Maseri A, Andreotti F, Biasucci L M, Rebuzzi A G
Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Roma.
Cardiologia. 1994 Dec;39(12 Suppl 1):7-13.
Intracoronary thrombosis is fundamental in the pathogenesis of acute coronary syndromes, although the causes of thrombosis are still unclear. As thrombin generation is crucial for thrombus formation, the inhibition of thrombin is a primary aim to prevent the evolution of an initial repair process into a pathological thrombus. Thrombin inhibition can be achieved by several drugs. Heparin is the principal antithrombin drug currently used in acute syndromes; it acts mainly by binding to antithrombin III and increasing its inhibitory effect on thrombin and other coagulation factors. The heparin-antithrombin III complex, however, does not inhibit thrombus-bound thrombin; moreover, iv heparin requires frequent laboratory monitoring and dose adjustments. Despite these limitations, continuous infusion of i.v. heparin has been found to be effective in unstable angina and in myocardial infarction, especially when treated with accelerated rt-PA. New antithrombin drugs that selectively and directly inhibit thrombin are hirudin, its synthetic derivate hirulog, and argatroban. These drugs have several theoretical advantages over heparin: greater stability of the aPTT--with the need for less laboratory monitoring--and greater efficacy--associated mainly with its capacity to inhibit clot-bound thrombin. Clinical pilot studies seem to indicate a greater antithrombotic efficacy compared with heparin, but a greater number of hemorrhagic events in patients with acute myocardial infarction receiving thrombolysis. In conclusion, the use of heparin is certainly indicated in patients with unstable angina and persistent ischemia and in acute myocardial infarction treated with accelerated rt-PA. The use of new antithrombin drugs, although promising, requires further clinical evaluation.
冠状动脉内血栓形成是急性冠状动脉综合征发病机制的关键因素，尽管血栓形成的原因仍不明确。由于凝血酶的生成对于血栓形成至关重要，抑制凝血酶是防止初始修复过程演变为病理性血栓的主要目标。凝血酶抑制可通过多种药物实现。肝素是目前用于急性综合征的主要抗凝血酶药物；它主要通过与抗凝血酶III结合并增强其对凝血酶和其他凝血因子的抑制作用来发挥作用。然而，肝素 - 抗凝血酶III复合物并不能抑制与血栓结合的凝血酶；此外，静脉注射肝素需要频繁的实验室监测和剂量调整。尽管存在这些局限性，但已发现持续静脉输注肝素在不稳定型心绞痛和心肌梗死中有效，尤其是在接受加速rt - PA治疗时。选择性直接抑制凝血酶的新型抗凝血酶药物有水蛭素、其合成衍生物水蛭肽和阿加曲班。这些药物相对于肝素具有几个理论优势：活化部分凝血活酶时间（aPTT）更稳定，所需的实验室监测更少；疗效更高，主要与其抑制与凝块结合的凝血酶的能力有关。临床初步研究似乎表明与肝素相比具有更大的抗血栓形成疗效，但在接受溶栓治疗的急性心肌梗死患者中出血事件更多。总之，肝素的使用对于不稳定型心绞痛和持续性缺血患者以及接受加速rt - PA治疗的急性心肌梗死患者肯定是适用的。新型抗凝血酶药物的使用虽然前景广阔，但需要进一步的临床评估。
