重组人血小板生成素治疗特发性血小板减少性紫癜的临床对照试验

目的:评价重组人血小板生成素(rhTPO)对特发性血小板减少性紫癜(ITP)的疗效和安全性。方法:21例ITP患者采用随机区组,分成试验组和对照组2组。试验组皮下注射rhTPO 1.0μg/kg,1次/d,疗程14 d。对照组在服用达那唑14 d后如血小板仍≤20×109/L,加用rhTPO皮下注射,1.0μg/kg,疗程14 d。2组在整个试验阶段均服用达那唑,0.2 g,每日3次。结果:试验组用药前血小板计数的中位数为8.0(4.0～15.0)×109/L,用rhTPO后血小板最高值为100.0(49.0～118.5)×109/L,与用药前相比P<0.01。停药后血小板计数逐渐回落,至开始治疗后28 d,血小板计数降至39.0(22.0～68.5)×109/L。对照组用药前血小板计数的中位数为6.0(4.0～10.0)×109/L,第1阶段(1～14 d)仅用达那唑治疗血小板最高值为33.0(23.0～72.0)×109/L。第2阶段(14～28 d)加用rhTPO,血小板计数最高值为111.5(60.0～152.0)×109/L,与用药前及第1阶段最高值相比均P<0.01。停药后血小板计数逐渐下降,至4...     

重组人血小板生成素的临床应用观察

目的:评价沈阳三生制药厂的重组人血小板生成素(rhTPO)对患者血小板减少的疗效和安全性。方法:11例血液恶性肿瘤患者和9 例难治性ITP患者皮下注射rhTPO1.0g/(kg·d),动态监测注射后血小板增长情况。结果:肿瘤化疗组使用rhTPO 9 d后,血小板计数较对照组明显升高(P<0.05),血小板恢复至100×109/L需19±9.4 d,较对照组24±6.2天明显缩短。难治性ITP组显效6例,良效3例,总有效率100%。无明显不良反应。结论:rhTPO对化疗后骨髓抑制引起的血小板减少及难治性ITP患者的严重血小板减少有促进血小板生成作用,无明显不良反应。     

重组人血小板生成素治疗儿童原发性免疫性血小板减少症的有效性和安全性

目的:评价重组人血小板生成素(rhTPO)治疗儿童原发性免疫性血小板减少症(ITP)的有效性和安全性。方法:从rhTPO上市后的2项临床试验中,选择年龄≤18岁的ITP患者数据进行统计分析。结果:来自31家医院的87例儿童ITP患者被纳入本研究,其中男45例,女40例,2例性别信息缺失。中位体重47kg,中位年龄12岁,中位ITP病程4个月。其中39例(44.8%)为新诊断ITP,21例(24.1%)为持续性ITP,27例(31.0%)为慢性ITP;31例为初治,56例既往接受过rhTPO或其他改善血小板的药物治疗。87例患儿接受rhTPO单独治疗或rhTPO联合其他药物治疗,接受rhTPO治疗的中位用药次数10次;基线期中位血小板计数为10.40×109/L,给药后第3天、第7天、第14天和停药后第14天中位血小板计数分别达35.00×109/L、56.00×109/L、80.00×109/L和120.00×109/L,与基线期比较,差异均有统计学意义(P0.05)。给药后第7天、第14天和停药后第14天,总有效率分别达57.5%、58.8%和85.7%。治疗前55.2%患儿有皮肤/黏膜出血,治疗后第14天降至6.1%,停药后第14天无一例出现皮肤/黏膜出血。未观察到与rhTPO相关的不良事件。结论:rhTPO单药或联合其他药物治疗儿童ITP具有良好的疗效和安全性。     

