活性炭逆转利伐沙班对凝血试验干扰的效果评价

目的 评价活性炭逆转利伐沙班对凝血试验干扰的效果。方法 取体检人群临床常规凝血项目检测后的枸橼酸钠抗凝血样本，每次方便抽取20例，重复24次，共纳入480例。将20例血浆样本混合配置成正常混合血浆（NPP），取1 mL NPP为N1组；NPP经活性炭处理后为N2组；NPP加入不同质量浓度的利伐沙班为N3组：100 μg/L（N3A组）、200 μg/L（N3B组）、300 μg/L（N3C组）、400 μg/L（N3D组），每个质量浓度重复6次；N3组经活性炭处理后为N4组。收集急诊科首次使用利伐沙班治疗的患者22例，首次服用利伐沙班前6 h和后6 h采集血样分别为S1组和S2组，S2组经活性炭处理后为S3组。液相色谱-联用串联质谱测定N3组和S2组的利伐沙班质量浓度。检测N1、N2、N3、N4组凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）及纤维蛋白原（FIB）水平，蛋白C（PC）、蛋白S（PS）、抗凝血酶Ⅲ（AT-Ⅲ）以及凝血因子FⅡ、FⅤ、FⅦ、FⅧ、FⅨ、FⅩ、FⅪ、FⅫ活性和N1、N2、N3、N4、S1、S2和S3组抗Xa因子（Anti-Xa）活性。结果 与N1组比较，N2组PT、APTT、INR、FIB、PC、PS、AT-Ⅲ、Anti-Xa、FⅡ、FⅤ、FⅦ、FⅧ、FⅨ、FⅩ、FⅪ、FⅫ活性差异无统计学意义；N3组PT、APTT延长，INR水平，PS、AT-Ⅲ和Anti-Xa活性升高，FⅡ、FⅤ、FⅦ、FⅧ、FⅨ、FⅩ、FⅪ、FⅫ活性降低（P<0.01），PC活性及FIB水平差异无统计学意义；N4组APTT延长，PS、FⅤ、FⅧ、FⅪ、FⅫ活性降低（P<0.01）。与N3组比较，N4组PT、APTT缩短，INR水平，PS、AT-Ⅲ和Anti-Xa活性明显降低，FⅡ、FⅤ、FⅦ、FⅧ、FⅨ、FⅩ、FⅪ、FⅫ活性升高（P<0.01），FIB水平和PC活性差异无统计学意义。与S1组比较，S2组Anti-Xa活性升高，APTT延长；S3组APTT延长（P<0.01）；与S2组比较，S3组Anti-Xa活性降低，APTT缩短。N3A、N3B、N3C和N3D组PT、INR、APTT、PS水平及Anti-Xa活性逐次升高，FⅤ、FⅦ、FⅧ、FⅨ、FⅪ活性逐次降低（P<0.01）；N3组、S2组利伐沙班质量浓度与Anti-Xa活性呈正相关（r_s分别为0.989、0.969，P<0.01）。结论 活性炭能有效去除血浆中的利伐沙班，可以逆转由利伐沙班引起的异常凝血指标。

Evaluation of the effect of activated carbon on reversing the interference of rivaroxaban on coagulation experiment

Objective To study the effect of activated charcoal treatment of rivaroxaban on the results of coagulation tests. Methods The sodium citrate anticoagulant blood samples were collected from the physical examination population after the detection of clinical routine coagulation items. Twenty cases were conveniently taken each time, repeated 24 times, and a total of 480 cases were included. Twenty plasma samples were mixed and configured as normal mixed plasma (NPP), and 1 mL NPP was set as the N1 group. NPP treated with activated carbon was used as the N2 group. NPP added with different mass concentrations of rivaroxaban was used as the N3 group, including 100 μg/L (the N3A group), 200 μg/L (the N3B group), 300 μg/L (the N3C group) and 400 μg/L (the N3D group). Each mass concentration was repeated 6 times. The N3 group was used as the N4 group after treatment with activated carbon. A total of 22 patients in the emergency department who were treated with rivaroxaban for the first time were collected. Blood samples collected 6 h before and 6 h after rivaroxaban were divided into the S1 group and the S2 group, respectively. After treatment with activated carbon, S2 group was used as the S3 group. The mass concentrations of rivaroxaban in the N3 group and the S2 group were determined by liquid chromatography-tandem mass spectrometry. The levels of prothrombin time (PT), activated partial thrombin time (APTT), thrombin time (TT) and fibrinogen (FIB) in the N1 group, the N2 group, the N3 group and the N4 group were detected. The activities of protein C (PC), protein S (PS), antithrombin Ⅲ (AT-Ⅲ) and coagulation factors FⅡ, FⅤ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ and FⅫ and the activities of anti-Xa factor (Anti-Xa) in the N1 group, the N2 group, the N3 group, the N4 group, the S1 group, the S2 group and the S3 group were also detected in each group. Results Compared with the N1 group, there were no significant differences in PT, APTT, INR, FIB, PC, PS, AT-Ⅲ, Anti-Xa, FⅡ, FⅤ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ and FⅫ activity in the N2 group. In the N3 group, PT and APTT were prolonged, INR levels were increased, PS, AT-Ⅲ and Anti-Xa activities were increased, and FⅡ, FⅤ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ and FⅫ activities were decreased (P<0.01). There were no significant differences in PC activity and FIB level. APTT was prolonged in the N4 group, while PS, FⅤ, FⅧ, FⅪ and FⅫ activities decreased (P<0.01). Compared with the N3 group, PT and APTT decreased, INR level, PS, AT-Ⅲ and Anti-Xa activity decreased significantly, FⅡ, FⅤ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ and FⅫ activities increased in the N4 group (P<0.01). There were no significant differences in FIB level and PC activity between the N3 group and the N4 group. Compared with the S1 group, Anti-Xa activity was increased and APTT was prolonged in the S2 group. APTT was prolonged in the S3 group (P<0.01). Compared with the S2 group, Anti-Xa activity was decreased and APTT was shortened in the S3 group. The levels of PT, INR, APTT and PS, and the activity of Anti-Xa were successively increased in the N3A group, the N3B group, the N3C group and the N3D group, while the activities of FⅤ, FⅦ, FⅧ, FⅨ and FⅪ were successively decreased (P<0.01). There was a positive correlation between rivaroxaban mass concentration and Anti-Xa activity in the N3 group and the S2 group (r_s = 0.989, 0.969, P<0.01). Conclusion Activated carbon can effectively remove rivaroxaban from plasma and reverse the abnormal coagulation index caused by rivaroxaban.