Görög P, Ridler C D, Kovacs I B
Department of Haematology, St. Bartholomew's Hospital, London, UK.
J Intern Med. 1990 Feb;227(2):125-32. doi: 10.1111/j.1365-2796.1990.tb00130.x.
Two in vitro models of coronary thrombolysis in man, i.e. dislodgement of thrombi formed from non-anticoagulated human blood, either by (i) shear-stress or (ii) interaction of platelets with type I collagen fibre, were studied. Heparinization (1 U/ml) of blood prior to thrombus formation by (i) strongly inhibited spontaneous dislodgement (P less than 0.0001). Heparin (1 U/ml), when added with streptokinase (SK) or tissue-type plasminogen activator (rt-PA) prior to thrombus formation, considerably delayed thrombolysis. Furthermore, thrombolysis occurred much earlier when thrombi were perfused with SK or rt-PA in native than in heparinized blood. Heparin inhibited binding of 125I-rt-PA (17%, P less than 0.02) and plasminogen (88%, P less than 0.0005) to platelets activated by ADP in citrated platelet-rich plasma. We conclude that heparin interferes with the fibrinolytic system at the surface of activated platelets. Our findings suggest that heparin administration prior to thrombolytic therapy for acute myocardial infarction should be questioned.
研究了两种人体冠状动脉溶栓的体外模型，即通过（i）剪切应力或（ii）血小板与I型胶原纤维的相互作用使由未抗凝人体血液形成的血栓脱落。在通过（i）形成血栓之前对血液进行肝素化（1 U/ml）可强烈抑制自发脱落（P<0.0001）。在形成血栓之前将肝素（1 U/ml）与链激酶（SK）或组织型纤溶酶原激活剂（rt-PA）一起添加时，会大大延迟溶栓。此外，当用SK或rt-PA灌注天然血液中的血栓时，溶栓发生的时间比肝素化血液中的血栓要早得多。肝素抑制125I-rt-PA（17%，P<0.02）和纤溶酶原（88%，P<0.0005）与枸橼酸化富血小板血浆中由ADP激活的血小板的结合。我们得出结论，肝素在活化血小板表面干扰纤维蛋白溶解系统。我们的研究结果表明，在急性心肌梗死溶栓治疗之前给予肝素值得质疑。