糖皮质激素联合重组人促血小板生成素治疗重症ITP的疗效

目的:评价糖皮质激素联合重组人促血小板生成素(rhTPO)治疗重症原发免疫性血小板减少症(ITP)的疗效和安全性。方法:收集符合诊断标准的重症ITP患者39例,其中采用rhTPO治疗21例作为研究组(rhTPO组),采用丙种球蛋白治疗18例作为对照组(丙球组)。采用独立样本的非参数检验比较2组的临床疗效。结果:1rhTPO组和丙球组治疗有效率分别为95.2%和100%,2组间差异无统计学意义(P0.05);2rhTPO组和丙球组血小板开始恢复时间分别为(4.44±0.88)d和(5.52±2.65)d,2组间差异无统计学意义(P0.05);3治疗7d后,rhTPO组和丙球组血小板计数分别为(81.8±29.1)×109/L和(130.0±56.5)×109/L;而治疗14d后,血小板计数分别为(238.3±95.3)×109/L和(221.4±83.3)×109/L,2组间比较均差异无统计学意义(P0.05)。结论:rhTPO联合地塞米松与丙种球蛋白联合地塞米松治疗重症ITP疗效相当,可作为重症ITP的一线治疗方法。     

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.     

rhTPO在系统性红斑狼疮合并难治性血小板减少性紫癜治疗中的应用

目的评价国产重组人血小板生成素（rhTPO）用于系统性红斑狼疮（SLE）合并难治性血小板减少性紫癜的可行性及安全性。方法对12例SLE并难治性血小板减少性紫癜患者行国产rhTPO皮下注射,15000U／d,疗程14d。检测用药前、用药后7、10、14d及停药3个月后的血小板数,判定疗效及不良反应情况。结果用药前血小板计数为（14．3±5．2）×10^9／L,用药后7、10、14d分别为（37．8±9．3）×10^9／L、（64．2±15．6）×10^9／L、（84．3±25．7）×10^9／L,与用药前相比,P均〈0．01。停药后3个月血小板计数为（53．2±15．6）×10^9／L,与治疗前比较,P〈0．01。总有效率为83．33％,仅2例出现轻微不良反应。结论rhTPO治疗SLE合并难治性血小板减少性紫癜疗效确切,且较为安全。     

应用重组人血小板生成素减少肝硬化患者术前血小板输注疗效初步研究*

目的 以输注血小板改善肝硬化并发血小板减少症患者出血风险的疗效不确切,且可能导致潜在的并发症。本研究的目的是探讨应用重组人血小板生成素注射液(rhTPO)能否减少肝硬化患者术前输注血小板。方法 2017年1月～2019年4月在西京医院消化内科住院并进行手术治疗的乙型肝炎肝硬化患者40例和肝细胞癌患者36例,均需行食管静脉曲张套扎和/或胃底静脉曲张组织胶注射术或经肝动脉化疗栓塞术(TACE)治疗。术前给予rhTPO 15000U皮下注射,1次/d,连续应用10 d。结果 在76例患者中,血小板计数为40～50×10⁹/L组23例,血小板计数<40×10⁹/L组53例;两组患者在治疗第8 d时,外周血血小板计数较基线明显升高【>50×10⁹/L,分别为(76.0±26.6)×10⁹/L和(54.4±24.3)×10⁹/L]。在治疗第12 d,两组外周血血小板计数达到高峰[分别为(95±34.8)×10⁹/L和(67.9±25.1)×10⁹/L],在治疗后第30 d,血小板计数降至基线水平;应用rhTPO治疗后,保证了手术的顺利进行,对血凝功能无明显影响,两组未观察到门静脉血栓形成。结论 rhTPO可作为肝硬化并发血小板减少症患者术前血小板输注的替代疗法,能降低术中出血风险,且安全,值得临床进一步验证。     

