (40%) patients overcoming platelet refractories assessed measuring the corrected platelet count increment (CCI) 10–60 min and 18–24 h post transfusion. Responding patients had a reduction in the requirement for subsequent platelet transfusions and had higher post-transfusion platelet increments for 14 days following eculizumab administration. Remarkably, three of the four responders met CCI criteria for response despite receiving HLA-incompatible platelets. Our results suggest that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo-immunization. This study establishes proof of principle that complement inhibition can treat platelet transfusion refractoriness, laying the foundation for a large multicentre trial to assess the overall efficacy of this approach (ClinicalTrials.gov, identifier: NCT02298933).     

Frequency and causes of refractoriness in multiply transfused patients

 The use of leukocyte-depleted blood components has become the standard therapy for multiply transfused patients during the past few years, as a measure to reduce the frequency of alloimmunization and refractoriness. We assessed frequency and causes of refractoriness, defined as a repeated 24-h post-transfusion platelet count below 20 000/μl, in 145 consecutive patients who received three or more single-donor platelet concentrates during a 1-year period. Flow-cytometric detection of anti-platelet antibodies and a glycoprotein-specific ELISA were applied for the diagnosis of alloimmunization. Forty patients (27.6%) had at least one episode of refractoriness. In 25 of these 40 patients (62.5%), nonimmune factors (fever, sepsis, coagulopathy, splenomegaly) alone were the cause. In 15 refractory patients alloantibodies were detected. In seven patients (17.5%), alloimmunization alone caused an inadequate transfusion response, while in eight refractory patients (20.0%) alloimmunization and fever or sepsis were present. HLA antibodies were detected in 17 patients (11.7%); three patients (2%) had platelet-specific antibodies in addition to HLA antibodies; in two patients panreactive platelet antibodies were detectable. All 17 patients had a history of previous transfusions or pregnancy. We did not observe primary immunization in patients transfused exclusively with filtered (leukodepleted) blood products. Our data suggest that alloimmunization in patients with a negative risk history can be prevented by the exclusive use of leukodepleted blood components. Received: 4 December 1996 / Accepted: 12 February 1997     

Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura

BACKGROUND: A relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has previously been reported. We determined the prevalence of H pylori infection in Japanese patients with chronic ITP and the effect of its eradication on platelet count. METHODS: The study population comprised 53 Japanese adults with chronic ITP and a platelet count of less than 100 x 10(3)/ micro L. A (13)C-urea breath test was performed to determine H pylori infection status. Those patients who were H pylori positive gave written informed consent and received eradication therapy. The effect of H pylori eradication on platelet count was evaluated up to 6 months after therapy. Clinical parameters were compared between responders to the therapy (increase in platelet count) and nonresponders, as well as between H pylori-positive and -negative patients. RESULTS: Of the 53 patients with chronic ITP in the study, 39 (74%) were H pylori positive. Of the 32 infected patients who received treatment, H pylori was successfully eradicated in 27 patients (84%). In 10 (37%) of these patients, this resulted in a favorable platelet response. A partial response was seen in 5 additional patients (19%). A significant (P<.001) increase in platelet count was demonstrated in patients in whom H pylori was successfully eradicated but not in patients who were unsuccessfully treated or in untreated patients. Current corticosteroid therapy was reported more often in nonresponders than in responders. CONCLUSION: Eradication of H pylori may prove effective in increasing platelet count in H pylori-positive patients with chronic ITP.