免疫性血小板减少症合并心肌损伤患儿临床分析

doi:10.12372/jcp.2022.21e1231

摘要/Abstract

摘要：

目的探讨合并心肌损伤的免疫性血小板减少症（ITP）患儿的临床特点。方法回顾分析2018年12月至2020年4月收治的新诊断ITP患儿的临床资料,根据是否合并心肌损伤将患儿分为非心肌损伤组和心肌损伤组,并分析两组的临床特点、实验室检查以及转归情况。结果新诊断ITP患儿360例,男240例、女120例,中位年龄3.0（2.0~6.0）岁,其中非心肌损伤组294例,心肌损伤组66例。与非心肌损伤组相比,心肌损伤组患儿肌酸激酶、肌酸激酶同工酶、乳酸脱氢酶-L明显升高,女性比例偏高,年龄偏低,血小板计数（PLT）较高,血栓弹力图最大振幅较大,PLT<10×10⁹/L以及出血评分>3分比例较低,白细胞、淋巴细胞、CD8⁺T淋巴细胞以及NK细胞计数均显著升高,IgE水平偏低,差异均有统计学意义（P<0.05）。Log-rank检验提示非心肌损伤组PLT升至≥30×10⁹/L时就诊天数短于心肌损伤组,差异有统计学意义（P<0.001）。结论 ITP患儿合并心肌损伤并非少见,且PLT恢复速度慢,但合并心肌损伤并未促进新确诊的ITP患儿进展为持续性ITP。

关键词: 免疫性血小板减少症, 心肌损伤, 凝血功能, 儿童

Abstract:

Objective To investigate the clinical characteristics of immune thrombocytopenia (ITP) children with myocardial injury. Methods Newly diagnosed ITP children hospitalized in Wuhan Children's Hospital from December 2018 to April 2020 were retrospectively analyzed. According to the complication, children were divided into the non-myocardial injury group and myocardial injury group. The clinical characteristics, laboratory examination and prognosis of the two groups were compared. Results In this study, 360 newly diagnosed ITP children were analyzed, including 240 boys and 120 girls, with a median age of 3.0 (2.0~6.0) years. Of the 360 children, 294 were in the non-myocardial injury group and 66 were in myocardial injury group. Compared with the non-myocardial injury group, levels of CK, CK-MB and LDH-L in myocardial injury group were higher, the proportions of girls and younger children were higher, the values of thromboelastogram-maximal amplitude were larger, the proportions of children with PLT <10×10 ⁹/L / bleeding score >3 were lower, the counts of platelet, white blood cells, CD8 ⁺T cells and NK cells were higher, the levels of IgE were lower. These differences were statistically significant (P<0.05). Log-rank analysis showed that platelet recovery of the myocardial injury group was slower than the non-myocardial injury group after treatment (P<0.001). Conclusion It is not rare for ITP children with myocardial injury. Although platelet recovery is slower at initial diagnosis, myocardial injury does not promote the progression of newly diagnosed ITP to persistent ITP.

Key words: immune thrombocytopenia, myocardial injury, coagulation function, child

祁闪闪, 王卓, 李建新, 陈晶佩, 杨时佳, 陈智, 孙鸣, 陈燕, 熊昊. 免疫性血小板减少症合并心肌损伤患儿临床分析[J]. 临床儿科杂志, 2022, 40(2): 101-106.

QI Shan-shan, WANG Zhuo, LI Jianxin, CHEN Jingpei, YANG Shijia, CHEN Zhi, SUN Ming, CHEN Yan, XIONG Hao. Analysis of clinical characteristics of immune thrombocytopenia children with myocardial injury[J]. Journal of Clinical Pediatrics, 2022, 40(2): 101-106.

