Weitz J I
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Thromb Haemost. 1996 Apr;75(4):529-35.
There is good evidence that thrombolytic therapy induces a procoagulant state that retards the lytic process and triggers reocclusion. Thus, both in experimental animal systems and in humans, potent inhibitors of platelets and antithrombin III-independent thrombin inhibitors have been shown to be better than heparin at accelerating thrombolysis and preventing reocclusion. These in vivo observations have lent credence to the concept that elevated FPA levels that are suppressed by heparin reflect systemic activation of coagulation during the thrombolytic process. However, this concept may not be correct. Thus, when heparin is given in conjunction with plasminogen activators only modest increases in FPA levels are found, and our data suggest that this is due, at least in part, to the activity of enzymes other than thrombin. In the absence of concomitant heparin, thrombolytic therapy causes a much greater increase in the FPA values. These high FPA values are rapidly reduced by heparin, even though heparin has limited antithrombotic activity in the setting of pharmacologic thrombolysis. Based on these considerations, we believe that plasma FPA and desarginine FPB levels should not be used as specific markers of thrombin activity during the course of thrombolytic therapy and suppression of elevated FPA values by heparin should not be accepted as evidence that heparin is effective in this clinical setting.
有充分证据表明，溶栓治疗会引发促凝状态，延缓溶解过程并引发再闭塞。因此，在实验动物系统和人类中，血小板强效抑制剂和非抗凝血酶III依赖性凝血酶抑制剂在加速溶栓和预防再闭塞方面已被证明比肝素更有效。这些体内观察结果支持了这样一种概念，即被肝素抑制的FPA水平升高反映了溶栓过程中凝血的全身激活。然而，这个概念可能并不正确。因此，当肝素与纤溶酶原激活剂联合使用时，仅发现FPA水平有适度升高，并且我们的数据表明，这至少部分归因于凝血酶以外的酶的活性。在没有同时使用肝素的情况下，溶栓治疗会使FPA值有更大的升高。即使肝素在药理溶栓的情况下抗血栓活性有限，但这些高FPA值会被肝素迅速降低。基于这些考虑，我们认为血浆FPA和去精氨酸FPB水平不应用作溶栓治疗过程中凝血酶活性的特异性标志物，并且肝素抑制升高的FPA值不应被视为肝素在这种临床环境中有效的证据。
