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中华脑血管病杂志(电子版) ›› 2023, Vol. 17 ›› Issue (01) : 9 -15. doi: 10.11817/j.issn.1673-9248.2023.01.002

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急性缺血性脑卒中静脉溶栓后出血转化危险因素的研究进展
李昕1, 杨建中1,†()   
  1. 1. 830000　乌鲁木齐，新疆医科大学第一附属医院急救创伤中心
  • 收稿日期:2022-06-14 出版日期:2023-02-01
  • 通信作者: 杨建中

Research progress in risk factors of hemorrhage transformation after intravenous thrombolysis in acute ischemic stroke

Xin Li1, Jianzhong Yang1,†()   

  1. 1. Emergency Trauma Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
  • Received:2022-06-14 Published:2023-02-01
  • Corresponding author: Jianzhong Yang
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李昕, 杨建中. 急性缺血性脑卒中静脉溶栓后出血转化危险因素的研究进展[J]. 中华脑血管病杂志(电子版), 2023, 17(01): 9-15.

Xin Li, Jianzhong Yang. Research progress in risk factors of hemorrhage transformation after intravenous thrombolysis in acute ischemic stroke[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2023, 17(01): 9-15.

急性缺血性脑卒中（AIS）是急诊最常见的疾病之一，具有高病死率、高致残率等特点。静脉溶栓（IVT）作为AIS的一线治疗方案目前应用较为普遍，溶栓后出血转化是常见的并发症之一。溶栓后出血转化的危险因素主要有年龄、体温、高血压等。目前在溶栓后出血转化的危险因素研究的基础上构建的危险预警模型，国外主要有iScore模型、SEDAN模型、THRIVE模型、SITS模型、STARTING-SICH模型、SICHSCORE模型共6种，国内有THRIVE-c模型、Xu团队的模型、常红团队的模型共3种。作为临床医师，掌握溶栓后出血转化的相关危险因素尤为重要。本文主要对近年来溶栓后出血转化危险因素的研究做一综述。

关键词: 急性缺血性脑卒中, 静脉溶栓, 出血转换

Acute ischemic stroke is one of the most common diseases in the emergency department. It is characterized by a high fatality rate and high disability rate. In acute ischemic stroke, intravenous thrombolysis is used widely as a first-line treatment. Hemorrhagic transformation is one of the common complications after thrombolysis, and the main risk factors include age, body temperature, hypertension, etc. Currently, based on the risk factors of hemorrhagic transformation after thrombolysis, there are mainly six foreign models of risk warning, including iScore model, SEDAN model, THRIVE model, SITS model, STARTING-SICH model, and SICH SCORE model; and three domestic models, including THRIVE-c model, model of Xu team, and model of Chang Hong team. As a clinician, it is particularly imperative to recognize the relevant risk factors of hemorrhagic transformation after thrombolysis. This review mainly focuses on the recent progress in the risk factors of hemorrhagic transformation after thrombolysis.

