替罗非班相关血小板减少的临床研究

发布时间：2018-11-07 16:21

【摘要】：背景和目的：抗栓治疗是当今治疗急性冠脉综合征（ACS）的主要手段。盐酸替罗非班（tirofibanhydrochloride)是一种可逆性非肽类血小板膜糖蛋白GP IIb/IIIa受体拮抗剂，能够作用于血小板聚集的最后通路，有明显的抗栓作用，但应用替罗非班等血小板膜糖蛋白GPIIb/IIIa受体拮抗剂有时会发现血小板减少的情况，甚至发生血小板减少症（Tirofibaninduced thrombocytopenia)，大大增加了出血风险。本实验旨在研究应用替罗非班后发生血小板减少及出血事件发生的情况，并初步探讨其影响因素，为临床合理用药及用药安全提供参考。方法：该研究为前瞻性研究。选择自2014年5月-2015年1月期间因冠心病于吉林大学中日联谊医院心内科住院治疗的患者，经过入选标准及排除标准筛选后，按2:1的比例随机分为实验组与对照组，并将实验组中应用替罗非班超过24小时患者划为实验亚组。共140名患者被纳入该研究，其中男性85名，女性55名。入组患者常规给予阿司匹林、氯吡格雷（或替格瑞洛）、肝素治疗，实验组按照替罗非班说明书，根据患者体重进行计算，给予替罗非班治疗；对照组不给予替罗非班治疗。记录所有入选患者的个人基本信息，包括：病历号、姓名、性别、年龄、身高、体重等；并记录患者是否应用低分子肝素（种类及剂量）、氯吡格雷/替格瑞洛。实验组及对照组分别于应用替罗非班后/造影术后2h、6h、9h、12h、24h分别静脉采血行血常规检测，并记录患者是否发生出血事件。血小板减少症的定义：血小板基线正常（100-300×109/L)或高于300×109/L，应用替罗非班后24h内出现下述情况：血小板计数＜100×109/L判定为血小板减少症。并分度如下：血小板计数在50-100×109/L范围内判定为轻度血小板减少症；血小板计数在20-50×109/L判定为重度血小板减少症；若血小板计数＜20×109/L应判定为极重度血小板减少症。出血事件：实验组应用替罗非班治疗后出现牙龈出血、术肢渗血或血肿、结膜充血、血尿等。对照组术后出血牙龈出血、术肢渗血或血肿、结膜充血、血尿等。最终实验数据借助SPSS13.0软件进行数据分析。计量资料经正态性检验后，若符合正态分布，则表示为均数±标准差（x±s)，并行方差齐性检验。方差齐，则进一步采取t检验；方差不齐则进一步采用非参数检验。若计量资料不符合正态分布，则表示为中位数，组间非参数检验。计数资料的统计学分析：定性数据以例数（百分比）表示，组间计数资料比较采用方差分析与卡方检验。如P＜0.05，，则判定为统计学有显著差异。结果：在应用替罗非班治疗的实验组中（N=84),发生血小板减少症的病例数为2例（2.35%），均为男性，血小板减少症的程度均为轻度，未发生重度及极重度的血小板减少。血小板减少症发生的时间为应用替罗非班后的2-9小时和6-12小时，检测到的血小板计数最低的时间点均为应用替罗非班后6小时(分别为95×109/L和87×109/L）。这两例血小板减少症患者中有一位表现为轻度的牙龈出血，另一位无明确出血表现。在实验组与对照组之间，与2小时血小板计数基线相比，6小时、9小时、12小时与24小时的血小板计数均无显著差异。2-6小时、6-9小时、9-12小时的血小板变化情况均无显著差异（P＞0.05），而12-24小时P＜0.05（t=-2.833，P=0.005），说明应用替罗非班后12-24小时，替罗非班对血小板计数的变化产生了影响。考虑到替罗非班对血小板计数的影响可能存在药物浓度依赖性，将实验组中超过24小时亚组的数据与对照组重新进行分析。结果仍显示与2小时血小板计数基线相比，6小时、9小时、12小时与24小时的血小板计数均无显著差异，而在2-9小时内实验亚组与对照组的血小板计数变化情况均有降低趋势，9-24小时实验亚组血小板计数变化情况有所回升，对照组无明显变化和有所升高。实验亚组与对照组在6-9小时的血小板计数变化情况P＜0.1，在9-12小时和12-24小时的血小板计数变化情况P＜0.05，有统计学差异。结论: 1.替罗非班可致血小板减少症，但概率较低。 2.替罗非班可导致用药早期（6-9小时）血小板计数降低幅度增大、用药后期（12-24小时）血小板计数回升幅度减小。 3.血小板数量改变多发生于应用替罗非班早期（2-9小时）。 4.应用替罗非班时酌情减慢给药速度可以降低出血风险。 5.应用替罗非班后会影响血小板计数的变化幅度，血小板计数降低幅度增大可能与出血风险相关，血小板计数是预测应用替罗非班出血风险的有效指标之一。
[Abstract]:Background and purpose: Antithrombotic therapy is the main factor in the treatment of acute coronary syndrome (ACS) The tirofiban hydrochloride is a reversible non-peptide platelet membrane glycoprotein GP IIb/ IIIa receptor antagonist, which can act on the last path of platelet aggregation, and has obvious anti-thrombus effect. The role of platelet membrane glycoprotein GPIIb/ IIIa receptor antagonists, such as tirofiban and the like, is sometimes found to be in the case of thrombocytopenia, and even thrombocytopenia, which greatly increases the bleeding The purpose of this study is to study the occurrence of thrombocytopenia and bleeding events after the non-shift of tiltropine, and to explore the influencing factors. Reference. The method comprises the following steps of: The study was a prospective study. From May 2014 to January 2015, patients who were hospitalized for coronary heart disease in the Department of Cardiology of the Sino-Japanese Liyi Hospital of Jilin University were selected to be randomly divided according to the ratio of 2: 1 after the inclusion criteria and the exclusion criteria were selected. The experimental group and the control group were used, and the treatment group was used in the treatment group for more than 24 hours. The patient was classified as an experimental subgroup. A total of 140 patients were included in the study, of which male 8 5, 55 women. The patients enrolled in the group were routinely given aspirin, chlorhexidine (or tegregrow), and heparin. The experimental group was given a non-shift treatment according to the weight of the patient according to the instructions for the non-shift of the patient; the control group did not Non-class treatment was given for tilo. Individual basic information for all enrolled patients was recorded, including medical record number, name, sex, age, height, body weight, etc., and whether the patient was using low molecular weight heparin (type and dose), chlorine, The experimental group and the control group were respectively subjected to routine blood collection and blood collection for 24h, 6h, 9h, 12h, and 24h, respectively, and recorded the