不同抗凝剂对血液透析过程凝血状态的影响

Influence of different anticoagulants on coagulation state in hemodialysis

目的探讨血液透析（HD）中不同抗凝剂的特点和合理选择。方法选取HD患者21例，分为普通肝素（UFH）组，10例，首剂3000U，追加1000U／h，下机前1h停止追加；达肝素钠组，11例，达肝素钠5000U透前30min静脉注射。另选取伴有出血倾向的HD患者10例，作为阿加曲班组，首剂8mg，追加6～8mg／h，总剂量1．5μg·kg^-1·min^-1，下机前20min停止追加。同时选取8例健康人为对照。在上机前管路动脉端、HD2h管路动、静脉端及下机前管路动脉端采血。应用Sonoclot分析仪测定前玻璃珠激活的凝血时间（gbACT）、凝血速率（CR）及血小板功能（PF）；酶联免疫法测定前凝血酶原片段1＋2（PF1＋2）及血小板表面仪颗粒膜蛋白（GMP-140）。健康对照组采血1次测定上述指标。结果（1）与健康对照组比较，全部患者上机前CR、PF1＋2和PF、GMP-140均显著增高（P〈0．05）。（2）UFH组：与透析前比较，HD管路2h动、静脉端及下机前的gbACT显著延长（P〈0．05），CR、PF和PF1＋2均显著减少（P〈0．05）；与健康对照组比较，下机前gbACT显著延长（P〈0．05），CR显著减少（P〈0．05）。（3）达肝素钠组：与透析前比较，HD管路2h动脉端的gbACT显著延长（P〈0．05），HD管路2h的动、静脉端的CR和PF1＋2均显著减少（P〈0．05），下机前CR仍减少（P〈0．05），但PF1＋2差异无统计学意义。2h管路动脉端gbACT延长与CR减少值大于静脉端；与健康对照组比较，下机前gbACT延长（P〈0．05），但CR差异无统计学意义。（4）阿加曲班组：与透析前比较，上机后的gbACT均无明显变化；管路2h的动、静脉端的CR均显著减少（P〈0．05），而以静脉端更明显；2h管路动脉端的CR与健康对照组相比，差异无统计学意义；下机前的CR大于对照组（P〈0．05）；在监测过程中PF1＋2呈上升趋势。结论UFH具有较强的抗凝血作用，HD过程中和结束后均有较大出血风险。达肝素钠具有良好的抗凝作用，但HD过程中有出血风险。阿加曲班适用于有出血或出血倾向的HD患者。

Objective To investigate the characteristics and proper use of anticoagulants in hemodialysis （HD）. Methods Thirty-one HD patients were enrolled in the study. Unfractionated heparins （UFH）, daheparin sodium or argatroban were used for HD anticoagulation respectively. Blood specimens were taken from the arterial line at the beginning （0 h） and at the end of HD （4 h）, and from the arterial （2a） and the venous （2v） line respectively at 2 h of the HD session. Glass bead activated clotting time （gbACT）, clot rate （CR） and platelet function （PF） were examined by Sonoclot analyzer. Prothrombin fragment 1＋2 （PF1＋2） and granule membrane protein- 140 （GMP-140） were assayed by ELISA. Meanwhile, blood was taken from 8 healthy volunteers to examine the above parameters as control. Results （1） Compared with the control group, CR,PF1＋2, PF, GMP-140 were increased significantly in all the patients （P〈0.05）. （2） UFH group： Compared with the 0 h point, gbACT of other time points increased significantly （P〈0.05）, CR, PF, and PF1＋2 decreased significantly （P〈0.05）. Compared with the control group, gbACT increased （P〈0.05） and CR decreased （P〈0.05） significantly at the end of the sessions. （3） Daheparin sodium group： Compared with the 0 h point, gbACT of 2a point increased significantly （P〈O.05）, CR and PF1＋2 of 2a, 2v and 4 h points decreased significantly （P〈O.05）, meanwhile, the extents of increased gbACT and decreased CR from the arterial line were greater than those from the venous line. Compared with the control group, gbACT increased significantly at the end of HD session （P〈0.05）, but CR was not significantly different. （4） Argatroban group： There were no significant differences of gbACT between 0 h and other time points. CR of 2a, 2v points decreased obviously than that of 0 h point, and CR of 2v decreased more significantly. CR of 2a point was not different from the control group, while CR of 4 h point was greater as compared to control group. During the monitoring, PF1 ＋2 tended to increase. Conclusions With intensive anticoagulant effect, UFH may induce the risk of hemorrhage not only during but also after the dialysis sessions. Dalteparin sodium, a good anticoagulant, is still related with the risk of hemorrhage during HD. Argatroban is an ideal anticoagulant for patients with the risk of hemorrhage.