Key words: Acute ischemic stroke, Intravenous thrombolysis, Hemorrhage transformation
图1 溶栓后颅内出血的影像学。图a、b 为出血性梗死；图c、d 为实质性血肿；图e为缺血灶外血肿
表1 海德堡出血分类系统
分类 分型 描述
1 梗死脑组织的出血转化
1a HI1 散在斑点状，无占位效应
1b HI2 融合的斑点状，无占位效应
1c PH1 梗死组织内的血肿＜30%，无实质性的占位效应
2 梗死脑组织内部或超出梗死组织的脑出血
PH2 血肿占梗死组织的30%或以上，占位效应明显
3 梗死脑组织外的脑出血或颅外出血
3a 远离梗死脑组织的实质性血肿
3b 脑室内出血
3c 蜘蛛膜下腔出血
3d 硬膜下出血
1
Wang W, Jiang B, Sun H, et al. NESS-China Investigators. Prevalence, incidence, and mortality of stroke in China: results from a nationwide population-based survey of 480 687 adults [J]. Circulation, 2017, 135(8): 759-771.
2
Yaghi S, Willey JZ, Cucchiara B, et al. American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Quality of Care and Outcomes Research. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association [J]. Stroke, 2017, 48(12): e343-e361.
3
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke [J]. N Engl J Med, 1995, 333(24): 1581-1587.
4
Venketasubramanian N, Yoon BW, Pandian J, et al. Stroke epidemiology in South, East, and South-East Asia: a review [J]. J Stroke, 2017, 19(3): 286-294.
5
Lei C, Wu B, Liu M, et al. Asymptomatic hemorrhagic transformation after acute ischemic stroke: is it clinically innocuous?[J]. J Stroke Cerebrovasc Dis, 2014, 23(10): 2767-2772.
6
Guo Y, Yan S, Zhang S, et al. Lower serum calcium level is associated with hemorrhagic transformation after thrombolysis [J]. Stroke, 2015, 46(5): 1359-1361.
7
中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南2018 [J]. 中华神经科杂志, 2018, 51(9): 666-682.
8
中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性脑梗死后出血转化诊治共识2019 [J]. 中华神经科杂志, 2019, 52(4): 252-265.
9
Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association [J]. Stroke, 2019, 50(12): e344-e418.
10
Schulman S, Beyth RJ, Kearon C, et al. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) [J]. Chest, 2008, 133(6 Suppl): 257S-298S.
11
von Kummer R, Broderick JP, Campbell BC, et al. The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy [J]. Stroke, 2015, 46(10): 2981-2986.
12
Brott TG, Haley EC, Levy DE, et al. Urgent therapy for stroke. Part Ⅰ. Pilot study of tissue plasminogen activator administered within 90 minutes [J]. Stroke, 1992, 23(5): 632-640.
13
Haley EC, Levy DE, Brott TG, et al. Urgent therapy for stroke. Part Ⅱ. Pilot study of tissue plasminogen activator administered 91-180 minutes from onset [J]. Stroke, 1992, 23(5): 641-645.
14
Anderson CS, Robinson T, Lindley RI, et al. ENCHANTED Investigators and Coordinators. Low-Dose versus Standard-Dose intravenous Alteplase in acute ischemic stroke [J]. N Engl J Med, 2016, 374(24): 2313-2323.
15
Bao H, Gao HR, Pan ML, et al. Comparative study on the efficacy and safety of alteplase and urokinase in the treatment of acute cerebral infarction [J]. Technol Health Care, 2021, 29(1): 85-90.
16
陈川. 阿替普酶与尿激酶静脉溶栓治疗急性缺血性脑卒中疗效和安全性的Meta分析 [D]. 桂林: 广西医科大学, 2016.
17
赵莉芳, 祝丹, 赵轶, 等. 功能性磁共振成像指导下阿替普酶静脉溶栓治疗觉醒性缺血型脑卒中的疗效及安全性评价 [J]. 中国新药与临床杂志, 2018, 37(5): 309-312.
18
郭红玲. 阿替普酶与尿激酶静脉溶栓在急性缺血性脑卒中的临床效果比较 [J]. 临床研究, 2019, 27(10): 54-55.
19
Huang X, Cheripelli BK, Lloyd SM, et al. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study [J]. Lancet Neurol, 2015,14(4): 368-376.
20
Whiteley WN, Slot KB, Fernandes P, et al. Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies [J]. Stroke, 2012, 43(11): 2904-2909.
21
严晓波, 张圣, 严慎强, 等. 不同严重程度急性缺血性卒中患者静脉溶栓预后的影响因素分析 [J]. 浙江大学学报(医学版), 2015, 44(1): 54-60.
