Assessment indicators for discontinuing treatment of low dose aspirin in children with Kawasaki disease

doi:10.3877/cma.j.issn.1673-5250.2018.06.011

Objective

To investigate the effect of discontinuing low dose aspirin treatment on the efficacy and prognosis of Kawasaki disease based on normalization time of inflammation indexes and thrombus markers, and echocardiography results.

Methods

From June 2013 to December 2017, a total of 82 children with Kawasaki disease who were hospitalized at the Children′s Hospital of Capital Institute of Pediatrics were chosen as research objects. According to the type of Kawasaki disease, 82 children were divided into complete Kawasaki disease (CKD) group (n=48) and incomplete Kawasaki disease (IKD) group (n=34). In addition, 82 children were also divided into coronary artery lesion (CAL) group (n=9) and none CAL group (n=73) according to whether complicated with CAL of the results of echocardiography at discharge from hospital. Low dose aspirin with 3-5 mg/(kg·d) by oral were given to all patients at the time point of 72 h of normal body temperature after acute phase treatment. During 8 weeks of follow up period after discharge from hospital, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) of inflammation indexes, as well as platelet and D-dimer levels of thrombus markers were monitored; when all these four indicators were normalized and CAL were not found by echocardiography, low dose aspirin were discontinued and still continued follow up until 8 weeks after discharge. Statistical analysis was performed on the following measurement and numeration data using t test, Wilcoxon rank sum test and chi-square test. ① Clinical data at admission, as well as normalization time of inflammatory indexes and thrombus markers after treatment between CKD group and IKD group, also between CAL group and none CAL group of children. ② Normalization time of inflammatory indexes of 82 cases of Kawasaki disease children among different conditions. This study was in line with World Medical Association Declaration of Helsinki revised in 2013.

Results

① Comparison of serum CRP and D-dimer levels in children with Kawasaki disease at admission: CRP and D-dimer levels were (10.2±4.9) mg/L and (1.1±0.3) mg/L, respectively in CKD group, which were higher than IKD group′s (7.4±3.9) mg/L and (0.9±0.5) mg/L; and those two indexes in CAL group were (13.9±7.6) mg/L and (1.7±1.5) mg/L, respectively, which were higher than none CAL group′s (8.5±3.9) mg/L and (1.0±0.7) mg/L, and all the differences above were statistically significant (t=2.638, P=0.007; t=2.716, P=0.027; t=3.402, P=0.001; t=0.382, P=0.017). Comparison of serum albumin levels in children with Kawasaki disease at admission: serum albumin level was (35.5±4.3) g/L in CKD group, which was lower than IKD group′s (37.5±3.6) g/L; and this index was (32.3±3.5) g/L in CAL group, which was lower than none CAL group′s (36.4±3.8) g/L, and the differences were statistically significant (t=2.324, P=0.016; t=4.170, P<0.001). ② There were no significant differences between CKD group and IKD group, or between CAL group and none CAL group in ratio of males, Harada scores, white blood cell count, hemoglobin (Hb) value, hematocrit (HCT), blood platelet count, erythrocyte sedimentation rate (ESR), aspartate aminotransferase (AST) and alanine transarninase (ALT) levels at admission, also normalization time of ESR, CRP, blood platelet count and D-dimer level after treatment (P>0.05). ③The normalization times of inflammatory indexes and thrombus markers in 82 children with Kawasaki disease after treatment were (44.2±9.4) d of ESR, (14.4±5.5) d of CRP, (31.5±10.9) d of blood platelet count and (33.5±6.3) d of D-dimer level. ④The normalization time of ESR and CRP in male children with Kawasaki disease of this study were (46.3±5.2) d and (16.4±5.6) d, respectively, which were longer than female children′s (43.4±5.0) d and (13.3±4.8) d, and the differences were statistically significant (t=2.106, P=0.012; t=2.308, P=0.010). There were no significant differences under the condition between the persistent of fever ≥7 d and <7 d, between response to and no response to intravenous immunoglobulin (IVIG), betweem Harada score ≥4 and <4 in normalization time of ESR and CRP (P>0.05). ⑤One CKD child complicated with CAL and the other 73 children without CAL at the time of discharge had normalized levels of inflammatory indexes and thrombus markers after 3-4 weeks of discharge, also no CAL by echocardiography. Therefore, low dose aspirin treatment was discontinued for these children, and no new CAL occurred during the follow up period.

