不同剂量白介素-11治疗化疗后血小板减少的临床对比研究

目的:研究不同剂量重组人白介素-11(rhIL-11)对恶性肿瘤患者化疗所致血小板减少的疗效及不良反应.方法:采用随机对照的方法,对46例因化疗引起血小板Ⅱ度以上减少的恶性肿瘤患者给予rhIL-11治疗.A组22例,rhIL-11用量为1.5mg/d,B组24例,3mg/d,皮下注射,血小板升高至正常时停止给药.结果:rhIL-11治疗后,血小板严重减少(20× 109/L)的持续天数,B组少于A组(p=0.031);血小板恢复至正常的时间,A、B组的中位数分别为11天和8天,有统计学意义.B组血小板最低值高于A组,PLT＜50 × 109/L持续天数,出血并发症以及减少血小板榆注的例数,B组亦少于A组,但两组比较没有显著性差异(p＞0.05).主要不良反应:四肢、腰背肌肉酸痛伴骨骼及关节疼痛、乏力、发热、头痛及头晕,均为Ⅰ-Ⅱ度,两组比较没有显著性差异(p＞0.05),停药后或口服"百服宁"均恢复.结论:rhIL-11是一种有效且安全的治疗恶性肿瘤患者化疗所致血小板减少药物,可以在临床常规应用.对比1.5mg,每天皮下注射3.0mg的剂量疗效可能更好些,不良反应可以耐受.     

重组人血小板生成素治疗血小板减少性紫癜

目的:分析重组人血小板生成素(rh TPO)治疗血小板减少性紫癜(ITP)的临床疗效。方法:选取100例难治性ITP患者为研究对象,随机分作两组,即观察组50例,采用rh TPO治疗;对照组50例,采用达那唑治疗。比较两组疗效及不良反应。结果:观察组总有效率90%优于对照组72%,差异明显有统计学意义(P<0.05);输注rh TPO之后,有7例患者出现不良反应,主要包括血清丙氨酸氨基转移酶升高、乏力、头晕以及注射处疼痛等,症状较轻且自行缓解。结论:在难治性ITP的临床治疗中,rh TPO具有诸多优势,不仅安全,而且有效,临床疗效优于达那唑,能够实现对出血症状的理想控制,表现出了比较良好的临床应用价值以及前景。     

环孢素A对难治性免疫性血小板减少性紫癜的辅助治疗

目的探讨环孢素A辅助治疗难治性免疫性血小板减少性紫癜(ITP)的临床疗效及对患者血小板计数和细胞因子的影响。方法选择2013年1月至2016年12月期间浙江省金华市人民医院收治的难治性ITP患者78例。按照随机数字表分为观察组39例与对照组39例。对照组患者给予利妥昔单抗治疗,观察组在对照组基础上结合环孢素A辅助治疗,两组患者疗程均为3个月。比较两组患者的疗效,治疗前后血小板计数变化,血小板恢复正常时间,治疗前后细胞因子变化及不良反应发生情况。结果观察组患者治疗总有效率(92.31%)高于对照组(69.23%),差异有统计学意义(χ2=6.6857,P0.05);两组患者治疗后血小板计数增加,观察组患者治疗后血小板计数高于对照组、血小板恢复正常时间低于对照组,差异均有统计学意义(t=20.6717、8.1189,P0.05);两组患者治疗后IFN-γ水平较治疗前降低,IL-4、IL-10水平升高,差异有统计学意义(观察组:t=22.9522、11.7500、11.9032,对照组:t=9.8537、7.2250、6.7012,P0.05),且治疗后观察组患者IFN-γ水平低于对照组,IL-4、IL-10水平高于对照组,差异有统计学意义(t=13.0096、3.8277、4.7989,P0.05);两组患者不良反应发生率比较差异无统计学意义(χ2=0.0000,P0.05)。结论环孢素A辅助治疗难治性ITP患者疗效显著,且可增加患者血小板数量,降低IFN-γ水平,增加IL-4、IL-10水平,提高患者免疫力。     

