Hafner Gerd, Roser Markus, Nauck Matthias
Zentrum für Labormedizin und Mikrobiologie, Essen, Germany.
Semin Thromb Hemost. 2002 Oct;28(5):425-30. doi: 10.1055/s-2002-35282.
Direct thrombin inhibitors are available for prophylactic as well as therapeutic purposes. Application of hirudin in therapeutic doses has been shown to require drug monitoring. Currently, most experience is available for recombinant hirudin, but the principle aspects of drug monitoring are the same for all direct thrombin inhibitors. Most frequently, activated partial thromboplastin time (aPTT) and modifications of the activated clotting time (ACT) have been used for the monitoring of hirudin therapy. However, these methods are insensitive at plasma levels higher than 0.6 mg/L of hirudin, so that overdoses may be missed despite monitoring. Correlations between ecarin clotting time (ECT), enzyme immunoassays, and chromogenic substrate assays on one side and global tests on the other side are poor. Fully automated chromogenic substrate-based assays, also available as point-of-care tests (POCT), are more precise and sensitive and are not disturbed by interferents such as heparin and antithrombin. Good correlations can be observed between chromogenic assays and the ECT performed in plasma or whole blood samples. ECT can also be determined with POCT systems. Test characteristics such as imprecision and measuring range are comparable to those of the chromogenic assays. In conclusion, therapy with direct thrombin inhibitors should be monitored with chromogenic assays or ECT.
直接凝血酶抑制剂可用于预防和治疗目的。已证明以治疗剂量应用水蛭素需要进行药物监测。目前，重组水蛭素的经验最为丰富，但所有直接凝血酶抑制剂的药物监测主要方面是相同的。最常用的是活化部分凝血活酶时间（aPTT）和活化凝血时间（ACT）的改良方法来监测水蛭素治疗。然而，这些方法在水蛭素血浆水平高于0.6mg/L时不敏感，因此尽管进行了监测，仍可能漏诊过量用药情况。一方面，蛇静脉酶凝血时间（ECT）、酶免疫测定和发色底物测定与另一方面的整体试验之间的相关性较差。基于发色底物的全自动测定法，也可作为即时检验（POCT），更为精确和敏感，且不受肝素和抗凝血酶等干扰物的影响。在血浆或全血样本中进行的发色测定与ECT之间可观察到良好的相关性。ECT也可用POCT系统测定。诸如不精密度和测量范围等检测特性与发色测定法相当。总之，直接凝血酶抑制剂治疗应采用发色测定法或ECT进行监测。
