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Journal of ZheJiang University(Medical Science)  2015, Vol. 44 Issue (6): 618-624    DOI: 10.3785/j.issn.1008-9292.2015.11.04
    
Safety of intravenous thrombolysis in cerebral microbleeds patients with prior antiplatelet therapy
YAN Shen-qiang, MAO Ying-ying, ZHONG Gen-long, ZHANG Sheng, LOU Min
Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
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Abstract  

Objective: To evaluate the safety of intravenous thrombolysis (IVT) in cerebral microbleeds (CMBs) patients with prior antiplatelet therapy. Methods: Four hundred and forty nine patients with acute ischemic stroke aged (66.8±12.9) years, including 298 males and 151 females, underwent susceptibility-weighted imaging (SWI) examination and MRI-guided IVT therapy between June 2009 and June 2015. The presence of CMBs, previous antiplatelet therapy, HT subtypes according to ECASS II criteria and functional outcome based on modified Rankin scale (mRS) at 3 months were analyzed in logistic regression model. Results: Total 934 CMBs were detected in 172 (38.3%) patients, among whom 63 (14.0%) previously received antiplatelet therapy. All patients received intravenous recombinant tissue-plasminogen activator (rt-PA) for thrombolysis with the onset-to needle time of (229.0±103.7) min. The pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 10 (IQR 5-15). Logistic regression analysis indicated that prior antiplatelet use increased neither risk of parenchymal hematoma (PH) (OR=0.809,95%CI:0.201-3.262,P=0.766) nor adverse functional outcome (OR=1.517, 95%CI:0.504-4.568, P=0.459) in patients with CMBs; while in patients with multiple CMBs (≥3) prior antiplatelet use increased risk of hemorrhagic transformation (OR=9.737, 95%CI: 1.364-69.494, P=0.023), but not adverse functional outcome (OR=1.697, 95%CI:0.275-10.487, P=0.569). Conclusion: The study indicates that in patients with CMBs, thrombolytic therapy should not be excluded due to the prior use of antiplatelet; however, the larger prospective studies are needed in future for patients with multiple CMBs.



Key wordsStroke/drug therapy      Acute disease      Brain ischemia/drug therapy      Tissue plasminogen activator/therapeutic use      Thrombolytic therapy      Infusions, intravenous      Prognosis      Platelet aggregation inhibitors     
Received: 08 September 2015      Published: 12 December 2015
CLC:  R743  
Cite this article:

YAN Shen-qiang, MAO Ying-ying, ZHONG Gen-long, ZHANG Sheng, LOU Min. Safety of intravenous thrombolysis in cerebral microbleeds patients with prior antiplatelet therapy. Journal of ZheJiang University(Medical Science), 2015, 44(6): 618-624.

URL:

http://www.zjujournals.com/xueshu/med/10.3785/j.issn.1008-9292.2015.11.04     OR     http://www.zjujournals.com/xueshu/med/Y2015/V44/I6/618


既往抗血小板治疗对合并颅内微出血急性缺血性卒中患者静脉溶栓的安全性分析

目的:本研究旨在探讨既往抗血小板药物使用对合并颅内微出血患者静脉溶栓后发生出血转化以及预后的影响。方法:连续分析2009年6月至2015年6月期间在浙江大学医学院附属第二医院神经内科接受重组组织型纤溶酶原激活剂静脉溶栓治疗的急性缺血性卒中患者临床资料,纳入溶栓前行磁敏感序列检查的患者,收集其既往抗血小板药物使用记录;根据ECASS Ⅱ标准评估溶栓后出血转化情况,随访3个月改良Rankin量表(mRS)评分。结果:最终纳入分析449例患者,平均年龄(66.8±12.9)岁,女性151例(33.6%),男性298例(66.4%),发病至溶栓时间为(229.0±103.7)min,溶栓前美国国立卫生研究院卒中量表评分为10(5~15)分;共172例(38.3%)合并颅内微出血,63例(14.0%)既往使用抗血小板药物。Logistic回归分析提示,既往抗血小板药物治疗不增加合并颅内微出血患者静脉溶栓后血肿型出血转化风险(OR=0.809;95%CI:0.201~3.262;P=0.766),也不增加其3个月神经功能结局不良(mRS ≥ 3)的比例(OR=1.517;95%CI:0.504~4.568;P=0.459)。而对于合并多发微出血(≥ 3)的患者,既往使用抗血小板药物增加其梗死外出血转化风险(OR=9.737;95%CI:1.364~69.494;P=0.023),但对神经功能结局无显著影响(OR=1.697;95%CI:0.275~10.487;P=0.569)。结论:目前没有证据显示需要将既往抗血小板药物使用作为合并颅内微出血患者静脉溶栓的禁忌,而合并多发颅内微出血的患者需要更大样本的研究。


