支架辅助弹簧圈栓塞颅内动脉瘤抗血小板聚集的治疗方案

Antiplatelet regimen following stent-assisted embolization for intracranial aneurysms

目的探讨支架辅助弹簧圈栓塞颅内动脉瘤抗血小板聚集药物治疗的方案。方法回顾性纳入2014年7月至2016年7月中国人民解放军武汉总医院神经外科行支架辅助弹簧圈栓塞的颅内动脉瘤患者，共684例。术中支架释放后静脉给予盐酸替罗非班，术后持续泵入24h。次日开始给予阿司匹林100mg／d＋氯吡格雷75mg／d。流式细胞仪动态监测血小板活化功能。2015年6月之前的486例，术后根据出血或缺血情况及血小板被抑制状态（二磷酸腺苷激活后CD62P阳性率〈20％）调整抗血小板聚集药物的剂量（被动调整组）；之后的198例，无论有无缺血或出血，根据血小板被抑制的状态主动调整药物的剂量（主动调整组）。结果684例中，67例（9．8％）有并发症，其中动脉瘤再破裂23例（3．4％），脑积水需要行脑室一腹腔分流术13例（1．9％），支架内血栓形成9例（1．3％），脑梗死6例（0．9％），颅内远隔部位血肿4例（0．6％），斑块脱落2例（0．3％），动脉瘤复发3例（0．4％）；死亡26例（3．8％）。共221例（32．3％）调整给药方案，被动调整组147例（30．2％，147／486），主动调整组74例（37．4％，74／198），被动和主动调整组出血性并发症的发生率分别为9．1％（44／486）、3．5％（7／198），差异有统计学意义（P〈0．05）；缺血性并发症的发生率分别为0．2％（1／462）、1．O％（2／196），差异无统计学意义（P=0．19）。在氯吡格雷减量过程中，有3例（0．4％）发生短暂性脑缺血发作，加量后缺血症状未再发生。无一例发生抗血小板聚集药物抵抗。结论采用血小板活化功能监测指导的抗血小板聚集治疗方案，可以有效地防止颅内动脉瘤支架辅助栓塞术后血栓形成和出血事件的发生。

Objective To investigate the efficacy and safety of one antiplatelet regimen following stent-assisted embolization for intracranial aneurysms. Methods Clinical data were analyzed retrospectively in 684 patients with intracranial aneurysms who underwent stent-assisted embolization from July 2014 to July 2016 at Wuhan General Hospital of the Chinese Liberation Army. Tirofiban hydrochloride was injected immediately after stent deploying and infused continuously by micro-pump for 24 hours. Dual antiplatelet therapy （ aspirin 100 mg/d ＋ clopidogrel 75 mg/d） started on the second day. Postoperatively, the platelet activation function was dynamically monitored by flow cytometry. The dose adjustment criteria of antiplatelet drugs were based on the platelet inhibition status （the positive rate of CD62P after adenosine diphosphate activation was below 20% ） and specific postoperative conditions such as hemorrhage or ischemia for 486 cases （passive adjustment group） before June 2015, and those for 198 cases （active adjustment group） after June 2015 were only according to the platelet inhibition status regardless of hemorrhage or ischemia. Results Complications were reported in 67 out of 684 （9.8%） cases and included aneurysm rerupture （ n = 23, 3.4% ）, hydrocephalus requiring ventriculoperitoneal shunting （ n = 13, 1.9% ）, stent thrombosis （n =9, 1.3% ）, cerebral infarction （n =6, 0.9% ）, intracranial hemorrhage in remote areas （n = 4, 0.6% ）, plaque shedding （n = 2, 0.3% ） cases, aneurysm recurrence （ n = 3, 0.4% ） and death （n = 26, 3.8% ）. The medication regimen was adjusted in a total of 221 （32.3%） patients including 147 （30.2%, 147/486） cases in the passive adjustment group and 74 （37.4%, 74/198） cases in the active adjustment group, There was significant difference in the complication rate of hemorrhage between passive and active adjustment groups （9. 1% [44/4861 vs. 3.5% [7/198], P 〈 0. 05）. No significant difference was identified in the complication rate of ischemia between the two groups （0.2% [ 1/462] vs. 1.0% [2/196], P = 0. 19）. Transient ischemic attack occurred in 3 （0, 4% ） cases during the process of dose reduction of clopidogrel which remitted following the dose increase. No case of resistance to antiplatelet therapy was found. Conclusion Antiplatelet therapy regimen guided by platelet activation assay could be useful for preventing thrombosis and hemorrhagic events following stent-assisted embolization for intracranial aneurysms.