Laboratory indicators in the early differential diagnosis of sepsis and Kawasaki disease

doi:10.3877/cma.j.issn.1673-5250.2022.04.012

Objective

To explore biomarkers for early differential diagnosis of sepsis and Kawasaki disease.

Methods

Children diagnosed with sepsis and Kawasaki disease at the discharge from West China Second Hospital, Sichuan University from January 1, 2017 to February 28, 2018 were selected into this study, and they were included into sepsis group (n=286) and Kawasaki disease group (n=326), respectively. The levels of white blood cell count (WBC), absolute neutrophil count (ANC), C-reactive protein (CRP), platelet count (PLT), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), mean platelet volume (MPV), aspartate aminotransferase (AST), alanine transferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), serum creatinine (SCr), D-dimer (DD), fibrinogen degradation (FDP), troponin I (cTnI), myoglobin (Mb), hemoglobin (Hb), fibrinogen (Fg), partial pressure of oxygen in artery (PaO₂), fraction of inspired oxygen (FiO₂), activated partial thromboplastin time (APTT), international normalized ratio (INR), and other laboratory indexes between two groups were statistically analyzed by Mann-Whitney U rank sum test. The mortality and the incidence of coronary artery dilatation between two groups were statistically analyzed by chi-square test, continuity correction of chi-square test. There was no significant difference in gender ratio between two groups (P>0.05). This study was in line with the World Medical Association Declaration of Helsinki revised in 2013.

Results

The age of children in sepsis group was younger than that in Kawasaki disease group, but the fever duration before admission in sepsis group was shorter than that in Kawasaki disease group, and the differences between two groups were statistically significant (P<0.05). ②The PCT level in sepsis group was higher than that in Kawasaki disease group, but the percentage of neutrophils, ANC and ESR levels were lower than those in Kawasaki disease group, and the differences between two groups were statistically significant (P<0.05). In addition, in sepsis group, the proportion of PCT value >0.5 ng/mL and PCT value >2 ng/mL were higher than those of Kawasaki disease group, while the proportion of CRP level >30 mg/L and ESR >40 mm/h were lower than those of Kawasaki disease group, and the difference between two groups in terms of above indexes were statistically significant (P<0.05). ③The levels of MPV, AST, LDH, BUN, SCr, Cl^-, DD, FDP, cTnI and Mb in sepsis group were higher than those in Kawasaki disease group (P<0.05). In addition, the levels of Hb, PLT, ALT and Fg in sepsis group were lower than those in Kawasaki disease group, and the differences between groups were statistically significant (P<0.05). ④There were significant differences in the proportion of respiratory system dysfunction, circulatory system dysfunction, digestive system dysfunction, urinary system dysfunction, coagulation dysfunction, blood electrolyte abnormality, anemia and thrombocytosis between two groups (P<0.05). ⑤The mortality rates of children in sepsis group and Kawasaki disease group were 5.2% (15 cases) and 0, respectively, and the difference was statistically significant (χ²=17.527, P<0.001).

Conclusions

Childhood sepsis and Kawasaki disease are difficult to differentiate in the early stages and are easily misdiagnosed. Although many laboratory results are similar, there are some differences between the two. In children with sepsis, the organ damage is more severe and the prognosis is worse.

Key words: Sepsis, Mucocutaneous lymph node syndrome, Biomarkers, Diagnosis, differential, Ultrasonography, Doppler, color, Child

表1 2组患儿一般临床资料比较[M(Q₁，Q₃)]

组别	例数	年龄(岁)	入院前发热时间(d)
脓毒症组	286	12.0(5.0，36.0)	4(2，6)
川崎病组	326	24.0(12.0，36.0)	6(4，7)
Z值		—6.800	—7.274
P值		<0.001	<0.001

表1 2组患儿一般临床资料比较[M(Q₁，Q₃)]

组别	例数	年龄(岁)	入院前发热时间(d)
脓毒症组	286	12.0(5.0，36.0)	4(2，6)
川崎病组	326	24.0(12.0，36.0)	6(4，7)
Z值		—6.800	—7.274
P值		<0.001	<0.001