图/表 5

表1

表2

表3

表4

图1

参考文献 29

[1]	Rodeghiero F, Stasi R, Gernsheimer T, et al. Stan-dardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group[J]. Blood, 2009, 113(11):2386-2393. doi: 10.1182/blood-2008-07-162503 pmid: 19005182
[2]	国家卫生健康委员会. 儿童原发性免疫性血小板减少症诊疗规范(2019年版)[J]. 全科医学临床与教育, 2019, 12(17):1059-1062.
[3]	Cines DB, Blanchette VS. Immune thrombocytopenic purpura[J]. N Engl J Med, 2002, 346(13):995-1008. doi: 10.1056/NEJMra010501
[4]	Giustino G, Croft LB, Stefanini GG, et al. Characterization of myocardial injury in patients with COVID-19[J]. J Am Coll Cardiol, 2020, 76(18):2043-2055. doi: 10.1016/j.jacc.2020.08.069
[5]	Yano M, Egami Y, Kawanami S, et al. Acute myocardial injury after radiofrequency catheter ablation: impact on pulmonary vein reconnection and relevant factors[J]. Heart Vessels, 2021. doi: 10.1007/s00380-021-01972-2. doi: 10.1007/s00380-021-01972-2
[6]	Nlemadim AC, Okpara HC, Anah MU, et al. Myocardial injury in patients with sickle cell anaemia and myocardial ischaemia in Calabar, Nigeria[J]. Paediatr Int Child Health, 2020, 40(4):231-237. doi: 10.1080/20469047.2020.1789398
[7]	Yoldaş T, Örün UA. What is the significance of elevated troponin I in children and adolescents? A diagnostic approach[J]. Pediatr Cardiol, 2019, 40(8):1638-1644. doi: 10.1007/s00246-019-02198-w pmid: 31485699
[8]	常梁翔. 实用小儿心电图学[J]. 2版. 北京: 北京人民卫生出版社, 1998: 20-55.
[9]	中华医学会儿科学分会血液学组. 儿童原发性免疫性血小板减少症诊疗建议[J]. 中华儿科杂志, 2013, 51(5):382-384.
[10]	Tunuguntla H, Jeewa A, Denfield SW. Acute myocarditis and pericarditis in children[J]. Pediatr Rev, 2019, 40(1):14-25. doi: 10.1542/pir.2018-0044 pmid: 30600275
[11]	Whittaker E, Bamford A, Kenny J, et al. Clinical characteristics of 58 children with a pediatric inflam-matory multisystem syndrome temporally associated with SARS-CoV-2[J]. JAMA, 2020, 324(3):259-269. doi: 10.1001/jama.2020.10369
[12]	王蓉, 蔡高涛, 邓英钊, 等. 2018年广州市花都区儿童肺炎支原体感染的流行病学特点和临床特征[J]. 检验医学与临床, 2019, 16(19):2878-2880.
[13]	覃丽君, 欧阳静萍, 张有为, 等. 儿童病毒性心肌炎左心室舒张功能与心肌损伤关系的研究[J]. 中华超声影像学杂志, 2003, 12(9):560.
[14]	黄娇甜, 祝益民, 卢秀兰, 等. 重症手足口病并心肌损伤的临床特征[J]. 实用儿科临床杂志, 2012, 27(18):1414-1417.
[15]	Rungjirajittranon T, Owattanapanich W. A serious thrombotic event in a patient with immune throm-bocytopenia requiring intravenous immunoglobulin: a case report[J]. J Med Case Rep, 2019, 13(1):25. doi: 10.1186/s13256-018-1955-x
[16]	Elkayam O, Paran D, Milo R, et al. Acute myocardial infarction associated with high dose intravenous immu-noglobulin infusion for autoimmune disorders. A study of four cases[J]. Ann Rheum Dis, 2000, 59(1):77-80. pmid: 10627434
[17]	Boughton BJ, Simpson AW, Bolt C, et al. Platelet membrane glycoprotein IIb/IIIa has sequence homologies with human virus proteins and synthetic viral peptides inhibit anti-GPIIb/IIIa antibodies in autoimmune thrombocytopenic purpura[J]. Platelets, 1995, 6(2):75-82. doi: 10.3109/09537109509078447 pmid: 21043697
[18]	Smalisz-Skrzypczyk K, Romiszewski M, Matysiak M, et al. The influence of primary cytomegalovirus or Epstein-Barr virus infection on the course of idiopathic thrombocytopenic purpura[J]. Adv Exp Med Biol, 2016, 878:83-88. pmid: 26269027
[19]	DiMaggio D, Anderson A, Bussel JB. Cytomegalovirus can make immune thrombocytopenic purpura refractory[J]. Br J Haematol, 2009, 146(1):104-112. doi: 10.1111/bjh.2009.146.issue-1
[20]	Kandolf R. Enteroviral myocarditis and dilated cardiomyopathy[J]. Med Klin (Munich), 1998, 93(4):215-222. doi: 10.1007/BF03044796
[21]	Grist NR, Reid D. Organisms in myocarditis/endocarditis viruses[J]. J Infect, 1997, 34(2):155. pmid: 9138141
[22]	McManus BM, Gauntt CJ, Cassling RS. Immuno-pathologic basis of myocardial injury[J]. Cardiovasc Clin, 1988, 18(2):163-184. pmid: 2820575
[23]	Gao X, Kim S, Zhao T, et al. Social defeat stress induces myocardial injury by modulating inflammatory factors[J]. J Int Med Res, 2020, 48(7):300060520936903.
[24]	Fang Z, Wu G, Zhang D, et al. Genistein protects against burn-induced myocardial injury via Notch1-mediated suppression of oxidative/nitrative stress[J]. Shock, 2020, 54(3):337-346. doi: 10.1097/SHK.0000000000001464
[25]	Ge C, Liu J, Dong S, miRNA-214 protects sepsis-induced myocardial injury[J]. Shock, 2018, 50(1):112-118. doi: 10.1097/SHK.0000000000000978
[26]	Audia S, Mahévas M, Samson M, et al. Pathogenesis of immune thrombocytopenia[J]. Autoimmun Rev, 2017, 16(6):620-632.
[27]	王厚才, 李文倩, 冯建明. 免疫性血小板减少性紫癜35例患者外周血免疫细胞亚群的检测及其临床意义[J]. 中华内科杂志, 2011, 9(50):763-765.
[28]	张玉娇, 瞿文, 刘惠, 等. 原发免疫性血小板减少症患者NK细胞相关免疫负调控的研究[J]. 中华血液学杂志, 2017, 38(5):399-403.
[29]	Zhang J, Zhang Q, Li Y, et al. Immune dysregulation in primary immune thrombocytopenia patients[J]. Hematology, 2018, 23(8):510-516. doi: 10.1080/10245332.2018.1435021

