Montaruli Barbara, Erroi Laura, Vitale Corrado, Berutti Silvia, Cosseddu Domenico, Sivera Piera, Coglitore Raimondo, Marangella Martino, Migliardi Marco
aLaboratory Analysis Department bNephrology and Dialysis Department cHaematology Department dCardiovascular Intensive Care Unit, AO Ordine Mauriziano, Turin, Italy.
Blood Coagul Fibrinolysis. 2015 Mar;26(2):225-9. doi: 10.1097/MBC.0000000000000221.
Dabigatran is an oral direct inhibitor indicated for stroke prevention in patients with atrial fibrillation. Unlike warfarin, dabigatran's observed therapeutic window and minimal drug-to-drug interaction suggest that laboratory test and dose adjustments are not necessary; nevertheless, circumstances of excessive anticoagulation, decreased kidney function, and instances of significant bleeding and thrombosis require laboratory assessment. In order to gather experience in the management of global [activated partial thromboplastin time (APTT) and thrombin time (TT) with extended endpoint] and specific [ecarin chromogenic assay (ECA) and diluted thrombin time (dTT)] laboratory coagulation tests in patients receiving dabigatran with untoward effects, we describe a case in which hemodialysis was used in attempt to remove dabigatran in a patient with excessive anticoagulation, rectal bleeding, and severe anemia. Our experience confirmed that APTT is an unreliable method for the assessment of dabigatran in patients with acute complications because it was often normal in spite of the therapeutic drug plasma levels. Both ECA and dTT showed a linear correlation with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels. TT assay, which is highly sensitive to dabigatran, correlated well and linearly not only with low drug levels, but also, because of the introduction of the extended endpoint (400 s), with high concentrations of the drug, and demonstrated to be a simple and reliable alternative to ECA and dTT to assess dabigatran in patients with acute complications.
达比加群是一种口服直接抑制剂，用于预防心房颤动患者的中风。与华法林不同，达比加群观察到的治疗窗和最小的药物相互作用表明无需进行实验室检测和剂量调整；然而，在抗凝过度、肾功能下降以及出现严重出血和血栓形成的情况下需要进行实验室评估。为了积累在接受达比加群且出现不良影响的患者中进行全球[活化部分凝血活酶时间（APTT）和凝血酶时间（TT）并延长终点]和特定[蛇静脉酶发色底物法（ECA）和稀释凝血酶时间（dTT）]实验室凝血检测管理方面的经验，我们描述了一例使用血液透析试图清除抗凝过度、直肠出血和严重贫血患者体内达比加群的病例。我们的经验证实，APTT是评估急性并发症患者体内达比加群的不可靠方法，因为尽管治疗药物血浆水平存在，但APTT通常正常。ECA和dTT在很宽的范围内均与达比加群水平呈线性相关，并能识别治疗水平和超治疗水平。TT检测对达比加群高度敏感，不仅与低药物水平相关性良好且呈线性关系，而且由于引入了延长终点（400秒），与高浓度药物也呈线性关系，并且已证明是评估急性并发症患者体内达比加群的一种简单可靠的替代方法，可替代ECA和dTT。
