阿加曲班预防儿童亲属活体肝移植术后早期血栓并发症

Clinical study of argatroban for preventing vascular thrombosis in the early period after pediatric living related liver transplantation

目的比较并分析肝素与阿加曲班对儿童亲属活体肝移植术后凝血功能的影响及预防术后血栓并发症的效果。方法收集2013年9月至2014年11月间接受亲属活体肝移植的先天性胆道闭锁患儿84例，根据随机原则将84例儿童受者分为肝素组和阿加曲班组（入组比例3：1），其中肝素组63例，阿加曲班组21例。肝素组受者术后应用肝素抗凝血治疗，阿加曲班组受者术后应用阿加曲班抗凝血治疗。检测并分析两组受者术后1～5d抗凝血酶Ⅲ（AT-Ⅲ）活性、活化部分凝血活酶时间（APlvr）及国际标准化比（INR）的变化情况。同时每天行腹部彩色多普勒检查了解移植肝形态、回声及肝动脉、肝静脉、门静脉血流情况，以判定有无移植肝血管内血栓形成。结果两组受者在性别（x^2=0．016，P=0．900）、年龄（t=0．066，P=0．948）、体质量（t=0．035，P=0．972）、移植物质量与受者体重量比（t=0．769，P=0．444）及是否接受过Kasai手术（x2=0．800，P=0．371）等指标的差异均无统计学意义。两组受者术后第1天AT-Ⅲ活性较低，随时间延长逐渐升高，两组间差异无统计学意义（P〉0．05）。术后即刻及术后第1天，两组受者间APTT和INR的差异均无统计学意义（P〉0．05），经相应抗凝血治疗后，术后2～5d两组受者间APTT和INR的差异均有统计学意义（P〈0．05）。肝素组术后早期血栓并发症发生率为4．76％，阿加曲班组为0，两组差异无统计学意义（P〉0．05）。两组受者在术后早期抗凝血治疗期间均未出现活动性出血及过敏等严重不良反应。结论阿加曲班作为不依赖AT-Ⅲ活性的直接抗凝血药物在预防儿童肝移植术后早期血栓并发症中效果良好。

Objective To evaluate the effect of heparin and argatroban on the coagulating function and the vascular thrombosis in the early period after pediatric living related liver transplantation （LRLT）. Method Eighty-four congenital biliary atresia pediatric patients who had performed LRLT were involved in this study. According to the method of anticoagulation, the patients were divided into two groups （heparin group and argatroban group）. Antithrombin III （AT-III） activity, activated partial thromboplastin time （APTT） and international normalized ratio （INR） of two groups were measured in the first 5 days after LRLT. In order to determine whether vascular thrombosis existed, Doppler ultrasound was performed daily. Result There were no significant differences in gender, age, body weight, graft-recipient weight ratio and whether to accept Kassi procedure between two groups. The AT-III activity of two groups was low and increased gradually after operation. There was no significant difference between two groups. There were no significant differences in APTT and INR between two groups immediate and at first day after operation. After anticoagulation, the differences in APTT and INR between two groups were significant. The incidence of vascular thrombosis was 4. 76% （3/63） and 0（0/21） respectively in heparin and argatroban groups. There was no significant difference between two groups. During treatment, there were no severe complications in two groups, such as active hemorrhage and allergy. Conclusion Argatrohan is a direct anticoagulant. It is independent on the level of AT-III activity. It may play an important role for preventing vascular thrombosis after pediatric LRLT.