Krishnaswamy Amar, Lincoff A Michael, Cannon Christopher P
Division of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.
Crit Pathw Cardiol. 2010 Mar;9(1):35-40. doi: 10.1097/HPC.0b013e3181d29713.
Despite the development of newer anticoagulants, unfractionated heparin remains an indispensible agent in the treatment of thrombotic disorders. Heparin exerts its major effect via antithrombin, converting antithrombin to a more efficient inhibitor of circulating thrombin (factor IIa), factor Xa, factor IXa, factor XIIa, and kallikrein. However, due to the multiple anticoagulant mechanisms of heparin, differential molecular weight-based clearance, issues of heparin resistance, and patient-specific characteristics (age, weight, gender, and tobacco), attaining therapeutic anticoagulation is complicated. As a result, a minority of patients in major clinical trials achieve an activated partial thromboplastin time within the target window in an appropriate time-frame despite the use of weight-based titration nomograms. The resultant under- or over-therapeutic anticoagulation is associated with increased risks of ischemic and bleeding complications, suggesting the importance of maintaining heparin anticoagulation within a relatively narrow therapeutic range. In this review we discuss the mechanisms of heparin action, clinical ramifications of incorrect dosing in major trials, and attempts to improve the achievement of therapeutic anticoagulation.
尽管新型抗凝剂不断发展，但普通肝素在血栓性疾病的治疗中仍然是不可或缺的药物。肝素主要通过抗凝血酶发挥作用，将抗凝血酶转化为循环凝血酶（因子IIa）、因子Xa、因子IXa、因子XIIa和激肽释放酶更有效的抑制剂。然而，由于肝素的多种抗凝机制、基于分子量的不同清除率、肝素抵抗问题以及患者的个体特征（年龄、体重、性别和吸烟情况），实现治疗性抗凝变得复杂。因此，尽管使用了基于体重的滴定量表，但在主要临床试验中，仍有少数患者在适当的时间范围内使活化部分凝血活酶时间达到目标范围。由此导致的抗凝不足或过量与缺血性和出血性并发症风险增加相关，这表明在相对狭窄的治疗范围内维持肝素抗凝的重要性。在本综述中，我们讨论了肝素的作用机制、主要试验中剂量不当的临床后果，以及为改善实现治疗性抗凝所做的尝试。