22
樊琦, 薛艺东, 石倩. 脑白质疏松与AIS静脉溶栓预后相关性研究进展 [J/OL]. 世界最新医学信息文摘, 2020, 20(41): 94-95.
23
Charidimou A, Pasi M, Fiorelli M, et al. Leukoaraiosis, cerebral hemorrhage, and outcome after intravenous thrombolysis for acute ischemic stroke: a Meta-analysis (v1) [J]. Stroke, 2016, 47(9): 2364-72.
24
Liu Y, Zhang M, Chen Y, et al. The degree of leukoaraiosis predicts clinical outcomes and prognosis in patients with middle cerebral artery occlusion after intravenous thrombolysis [J]. Brain Res, 2018, 1681: 28-33.
25
Sarikaya H, Arnold M, Engelter ST, et al. Outcomes of intravenous thrombolysis in posterior versus anterior circulation stroke [J]. Stroke, 2011, 42(9): 2498-502.
26
Tong X, Liao X, Pan Y, et al. Thrombolysis Implementation, Monitor of Acute Ischemic Stroke in China (TIMS-China) Investigators. Intravenous thrombolysis is more safe and effective for posterior circulation stroke: data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) [J]. Medicine (Baltimore), 2016, 95(24): e3848.
27
Zhu X, Wang N, Lin H, et al. Safety and efficacy of intravenous thrombolytic therapy in patients with acute posterior circulation stroke: a single-center study [J]. J Stroke Cerebrovasc Dis, 2020, 29(2): 104537.
28
Wang L, Song Q, Wang C, et al. Neutrophil to lymphocyte ratio predicts poor outcomes after acute ischemic stroke: a cohort study and systematic review [J]. J Neurol Sci, 2019, 406: 116445.
29
Song SY, Zhao XX, Rajah G, et al. Clinical significance of baseline neutrophil-to-lymphocyte ratio in patients with ischemic stroke or hemorrhagic stroke: an updated Meta-analysis [J]. Front Neurol, 2019, 10: 1032.
30
Wang C, Zhang Q, Ji M, et al. Prognostic value of the neutrophil-to-lymphocyte ratio in acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis [J]. BMC Neurol, 2021, 21(1): 191.
31
Kamal H, Mehta BK, Ahmed MK, et al. Laboratory factors associated with symptomatic hemorrhagic conversion of acute stroke after systemic thrombolysis [J]. J Neurol Sci, 2021, 420: 117265.
32
Che R, Huang X, Zhao W, et al. Low serum albumin level as a predictor of hemorrhage transformation after intravenous thrombolysis in ischemic stroke patients [J]. Sci Rep, 2017, 7(1): 7776.
33
Babu MS, Kaul S, Dadheech S, et al. Serum albumin levels in ischemic stroke and its subtypes: correlation with clinical outcome [J]. Nutrition, 2013, 29(6): 872-875.
34
Cho BH, Kim JT, Chang J, et al. Prediction of hemorrhagic transformation in acute ischaemic stroke by micro- and macroalbuminuria after intravenous thrombolysis [J]. Eur J Neurol, 2013, 20(8): 1145-1152.
35
Cheng Z, Huang X, Muse FM, et al. Low serum Magnesium levels are associated with hemorrhagic transformation after thrombolysis in acute ischemic stroke [J]. Front Neurol, 2020, 11: 962.
36
Zhu D, You J, Zhao N, et al. Magnesium Regulates Endothelial Barrier Functions through TRPM7, MagT1, and S1P1 [J]. Adv Sci (Weinh), 2019, 6(18): 1901166.
37
Bang OY, Saver JL, Liebeskind DS, et al. Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis [J]. Neurology, 2007, 68(10): 737-742.
38
D'Amelio M, Terruso V, Famoso G, et al. Cholesterol levels and risk of hemorrhagic transformation after acute ischemic stroke [J]. Cerebrovasc Dis, 2011, 32(3): 234-238.
39
Lin SF, Chao AC, Hu HH, et al. Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group. Low cholesterol levels increase symptomatic intracranial hemorrhage rates after intravenous thrombolysis: a multicenter cohort validation study [J]. J Atheroscler Thromb, 2019, 26(6): 513-527.