Conclusions

By monitoring the levels of inflammatory indexes and thrombus markers, and with echocardiography, low dose aspirin treatment after acute phase of Kawasaki disease can be adjusted individually without affecting clinical efficacy and prognosis.

Key words: Mucocutaneous lymph node syndrome, Aspirin, Blood sedimentation, C-reactive protein, Thrombosis, Echocardiography, Child

表1 CKD组与IKD组患儿入院时临床资料，以及治疗后炎症指标和血栓标志物恢复正常的时间比较

组别	例数	年龄(岁，±s)	男性[例数(%)]	Harada评分(分，±s)	白细胞计数(×10⁹/L，±s)	Hb(g/L，±s)	HCT(%，±s)
CKD组	48	2.6±1.5	32(66.7)	3.5±1.1	15.9±4.9	115.6±7.3	33.6±1.9
IKD组	34	2.0±1.6	17(50.0)	3.7±1.0	16.0±4.6	115.8±9.2	33.4±2.1
检验值	?	t＝1.571	χ²＝0.129	t＝0.842	t＝0.112	t＝0.000	t＝0.317
P值	?	0.086	0.129	0.402	0.926	1.000	0.654
组别	例数	血小板计数(×10⁹/L，±s)	ESR(mm/h，±s )	CRP(mg/L，±s)	D-二聚体(mg/L，±s)	AST[IU/L，M(P₂₅～P₇₅)]	ALT[IU/L，M(P₂₅～P₇₅)]
CKD组	48	351.3±27.8	78.6±27.8	10.2±4.9	1.1±0.3	99(57～312)	108(54～256)
IKD组	34	336.1±75.6	71.1±26.7	7.4±3.9	0.9±0.5	67(55～179)	82(50～257)
检验值	?	t＝1.281	t＝1.196	t＝2.638	t＝2.716	T＝37.000	T＝29.000
P值	?	0.205	0.225	0.007	0.027	0.266	0.422
组别	例数	血清白蛋白(g/L，±s)	炎症指标和血栓标志物恢复正常的时间(d，±s)
组别	例数	血清白蛋白(g/L，±s)	ESR	CRP	血小板计数	D-二聚体
CKD组	48	35.5±4.3	44.8±8.5	14.7±4.5	31.8±9.5	32.3±6.4
IKD组	34	37.5±3.6	43.4±8.2	13.5±5.7	30.6±8.5	35.0±6.7
检验值	?	t＝2.324	t＝1.332	t＝0.763	t＝0.205	t＝1.105
P值	?	0.016	0.641	0.466	0.719	0.238