patients in the experimental group and the control group. Whether the bleeding event occurred. The definition of thrombocytopenia: the platelet baseline was normal (100-300/ 109/ L) or higher than 300-109/ L, and the following conditions occurred in 24h after the application of tetropine: platelet count <100-109/ L It is defined as thrombocytopenia. The index is as follows: the platelet count is determined to be mild thrombocytopenia in the range of 50-100-109/ L; the platelet count is determined to be severe thrombocytopenia at 20-50-109/ L; if the platelet count is less than 20-109/ L, it is determined that the platelet count is extremely low Severe thrombocytopenia. Bleeding event: The experimental group was treated with terotherapy for gingival bleeding, bleeding or hematomas, Conjunctival congestion, hematuria, etc. In the control group, bleeding, bleeding, or hematomas, Conjunctival congestion, hematuria, etc. The final experimental data was by means of SPSS13. 0 Data analysis is performed on the software. After the measurement data is tested in positive state, if the normal distribution is met, it is expressed as the average standard deviation (x/ s). If the variance is equal, the t-test is further adopted; if the variance is not the same, the variance is equal to one. Step is non-normal test. If the measurement data does not meet the normal distribution, it is expressed as the median Statistical analysis of counting data: the qualitative data is expressed in number (percentage), and the inter-group counting data is used by the party The difference analysis and the card-side test. If P <0.05, it is determined that statistics Results: In the experimental group (N = 84), the number of cases of thrombocytopenia was 2 (2.35%). There was a severe and very severe thrombocytopenia. The time for thrombocytopenia was 2-9 hours and 6-12 hours after the application of tetropine, and the lowest time point for the detected platelet count was 6 hours after the non-shift in the application (95% 1, respectively). 09/ L and 87 (109/ L), one of the two thrombocytopenia patients showed mild teeth There was no significant difference in the platelet count between the experimental group and the control group, 6 hours, 9 hours, 12 hours and 24 hours compared with the 2-hour platelet count baseline (P> 0.05), while 12-24 h p <0.05 (t =-2.833, p = 0. 005), for 12-24 hours after the application of tiropin, for example, The effect of non-shift on platelet count has been affected. In consideration of the potential for drug concentration dependence on the effects of tetroban on platelet count, more than 24 in the experimental group The data of the hour sub-group was re-analyzed with the control group. The results still showed no significant difference in platelet counts for 6 hours, 9 hours, 12 hours, and 24 hours compared to the 2-hour platelet count baseline, whereas in the 2-9-hour test sub-group and the control There was a tendency to decrease the platelet count in the group, and the changes of platelet count in the subgroup at 9-24 h were observed. The platelet count in the experimental subgroup and the control group at 6-9 hours was significantly higher than that in the control group (P <0.01), and the platelet count in 9-12 hours and 12-24 hours change There was a statistical difference between P <0.05 and P <0.05. Conclusion: 1. The titilin non-class can cause thrombocytopenia, but the probability is low. 2. tetroban may lead to an early (6-9 hour) decrease in platelet count by an increase in platelet count The platelet count recovered in the later period (12-24 hours) was decreased. 3. The change in the number of platelets occurs more than in the early (2-9) phase of the application (h). 4. The administration speed can be slowed down as appropriate when applied to the roo non-class, and the risk of bleeding can be reduced. 5. The change in the platelet count will be affected after the application of the tetroban, and the decrease in platelet count is increased.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R541.4

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