项目	心肌损伤组(n=66)	非心肌损伤组(n=294)	统计量	P
性别男[n(%)]	24(36.4)	216(73.5)	χ²=33.40	<0.001
年龄[M(P₂₅~P₇₅)]/岁	1.0(0.4~2.0)	3.0(0.8~5.0)	Z=2.19	0.029
肝肿大[n(%)]	6(9.1)	54(18.4)	χ²=3.34	0.068
脾肿大[n(%)]	6(9.1)	12(4.1)	χ²=2.85	0.092
接受糖皮质激素治疗[n(%)]	24(36.4)	114(38.8)	χ²=0.13	0.716
CK[M(P₂₅~P₇₅)]/U·L^-1	59.0(27.0~131.0)	84.0(59.5~128.5)	Z=2.16	0.030
CK-MB[M(P₂₅~P₇₅)]/U·L^-1	91.0(68.0~156.0)	33.0(25.0~49.0)	Z=9.91	<0.001
LDH-L[M(P₂₅~P₇₅)]/U·L^-1	414.0(279.0~504.0)	300.0(234.8~336.0)	Z=4.16	<0.001

凝血指标	心肌损伤组(n=66)	非心肌损伤组(n=294)	统计量	P
PLT[M(P₂₅~P₇₅)]×10⁹·L^-1	21.0(13.0~38.0)	9.0(3.0~21.0)	Z=2.39	0.017
PLT<10×10⁹·L^-1 [n(%)]	6(9.1)	156(53.1)	χ²=42.11	<0.001
血栓弹力图检测(x±s)
凝血反应时间/min 纤维蛋白生成速率/deg 最大振幅/mm	6.8±1.8	7.2±2.0	t=0.74	0.491
	50.5±8.8	47.1±12.2	t=1.03	0.369
	37.0±7.4	28.1±13.2	t=2.89	0.010
出血评分>3分[n(%)]	6(9.1)	90(30.6)	χ²=12.77	<0.001
巨核细胞成熟障碍[n(%)]¹⁾	6(25.0)	30(17.9)	χ²=0.70	0.406

免疫指标	心肌损伤组(n=66)	非心肌损伤组(n=294)	统计量	P
WBC×10⁹·L^-1	9.2(7.3~25.3)	7.8(6.1~9.4)	Z=4.67	<0.001
NEU×10⁹·L^-1	2.3(1.9~3.3)	2.8(1.7~5.1)	Z=1.64	0.101
LYM×10⁹·L^-1	6.3(3.1~10.9)	3.4(2.1~5.3)	Z=6.04	<0.001
MONO×10⁹·L^-1	0.6(0.4~0.8)	0.7(0.4~0.7)	Z=0.29	0.769
CD3⁺ T淋巴细胞×10⁹·L^-1	3.6(1.8~5.8)	2.9(1.9~3.8)	Z=1.58	0.112
CD4⁺ T淋巴细胞×10⁹·L^-1	1.2(0.5~2.7)	1.6(0.9~2.3)	Z=0.20	0.845
CD8⁺ T淋巴细胞×10⁹·L^-1	1.1(0.8~2.8)	1.0(0.6~1.5)	Z=3.30	0.010
NK细胞×10⁹·L^-1	0.5(0.3~0.8)	0.3(0.2~0.6)	Z=5.14	0.001
B淋巴细胞×10⁹·L^-1	0.9(0.4~1.4)	0.8(0.4~1.3)	Z=1.45	0.147
Treg×10⁹·L^-1	0.2(0.1~0.3)	0.2(0.1~0.3)	Z=1.42	0.157
lgG/g·L^-1	7.4(6.3~8.3)	8.1(6.5~8.9)	Z=1.63	0.103
lgA/g·L^-1	0.6(0.4~1.0)	0.7(0.4~1.0)	Z=0.91	0.363
lgM/g·L^-1	0.8(0.7~1.0)	0.9(0.7~1.2)	Z=1.67	0.094
lgE/g·L^-1	15.1(4.7~40.5)	40.1(14.7~79.3)	Z=4.51	<0.001
补体C3/g·L^-1	1.1±0.2	1.1±0.3	t=1.26	0.573
补体C4/g·L^-1	0.2(0.1~0.4)	0.2(0.1~0.3)	Z=1.55	0.121

治疗天数	外周血血小板升高倍数		统计量	P
治疗天数	心肌损伤组(n=66)	非心肌损伤组(n=294)	统计量	P
第1天	1.4±0.6	1.5±0.8	t=1.45	0.151
第2天	3.8±1.7	4.3±2.8	t=1.70	0.090
第3天	8.59(0.43~17.79)	18.39(1.67~30.05)	Z=3.16	0.002
第4天	9.59(1.24~18.77)	23.04(2.18~46.94)	Z=3.61	<0.001