脾动脉结扎联合肝癌切除术治疗肝癌并门静脉高压症临床研究

目的:探讨脾动脉结扎联合肝癌切除术对肝癌并门静脉高压症的治疗效果和临床应用的价值。方法:对2008年10月至2013年10月期间我院收治的84例肝癌并门静脉高压症患者的资料进行回顾性分析,其中脾动脉结扎联合肝癌切除手术的患者50例为研究组,患者34例行肝癌切除及脾切断流术为对照组。比较两组治疗效果及患者术前、术后情况。结果:研究组术前白细胞计数、血小板计数、红细胞计数为(3.1±0.9)×109/L、(58.6±12.7)×109/L、(3.4±0.4)×109/L,术后2周白细胞计数、血小板计数、红细胞计数分别为(5.9±1.5)×109/L、(140.3±50.1)×109/L、(3.6±0.7)×109/L;对照组为术前白细胞计数、血小板计数、红细胞计数为(2.8±1.2)×109/L、(45.8±20.5)×109/L、(3.4±0.4)×109/L,术后2周白细胞计数、血小板计数、红细胞计数为(6.2±0.7)×109/L、(172.5±32.7)×109/L、(3.6±0.3)×109/L。研究组与对照组相比,术后2周白细胞计数、红细胞计数相比差异无统计学意义(P0.05),但术后2周血小板计数研究组低于对照组,差异有统计学意义(P0.05)。研究组术前与术后的白细胞计数、血小板计数、红细胞计数相比,差异均有统计学意义(P0.05)。研究组有17例患者出现术后并发症,占16.0%;对照组有20例患者出现术后并发症,占38.2%;两组对比差异有统计学意义(P0.05)。结论:根据病情合理选择使用脾动脉结扎联合肝癌切除术治疗肝癌并门静脉高压症,可以有效治疗肝癌和脾功能亢进,促进肝功能恢复,对延长原发性肝癌合并肝硬化脾功能亢进患者的生存时间,提高生活质量,具有重要意义。     

不稳定型心绞痛患者血小板计数对低分子肝素抗凝有效性的影响

目的:通过检测抗Xa因子活性,探讨不稳定型心绞痛患者血小板计数(PLT)对低分子肝素抗凝有效性的影响。方法:入选不稳定型心绞痛患者63例,分为两组,A组(n=24):PLT≥240×109/L,B组(n=39):PLT240×109/L。首先比较两组患者之间一般情况有无差异,而后在两组患者皮下注射那曲肝素前及注射后8 h两个时间点分别进行抗Xa因子活性检测并记录结果,分析两组患者抗Xa因子活性水平并比较活性低于0.5 IU·mL-1患者所占比例。结果:两组患者之间一般情况无显著性差异,抗Xa因子活性治疗前后差异在两组中均有统计学意义,A组治疗后抗Xa因子活性均值低于B组,抗Xa因子0.5 IU·mL-1的患者比率高于B组,组间比较差异显著。结论:在低分子肝素抗凝治疗中,血小板计数≥240×109/L的患者抗Xa因子活性较低,提示不稳定型心绞痛患者在应用低分子肝素后的抗凝力度不足与血小板计数偏高相关。     

双歧杆菌三联活菌胶囊对进展期胃癌术后 化疗患者化疗副作用及肠道菌群的影响

目的探讨口服双歧杆菌三联活菌胶囊(BTVC)对进展期胃癌术后化疗患者的化疗副作用及肠道菌群影响。方法选取铜陵市人民医院2016年2月至2017年1月收治的根治性胃癌术后首次化疗患者为研究对象,随机分成奥沙利铂+替吉奥联合化疗方案组32例(对照组),奥沙利铂+卡培他滨+BTVC联合治疗组26例(观察组)。检测两组患者肠道菌群变化及记录患者不良反应情况。结果治疗后对照组中白细胞3×109/L、粒细胞2×109/L、血红蛋白110g/L、血小板100×109/L、肝功能损害、周围神经炎、恶心/呕吐、腹泻及Ⅲ/Ⅳ级不良反应发生例数均多于观察组(P0.05)。治疗前两组患者肠道各菌群数量差异无统计学意义(P0.05);治疗后对照组患者乳杆菌、双歧杆菌数量及杆/球比明显少于观察组(P0.01),而肠球菌、大肠埃希菌数量明显多于观察组(P0.01)。治疗后对照组患者乳杆菌、双歧杆菌数量及杆/球比明显少于治疗前(P0.01),而肠球菌、大肠埃希菌数量多于治疗前(P0.05)。治疗后观察组患者乳杆菌、双歧杆菌数量及杆/球比多于治疗前(P0.05);而肠球菌、大肠埃希菌数量与治疗前差异无统计学意义(P0.05)。结论 BTVC对胃癌术后化疗副作用有预防作用,并可调节患者肠道菌群。     

血小板生成素基因治疗血小板减少症的研究

血小板生成素 (TPO)有望成为特异性治疗血小板减少症的理想药物 .对TPOcDNA离体细胞表达和基因治疗血小板减少症进行了初步尝试 :构建了pcDNA3 TPO高表达质粒 ,基因转移离体细胞 ,检测表达产物rhTPO具有完整的生物学活性 ;pcDNA3 TPO分别注射正常小鼠和血小板减少症小鼠 ,小鼠血浆中检测到rhTPO的表达 ,并且正常小鼠血小板水平上升至 1 .9倍 ,血小板减少症小鼠血小板降低的幅度减小、恢复的速度加快并达到原来值的 1 .8～ 2 .0倍 .该结果为TPO基因治疗血小板减少症提供了实验依据 .     