表1 CKD组与IKD组患儿入院时临床资料，以及治疗后炎症指标和血栓标志物恢复正常的时间比较

组别	例数	年龄(岁，±s)	男性[例数(%)]	Harada评分(分，±s)	白细胞计数(×10⁹/L，±s)	Hb(g/L，±s)	HCT(%，±s)
CKD组	48	2.6±1.5	32(66.7)	3.5±1.1	15.9±4.9	115.6±7.3	33.6±1.9
IKD组	34	2.0±1.6	17(50.0)	3.7±1.0	16.0±4.6	115.8±9.2	33.4±2.1
检验值	?	t＝1.571	χ²＝0.129	t＝0.842	t＝0.112	t＝0.000	t＝0.317
P值	?	0.086	0.129	0.402	0.926	1.000	0.654
组别	例数	血小板计数(×10⁹/L，±s)	ESR(mm/h，±s )	CRP(mg/L，±s)	D-二聚体(mg/L，±s)	AST[IU/L，M(P₂₅～P₇₅)]	ALT[IU/L，M(P₂₅～P₇₅)]
CKD组	48	351.3±27.8	78.6±27.8	10.2±4.9	1.1±0.3	99(57～312)	108(54～256)
IKD组	34	336.1±75.6	71.1±26.7	7.4±3.9	0.9±0.5	67(55～179)	82(50～257)
检验值	?	t＝1.281	t＝1.196	t＝2.638	t＝2.716	T＝37.000	T＝29.000
P值	?	0.205	0.225	0.007	0.027	0.266	0.422
组别	例数	血清白蛋白(g/L，±s)	炎症指标和血栓标志物恢复正常的时间(d，±s)
组别	例数	血清白蛋白(g/L，±s)	ESR	CRP	血小板计数	D-二聚体
CKD组	48	35.5±4.3	44.8±8.5	14.7±4.5	31.8±9.5	32.3±6.4
IKD组	34	37.5±3.6	43.4±8.2	13.5±5.7	30.6±8.5	35.0±6.7
检验值	?	t＝2.324	t＝1.332	t＝0.763	t＝0.205	t＝1.105
P值	?	0.016	0.641	0.466	0.719	0.238

表2 CAL组与无CAL组患儿入院时临床资料，以及治疗后炎症指标和血栓标志物恢复正常的时间比较

组别	例数	年龄(岁，±s)	男性[例数(%)]	Harada评分(分，±s)	白细胞计数(×10⁹/L，±s)	Hb(g/L，±s)	HCT(%，±s)
CAL组	9	3.6±1.5	7(77.8)	4.2±1.7	18.8±5.4	113.4±6.5	33.3±1.4
无CAL组	73	2.2±1.5	42(57.5)	3.6±1.0	15.6±4.6	116.7±8.9	33.5±2.0
检验值	?	t＝0.021	χ²＝1.167	t＝1.517	t＝1.816	t＝1.063	t＝0.087
P值	?	0.010	0.243	0.123	0.057	0.281	0.772
组别	例数	血小板计数(×10⁹/L，±s)	ESR(mm/h，±s )	CRP(mg/L，±s)	D-二聚体(mg/L，±s)	AST[IU/L，M(P₂₅～P₇₅)]	ALT[IU/L，M(P₂₅～P₇₅)]
CAL组	9	376.3±19.5	85.1±28.6	13.9±7.6	1.7±1.5	100(60～285)	140(55～312)
无CAL组	73	341.2±75.5	74.4±27.3	8.5±3.9	1.0±0.7	85(47～300)	90(48～276)
检验值	?	t＝0.364	t＝1.087	t＝3.402	t＝0.382	T＝23.000	T＝34.000
P值	?	0.171	0.273	0.001	0.017	0.790	0.295
组别	例数	血清白蛋白(g/L，±s)	炎症指标和血栓标志物恢复正常的时间(d，±s)
组别	例数	血清白蛋白(g/L，±s)	ESR	CRP	血小板计数	D-二聚体
CAL组	9	32.3±3.5	46.2±9.1	14.5±5.1	36.5±9.7	30.8±5.7
无CAL组	73	36.4±3.8	40.6±8.2	14.3±4.6	30.8±10.7	34.3±6.9
检验值	?	t＝4.170	t＝0.131	t＝0.425	t＝1.463	t＝1.376
P值	?	<0.001	0.060	0.904	0.132	0.148