41例白血病患者预防性输注血小板临床观察

目的观察白血病患者预防性输注机采血小板的效果。方法 41例白血病患者,采用ABO同型输注机采血小板,且均在30 min内输注完毕。按照输血小板前血小板计数分为A组(血小板计数<10×109/L)、B组[血小板计数为(10~20)×109/L],对两组患者输注机采血小板的效果进行观察分析。结果 41例白血病患者共预防性输注机采血小板126例次,输注后有效率均达到80%。A、B组分别预防性输注66、60例次,输注前血小板计数分别为(6.29±2.02)×109/L、(13.07±2.95)×109/L,输注后血小板计数分别为(21.71±11.37)×109/L、(28.12±11.72)×109/L,输注后24 h血小板增加校正指数(CCI)分别为(12.54±8.94)×109/L、(13.38±10.16)×109/L,有效率分别为80.3%、80.0%,两组输注后24 h CCI及有效率比较差异无统计学意义。结论白血病患者预防性输注机采血小板可提高其血液中的血小板数量,能够有效预防出血;以10×109/L作为白血病患者预防性输注阈值安全有效。     

联合应用重组人血小板生成素安全有效治疗婴幼儿重症原发免疫性血小板减少症——单中心数据分析

目的:通过对国产重组人血小板生成素(rhTPO)治疗3岁以下婴幼儿重症原发免疫性血小板减少症(SITP)的临床资料进行分析,为该年龄段SITP患儿临床联合应用rhTPO的有效性及安全性提供依据。方法:采用回顾性方法收集3岁以下联合应用rhTPO治疗的SITP患儿治疗前后相关临床数据并进行比较,分析其安全性及有效性。结果:①共有55例3岁以下SITP患儿纳入本研究,其中男37例,女18例;中位月龄为19(1.37～34.50)个月;中位病程为0.67(0～12)个月;41例(74.5%)为新诊断的ITP,11例(20.0%)为持续性ITP,3例(5.5%)为慢性ITP。患儿基线血小板计数为6(1～9)×10~9/L。出血情况:Ⅱ级42例,Ⅲ级11例,Ⅳ级2例。②患儿均为联合用药,其中10例rhTPO单独联合丙种球蛋白,45例同时联合激素及丙种球蛋白。③给药后第1天、第3天、第7天、第14天及停药后第7天,血小板中位计数分别为17(0～121)×10~9/L、63(1～349)×10~9/L、91(4～996)×10~9/L、176(11～1 687)×10~9/L及129(1～697)×10~9/L。在给药第7天、第14天及停药后第7天,患儿总有效率分别达76.0%、90.2%、73.9%。④在联合应用rhTPO第3天有6例患儿出血评分降为0级,第7天有11例患儿出血降为0级,其余患儿在停药7天出血降为0级。⑤未观察到发热、皮疹等与rhTPO相关不良反应发生。结论:rhTPO可协同免疫治疗,迅速有效提高婴幼儿SITP患儿血小板水平,帮助其度过危险期,有望提高疗效。     

成人特发性血小板减少性紫癜患者生活质量研究

目的:评价成人特发性血小板减少性紫癜(ITP)对患者生活质量(QoL)的影响.方法:使用Medical Outcome Study SF-36 form(SF-36)中文版对中国医学科学院血液病医院236例成人ITP患者进行QoL调查.按照血小板计数,将患者分为3组[PLT<30×109/L;PLT(30～100)×109/L;PLT>100×109/L].SF-36的8个维度作为测量结果:躯体健康(PF);社会功能(SF);躯体角色功能(RP);躯体疼痛(BP);心理健康(MH);情绪角色功能(RE);精力(VT);总体健康(GH).结果:在8个维度ITP患者和正常人相比SF-36 QoL均降低.在PF、RP、BP、GH、SF和RE等6个维度中QoL得分差异有统计学意义.急性ITP患者在GH、VT和RE 3个维度与慢性患者相比QoL得分的差异有统计学意义.同时,在根据血小板计数分组的比较中,在PF、GH和SF 3个维度显示了明显的差别.年龄是除了SF以外其他所有维度的负性预测因子.当前血小板计数是BP,SF和GH的负性预测因子.而且治疗费用也影响了QoL得分.对出血的恐惧作为主观指标对QoL有明显的负面影响.结论:成人ITP患者的QoL明显降低,年龄、血小板计数和出血的恐惧对QoL有明显的负面影响.本研究为ITP的临床研究提供了基于询证的证据.     

