重组人白细胞介素-11联合糖皮质激素治疗免疫性血小板减少症的疗效分析

Analysis of therapeutic effect of recombinant human interleukin-11 combined with glucocorticoid in treatment of immune thrombocytopenia

目的探讨采用重组人白细胞介素（rhIL）-11联合糖皮质激素治疗初治免疫性血小板减少症（ITP）患者的疗效及安全性。方法选取2011年12月至2014年12月于江苏省张家港市第一人民医院血液科接受住院治疗的60例初治ITP患者为研究对象。按照简单随机抽样法将60例初治ITP患者分为研究组（n=30）与对照组（n=30）。研究组患者采用rhIL-11联合糖皮质激素方案进行治疗；对照组患者单用糖皮质激素进行治疗。本研究纳入标准：符合ITP诊断标准的初治患者，年龄大于18岁。排除标准：继发性血小板减少症患者，以及伴有基础疾病，如糖尿病、心功能不全或心律失常的ITP患者。检测并记录两组患者治疗前、治疗第4、7天血小板计数的变化情况及其血小板计数≥100×10。／L的平均时间，根据ITP-出血评分表（BAT）统计出血评分，以及治疗第7天患者的疗效评价、不良反应，并进行统计学分析。本研究遵循的程序符合江苏省张家港市第一人民医院人体试验委员会所制定的伦理学标准，得到该委员会批准。两组患者年龄与性别构成比等一般临床资料，以及治疗前血小板计数、出血评分比较，差异均无统计学意义（P〉0．05）。结果①两组初治ITP患者治疗后血小板计数均逐步增高。研究组患者治疗第4天血小板计数[（37．9±30．4）×10^9／L]显著高于对照组[（22．5±16．0）×10^9／L]，且差异有统计学意义（t=2．308，P=0．028）；研究组患者治疗第7天血小板计数[（121．8±29．2）×10^9／L]亦显著高于对照组[（91．2±28．7）×10^9／L]，且差异亦有统计学意义（t=5．444，P=0．000）。但研究组血小板计数≥100×10^9／L的时间[（7．0±1．4）d]较对照组[（9．3±3．5）d]缩短，且差异有统计学意义（t=3．820，P=0．001）。②两组初治ITP患者治疗后出血评分均逐步减低。研究组患者治疗第4天出血评分[（2．0±1．1）分]显著低于对照组[（2．7±1．0）分]，且差异有统计学意义（t=-2．588，P=0．015）；研究组患者治疗第7天出血评分E（o．1±0．4）分]亦显著低于对照组[（0．5±1．2）分]，且差异亦有统计学意义（t=-2．249，P=0．032）。③研究组治疗第7天完全有效率达90．0％显著高于对照组（60．0％），且差异亦有统计学意义（Х^2=5．69，P〈0．05）。④研究组初治ITP患者中有6例（20．0％，6／30）出现水、钠潴留，采用利尿剂治疗后好转；3例（10．0％，3／30）自感心悸，2例（6．7％，2／30）心电图结果示频发心房早搏，停药后均好转；1例（3．3％，1／30）快速房颤，停用rhIL-11，予毛花苷丙（西地兰）静脉注射后好转；20例（66．7％，20／30）发生结膜充血，未行特殊处理；其中有2例患者合并2种不良反应。对照组初治ITP患者中有5例（16．7％，5／30）患者出现体重轻度增加，无下肢浮肿，未行特殊处理；2例（6．7％，2／30）出现窦性心动过速，停药后好转；其余患者均无不良反应。结论rhIL-11联合糖皮质激素治疗初治ITP患者起效快、疗效好、安全性高，且患者可耐受。

Objective To investigate the efficacy and safety of recombinant human interleukin （rhIL）-11 combined with glucocorticoid in treatment of newly diagnosed immune thrombocytopenia （ITP） patients. Methods From December 2011 to December 2013, a total of 60 cases of newly diagnosed ITP patients who were received in First People＇s Hospital of Zhangjiagang were collected into this study. These 60 cases of 1TP patients were randomly divided into two groups, as study group （n=30） and control group （n = 30） by simple random samping method. The study group was used rhIL-11 combined with glucocorticoid, and control group was used glucocorticoid only. The study inclusion criteria were newly diagnosed ITP patients who were older than 18 years old. Secondary thrombocytopenia and ITP accompanied with other diseases, for example diabete, cardiac insufficiency and arrhythmia were excluded. Two groups＇ platelet count prior treatment, after 4 days and 7 days treatments, and average time of platelet count which is greater than or equal to 100 × 10^9/L were tested. Bleeding score, therapeutic efficiency evaluation and adverse reactions after 7 days treatment were calculated. The study protocol was approved by the Ethical Review Board of Investigation in Human at First Peoplers Hospital of Zhangjiagang. Informed consent was obtained from all participants. There were no significant differences of patients＇ clinical data in two groups, such as age and gender composition, platelet count and bleeding score before treatment （P 〉 0. 05）. Results OPlatelet counts of both groups were increased gradually after treatment, but platelet count in study group [（37.9± 30.4） ×10^9/L] was higher than that of the control group [（22.5± 16.0） × 10^9/L] after 4 days treatment. The difference was statistically significant（t= 2. 308,P= 0. 028）. Platelet count in study group[（121.8±29.2）×10^9/L] was also higher than that of control group[（91.2±28.7）× 10^9/L] after 7 days treatment, the difference was statistically significant（t= 5. 444, P= 0. 000）. In study group, the time [ （7.0 ±1.4） d] that platelet count recovered greater than or equal to 100 × 10^9/L was shorter than that of control group [（9. 3 ± 3. 5） d], the difference was statistically significant （t = - 3. 820, P = 0. 001 ）. ② Bleeding score evaluated by ITP-bleeding assessment tool （BAT） was decreased gradually in two groups after treatment. But bleeding score of study group[（2.0±1.1） score] was significantly lower than that of the control group [ （2.7 ± 1.0） score] after 4 days treatment, the difference was statistically significant（t= -2. 588,P=0. 015）. The bleeding score of study group[（0. 1 !0. 4） score] was also significantly lower than that of the control group[（0.5± 1.2） score] after 7 days treatment , the difference was statistically significant（t=-2. 249,P：0. 032）. ③ The total effective rate was 90.0% in study group, but 60.0% in control group after 7 days treatment, and the difference was statistically significant （Х^2= 5.69, P〈0.05）. ④In study group, 6 cases（20.0% ,6/30） had water-sodium retention and relieved by diuretics. Three cases （10.0% ,3/30）had arrhythmia. 2 cases（6.7% ,2/30） had atrial premature beats noted on electrocardiogram （ECG）. One case （3.3%, 1/30） had atrial fibrillation, and recovered after injection lantoside C （cedilanid） and stopping rhIL-11 subscutaneous injection. 20 cases（66.7%,20/30） had bulbar conjunctiva hyperemia, but needn＇t treatment. Among these patients, two cases in study group had two adverse affects. In control group, 5 cases（16.7% ,5/30） had slight weight gain without edema lower extremity, but needn＇t treatment. And 2 cases （6. 7%, 2/30） had sinus tachycardia, and recovered after stopping rhIL-11 subscutaneous injection. Others had no adverse affects. Conclusions rhIL-11 combined with glucocorticoid therapeutic regimen for newly diagnosed ITP took action faster and had significant effect. At the same time, adverse affects were tolerable.