溶栓和抗凝治疗对肺血栓栓塞患者血管内皮细胞及凝血纤溶功能的影响

目的探讨肺血栓栓塞症(PTE)患者溶栓、抗凝治疗前后不同时相血管内皮细胞和凝血纤溶功能的变化及其临床意义。方法用重组组织型纤溶酶原激活物(rt-PA)溶栓治疗PTE患者7例(溶栓组),用低分子肝素(LMWH)为主的抗凝药物治疗PTE患者17例(抗凝组),动态观察两组患者溶栓、抗凝前后不同时相(溶栓组于溶栓治疗前及治疗结束后4、24h,4、7d5个时相;抗凝组于抗凝治疗前及治疗开始后24h,7、14d4个时相)内皮素-1(ET-1)、一氧化氮(NO)、组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物1(PAI-1)、抗凝血酶Ⅲ(AT-Ⅲ)、D-二聚体(D-dimer)等指标的变化,并将两组患者治疗前上述指标的检测结果与20名正常人(对照组)的结果进行比较。结果溶栓组溶栓后4h ET-1、D-dimer均有一明显的高峰出现,分别为(103.7±26.6)ng/L、(5.0±1.7)mg/L,与其他时相比差异均有统计学意义(前者P<0.05、后者P<0.01)。抗凝组抗凝后14d与抗凝前比较,ET-1由(72.0±18.3)ng/L降至(52.8±13.9)ng/L,NO由(48±14)μmol/L升至(66±24)μmol/L,AT-Ⅲ由(90±7)%升至(99±4)%(P均<0.05)。溶栓后4h ET-1的升高与PaO2、D-dimer的升高程度正相关(r值分别为0.751、0.782,P均<0.05)。结论ET-1、D-dimer的水平在溶栓前后,ET-1、NO、AT-Ⅲ的水平在抗凝前后均发生了变化,溶栓后早期ET-1、D-dimer的变化可反映溶栓效果。溶栓和抗凝治疗有助于调节凝血纤溶平衡和保护血管内皮细胞功能。

Effects of thrombolysis and anticoagulation on the functions of vascular endothelial cells and coagulation and fibrinolysis in patients with pulmonary thromboembolism

OBJECTIVE: To investigate the effects of thrombolysis and anticoagulation on the functions of vascular endothelial cells and coagulation and fibrinolysis in patients with pulmonary thromboembolism. METHODS: Twenty-four patients with documented pulmonary thromboembolism and 20 normal subjects were included. Of the 24 patients with pulmonary thromboembolism, 7 were treated with recombinant tissue-type plasminogen activator intravenously, and 17 with low molecular weight heparin. The plasma levels of endothelin 1 (ET-1), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), antithrombin III (AT-III) and D-dimer and the blood serum levels of nitrogen monoxide (NO) were measured in the control group and in the patients at different time points before and after therapies. RESULTS: In patients receiving thrombolytic therapy, ET-1 (103.7 +/- 26.6) ng/L] and D-dimer (5.0 +/- 1.7) mg/L] increased significantly at 4 h after the treatment, and were higher than those at other time points (P < 0.05 and P < 0.01, respectively). The level of ET-1 was correlated positively with PaO(2) and D-dimer (r = 0.751, and 0.782 respectively, P < 0.05). In patients receiving anticoagulation therapy, compared with pretreatment data, NO and AT-III increased and ET-1 decreased significantly at 14 d after the start of low molecular weight heparin therapy, (48 +/- 14) micromol/L vs (66 +/- 24) micromol/L for NO, (90 +/- 7)% vs (99 +/- 4)% for AT-III, (72.0 +/- 18.3) ng/L vs (52.8 +/- 13.9) ng/L for ET-1, all P < 0.05. CONCLUSIONS: ET-1 and D-dimer changed significantly after thrombolytic therapy, while ET-1, NO and AT-III showed dramatic change after anticoagulation therapy. The change of ET-1 and D-dimer reflects the therapeutic effects. Thrombolytic and anticoagulation therapies are beneficial in keeping the balance between coagulation and fibrinolysis and protecting the functions of vascular endothelial cells in patients with pulmonary thromboembolism.