合并血小板减少症的非心源性轻型脑卒中患者早期抗血小板治疗的安全性研究

Safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia

目的:探讨合并血小板减少症的非心源性轻型脑卒中患者早期接受抗血小板治疗的安全性。方法:从多中心登记数据库中纳入基线美国国立卫生研究院卒中量表评分3分及以下且血小板计数低于100×10^(9)/L的急性缺血性脑卒中患者,并排除需要抗凝治疗或存在其他抗血小板治疗禁忌证者。短期安全性结局为院内出血事件,长期安全性结局为1年全因死亡,短期神经功能结局使用出院时改良Rankin量表(mRS)评分进行评价。采用二元logistic回归分析模型分析抗血小板治疗对患者临床结局的影响。结果:最终共1868例合并血小板减少症的非心源性轻型脑卒中患者纳入本研究。多因素回归分析显示,相比未接受抗血小板治疗,单抗治疗可以显著提高患者出院时mRS评分0~1分的比例(OR=1.657,95%CI:1.253~2.192,P<0.01),且不增加颅内出血的风险(OR=2.359,95%CI:0.301~18.503,P>0.05)。而相比于单抗治疗,双抗治疗并没有带来更多的神经功能获益(OR=0.923,95%CI:0.690~1.234,P>0.05),反而增加了胃肠道出血风险(OR=2.837,95%CI:1.311~6.136,P<0.01)。对于血小板计数75×10^(9)/L及以下和90×10^(9)/L以上的患者,抗血小板治疗显著改善了神经功能结局(均P<0.05),而对于血小板计数为(>75~90)×10^(9)/L的患者,抗血小板治疗显著改善了1年生存曲线(P<0.05)。即使患者同时存在凝血功能异常,单抗治疗也未增加各种类型出血风险(均P>0.05),且能改善神经功能结局(均P<0.01)。对于单抗药物的选择,无论使用阿司匹林还是氯吡格雷,在各类出血事件、1年全因死亡风险以及神经功能结局上差异均无统计学意义(均P>0.05)。结论:对于合并血小板减少症的非心源性轻型脑卒中患者,抗血小板治疗仍是合理的,且单抗治疗相比双抗治疗神经功能结局改善效果相当、胃肠道出血风险更低。

Objective:To investigate the safety of early antiplatelet therapy for non�cardioembolic mild stroke patients with thrombocytopenia.Methods:Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale(NIHSS)score≤3 and a platelet count<100×10^(9)/L were obtained from a multicenter register.Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded.Short-term safety outcomes were in-hospital bleeding events,while the long-term safety outcome was a 1-year all-cause death.The short-term neurological outcomes were evaluated by modified Rankin scale(mRS)score at discharge.Results:A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled.Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge(OR=1.657,95%CI:1.253-2.192,P<0.01)and did not increase the risk of intracranial hemorrhage(OR=2.359,95%CI:0.301-18.503,P>0.05),compared with those without antiplatelet therapy.However,dual-antiplatelet therapy did not bring more neurological benefits(OR=0.923,95%CI:0.690-1.234,P>0.05),but increased the risk of gastrointestinal bleeding(OR=2.837,95%CI:1.311-6.136,P<0.01)compared with those with mono-antiplatelet therapy.For patients with platelet counts≤75×10^(9)/L and>90×10^(9)/L,antiplatelet therapy significantly improved neurological functional outcomes(both P<0.05).For those with platelet counts(>75-90)×10^(9)/L,antiplatelet therapy resulted in a significant improvement of 1-year survival(P<0.05).For patients even with concurrent coagulation abnormalities,mono-antiplatelet therapy did not increase the risk of various types of bleeding(all P>0.05)but improved neurological functional outcomes(all P<0.01).There was no significant difference in the occurrence of bleeding events,1-year all-cause mortality risk,and neurological functional outcomes between aspirin and clopidogrel(all P>0.05).Conclusions:For non-cardioembolic mild stroke patients with thrombocytopenia,antiplatelet therapy remains a reasonable choice.Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.