Christopoulos Christos, Farag Mohamed, Sullivan Keith, Wellsted David, Gorog Diana A
Prof. Diana A. Gorog, Imperial College, London, UK, Tel.: +44 207 034 8934, E-mail:
Thromb Haemost. 2017 Feb 28;117(3):457-470. doi: 10.1160/TH16-09-0712. Epub 2015 Dec 22.
Antithrombotic medications reduce thrombosis but increase bleeding. Identification of ST-elevation myocardial infarction (STEMI) patients at risk of recurrent thrombosis could allow targeted treatment with potent antithrombotic medications, with less potent agents in others, to reduce bleeding. Conventional platelet function tests assess platelet reactivity only, yet there is increasing evidence that endogenous thrombolytic potential determines outcome following thrombus initiation. We investigated whether assessing both platelet reactivity and endogenous thrombolysis, could identify STEMI patients at high-risk of recurrent thrombotic events. Thrombotic status was assessed in STEMI patients, before and after primary percutaneous coronary intervention (PPCI), at discharge and at 30 days; with 12 months' follow-up. The time to form an occlusive thrombus under high shear (occlusion time, OT), and time to restore flow by endogenous thrombolysis (lysis time, LT) was measured using the point-of-care Global Thrombosis Test (GTT) in the cardiac catheterisation laboratory. Impaired endogenous thrombolysis (prolonged LT ≥ 3000 s), seen in 13 % patients pre-PPCI, was related to major adverse cardiac events, MACE (HR: 3.31, 95 %CI: 1.02-10.78, p = 0.045), driven by cardiovascular death (HR: 4.17, 95 %CI: 0.99-17.51, p = 0.05). Enhanced (rapid) endogenous thrombolysis (LT < 1000 s) was associated with spontaneous reperfusion, ST-segment resolution and Thrombolysis In Myocardial Infarction 3 flow pre-PPCI. Baseline OT was shorter in those with MACE (especially recurrent myocardial infarction and stroke) than those without (253 ± 150 s vs 354 ± 134 s, p=0.017). Endogenous thrombolysis, when impaired, is associated with increased cardiovascular risk, and when enhanced, with spontaneous reperfusion. Endogenous thrombolysis may be a novel target for pharmacological intervention, and allow targeting of potent antithrombotic medications to high-risk patients.
抗血栓药物可减少血栓形成，但会增加出血风险。识别有复发性血栓形成风险的ST段抬高型心肌梗死（STEMI）患者，可针对性地使用强效抗血栓药物进行治疗，其他患者则使用效力较弱的药物，以减少出血。传统的血小板功能测试仅评估血小板反应性，但越来越多的证据表明，内源性溶栓潜力决定血栓形成后的结果。我们研究了评估血小板反应性和内源性溶栓是否能识别有复发性血栓事件高风险的STEMI患者。在STEMI患者中，于初次经皮冠状动脉介入治疗（PPCI）前后、出院时及30天时评估血栓形成状态，并进行12个月的随访。在心脏导管实验室中，使用即时全球血栓形成测试（GTT）测量在高切变率下形成闭塞性血栓的时间（闭塞时间，OT）以及通过内源性溶栓恢复血流的时间（溶解时间，LT）。13%的患者在PPCI前出现内源性溶栓受损（LT延长≥3000秒），这与主要不良心脏事件（MACE）相关（HR：3.31，95%CI：1.02 - 10.78，p = 0.045），主要由心血管死亡驱动（HR：4.17，95%CI：0.99 - 17.51，p = 0.05）。增强的（快速）内源性溶栓（LT < 1000秒）与自发再灌注、ST段回落以及PPCI前心肌梗死溶栓试验3级血流相关。发生MACE（尤其是复发性心肌梗死和中风）的患者基线OT比未发生者短（253 ± 150秒对354 ± 134秒，p = 0.017）。内源性溶栓受损时与心血管风险增加相关，增强时与自发再灌注相关。内源性溶栓可能是药物干预的一个新靶点，并可将强效抗血栓药物用于高风险患者。