表2 2组患儿入院时炎症指标比较

组别	例数	WBC[×10⁹/L，M(Q₁，Q₃)]	中性粒细胞百分比[%，M(Q₁，Q₃)]	ANC[×10⁹/L，M(Q₁，Q₃)]	CRP[g/L，M(Q₁，Q₃)]	PCT[ng/mL，M(Q₁，Q₃)])	ESR[mm/h, M(Q₁，Q₃)]
脓毒症组	286	14.6(8.7，20.7)	60.6(45.9，76.9)	7.7(4.0，15.8)	84.0(30.0，150.5)	4.0(0.6，17.3)	46.0(19.0，65.5)
川崎病组	326	14.0(11.5，17.5)	70.2(59.5，80.0)	9.8(7.4，12.7)	82.0(50.0，117.3)	0.6(0.2，2.4)	59.5(45.8，80.2)
统计量		Z＝－0.422	Z＝－5.088	Z＝－2.378	Z＝－0.061	Z＝－7.397	Z＝－4.007
P值		0.673	<0.001	0.017	0.952	<0.001	<0.001
组别	例数	WBC>15×10⁹/L[例数(%)]	中性粒细胞百分比>80%[例数(%)]	CRP>30 mg/L[例数(%)]	PCT>0.5 ng/mL[%(n/n′)]	PCT>2.0 ng/mL[%(n/n′)]	ESR>40 mm/h[%(n/n′)]
脓毒症组	286	137(47.9)	55(19.2)	214(74.8)	81.3(139/171)	57.9(99/171)	55.1(38/69)
川崎病组	326	134(41.1)	81(24.8)	289(88.7)	56.7(123/217)	26.3(57/217)	82.1(225/274)
统计量		χ²＝2.853	χ²＝2.781	χ²＝19.892	χ²＝26.403	χ²＝39.793	χ²＝22.542
P值		0.091	0.095	<0.001	<0.001	<0.001	<0.001

表2 2组患儿入院时炎症指标比较

组别	例数	WBC[×10⁹/L，M(Q₁，Q₃)]	中性粒细胞百分比[%，M(Q₁，Q₃)]	ANC[×10⁹/L，M(Q₁，Q₃)]	CRP[g/L，M(Q₁，Q₃)]	PCT[ng/mL，M(Q₁，Q₃)])	ESR[mm/h, M(Q₁，Q₃)]
脓毒症组	286	14.6(8.7，20.7)	60.6(45.9，76.9)	7.7(4.0，15.8)	84.0(30.0，150.5)	4.0(0.6，17.3)	46.0(19.0，65.5)
川崎病组	326	14.0(11.5，17.5)	70.2(59.5，80.0)	9.8(7.4，12.7)	82.0(50.0，117.3)	0.6(0.2，2.4)	59.5(45.8，80.2)
统计量		Z＝－0.422	Z＝－5.088	Z＝－2.378	Z＝－0.061	Z＝－7.397	Z＝－4.007
P值		0.673	<0.001	0.017	0.952	<0.001	<0.001
组别	例数	WBC>15×10⁹/L[例数(%)]	中性粒细胞百分比>80%[例数(%)]	CRP>30 mg/L[例数(%)]	PCT>0.5 ng/mL[%(n/n′)]	PCT>2.0 ng/mL[%(n/n′)]	ESR>40 mm/h[%(n/n′)]
脓毒症组	286	137(47.9)	55(19.2)	214(74.8)	81.3(139/171)	57.9(99/171)	55.1(38/69)
川崎病组	326	134(41.1)	81(24.8)	289(88.7)	56.7(123/217)	26.3(57/217)	82.1(225/274)
统计量		χ²＝2.853	χ²＝2.781	χ²＝19.892	χ²＝26.403	χ²＝39.793	χ²＝22.542
P值		0.091	0.095	<0.001	<0.001	<0.001	<0.001

表3 脓毒症组与川崎病组其他实验室检查指标比较[M(Q₁，Q₃)]

组别	例数	Hb(g/L)	PLT(×10⁹/L)	MPV(fL)	ALT(U/L)	AST(U/L)	白蛋白((g/L)
脓毒症组	286	107.0(93.0，115.0)	287.0(197.0，396.2)	9.7(9.0，10.6)	35.0(27.0，48.0)	38.0(31.0，54.0)	37.3(32.5，40.6)
川崎病组	326	110.0(103.0，116.0)	321.5(274.0，395.0)	9.4(8.9，10.1)	40.0(27.0，86.5)	34.0(28.0，53.3)	37.3(34.1，40.8)
Z值		－3.727	－3.977	－2.597	－2.503	－2.838	－0.699
P值		<0.001	<0.001	0.009	0.012	0.005	0.484
组别	例数	TB(μmol/L)	IBIL(μmol/L)	LDH(U/L)	SCr(μmol/L)	BUN(mmol/L)	Na^＋(mmol/L)
脓毒症组	286	4.8(2.6，8.3)	4.3(2.4，7.8)	602.0(494.0，815.0)	31.0(26.0，40.0)	3.2(2.2，4.5)	135.8(132.9，138.0)
川崎病组	326	4.9(3.1，7.7)	4.2(2.5，6.1)	515.0(360.0，636.0)	29.0(25.0，34.0)	2.6(2.0，3.3)	136.0(133.4，138.6)
Z值		－0.444	－1.443	－6.530	－3.048	－4.715	－1.655
P值		0.657	0.149	<0.001	0.002	<0.001	0.098
组别	例数	K^＋(mmol/L)	Cl^－(mmol/L)	Ca^2＋(mmol/L)	血糖(mmol/L)	Fg(mg/dL)	DD(mg/L)
脓毒症组	286	4.1(3.7，4.5)	102.4(99.2，105.0)	2.3(2.1，2.4)	5.7(4.9，6.4)	391.0(257.0，570.0)	2.3(0.8，4.4)
川崎病组	326	4.1(3.6，4.4)	100.6(97.8，103.0)	2.3(2.2，2.4)	5.5(4.8，6.2)	570.0(455.0，644.0)	1.4(0.9，2.6)
Z值		－1.408	－4.649	－0.321	－1.699	－7.021	－2.037
P值		0.159	<0.001	0.749	0.089	<0.001	0.042
组别	例数	FDP(μg/L)	NTBNP(pg/mL)	cTnI(μg/L)	Mb(μg/L)	乳酸(mmol/L)
脓毒症组	286	8.7(4.9，17.1)	1 180.0(424.0，3 740.0)	0.012(0.012，0.017)	24.9(16.4，72.9)	1.7(1.2，2.6)
川崎病组	326	7.0(4.4，12.0)	1 010.0(387.0，3 070.0)	0.012(0.012，0.012)	16.2(12.4，25.6)	1.3(1.0，1.6)
Z值		－2.283	－0.545	－3.697	－6.131	－1.954
P值		0.022	0.586	<0.001	<0.001	0.051