Multiple cycles of recombinant human thrombopoietin therapy in a patient with chronic refractory idiopathic thrombocytopenic purpura.

We describe a 41-year-old woman with chronic idiopathic thrombocytopenic purpura who received recombinant human thrombopoietin (rhTPO) therapy. rhTPO was administrated subcutaneously at a dosage of 1.0 mug/kg daily for a maximum of 14 days until the platelet count was more than 50 x 10/l. The patient received three cycles (six, 13, and eight doses each) of rhTPO, each initiated when the platelet counts was less than 10 x 10/l. The platelet count increased to above 50 x 10/l on days 5, 11 and 8, and peaked at 456 x 10/l, 130 x 10/l and 82 x 10/l on days 9, 15 and 13 in the three respective cycles, each followed by a gradual decline. The durations of platelet counts at more than 50 x 10/l in the three cycles were 13, 7 and 10 days, respectively. rhTPO was well tolerated with no adverse event observed. Antibodies to rhTPO by enzyme-linked immunosorbent assay were not detected. Our observations suggested that rhTPO could transiently increase the peripheral platelet count in patients with chronic refractory idiopathic thrombocytopenic purpura. The reasons why the peak platelet counts decreased and the duration of response shortened after successive cycles of treatment were unclear.     

Cyclosporin therapy for idiopathic thrombocytopenic purpura

Nine adult patients with chronic idiopathic thrombocytopenic purpura (ITP) were treated with cyclosporin. Their platelet counts were all below 5 x 10(4)/microliters. It was administered orally at 5 mg/kg/day for 8 weeks. In one patient, the platelet count increased over 10 x 10(4)/microliters in 4 patients it did over 5 x 10(4)/microliters. Gingival hyperplasia was observed in one patient. Renal dysfunction was not observed in any patients. The elevation of PAIgG declined during the period of treatment. These results suggest that this therapy may be useful in refractory idiopathic thrombocytopenic purpura.     

Efficacy of Helicobacter pylori eradication in raising platelet count in adult patients with idiopathic thrombocytopenic purpura

BACKGROUND AND OBJECTIVES: There are data consistent with an association between idiopathic thrombocytopenic purpura (ITP) and Helicobacter pylori (HP) infection. In addition, a significant increase of platelet count following HP eradication has been reported in a proportion of ITP patients. We describe here our experience on the efficacy of anti-HP treatment in ITP patients. DESIGN AND METHODS: Between December 1998 and May 2001 sixteen adult patients with ITP and documented HP infection were treated with standard antibiotic therapy for HP eradication (amoxicillin and clarithromycin plus pantoprazole combination). Of these patients, 7 had untreated ITP with mild/moderate thrombocytopenia (median platelet count 70x10(9)/L, range 41-91), 5 had relapsed following a previous steroid treatment (median platelet count 39x10(9)/L, range 30-90) and 4 were refractory to steroids (median platelet count 18.5x10(9)/L, range 9-30). RESULTS: An improvement of platelet count was observed in 11/15 patients (73.3%) who achieved HP eradication. The difference between the mean platelet count SD before and after HP eradication was statistically significant (51.6 28.2x10(9)/L vs. 143.3 131.1x10(9)/L; p=0.01). Complete or partial responses were obtained in 11/16 treated patients (68.7%). This result still persisted after a median follow-up of 11.7 months. INTERPRETATION AND CONCLUSIONS: Our data confirm the efficacy of Helicobacter pylori eradication in increasing platelet count in adult ITP patients.     

