重组组织型纤溶酶原激活剂治疗妊娠合并肺栓塞有效性与安全性的文献病例分析

Literature review of the safety and efficacy of recombinant tissue-type plasminogen activator in the pulmonary embolism patients with pregnancy

目的了解重组组织型纤溶酶原激活剂（rtPA）治疗妊娠合并肺栓塞的有效性与安全性。方法检索有关数据库，收集应用rtPA治疗妊娠合并肺栓塞的文献，记录患者基本情况、溶栓治疗情况（rtPA品种、剂量、用法和溶栓结局）、不良反应发生情况和妊娠结局，并进行描述性统计分析。结果共纳入16篇病例报告（英文15篇，中文1篇）。所报道的16例患者年龄21～40岁，平均（32±6）岁；妊娠早期6例（37.5%），中期4例（25.0%），晚期6例（37.5%）。临床表现包括休克（11例）、胸痛（8例）、气短（8例）、晕厥（2例），血压67～122/40～87 mmHg，心率106～158次/min，血氧饱和度79%～96%。经心脏彩色多普勒超声检查（13例）、肺通气灌注扫描（6例）和螺旋CT肺动脉造影（2例）确诊为急性肺栓塞。溶栓治疗应用阿替普酶者15例，14例用药剂量为41～100 mg，用药时间2.0～4.5 h，1例无记录；使用孟替普酶者1例，用药剂量为160万U，用药时间2 h，给药途径均为静脉注射。溶栓治疗14 d后，1例患者死于复发性肺栓塞，其余患者肺栓塞临床症状均消失。16例患者中4例（25.0%）在溶栓治疗后发生出血，其中生产时阴道大出血2例（12.5%），出血量分别为8 900和2 238 ml，输血治疗后血止；穿刺部位出血及鼻出血各1例，局部压迫48 h后血止。妊娠结局：16例中娩出活胎者13例，其中早产、胎盘早剥者各1例；妊娠早期自愿引产者2例；妊娠28周因胎死宫内流产者1例。13例活产儿中1例在出生后14 d因急性呼吸窘迫综合征死亡。结论妊娠合并肺栓塞患者应用rtPA溶栓有效且较安全。

ObjectiveTo explore the safety and efficacy of recombinant tissue-type plasminogen activator （rtPA） and to do the literature case reviewMethods The related data-bases were searched. The literatures about treatment for pregnant women with pulmonary embolism by rtPA was collected. The patients′basic information, the situation of fibrinolytic therapy （including type, dosage, and usage of rtPA, and the outcomes of fibrinolytic therapy）, the occurrence of ADR, and the outcomes of pregnancy were recorded. A descriptive statistical analysis for the above-mentioned results was performed.ResultsReports involving 16 patients were enrolled into the study, 15 papers in English and 1 in Chinese. The average age of the 16 patients were （32±6） years （21-40 years）. The numbers of cases in early, interim, and late stage of pregnancy were 6 （37.5%）, 4 （25.0%） and 6 （37.5%）, respectively. The patient′clinical manifestations included shock （11 cases）, chest pain （8 cases）, dyspnea （8 cases）, syncope （2 cases）, with blood pressure 67-122/40-87mmHg, heart rate 106-158 beats/min, and oxyhemoglobin saturation 79%-96%. The number of patients who were diagnosed as acute pulmonary embolism by color doppler echocardiography, pulmonary ventilation and perfusion scan, and spiral CT pulmonary arteriography were 13, 6 and 2, respectively. Fifteen patients received ateplase for fibrinolytic therapy, among them 14 cases′dosages were 41-100 mg/2.0-4.5 hours, another patient had no record of dosage. One patient received monteplase for fibrinolytic therapy, the dosage was 1 600 000 U/2 hours. The route of administration was intravenous injection. After 14 days of fibrinolytic therapy, a patient died of recurrent pulmonary embolism. The other patients′all clinical manifestations disappeared. Four patients （25%） had bleeding after fibrinolytic therapy. Two of the 4 patients presented with vaginal bleeding during childbirth, the amount of bleeding were 8 900 ml and 2 238 ml, respectively. Their vaginal bleeding was stopped after the blood transfusion therapy. The other 2 of the 4 patients had bleeding at puncture site and nose, respectively. The bleeding was stopped after 48 hours by local compression. The outcome of pregnancy showed that 13 of the 16 pregnant woman delivered live births including one case of premature delivery and placental abruption. Two of the other three of the 16 pregnant women underwent voluntary induction of labor in early pregnancy and one had abortion due to dead fetus in uterus after 28 weeks of pregnancy. There was a live-born infant who died from acute respiratory distress syndrome on 14th day after birth in 13 live-born infants.ConclusionTreatment with rtPA for thrombolytic therapy is effective and relatively safe for the pregnant women with pulmonary embolism.