Martinuzzo Marta E, Duboscq Cristina, Viñuales Estela S, Girardi Beatriz, Penchasky Diana, Ceresetto José, Stemmelin Germán, Otero Victoria, Barrera Luis H, López Marina S, Otaso Juan C, Hoyhamburu José
Grupo Bioquímico, Laboratorio Central, Hospital Italiano de Buenos Aires, Argentina. E-mail:
Instituto Universitario Hospital Italiano, Buenos Aires, Argentina. E-mail:
Medicina (B Aires). 2017;77(1):31-36.
Dabigatran etexilate (direct thrombin inhibitor) is effective in preventing embolic stroke in patients with atrial fibrillation. It does not require laboratory control, but given the high renal elimination, its measurement in plasma is important in renal failure. The objectives of the study were to verify the analytical quality of the diluted thrombin time assay for measurement of dabigatran plasma concentration (cc), correlate cc with classic coagulation assays, prothrombin time (PT) and activated partial thromboplastin time (APTT), and evaluate them according to the creatinine clearance (CLCr). Forty plasma samples of patients (34 consecutive and 6 suspected of drug accumulation) receiving dabigatran at 150 (n = 19) or 110 (n = 21) mg/12 hours were collected. Blood samples were drawn at 10-14 hours of the last intake. Dabigatran concentration was determined by diluted thrombin time (HemosIl DTI, Instrumentation Laboratory (IL). PT and APTT (IL) were performed on two fotooptical coagulometers, ACL TOP 300 and 500 (IL). DTI presented intra-assay coefficient of variation < 5.4% and inter-assay < 6%, linearity range 0-493 ng/ml. Patients' cc: median 83 (4-945) ng/ml. Individuals with CLCr in the lowest tertile (22.6-46.1 ml/min) showed significantly higher median cc: 308 (49-945), compared to the average 72 (12-190) and highest tertile, 60 (4-118) ng/ml. Correlation between cc and APTT or PT were moderate, r2 = 0.59 and -0.66, p < 0.0001, respectively. DTI test allowed us to quantify plasma dabigatran levels, both in patients with normal or altered renal function, representing a useful tool in clinical situations such as renal failure, pre surgery or emergencies.
达比加群酯（直接凝血酶抑制剂）在预防心房颤动患者的栓塞性卒中方面有效。它无需实验室监测，但鉴于其经肾脏大量清除，在肾衰竭患者中测定其血浆浓度很重要。本研究的目的是验证用于测定达比加群血浆浓度（cc）的稀释凝血酶时间测定法的分析质量，将cc与经典凝血试验、凝血酶原时间（PT）和活化部分凝血活酶时间（APTT）进行关联，并根据肌酐清除率（CLCr）对它们进行评估。收集了40例接受150（n = 19）或110（n = 21）mg/12小时达比加群治疗的患者的血浆样本（34例连续样本和6例疑似药物蓄积患者）。在最后一次服药10 - 14小时采集血样。通过稀释凝血酶时间（HemosIl DTI，仪器实验室（IL））测定达比加群浓度。PT和APTT（IL）在两台光学凝血仪ACL TOP 300和500（IL）上进行检测。DTI的批内变异系数<5.4%，批间变异系数<6%，线性范围为0 - 493 ng/ml。患者的cc：中位数为83（4 - 945）ng/ml。CLCr处于最低三分位数（22.6 - 46.1 ml/min）的个体的cc中位数显著更高：308（49 - 945），而平均水平为72（12 - 190），最高三分位数为60（4 - 118）ng/ml。cc与APTT或PT之间的相关性为中等，r2分别为0.59和 - 0.66，p < 0.0001。DTI检测使我们能够对肾功能正常或异常的患者的血浆达比加群水平进行定量，是肾衰竭、术前或紧急情况等临床情况下的有用工具。