Analysis of outcome of laparoscopic splenectomy for idiopathic thrombocytopenic purpura by platelet count

Laparoscopic splenectomy (LS) is now performed routinely in patients with idiopathic thrombocytopenic purpura (ITP) refractory to the medical treatment. Low preoperative platelet count was deemed to be a contraindication for a laparoscopic approach; however, there is no data reporting the outcome in those patients. We aimed to evaluate the influence of the preoperative platelet count on the operative and postoperative course and complication rate. Retrospective cohort study that was conducted in tertiary care university-affiliated medical center and included 110 consecutive patients who underwent LS. All patients were divided into three groups by their preoperative platelet counts: 50 x 10(9)/L (n = 80). The outcome and the influence of preoperative factors predictive of complications, blood transfusion, and length of stay were compared between the groups. Patients with a platelet count of 20 x 10(9)/L before surgery. Patients with counts >20 x 10(9)/L can safely undergo LS.     

Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic thrombocytopenic purpura

We conducted a phase 1-2 clinical trial to evaluate the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with chronic idiopathic thrombocytopenic purpura (ITP) refractory to standard therapy who had platelet counts below 30 x 10(9)/L. Four patients received PEG-rHuMGDF (0.5 microg/kg of body weight per day) by daily intravenous injection for up to 7 days. Administration of PEG-rHuMGDF increased platelet counts in 3 patients. A striking thrombocytosis occurred in 2 patients, whose platelet counts were elevated to more than 700 x 10(9)/L a week after the last administration of PEG-rHuMGDF and returned to baseline levels within 4 to 6 weeks. Before the platelet peak, the percentage of reticulated platelets increased transiently in 3 patients tested, including one patient who had no response. Bleeding episodes decreased after the start of PEG-rHuMGDF therapy. These results suggest that PEG-rHuMGDF might have a clinical benefit in ameliorating thrombocytopenia associated with ITP.     

Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura

Rituximab 375 mg/m(2) weekly for four weeks has significant activity in patients with immune thrombocytopenia. We evaluated the activity of lower dose rituximab (100 mg iv weekly for 4 weeks) in 28 adults with idiopathic thrombocytopenic purpura. Overall (platelet count > 50 x 10(9)/L) and complete responses (platelet count > 100 x 10(9)/L) were achieved in 21/28 (75%) and 12/28 (43%) patients respectively. The median time to response and time to complete response were 31 and 44 days respectively. After a median follow-up of 11 months (range 3-18), 7/21 (33%) patients relapsed and 3 needed further treatments. In patients with idiopathic thrombocytopenic purpura, lower dose rituximab seems to show similar activity to standard dose.     

Danazol for the treatment of idiopathic thrombocytopenic purpura

Fourteen patients with idiopathic thrombocytopenic purpura (ITP) refractory to steroids and/or splenectomy were treated with danazol (200 mg 3 times a day) for 2 months. The following responses were achieved: excellent (platelet count greater than 100 X 10(9)/l) in 5 patients; good (greater than 50 X 10(9)/l, but less than 100 X 10(9)/l) in 2 patients, and poor in (no increase of platelet count) 7 patients. In three cases remission lasted more than 7 months. Danazol was well tolerated and in most patients better suited than steroids for long-term intake.     

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura

The role of rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between 2 and 5 different therapeutic regimens, including 8 patients who had already failed splenectomy. Patients were scheduled to receive intravenous rituximab at the dose of 375 mg/m(2) once weekly for 4 weeks. Rituximab infusion-related side effects were observed in 18 patients, but were of modest intensity and did not require discontinuation of treatment. A complete response (platelet count greater than 100 x 10(9)/L) was observed in 5 cases, a partial response (platelet count between 50 and 100 x 10(9)/L) in 5 cases, and a minor response (platelet count below 50 x 10(9)/L, with no need for continued treatment) in 3 cases, with an overall response rate of 52%. In 7 cases, responses were sustained (6 months or longer). In 2 patients with relapsed disease, repeat challenge with rituximab induced a new response. In patients with a complete or partial response, a significant rise in platelet concentrations was observed early during the course of treatment, usually 1 week after the first rituximab infusion. No clinical or laboratory parameter was found to predict treatment outcome, although there was a suggestion that women and younger patients have a better chance of response. In conclusion, rituximab therapy has a limited but valuable effect in patients with chronic ITP. In view of its mild toxicity and the lack of effective alternative treatments, its use in the setting of chronic refractory ITP is warranted. (Blood. 2001;98:952-957)     

