Klement P, Liao P, Hirsh J, Johnston M, Weitz J I
McMaster University and Hamilton Civic Hospitals Research Centre, Ontario, Canada.
J Lab Clin Med. 1998 Sep;132(3):181-5. doi: 10.1016/s0022-2143(98)90166-4.
This study was undertaken to determine the appropriateness of the current practice of using the activated partial thromboplastin time (APTT) to select hirudin doses. A rabbit bleeding ear model was used to compare the effects of various doses of heparin and hirudin on the relationship between the APTT and bleeding. In addition, the effects of these agents on the thrombin clotting time (TCT) and factor Xa clotting time also were examined. Both heparin and hirudin produced a concentration-dependent increase in bleeding. When bleeding was plotted as a function of APTT ratio, even a small increase in APTT ratio within the therapeutic range of 1.5 to 2.5 resulted in a marked increase in bleeding with hirudin but not with heparin. The TCT was more responsive than the APTT or factor Xa clotting time to increases in hirudin-induced bleeding. In this model, hirudin produces more bleeding than heparin when the agents are used in doses that increase the APTT ratio to the same extent. These studies highlight the pitfalls of extrapolating from experience with heparin when choosing a test to monitor new antithrombotics. Our findings also suggest that the TCT may be more responsive than the APTT for monitoring hirudin therapy.
本研究旨在确定目前使用活化部分凝血活酶时间（APTT）来选择水蛭素剂量的做法是否恰当。采用兔耳出血模型比较不同剂量肝素和水蛭素对APTT与出血之间关系的影响。此外，还研究了这些药物对凝血酶凝血时间（TCT）和因子Xa凝血时间的影响。肝素和水蛭素均产生浓度依赖性的出血增加。当将出血情况绘制为APTT比值的函数时，在1.5至2.5的治疗范围内，即使APTT比值有小幅增加，水蛭素导致的出血也会显著增加，而肝素则不会。TCT比APTT或因子Xa凝血时间对水蛭素诱导的出血增加更敏感。在该模型中，当以相同程度增加APTT比值使用药物时，水蛭素比肝素导致更多出血。这些研究突出了在选择监测新型抗血栓药物的检测方法时，从肝素经验进行推断所存在的缺陷。我们的研究结果还表明，TCT在监测水蛭素治疗方面可能比APTT更敏感。