40
Masrur S, Cox M, Bhatt DL, et al. Association of acute and chronic hyperglycemia with acute ischemic stroke outcomes post-thrombolysis: findings from get with the guidelines-stroke [J]. J Am Heart Assoc, 2015, 4(10): e002193.
41
Jalal DI, Chonchol M, Targher G. Disorders of hemostasis associated with chronic kidney disease [J]. Semin Thromb Hemost, 2010, 36(1): 34-40.
42
Lee JG, Lee KB, Jang IM, et al. Low glomerular filtration rate increases hemorrhagic transformation in acute ischemic stroke [J]. Cerebrovasc Dis, 2013, 35(1): 53-59.
43
Cho AH, Lee SB, Han SJ, et al. Impaired kidney function and cerebral microbleeds in patients with acute ischemic stroke [J]. Neurology, 2009, 73(20): 1645-1648.
44
Ovbiagele B, Smith EE, Schwamm LH, et al. Chronic kidney disease and bleeding complications after intravenous thrombolytic therapy for acute ischemic stroke [J]. Circ Cardiovasc Qual Outcomes, 2014, 7(6): 929-935.
45
Liu MS, Liao Y, Li GQ. Glomerular filtration rate is associated with hemorrhagic transformation in acute ischemic stroke patients without thrombolytic therapy [J]. Chin Med J (Engl), 2018, 131(14): 1639-1644.
46
Tu HT, Campbell BC, Christensen S, et al. EPITHET-DEFUSE Investigators. Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation [J]. Int J Stroke, 2015, 10(4): 534-540.
47
Okada Y, Yamaguchi T, Minematsu K, et al. Hemorrhagic transformation in cerebral embolism [J]. Stroke, 1989, 20(5): 598-603.
48
IST-3 collaborative group, Sandercock P, Wardlaw JM, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke [the third international stroke trial (IST-3)]: a randomised controlled trial [J]. Lancet, 2012, 379(9834): 2352-2363.
49
Álvarez-Sabín J, Maisterra O, Santamarina E, et al. Factors influencing haemorrhagic transformation in ischaemic stroke [J]. Lancet Neurol, 2013, 12(7): 689-705.
50
Butcher K, Christensen S, Parsons M, et al. EPITHET Investigators. Postthrombolysis blood pressure elevation is associated with hemorrhagic transformation [J]. Stroke, 2010, 41(1): 72-77.
51
Larrue V, von Kummer RR, 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.
52
Leira R, Sobrino T, Blanco M, et al. A higher body temperature is associated with haemorrhagic transformation in patients with acute stroke untreated with recombinant tissue-type plasminogen activator (rtPA) [J]. Clin Sci (Lond), 2012, 122(3): 113-119.
53
Bravo Y, Martí-Fàbregas J, Cocho D, et al. Influence of antiplatelet pre-treatment on the risk of symptomatic intracranial haemorrhage after intravenous thrombolysis [J]. Cerebrovasc Dis, 2008, 26(2): 126-133.
54
Uyttenboogaart M, Koch MW, Koopman K, et al. Safety of antiplatelet therapy prior to intravenous thrombolysis in acute ischemic stroke [J]. Arch Neurol, 2008, 65(5): 607-611.
55
Prabhakaran S, Rivolta J, Vieira JR, et al. Symptomatic intracerebral hemorrhage among eligible warfarin-treated patients receiving intravenous tissue plasminogen activator for acute ischemic stroke [J]. Arch Neurol, 2010, 67(5): 559-563.
56
Shahjouei S, Tsivgoulis G, Goyal N, et al. Safety of intravenous thrombolysis among patients taking direct oral anticoagulants: a systematic review and Meta-analysis [J]. Stroke, 2020, 51(2): 533-541.
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