表2 CAL组与无CAL组患儿入院时临床资料，以及治疗后炎症指标和血栓标志物恢复正常的时间比较

组别	例数	年龄(岁，±s)	男性[例数(%)]	Harada评分(分，±s)	白细胞计数(×10⁹/L，±s)	Hb(g/L，±s)	HCT(%，±s)
CAL组	9	3.6±1.5	7(77.8)	4.2±1.7	18.8±5.4	113.4±6.5	33.3±1.4
无CAL组	73	2.2±1.5	42(57.5)	3.6±1.0	15.6±4.6	116.7±8.9	33.5±2.0
检验值	?	t＝0.021	χ²＝1.167	t＝1.517	t＝1.816	t＝1.063	t＝0.087
P值	?	0.010	0.243	0.123	0.057	0.281	0.772
组别	例数	血小板计数(×10⁹/L，±s)	ESR(mm/h，±s )	CRP(mg/L，±s)	D-二聚体(mg/L，±s)	AST[IU/L，M(P₂₅～P₇₅)]	ALT[IU/L，M(P₂₅～P₇₅)]
CAL组	9	376.3±19.5	85.1±28.6	13.9±7.6	1.7±1.5	100(60～285)	140(55～312)
无CAL组	73	341.2±75.5	74.4±27.3	8.5±3.9	1.0±0.7	85(47～300)	90(48～276)
检验值	?	t＝0.364	t＝1.087	t＝3.402	t＝0.382	T＝23.000	T＝34.000
P值	?	0.171	0.273	0.001	0.017	0.790	0.295
组别	例数	血清白蛋白(g/L，±s)	炎症指标和血栓标志物恢复正常的时间(d，±s)
组别	例数	血清白蛋白(g/L，±s)	ESR	CRP	血小板计数	D-二聚体
CAL组	9	32.3±3.5	46.2±9.1	14.5±5.1	36.5±9.7	30.8±5.7
无CAL组	73	36.4±3.8	40.6±8.2	14.3±4.6	30.8±10.7	34.3±6.9
检验值	?	t＝4.170	t＝0.131	t＝0.425	t＝1.463	t＝1.376
P值	?	<0.001	0.060	0.904	0.132	0.148

表3 川崎病患儿按照不同分类情况下炎症指标恢复正常的时间比较

项目		例数	炎症指标恢复正常的时间
项目		例数	ESR(d，±s)	t值	P值	CRP(d，±s)	t值	P值
性别		?	?	2.106	0.012	?	2.308	0.010
?	男	49	46.3±5.2	?	?	16.4±5.6	?	?
?	女	33	43.4±5.0	?	?	13.3±4.8	?	?
发热持续时间(d)		?	?	1.046	0.162	?	0.746	0.182
?	≥7	20	47.0±8.5	?	?	41.6±6.9	?	?
?	<7	62	43.2±11.0	?	?	44.5±8.6	?	?
对IVIG的反应		?	?	1.053	0.160	?	0.835	0.207
?	有反应	70	46.4±10.6	?	?	41.6±6.9	?	?
?	无反应	12	50.9±7.4	?	?	54.5±8.6	?	?
Harada评分(分)		?	?	0.326	0.701	?	0.412	0.524
?	≥4	50	45.1±9.6	?	?	33.6±8.3	?	?
?	<4	32	44.2±10.0	?	?	32.4±6.8	?	?

表3 川崎病患儿按照不同分类情况下炎症指标恢复正常的时间比较

项目		例数	炎症指标恢复正常的时间
项目		例数	ESR(d，±s)	t值	P值	CRP(d，±s)	t值	P值
性别		?	?	2.106	0.012	?	2.308	0.010
?	男	49	46.3±5.2	?	?	16.4±5.6	?	?
?	女	33	43.4±5.0	?	?	13.3±4.8	?	?
发热持续时间(d)		?	?	1.046	0.162	?	0.746	0.182
?	≥7	20	47.0±8.5	?	?	41.6±6.9	?	?
?	<7	62	43.2±11.0	?	?	44.5±8.6	?	?
对IVIG的反应		?	?	1.053	0.160	?	0.835	0.207
?	有反应	70	46.4±10.6	?	?	41.6±6.9	?	?
?	无反应	12	50.9±7.4	?	?	54.5±8.6	?	?
Harada评分(分)		?	?	0.326	0.701	?	0.412	0.524
?	≥4	50	45.1±9.6	?	?	33.6±8.3	?	?
?	<4	32	44.2±10.0	?	?	32.4±6.8	?	?