关键词: 卒中/药物疗法,  急性病,  脑缺血/药物疗法,  组织型纤溶酶原激活物/治疗应用,  血栓溶解疗法,  输注,静脉内,  预后,  血小板聚集抑制剂 
[[1]]   GREENBERG S M, VERNOOIJ M W, CORDONNIER C, et al. Cerebral microbleeds: a guide to detection and interpretation[J]. Lancet Neurol, 2009, 8(2):165-174.
[[2]]   VERNOOIJ M W, VAN DER LUGT A, IKRAM M A, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study[J]. Neurology, 2008, 70(14):1208-1214.
[[3]]   WERRING D J, COWARD L J, LOSSEFF N A, et al. Cerebral microbleeds are common in ischemic stroke but rare in TIA[J]. Neurology, 2005, 65(12):1914-1918.
[[4]]   FAZEKAS F, KLEINERT R, ROOB G, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds[J]. Am J Neuroradiol, 1999, 20(4):637-642.
[[5]]   LOVELOCK C E, CORDONNIER C, NAKA H, et al. Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies[J]. Stroke, 2010, 41(6):1222-1228.
[[6]]   CHARIDIMOU A, SHOAMANESH A, WILSON D, et al. Cerebral microbleeds and postthrombolysis intracerebral hemorrhage risk: updated meta-analysis[J]. Neurology, 2015, 85(11):927-934.
[[7]]   林悦涵, 楼 敏,朱仁洋,等. 多模式MRI 指导缺血性脑卒中静脉溶栓降低出血转化的研究[J]. 浙江大学学报(医学版),2012,41(6):665-671. LIN Yue-han,LOU Min,ZHU Ren-yang, et al. Multi-mode MRI-based intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) reduces hemorrhagic transformation in ischemic stroke patients[J]. Journal of Zhejiang University(Medical Sciences),2012, 41(6):665-671.(in Chinese)
[[8]]   中华医学会神经病学分会脑血管病学组急性缺血性脑卒中诊治指南撰写组. 中国急性缺血性脑卒中诊治指南2010[J]. 中华神经科杂志,2010,43(2):146-152. The Chinese Medical Association Credits Will Cerebrovascular Disease Neuropathy Study Group with Acute Ischemic Stroke Treatment Guidelines Writing Group. Chinese acute ischemic stroke treatment guidelines 2010[J]. Chinese Journal of Neurology, 2010, 43(2):146-152.(in Chinese)
[[9]]   GREGOIRE S M, CHAUDHARY U J, BROWN M M, et al. The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds[J]. Neurology, 2009, 73(21):1759-1766.
[[10]]   HACKE W, KASTE M, BLUHMKI E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke[J]. N Engl J Med, 2008, 359(13):1317-1329.
[[11]]   LARRUE V, VON KUMMER R R, MÜLLER A, et al. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II)[J]. Stroke, 2001, 32(2):438-441.
[[12]]   YAN S, CHEN Y, ZHANG X, et al. New microbleeds after thrombolysis: contiguous thin-slice 3T MRI[J]. Medicine (Baltimore), 2014, 93(20):e99.
[[13]]   ROOB G, SCHMIDT R, KAPELLER P, et al. MRI evidence of past cerebral microbleeds in a healthy elderly population[J]. Neurology, 1999, 52(5):991-994.
[[14]]   JEERAKATHIL T, WOLF P A, BEISER A, et al. Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study[J]. Stroke, 2004, 35(8):1831-1835.
[[15]]   SVEINBJORNSDOTTIR S, SIGURDSSON S, ASPELUND T, et al. Cerebral microbleeds in the population based AGES-Reykjavik study: prevalence and location[J]. J Neurol Neurosurg Psychiatry, 2008, 79(9):1002-1006.
[[16]]   POELS M M, VERNOOIJ M W, IKRAM M A, et al. Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study[J]. Stroke, 2010,41(10 Suppl):S103-S106.
[[17]]   CORDONNIER C, AL-SHAHI SALMAN R, WARDLAW J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting[J]. Brain, 2007, 130(Pt 8):1988-2003.
[[18]]   ZINKSTOK S M, ROOS Y B; ARTIS invesigatiors. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial[J]. Lancet, 2012, 380(9843):731-737.
[[19]]   MESEGUER E, LABREUCHE J, GUIDOUX C, et al. Outcomes after stroke thrombolysis according to prior antiplatelet use[J]. Int J Stroke, 2015, 10(2):163-169.
[[20]]   PAN X, ZHU Y, ZHENG D, et al. Prior antiplatelet agent use and outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke: a meta-analysis of cohort studies and randomized controlled trials[J]. Int J Stroke, 2015, 10(3):317-323.
[[21]]   MEURER W J, KWOK H, SKOLARUS L E, et al. Does preexisting antiplatelet treatment influence postthrombolysis intracranial hemorrhage in community-treated ischemic stroke patients? An observational study[J]. Acad Emerg Med, 2013, 20(2):146-154.
[[22]]   YAN S, JIN X, ZHANG X, et al. Extensive cerebral microbleeds predict parenchymal haemorrhage and poor outcome after intravenous thrombolysis[J]. J Neurol Neurosurg Psychiatry, 2015, 86(11):1267-1672.
[[23]]   TROUILLAS P, VON KUMMER R. Classification and pathogenesis of cerebral hemorrhages after thrombolysis in ischemic stroke[J]. Stroke, 2006, 37(2):556-561.
[[24]]   VAN ROODEN S, VAN DER GROND J, VAN DEN BOOM R, et al. Descriptive analysis of the Boston criteria applied to a Dutch-type cerebral amyloid angiopathy population[J]. Stroke, 2009, 40(9):3022-3027.
[[25]]   PAN Y, CHEN Q, LIAO X, et al. Preexisting dual antiplatelet treatment increases the risk of post-thrombolysis intracranial hemorrhage in Chinese stroke patients[J]. Neurol Res, 2015, 37(1):64-68.
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