切换至 "中华医学电子期刊资源库"

中华脑血管病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (04) : 332 -339. doi: 10.3877/cma.j.issn.1673-9248.2025.04.011

综述

抗磷脂综合征相关缺血性卒中诊治进展
高海铨, 周立新(), 倪俊()   
  1. 100730 中国医学科学院 北京协和医学院 北京协和医院神经科
  • 收稿日期:2025-04-15 出版日期:2025-08-01
  • 通信作者: 周立新, 倪俊
  • 基金资助:
    北京协和医院中央高水平医院临床科研专项(2022-PUMCH-D-007)

Advances in diagnosis and treatment of antiphospholipid syndrome-related ischemic stroke

Haiquan Gao, Lixin Zhou(), Jun Ni()   

  1. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
  • Received:2025-04-15 Published:2025-08-01
  • Corresponding author: Lixin Zhou, Jun Ni
引用本文:

高海铨, 周立新, 倪俊. 抗磷脂综合征相关缺血性卒中诊治进展[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(04): 332-339.

Haiquan Gao, Lixin Zhou, Jun Ni. Advances in diagnosis and treatment of antiphospholipid syndrome-related ischemic stroke[J/OL]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2025, 19(04): 332-339.

抗磷脂综合征(APS)作为获得性血栓形成性疾病,在缺血性卒中尤其是青年卒中和隐源性卒中领域具有重要临床意义。抗磷脂抗体通过激活血管内皮、血小板及补体系统等多重致栓机制显著增加卒中风险,其血栓风险分层需综合抗体谱特征(如三重阳性、狼疮抗凝物阳性等)、合并系统性红斑狼疮及传统心血管危险因素等指标。APS相关缺血性卒中的机制复杂,可通过高凝易栓、心源性栓塞、大动脉粥样硬化及小动脉闭塞等多种机制介导缺血性卒中,且缺乏特异性临床影像特征,早期诊断面临挑战。APS相关缺血性卒中复发风险高,预后不良。现有证据支持长期抗凝治疗作为二级预防基石,对于三重抗体阳性等高危患者可考虑联合抗血小板或免疫抑制剂治疗。本文强调临床需重视APS相关缺血性卒中的早期识别和诊断,加强APS相关缺血性卒中复发风险因素评估和管理,并进一步探究卒中的发生机制及基于卒中机制的精准二级预防方案,以改善患者预后。

Antiphospholipid syndrome (APS) is an acquired thrombotic disorder with major clinical implications in ischemic stroke, particularly among young adults and in case of cryptogenic stroke. Antiphospholipid antibodies (aPLs) substantially increase stroke risk through multiple prothrombotic mechanisms, including vascular endothelial dysfunction, platelet activation, and complement system dysregulation. Thrombotic risk stratification requires comprehensive assessment of antibody profiles (e.g., triple positivity or positivity lupus anticoagulant), coexisting systemic lupus erythematosus (SLE), and traditional cardiovascular risk factors. APS-associated ischemic stroke exhibits complex pathophysiology, mediated by hypercoagulability, cardioembolism, large artery atherosclerosis, or small vessel occlusion. However, the absence of specific clinical or imaging biomarkers, complicates early diagnosis. Additionally, APS-related stroke is associated with a high recurrent rate and poor prognosis. Current evidence supports long-term anticoagulation as the cornerstone of secondary prevention, while high-risk patients (e.g., those with triple-positive antibody profiles) may benefit from combined antiplatelet agents or immunosuppressive therapies. This review emphasizes the urgent need to enhance early recognition and diagnosis of APS-related stroke, refine risk stratification for recurrence, and advance mechanistic research to develop precision secondary prevention strategies that address the underlying pathogenesis, ultimately improving clinical outcomes.