[1]	谢添. 川崎病的治疗与随访[J]. 国际儿科学杂志，2017, 44(11): 757-760, 764.
[2]	余莉，王一斌，乔莉娜，等. 川崎病并发冠状动脉损伤的危险因素分析[J/CD]. 中华妇幼临床医学杂志(电子版), 2015, 11(2): 240-243.
[3]	JCS Joint Working Group. Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease (JCS 2013). Digest version[J]. Circ J, 2014, 78(10): 2521-2562.
[4]	周东春. 小儿川崎病的临床诊治进展[J]. 医药前沿，2017, 7 (22): 6-8.
[5]	林瑶，李晓惠，石琳，等. 2017年版《川崎病的诊断、治疗及远期管理—美国心脏协会对医疗专业人员的科学声明》解读[J]. 中国实用儿科杂志，2017, 32(9): 641-648.
[6]	McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association[J]. Circulation, 2017, 135(17): e927-e999.
[7]	世界华人检验与病理医师协会，中国医师协会检验医师分会，心血管检验医学专业委员会. 血小板功能检测在急性冠脉综合征患者抗血小板治疗中的应用专家共识[J]. 中华医学杂志，2018, 98(22): 1743-1751.
[8]	司博林，申瑞芳，罗燕萍，等. 腹膜透析患者残肾功能对血管内皮细胞功能的影响[J]. 临床荟萃，2017, 32(8): 691-694.
[9]	马乐，杜忠东. 川崎病血管内皮细胞损伤机制的研究进展[J]. 中华儿科杂志，2016, 54(2): 158-160.
[10]	陈芳，杨作成. 内皮细胞功能障碍与川崎病冠状动脉病变的关系[J]. 中华实用儿科临床杂志，2014, 29(9): 704-706.
[11]	张海明. 小儿川崎病应用丙种球蛋白联合阿司匹林治疗的临床疗效观察[J]. 中国社区医师，2018(4): 82-83.
[12]	吴美，王川，华益民，等. 川崎病静脉注射免疫球蛋白抵抗评分系统研究进展[J/CD]. 中华妇幼临床医学杂志(电子版), 2017, 13(1): 99-104.
[13]	Agarwal S, Agrawal DK. Kawasaki disease: etiopathogenesis and novel treatment strategies[J]. Expert Rev Clin Immunol, 2017, 13(3): 247-258.
[14]	Oh IJ, Moon KH, Hong ME, et al. Clinical significance of follow-up laboratory tests, performed at 6 weeks after the onset of Kawasaki disease[J]. Korean J Pediatr, 2006, 49(6): 672-676.
[15]	Ou CY, Tseng YF, Lee CL, et al. Significant relationship between serum high-sensitivity C-reactive protein, high-density lipoprotein cholesterol levels and children with Kawasaki disease and coronary artery lesions[J]. J Formos Med Assoc, 2009, 108(9): 719-724.
[16]	赵丽丽，王一彪，索琳. C反应蛋白与川崎病并发冠状动脉病变的关系[J]. 山东大学学报(医学版), 2011, 49(8): 128-132.
[17]	张丽，曹睿，虢艳，等. 川崎病冠状动脉病变的超声心动图诊断[J]. 中华实用儿科临床杂志，2014, 29(13): 963-965.
[18]	Yoshino A, Tanaka R, Takano T, et al. Afebrile Kawasaki disease with coronary artery dilatation[J]. Pediatr Int, 2017, 59(3): 375-377.
[19]	Wang Z, Weng F, Li C, et al. Neutropenia after intravenous immunoglobulin therapy is associated with coronary artery lesions in children with Kawasaki disease: a case control study[J]. BMC Pediatr, 2018, 18(1): 76.
[20]	Xie L, Wang R, Huang M, et al. Quantitative evaluation of myocardial fibrosis by cardiac integrated backscatter analysis in Kawasaki disease[J]. Cardiovasc Ultrasound, 2016, 14: 3.

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