小剂量利妥昔单抗联合龙花胶囊对成人血小板减少症患者促血小板生成素及肾功能水平的影响

目的:探讨小剂量利妥昔单抗联合龙花胶囊对成人血小板减少症患者促血小板生成素,肾功能水平及临床疗效的影响。方法:收集我院就收治的90例免疫性血小板减少症患者,随机分为实验组和对照组,每组45例。对照组患者给予小剂量利妥昔单抗治疗;实验组患者在对照组基础上使用龙花胶囊治疗。观察并比较两组患者血小板(PLT)计数、促血小板生成素(TPO)、肾功能水平以及临床治疗总有效率。结果:与治疗前相比,治疗后两组患者的PLT、TPO水平均升高,差异具有统计学意义(P0.05);与治疗前相比,治疗后两组患者的肌酐(Scr)、尿素氮(BUN)水平均下降,差异具有统计学意义(P0.05);与对照组相比,实验组患者PLT、TPO水平较低,Scr、BUN水平较高,差异具有统计学意义(P0.05);与对照组相比,实验组患者临床治疗有效率较高,差异具有统计学意义(P0.05)。结论:小剂量利妥昔单抗联合龙花胶囊能够升高血小板减少症患者血小板以及促血小板生成素水平,改善患者肾功能,临床疗效较好,提高了治疗效果。     

人血小板生成素的研究进展

血小板生成素是新近发现的一个非常重要的造血调控因子。经过40多年的不懈努力,基本上阐明了血小板生成素及其受体系统（TPO/c-Mpl)在造血调控方面的作用。并在此基础上,研制了重组血小板生成素,以治疗放疗和化疗引发的血小板减少症,本综述了近年TPO及其受体c-Mpl系统对造血调控的研究进展,涉及TPO和c-Mpl的基因和蛋白分子结构。基因表达调控、可能经历的信号传导途径、TPO/c-Mpl系统主要的生理作用、TPO在血液循环中的代谢过程以及目前重组血小板生成素的临床研究现状等六个方面。深入理解TPO/c-Mpl系统的结构和作用。将加深人们对机体的造血调控和血液病的认识,并将有助于相关疾病的临床治疗。     

PLT,MPV,PDW对单采血小板产品聚集的影响

目的：探讨血小板含量（PLT）,血小板平均分布宽度（PDW）,血小板平均体积（MPV）对单采血小板聚集的影响,方法：随机抽取68例血小板捐献者,均成功捐献单采血小板,分为聚集组和对照组。献血前抽取静脉血,采用麦道尼克CA620血细胞分析仪进行血细胞分析,检测PLT,MPV,PDW。结果：聚集组（%）PDW 17.5±1.8,高于对照组（%）PDW12.1±0.9（P〈0.05）。聚集组（fl）MPV 11.0±0.9高于对照组（fl）MPV 7.8±0.8（P〈0.05）,差异有统计学意义,聚集组PLT（187±13.3）×109,对照组PLT（195±11.0）×109,二者无明显统计学差异（P〉0.05）。MPV,PDW分别与PLT进行相关性分析,PLT与MPV无显著相关（r=0.132,P〉0.05）;PLT与PDW无显著相关（r=0.147,P〉0.05）。结论：单采血小板产品出现聚集,其捐献者PDW,MPV高于单采产品正常捐献者,与献血者PLT计数无明显关系。     

利福平导致严重血小板减少1例

利福平主要用于结核病的治疗,能引起血小板减少等不良反应。本病例使用利福平后出现严重血小板减少,血小板下降至4×10⁹/L,立即停用利福平并输注血小板后血小板恢复正常。因此,在利福平使用过程中应密切观察病情,监测血常规、肝肾功能等,及时发现不良反应,必要时立即停药,并对血小板明显下降者(<30×10⁹/L)给予补充血小板等治疗。对明确由利福平引起血小板减少者,治疗时应不再使用该药,以避免药物不良事件的发生。     

Thrombopoietin induces p-selectin expression on platelets and subsequent platelet/leukocyte interactions