表1 调整后的全球抗磷脂综合征评分(分)
图1 抗磷脂综合征(APS)相关缺血性卒中的影像学图像。图a~d为24岁女性患者,诊断APS,反复一过性左侧肢体无力,头磁共振弥散加权成像(DWI)序列未见高信号,诊断为短暂性脑缺血发作。磁共振血管造影(MRA;图a)可见右侧大脑中动脉M1段中段重度狭窄,高分辨磁共振脑血管成像(图b~d)可见右侧大脑中动脉M1段偏心性狭窄,狭窄处可见动脉粥样硬化斑块,局部明显硬化。图e~h为38岁女性患者,诊断为系统性红斑狼疮,继发性APS;头磁共振成像(MRI)侧脑室层面(图e)及半卵圆中心层面(图f)提示右侧额叶见斑片状DWI高信号,左侧额叶白质内见小片状DWI稍高信号,提示亚急性多发性脑梗死;MRA(俯视图g、正视图h)显示颅内动脉未见明显狭窄;经胸超声心动可见二尖瓣前叶瓣尖左心房面强回声团块影,大小为6 mm×4 mm,提示Libman-Sacks赘生物可能性大;考虑患者卒中病因为APS相关心脏瓣膜病所致的心源性栓塞。图i~l为71岁男性患者,诊断为APS。头MRI(图i~k)显示双侧大脑皮质及皮质下、基底节、侧脑室旁、脑干及小脑可见弥漫不均匀分布的点状、小结节状DWI高信号,考虑多发性急性或亚急性脑梗死;MRA(图l)未见颅内动脉狭窄;心脏相关检查未发现心房颤动及瓣膜赘生物等心脏病变,提示高凝机制所致缺血性卒中可能性大
表2 2006年抗磷脂综合征悉尼修订的分类标准
1
GBD 2021 Stroke Risk Factor Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 [J]. Lancet Neurol, 2024, 23(10): 973-1003.
2
Diener HC, Easton JD, Hart RG, et al. Review and update of the concept of embolic stroke of undetermined source [J]. Nat Rev Neurol, 2022, 18(8): 455-465.
3
赵久良, 沈海丽, 柴克霞, 等. 抗磷脂综合征诊疗规范 [J]. 中华内科杂志, 2022, 61(9): 1000-1007.
4
Mittal P, Quattrocchi G, Tohidi-Esfahani I, et al. Antiphospholipid syndrome, antiphospholipid antibodies, and stroke [J]. Int J Stroke, 2023, 18(4): 383-391.
5
Torricelli AK, Ugolini-Lopes MR, Bonfá E, et al. Antiphospholipid syndrome damage index (DIAPS): distinct long-term kinetic in primary antiphospholipid syndrome and antiphospholipid syndrome related to systemic lupus erythematosus [J]. Lupus, 2020, 29(3): 256-262.
6
Cervera R, Serrano R, Pons-Estel GJ, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients [J]. Ann Rheum Dis, 2015, 74(6): 1011-1018.
7
Gaspar P, Sciascia S, Tektonidou MG. Epidemiology of antiphospholipid syndrome: macro- and microvascular manifestations [J]. Rheumatology, 2024, 63(SI): SI24-SI36.
8
Cervera R, Piette J, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients [J]. Arthritis Rheum, 2002, 46(4): 1019-1027.
9
Grimaud F, Yelnik C, Pineton De Chambrun M, et al. Clinical and immunological features of antiphospholipid syndrome in the elderly: a retrospective national multicentre study [J]. Rheumatology, 2019, 58(6): 1006-1010.
10
Shi H, Teng J, Sun Y, et al. Clinical characteristics and laboratory findings of 252 Chinese patients with anti-phospholipid syndrome: comparison with Euro-Phospholipid cohort [J]. Clin Rheumatol, 2017, 36(3): 599-608.
11
Liu M, Li G, Song X, et al. Prevalence, risk factors, and prognosis of central nervous system manifestations in antiphospholipid syndrome [J]. Sci Rep, 2023, 13(1): 8915.
12
Sciascia S, Sanna G, Khamashta MA, et al. The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review [J]. Ann Rheum Dis, 2015, 74(11): 2028-2033.
13
Yang W, Kang MK, Ha SY, et al. Current status and role of antiphospholipid antibody testing in cryptogenic stroke [J]. Eur J Neurol, 2022, 29(3): 753-760.
14
Tektonidou MG. Cardiovascular disease risk in antiphospholipid syndrome: thrombo-inflammation and atherothrombosis [J]. J Autoimmun, 2022, 128: 102813.
15
Osmundo GS, Carvalho JF, Bortolotto LA, et al. Large artery dysfunction in primary antiphospholipid syndrome [J]. J Clin Rheumatol, 2018, 24(1): 14-17.
16
