Rapold H J, Grimaudo V, Declerck P J, Kruithof E K, Bachmann F
Department of Medicine, University Hospital of Lausanne, Switzerland.
Blood. 1991 Sep 15;78(6):1490-5.
Plasma levels of plasminogen activator inhibitor type-1 (PAI-1), beta-thromboglobulin (beta TG), and fibrinopeptide A (FPA) were followed over 24 hours in 30 patients treated with alteplase for acute myocardial infarction. Samples were taken at baseline (T Oh), after 90 minutes (under alteplase, no heparin, T 1.5h), after 120 minutes (under alteplase and heparin, T 2h), 30 minutes after thrombolytic therapy (T 3.5h), as well as 12 hours (T 12h) and 24 hours (T 24h) after baseline. PAI-1 antigen levels (55 +/- 9 ng/mL at T Oh, mean +/- SEM) decreased to 35 +/- 5 (T 1.5h) and 40 +/- 6 (T 2h) ng/mL under alteplase, before increasing to 84 +/- 22 (T 3.5h), 130 +/- 30 (T 12h), and 64 +/- 7 (T 24h) ng/mL after therapy, P less than .001. A high baseline PAI-1 activity (18 +/- 3 ng/mL) decreased to 2.0 +/- 0.4 (T 1.5h) and 1.7 +/- 0.2 (T 2h) under alteplase and increased to 32 +/- 5 (T 12h) and 19 +/- 3 (T 24h) ng/mL after therapy (P less than .0001). beta TG levels (339 +/- 105 ng/mL at T Oh) decreased to 203 +/- 48 (T 2h), 154 +/- 51 (T 3.5h), 187 +/- 40 (T 12h), and 142 +/- 32 (T 24h) ng/mL under heparin (P less than .01). FPA levels (34 +/- 9 ng/mL at T Oh) increased to 85 +/- 15 ng/mL under alteplase alone (T 1.5h) and normalized under heparin (11 +/- 4, 6 +/- 2, 4 +/- 2, and 3 +/- 1 ng/mL at T 2h, T 3.5h, T 12h, and T 24h, respectively). A high level of FPA at T 3.5h correlated with reocclusion (33 +/- 12 ng/mL, n = 4 v 2.9 +/- 0.5 ng/mL, n = 21, P less than .005). We conclude that plasma levels of PAI-1 antigen as well as activity markedly increase after alteplase therapy of acute myocardial infarction. The high activity of PAI-1 and decreasing beta TG levels suggest that platelets do not contribute significantly to this phenomenon. The marked increase of FPA levels under recombinant tissue-type plasminogen activator alone and its normalization under heparin emphasize the important role of concomitant anticoagulation in controlling further intravasal fibrin generation under alteplase.
在30例接受阿替普酶治疗急性心肌梗死的患者中，对纤溶酶原激活物抑制剂1型（PAI-1）、β-血小板球蛋白（βTG）和纤维蛋白肽A（FPA）的血浆水平进行了24小时的监测。在基线时（T0小时）、90分钟后（使用阿替普酶，未使用肝素，T1.5小时）、120分钟后（使用阿替普酶和肝素，T2小时）、溶栓治疗后30分钟（T3.5小时）以及基线后12小时（T12小时）和24小时（T24小时）采集样本。PAI-1抗原水平（T0小时为55±9 ng/mL，均值±标准误）在阿替普酶治疗下降至35±5（T1.5小时）和40±6（T2小时）ng/mL，然后在治疗后升至84±22（T3.5小时）、130±30（T12小时）和64±7（T24小时）ng/mL，P<0.001。高基线PAI-1活性（18±3 ng/mL）在阿替普酶治疗下降至2.0±0.4（T1.5小时）和1.7±0.2（T2小时），并在治疗后升至32±5（T12小时）和19±3（T24小时）ng/mL（P<0.0001）。βTG水平（T0小时为339±105 ng/mL）在肝素治疗下降至203±48（T2小时）、154±51（T3.5小时）、187±40（T12小时）和142±32（T24小时）ng/mL（P<0.01）。FPA水平（T0小时为34±9 ng/mL）在仅使用阿替普酶时升至85±15 ng/mL（T1.5小时），并在肝素治疗下恢复正常（T2小时、T3.5小时、T12小时和T24小时分别为11±4、6±2、4±2和3±1 ng/mL）。T3.5小时时高水平的FPA与再闭塞相关（33±12 ng/mL，n = 4对比2.9±0.5 ng/mL，n = 21，P<0.005）。我们得出结论，急性心肌梗死患者接受阿替普酶治疗后，血浆PAI-1抗原水平以及活性显著升高。PAI-1的高活性和βTG水平的降低表明血小板对这一现象的贡献不大。单独使用重组组织型纤溶酶原激活物时FPA水平显著升高，而在肝素治疗下恢复正常，这强调了在阿替普酶治疗下联合抗凝在控制进一步血管内纤维蛋白生成中的重要作用。