Ligation of thrombopoietin (TPO) to the platelet c-Mpl receptor induces numerous biochemical pathways in the absence of aggregation. Two forms of recombinant TPO are currently in clinical trials for the treatment of thrombocytopenia. This study focuses on the effects of the full-length recombinant human TPO (rhTPO) on platelets in a whole blood system. Platelet-leukocyte associations (PLAs) were visualized following rhTPO stimulation as CD42b/CD 45 double positive clusters by FACS analysis. Treatment of washed platelets with rhTPO induced granule release and expression of the leukocyte adhesion receptor P-selectin (CD 62P) in the absence of aggregation and calcium mobilization. RhTPO also induced platelet-leukocyte interactions in whole blood. Following stimulation, leukocytes were recruited by platelets through P-selectin in a calcium-dependent manner. rhTPO stimulates platelet-leukocyte associations in whole blood through expression of platelet P-selectin. To our knowledge, this is the first report that identifies TPO as a promoter of platelet-leukocyte interactions.     

Expression, purification, and characterization of human recombinant thrombopoietin in Chinese hamster ovary cells

Thrombopoietin (TPO) is a primary regulator of megakaryocytopoiesis, a process through which megakaryocytes proliferate and mature into platelets. Recombinant human TPO (rhTPO) was expressed in Chinese hamster ovary (CHO) cells and purified from the culture medium. The cDNA encoding full-length TPO, including the native signal peptide sequence, was amplified by PCR from a human fetal liver cDNA library. The product was cloned into a mammalian expression vector under the control of the SV40 early promoter and enhancer. Secreted rhTPO was purified in three conventional chromatography steps. It migrates on SDS-PAGE as a broad band, characteristic of a heavily glycosylated protein, with an average molecular mass of 85 kDa. rhTPO expressed in CHO cells is biologically active in vitro as demonstrated by its ability to stimulate the proliferation of a megakaryocytic cell line and to trigger the JAK/STAT signal transduction pathway. rhTPO also shows activity in vivo as judged by the elevation of platelet count in treated mice.     

Study of thrombopoietin for gene therapy of thrombocytopenia

Thrombopoietin (TPO) is likely to he a potent, specific and reliable medication in the treatment of thrombocytopenia. A TPO-highly-expressed plasmid pcDNA3-TPO was constructed and a primary study was made on the expression of TPO cDNAin vitro and gene transfer study for thrombocytopeniain vivo. rhTPO showed complete and stable bioactivity by a series of indicators. High expression of TPO was detected in plasma from healthy mice or thrombocytopenia mice model receiving direct intramuscular injection of pcDNA3-TPO. And the platelet level of healthy mice peaked to 1.9-fold of baseline. Mice with CTX-induced thrombocytopenia achieved profound nadirs, acceleration of recovery, even 1.8–2.0-fold supranormal levels of peripheral platelet counts. The results offered experimental support for clinical application of gene therapy for thrombocytopenia via direct intramuscular injection of TPO cDNA.     

部分脾动脉栓塞术治疗原发性肝癌合并脾功能亢进的临床疗效观察

目的:探讨部分性脾动脉栓塞术(PSE)治疗原发性肝癌合并脾功能亢进的临床疗效及安全性。方法:选择2008年5月至2013年4月我科收治的160例原发性肝癌合并有脾功亢进患者为研究对象,患者在行肝动脉化疗栓塞术(TACE)的同时进行PSE,PSE栓塞面积在30%~60%之间,观察治疗后3天、7天、1个月、3个月、6个月患者白细胞(WBC)计数和血小板(PLT)计数的动态变化情况。结果:以外周血白细胞计数达到4.0~13×109/L、血小板达计数到50×109/L为治疗有效,160例患者术后3个月时外周血白细胞治疗有效为151例(94.38%),血小板治疗有效为155例(96.88%),术后6个月时白细胞治疗有效136例(85%),血小板治疗有效125例(78.13%)。所有患者术后6个月均未发生严重并发症。结论:PSE联合TACE治疗原发性肝癌合并有脾功亢进患者具有良好的疗效,且安全性较高。     

Relationship of thrombopoietin and interleukin-11 levels to thrombocytopenia associated with dengue disease

Thrombocytopenia is one of the main clinical findings of dengue. In this work we examined the levels of thrombopoietin (TPO) and interleukin-11 (IL-11), two of the most potent regulators of platelet production, in serum from 28 patients with dengue fever (DF). Patients with DF had increased levels of TPO, compared with healthy individuals (p<0.005). Patients with dengue hemorrhagic fever (DHF, n=7), the more severe form of dengue, had higher TPO levels than patients with DF (p<0.001). Serum TPO levels and platelet counts were inversely correlated in both DF and DHF patients. IL-11 was detectable in neither DF nor DHF patients. Our results demonstrate that thrombocytopenia in dengue disease is associated with changes in the serum levels of TPO, but not IL-11, suggesting that this cytokine could be a potential early clinical marker of the severity of dengue disease.     