Liestøl S, Sandset PM, Jacobsen EM, et al. Decreased anticoagulant response to tissue factor pathway inhibitor type 1 in plasmas from patients with lupus anticoagulants [J]. Br J Haematol, 2007, 136(1): 131-137.
17
Oku K, Amengual O, Hisada R, et al. Autoantibodies against a complement component 1 q subcomponent contribute to complement activation and recurrent thrombosis/pregnancy morbidity in anti-phospholipid syndrome [J]. Rheumatology, 2016, 55(8): 1403-1411.
18
Arachchillage DRJ, Efthymiou M, Mackie IJ, et al. Anti‐protein C antibodies are associated with resistance to endogenous protein C activation and a severe thrombotic phenotype in antiphospholipid syndrome [J]. J Thromb Haemost, 2014, 12(11): 1801-1809.
19
Breen KA, Seed P, Parmar K, et al. Complement activation in patients with isolated antiphospholipid antibodies or primary antiphospholipid syndrome [J]. Thromb Haemost, 2012, 107(3): 423-429.
20
Meroni PL, Riboldi P. Pathogenic mechanisms mediating antiphospholipid syndrome [J]. Curr Opin Rheumatol, 2001, 13(5): 377-382.
21
Lopez-Pedrera C, Barbarroja N, Patiño-Trives AM, et al. New biomarkers for atherothrombosis in antiphospholipid syndrome: genomics and epigenetics approaches [J]. Front Immunol, 2019, 10: 764.
22
Ha SH, Kim SU, Huh J, et al. Risk factors for cerebral infarction and cerebrovascular stenosis in antiphospholipid antibody-positive patients: a retrospective single-center study with propensity score matching analysis [J]. Medicine, 2024, 103(39): e39890.
23
Erkan D, Lockshin M. Non-criteria manifestations of antiphospholipid syndrome [J]. Lupus, 2010, 19(4): 424-427.
24
Provenzale JM, Barboriak DP, Allen NB, et al. Patients with antiphospholipid antibodies: CT and MR findings of the brain [J]. AJR Am J Roentgenol, 1996, 167(6): 1573-1578.
25
Donnellan C, Cohen H, Werring DJ. Cognitive dysfunction and associated neuroimaging biomarkers in antiphospholipid syndrome: a systematic review [J]. Rheumatology, 2021, 61(1): 24-41.
26
Knight JS, Kanthi Y. Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome [J]. Semin Immunopathol, 2022, 44(3): 347-362.
27
Barbhaiya M, Zuily S, Naden R, et al. 2023 ACR/EULAR antiphospholipid syndrome classification criteria [J]. Ann Rheum Dis, 2023, 82(10): 1258-1270.
28
Pengo V, Ruffatti A, Legnani C, et al. Clinical course of high‐risk patients diagnosed with antiphospholipid syndrome [J]. J Thromb Haemost, 2010, 8(2): 237-242.
29
Galli M, Luciani D, Bertolini G, et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature [J]. Blood, 2003, 101(5): 1827-1832.
30
Vreede AP, Bockenstedt PL, McCune WJ, et al. Cryptic conspirators: a conversation about thrombocytopenia and antiphospholipid syndrome [J]. Curr Opin Rheumatol, 2019, 31(3): 231-240.
31
Da Silva FF, Levy RA, De Carvalho JF. Cardiovascular risk factors in the antiphospholipid syndrome [J]. J Immunol Res, 2014, 2014: 1-6.
32
De Souza AWS, Silva NP, De Carvalho JF, et al. Impact of hypertension and hyperhomocysteinemia on arterial thrombosis in primary antiphospholipid syndrome [J]. Lupus, 2007, 16(10): 782-787.
33
Saraiva SDS, Custódio IF, Mazetto BDM, et al. Recurrent thrombosis in antiphospholipid syndrome may be associated with cardiovascular risk factors and inflammatory response [J]. Thromb Res, 2015, 136(6): 1174-1178.