Treatment of myelodysplastic syndrome with low-dose human granulocyte colony-stimulating factor: a multicenter study

The objective of this study was to determine the hematopoietic effects and toxicity of low-dose granulocyte colony-stimulating factor (G-CSF) in myelodysplastic syndrome (MDS) patients with neutropenia. Recombinant human G-CSF (Lenograstim) was administered by daily subcutaneous injection with an initial dosage of 0.5 microg/kg per day for 2 weeks. Patients not responding to the initial dosage received the escalated dosage, 1 to 2 microg/kg per day for 2 weeks. Eligibility criteria were the following: French-American-British disease classification subtype refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) with an absolute neutrophil count (ANC) of <1.5 x 10(9)/L. Criteria indicating response to treatment were ANC of >1.5 x 10(9)/L and doubling of ANC on at least 2 occasions. Thirty-two MDS patients were recruited from 6 university hospitals. Eighteen patients had RA, 4 had RARS, and 10 had RAEB. Median age was 56.4 years (range, 28-87 years). Twenty-six patients (81.2%) had an increase in ANC from a median of 0.94+/-0.35 x 10(9)/L to 4.24+/-3.78 x 10(9)/L.Three of 6 patients who did not respond to the initial dosage responded to the escalated dosage of 1 microg/kg per day. Eighteen (81.8%) of 22 patients with RA or RARS responded compared with 8 (80%) of 10 patients with RAEB. The response rates in patients with ANCs of <0.5 x 10(9)/L. 0.5 to <1.0 x 10(9)/L, and 1.0 to 1.5 x 10(9)/L were 80%, 70%, and 88.2%, respectively. The side effects were minimal. No significant changes in hemoglobin levels or platelet counts were observed. In conclusion, low-dose G-CSF administered by subcutaneous injection is well tolerated and effective in improving neutropenia in MDS patients.     

Splenectomy for refractory thrombocytopenia in the antiphospholipid syndrome.

OBJECTIVE: Thrombocytopenia, usually mild, is one of the clinical criteria of the antiphospholipid syndrome (APS). Rarely, this disorder requires treatment and, due to the shared characteristics with idiopathic thrombocytopenic purpura (ITP), similar rules are followed. We report our experience in patients who required splenectomy after being refractory to steroids and immunosuppressive therapy. METHODS: Fifty-five APS patients with a platelet count of < 100 x 10(9)/l at least twice were analysed retrospectively. Therapeutic response or remission was considered when the platelet count was > 100 x 10(9)/l after 1 month and with no relapse on stopping or tapering the steroid dose. No response or refractory disease was defined as an absence of increase in platelet count, a total count that never exceeded 50 x 10(9)/l during treatment or when the dose requirements were such that the patient developed serious side-effects. RESULTS: Fifty patients were classified as having secondary APS associated with systemic lupus erythematosus (SLE) and five were identified as primary APS (PAPS). Splenectomy was performed in 11 cases (20%), two PAPS and nine SLE-APS, with an average time of 28 +/- 9 months after the development of thrombocytopenia. Eight patients were initially characterized as ITP (six SLE-APS, two PAPS) with an average time of 4.4 +/- 1.1 yr until the APS diagnosis. All but two were responsive to splenectomy. CONCLUSION: Splenectomy was required in 11 (20%) of the patients with APS-associated thrombocytopenia. There was a high rate of good and long-term response.