Marco P, Tarín F, Lucas J
Sección de Hemostasia y Trombosis, Servicio de Hematología y Hemoterapia, Universidad Miguel Hernández, Hospital General Universitario, Alicante, España.
Med Clin (Barc). 2008 Nov;131 Suppl 2:66-9. doi: 10.1016/s0025-7753(08)76452-2.
The search for the ideal anticoagulant has been one of the most active research fields in medicine in the past few years. Anti-vitamin K replacement, particularly in the long term treatment of venous thromboembolism is a difficult objective to achieve due to the wide experience gathered in normal practice and low costs. But to improve the weak points of these drugs is an attractive challenge and would have a great health and social impact. It can be seen that the low molecular weight heparins, or even pentasaccharide, drugs that are already available on the market, although the have very predictable pharmacokinetics, their parenteral use, or their long half life, they are far from being ideal anticoagulants. Ximelagatran, a promising drug, a direct inhibitor of thrombin seemed to be a step forward, but the appearance of undesirable side effects led to its withdrawal. However, this line of investigation has remained open, as such that we now have data from clinical trials that back it up: the direct inhibition of thrombin and activated factor X. These two different mechanisms of action are showing promising results, in that the direct inhibitors of thrombin (dabigatran, hirudins...) are showing not to be inferior in efficacy and safety to enoxaparin in the primary prophylaxis of venous thromboembolism. Similarly, the activated factor X inhibitors (Rivaroxaban, Apixaban ) are also showing the same and in some cases, superior in its prevention. This review looks at the mechanisms of action of both pharmacological groups, their effects on haemostasis, and how they are reflected in coagulation times, their pharmacokinetics and pharmacodynamics. These new anticoagulants are nearer to the ideal anticoagulant and may, in the near future, change the panorama of anticoagulation, not only at health level, but also by achieving improved levels in the quality of life of the patients.
在过去几年中，寻找理想的抗凝剂一直是医学领域最活跃的研究方向之一。抗维生素K替代疗法，尤其是在静脉血栓栓塞的长期治疗中，由于在常规实践中积累的丰富经验和低成本，是一个难以实现的目标。但是，改善这些药物的弱点是一项具有吸引力的挑战，并且将对健康和社会产生重大影响。可以看出，低分子量肝素，甚至是五糖，这些市场上已有的药物，尽管它们具有非常可预测的药代动力学、肠胃外给药方式或较长的半衰期，但它们远非理想的抗凝剂。希美加群，一种有前景的药物，凝血酶直接抑制剂，似乎是向前迈进了一步，但不良副作用的出现导致其撤市。然而，这一研究方向仍然开放，以至于我们现在有临床试验数据支持：凝血酶和活化因子X的直接抑制。这两种不同的作用机制显示出有希望的结果，即凝血酶直接抑制剂（达比加群、水蛭素等）在静脉血栓栓塞的一级预防中显示出在疗效和安全性上不劣于依诺肝素。同样，活化因子X抑制剂（利伐沙班、阿哌沙班）也显示出相同的效果，在某些情况下，在预防方面更具优势。这篇综述探讨了这两类药物的作用机制、它们对止血的影响，以及它们如何反映在凝血时间、药代动力学和药效学上。这些新型抗凝剂更接近理想的抗凝剂，并且在不久的将来，可能会改变抗凝的局面，不仅在健康层面，而且通过提高患者的生活质量来实现。