34
Radin M, Sciascia S, Erkan D, et al. The adjusted global antiphospholipid syndrome score (aGAPSS) and the risk of recurrent thrombosis: results from the APS ACTION cohort [J]. Semin Arthritis Rheum, 2019, 49(3): 464-468.
35
Barilaro G, Esteves A, Della Rocca C, et al. Predictive value of the adjusted Global Anti-Phospholipid Syndrome Score on clinical recurrence in APS patients: a longitudinal study [J]. Rheumatology, 2023, 62(4): 1576-1585.
36
Radin M, Schreiber K, Cecchi I, et al. The risk of ischaemic stroke in primary antiphospholipid syndrome patients: a prospective study [J]. Eur J Neurol, 2018, 25(2): 320-325.
37
Song X, Fan Y, Jia Y, et al. A novel aGAPSS-based nomogram for the prediction of ischemic stroke in patients with antiphospholipid syndrome [J]. Front Immunol, 2022, 13: 930087.
38
Fan Y, Xu Y, Zhang S, et al. Stroke and risk factors in antiphospholipid syndrome [J]. J Pers Med, 2023, 14(1): 24.
39
Urbanus RT, Siegerink B, Roest M, et al. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study [J]. Lancet Neurol, 2009, 8(11): 998-1005.
40
Wang Q, Han G, Sha Y, et al. Current status and value of testing antiphospholipid antibody in patients with acute ischemic stroke: a retrospective single-center study in China [J]. Neurol Sci, 2024, 45(3): 1121-1128.
41
Matus-Mayorga R, Barrera-Vargas A, Rull-Gabayet M, et al. Risk factors for ischemic antiphospholipid syndrome: a case-control study [J]. Clin Neurol Neurosurg, 2021, 202: 106492.
42
Yang W, Kang DW, Kim JM, et al. Neuroimaging features of antiphospholipid antibody-related stroke compared with atrial fibrillation-related stroke [J]. Sci Rep, 2022, 12(1): 11686.
43
Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis [J]. BMJ, 2010, 341(jul26 1): c3666-c3666.
44
Naftali J, Barnea R, Eliahou R, et al. Significance of cerebral microinfarcts in antiphospholipid syndrome: a population-based study [J]. Int J Stroke, 2025, 20(2): 186-195.
45
Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) [J]. J Thromb Haemost, 2006, 4(2): 295-306.
46
Devreese KMJ, De Groot PG, De Laat B, et al. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis [J]. J Thromb Haemost, 2020, 18(11): 2828-2839.
47
Cohen H, Werring DJ, Chandratheva A, et al. Survey on antiphospholipid syndrome diagnosis and antithrombotic treatment in patients with ischemic stroke, other brain ischemic injury, or arterial thromboembolism in other sites: communication from ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies [J]. J Thromb Haemost, 2023, 21(10): 2963-2976.
48
Hanarz M, Ząbczyk M, Natorska J, et al. Positive antiphospholipid antibodies increase the risk of ischemic stroke in patients with atrial fibrillation [J]. J Thromb Haemost, 2024, 22(10): 2797-2809.
49
Drosos GC, Vedder D, Houben E, et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome [J]. Ann Rheum Dis, 2022, 81(6): 768-779.
50
Arnaud L, Mathian A, Ruffatti A, et al. Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: an international and collaborative meta-analysis [J]. Autoimmun Rev, 2014, 13(3): 281-291.
51