Study of thrombopoietin for gene therapy of thrombocytopenia

Thrombopoietin (TPO) is likely to be a potent, specific and reliable medication in the treatment of thrombocytopenia. A TPO-highly-expressed plasmid pcDNA3-TPO was constructed and a primary study was made on the expression of TPO cDNA in vitro and gene transfer study for thrombocytopenia in vivo. rhTPO showed complete and stable bioactivity by a series of indicators. High expression of TPO was detected in plasma from healthy mice or thrombocytopenia mice model receiving direct intramuscular injection of pcDNA3-TPO. And the platelet level of healthy mice peaked to 1.9-fold of baseline. Mice with CTX-induced thrombocytopenia achieved profound nadirs, acceleration of recovery, even 1.8—2.0-fold supranormal levels of peripheral platelet counts. The results offered experimental support for clinical application of gene therapy for thrombocytopenia via direct intramuscular injection of TPO cDNA.     

Platelet sparing effect of COX II inhibition used with pegylated interferon alfa-2a for the treatment of chronic hepatitis C: a short term pilot study

The role of a cyclooxygenase (COX) II inhibitor in reducing microvascular inflammation and the platelet count associated with interferon (IFN) plus ribavirin therapy of chronic hepatitis C (HCV) was assessed. Three plasma mediators (biomarkers) associated with platelet activation, inflammation and fibrosis were measured. Eighteen IFN na?ve patients were studied. Nine were treated with pegylated IFN alfa-2a (PEG-IFN alpha-2a) plus ribavirin and rofecoxib; nine were treated with PEG-IFN alpha-2a plus ribavirin. A complete blood count, liver panel and HCV-RNA were assayed weekly. Human soluble P-selectin (hs-P-selectin), human interleukin-8 (IL-8), human interleukin-13 (IL-13) and human thrombopoietin (TPO) were assayed at 4 week intervals. The COX II inhibitor reduced the platelet reduction experienced with PEG-IFN alpha-2a treatment of HCV despite a reduction in the plasma TPO level. Hs-P-selectin was increased in both groups. In contrast, human IL-8 levels declined to undetectable levels in virologic responders. Similarly, human IL-13 levels declined with therapy (P < 0.001). These data suggest that: (1) a COX II inhibition is associated with an increase in the platelet count despite a reduction in the TPO level; (2) human IL-8 and human IL-13 but not hs-P-selectin levels decline in those who experience an early virologic response.     

Obesity, white blood cell counts, and platelet counts among police officers

Objective: To determine the association between several obesity indices (BMI, waist circumference, waist‐to‐hip and waist‐to‐height ratios, and abdominal height) and hematologic parameters [white blood cell (WBC) and platelet counts] among police officers. Research Methods and Procedures: The authors conducted this cross‐sectional study among 104 randomly selected officers (41 women and 63 men) from the Buffalo, NY, Police Department. Anthropometric measures were performed by clinic staff, and fasting blood samples were drawn for complete blood counts. Pearson's correlation, Student's t tests, ANOVA, analysis of covariance, and linear regression were used to assess the associations. Results: Officers ranged in age from 26 to 61 years old and were predominantly white. Among women, current smokers had significantly higher WBC counts (7.4 × 10³ cells/µL ± 1.4) than former (5.2 × 10³ cells/µL ± 1.4) or never smokers (5.6 × 10³ cells/µL ± 1.5) (p = 0.002). Women had similar WBC counts but higher mean platelet counts than men (p = 0.005). Among women, abdominal height was positively associated with platelet count after adjustment for depression (p for trend = 0.039). Among women and men, a non‐significant step‐wise trend was observed between abdominal height and mean WBC counts before and after adjustment for smoking, race, and physical activity. No association was observed between obesity and platelet count among men. Discussion: Abdominal height was significantly associated with increased platelet counts among female officers. No significant associations were observed between obesity and WBC or platelet counts among male officers.     

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts

Background

Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100?×?10⁹/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100?×?10⁹/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100?×?10⁹/L are reported.

Methods

Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability.

Results

By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75?×?10⁹/L. Seven patients experienced platelet count increases ≥15?×?10⁹/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia.

Conclusions

Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts.

Trial registration

ClinicalTrials.gov:NCT01348490.