Bushnell C, Kernan WN, Sharrief AZ, et al. 2024 guideline for the primary prevention of stroke: a guideline from the American Heart Association/American Stroke Association [J]. Stroke, 2024, 55(12): e344-e424.
52
Pengo V, Ruffatti A, Legnani C, et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study [J]. Blood, 2011, 118(17): 4714-4718.
53
Khamashta MA, Cuadrado MJ, Mujic F, et al. The management of thrombosis in the antiphospholipid-antibody syndrome [J]. N Engl J Med, 1995, 332(15): 993-997.
54
Arachchillage DJ, Platton S, Hickey K, et al. Guidelines on the investigation and management of antiphospholipid syndrome [J]. Br J Haematol, 2024, 205(3): 855-880.
55
Finazzi G, Marchioli R, Brancaccio V, et al. A randomized clinical trial of high‐intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS) [J]. J Thromb Haemost, 2005, 3(5): 848-853.
56
Jackson WG, Oromendia C, Unlu O, et al. Recurrent thrombosis in patients with antiphospholipid antibodies and arterial thrombosis on antithrombotic therapy [J]. Blood Adv, 2017, 1(25): 2320-2324.
57
Khairani CD, Bejjani A, Piazza G, et al. Direct oral anticoagulants vs vitamin K antagonists in patients with antiphospholipid syndromes [J]. J Am Coll Cardiol, 2023, 81(1): 16-30.
58
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. 中国缺血性卒中和短暂性脑缺血发作二级预防指南2022 [J]. 中华神经科杂志, 2022, 55(10): 1071-1110.
59
Kwon OC, Park YB, Park MC. Effect of statins on the prevention of recurrent thrombosis in thrombotic antiphospholipid syndrome [J]. Rheumatology, 2022, 61(4): 1548-1555.
[1] 高焱, 郝彦明, 叶晓生, 钱荣勋, 陆轲, 高晓明, 李翀, 徐又佳. 氨甲环酸对下肢关节置换术后贫血及凝血功能的影响[J/OL]. 中华关节外科杂志(电子版), 2025, 19(04): 409-417.
[2] 谢挺. 创面诊断[J/OL]. 中华损伤与修复杂志(电子版), 2025, 20(03): 276-276.
[3] 康宜晖, 梁伊妍, 郑晓汾, 张帅. 山西省感染性眼内炎临床特征及预后影响因素的临床研究[J/OL]. 中华眼科医学杂志(电子版), 2025, 15(02): 104-108.
[4] 周骞, 夏春华, 陈兵. 弥散张量成像联合血清Hcy对缺血性卒中合并颈动脉斑块患者的诊断价值分析[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(06): 367-372.
[5] 袁伟, 郑肖肖, 李秀丽, 冯新红. 复杂腰骶神经根病的临床特征分析[J/OL]. 中华老年骨科与康复电子杂志, 2025, 11(04): 214-221.
[6] 张丽娜, 谌楚宇, 杨新宇, 邱海波, 吕奔. 脓毒症凝血功能障碍:2024 年度进展与展望[J/OL]. 中华重症医学电子杂志, 2025, 11(02): 105-111.
[7] 屠国伟, 李敏, 罗哲. 《成人体外膜肺氧合技术操作规范(2024年版)》解读:抗凝与出血并发症防治[J/OL]. 中华重症医学电子杂志, 2025, 11(01): 55-59.
[8] 郑鸥, 黄信全, 李学杰, 黄年平, 谭支文. 血浆MCP-1、YKL-40与单侧症状性MCA-M1段重度狭窄或闭塞的AIS患者脑侧支循环不良的关系[J/OL]. 中华脑科疾病与康复杂志(电子版), 2025, 15(02): 115-121.
[9] 王建华, 范玮丽, 郭海涵, 孙璐, 张萌, 徐健, 李述峰, 曹威. 规范抗凝后非瓣膜性心房颤动患者血栓形成的相关性因素研究[J/OL]. 中华心脏与心律电子杂志, 2025, 13(01): 38-46.
[10] 赵秋灵, 李红平, 文皓, 周微薇, 罗宇, 何朝晖. 慢性肾脏病并发上消化道出血的研究进展[J/OL]. 中华胃肠内镜电子杂志, 2025, 12(01): 54-57.
[11] 于棋, 李兰君, 韩红星, 王贤军, 王蒙恩. 晚窗血管内治疗不同病因类型急性大血管闭塞性缺血性卒中的临床疗效[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(04): 296-303.
[12] 付志勇, 马欣, 董静, 杜祥颖, 尹春琳. 压力感受器分布动脉的粥样硬化总负荷对卒中后新监测到的心房颤动的影响[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(03): 175-183.
[13] 武德崴, 王秀玲, 郭呈龙, 褚研研, 高敬, 王宇彬, 尹春琳. CT肺动脉造影不可见的肺动静脉交通与心源性栓塞的关系[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(03): 207-212.
[14] 肖瑶, 白玉瀛, 陶文丹, 吴波. 心房颤动治疗对认知功能影响的系统评价再评价[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(03): 234-243.
[15] 马芬, 王保爱. 细胞间黏附分子-1与卒中的相关性研究进展[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(03): 244-249.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?