表3 脓毒症组与川崎病组其他实验室检查指标比较[M(Q₁，Q₃)]

组别	例数	Hb(g/L)	PLT(×10⁹/L)	MPV(fL)	ALT(U/L)	AST(U/L)	白蛋白((g/L)
脓毒症组	286	107.0(93.0，115.0)	287.0(197.0，396.2)	9.7(9.0，10.6)	35.0(27.0，48.0)	38.0(31.0，54.0)	37.3(32.5，40.6)
川崎病组	326	110.0(103.0，116.0)	321.5(274.0，395.0)	9.4(8.9，10.1)	40.0(27.0，86.5)	34.0(28.0，53.3)	37.3(34.1，40.8)
Z值		－3.727	－3.977	－2.597	－2.503	－2.838	－0.699
P值		<0.001	<0.001	0.009	0.012	0.005	0.484
组别	例数	TB(μmol/L)	IBIL(μmol/L)	LDH(U/L)	SCr(μmol/L)	BUN(mmol/L)	Na^＋(mmol/L)
脓毒症组	286	4.8(2.6，8.3)	4.3(2.4，7.8)	602.0(494.0，815.0)	31.0(26.0，40.0)	3.2(2.2，4.5)	135.8(132.9，138.0)
川崎病组	326	4.9(3.1，7.7)	4.2(2.5，6.1)	515.0(360.0，636.0)	29.0(25.0，34.0)	2.6(2.0，3.3)	136.0(133.4，138.6)
Z值		－0.444	－1.443	－6.530	－3.048	－4.715	－1.655
P值		0.657	0.149	<0.001	0.002	<0.001	0.098
组别	例数	K^＋(mmol/L)	Cl^－(mmol/L)	Ca^2＋(mmol/L)	血糖(mmol/L)	Fg(mg/dL)	DD(mg/L)
脓毒症组	286	4.1(3.7，4.5)	102.4(99.2，105.0)	2.3(2.1，2.4)	5.7(4.9，6.4)	391.0(257.0，570.0)	2.3(0.8，4.4)
川崎病组	326	4.1(3.6，4.4)	100.6(97.8，103.0)	2.3(2.2，2.4)	5.5(4.8，6.2)	570.0(455.0，644.0)	1.4(0.9，2.6)
Z值		－1.408	－4.649	－0.321	－1.699	－7.021	－2.037
P值		0.159	<0.001	0.749	0.089	<0.001	0.042
组别	例数	FDP(μg/L)	NTBNP(pg/mL)	cTnI(μg/L)	Mb(μg/L)	乳酸(mmol/L)
脓毒症组	286	8.7(4.9，17.1)	1 180.0(424.0，3 740.0)	0.012(0.012，0.017)	24.9(16.4，72.9)	1.7(1.2，2.6)
川崎病组	326	7.0(4.4，12.0)	1 010.0(387.0，3 070.0)	0.012(0.012，0.012)	16.2(12.4，25.6)	1.3(1.0，1.6)
Z值		－2.283	－0.545	－3.697	－6.131	－1.954
P值		0.022	0.586	<0.001	<0.001	0.051

表4 2组患儿影像学及尿常规检查结果比较[%(n/n′)]

组别	例数	尿常规结果异常^a	胸部影像学检查提示炎性渗出	超声心动图
组别	例数	尿常规结果异常^a	胸部影像学检查提示炎性渗出	结果异常^b	冠状动脉扩张
脓毒症组	286	17.9(48/268)	70.7(152/215)	5.4(5/93)	0(0/93)
川崎病组	326	24.2(71/293)	52.3(68/130)	10.5(34/323)	10.8(35/323)
χ²值		3.347	11.859	2.254	11.003
P值		0.067	0.001	0.133	0.001

表4 2组患儿影像学及尿常规检查结果比较[%(n/n′)]

组别	例数	尿常规结果异常^a	胸部影像学检查提示炎性渗出	超声心动图
组别	例数	尿常规结果异常^a	胸部影像学检查提示炎性渗出	结果异常^b	冠状动脉扩张
脓毒症组	286	17.9(48/268)	70.7(152/215)	5.4(5/93)	0(0/93)
川崎病组	326	24.2(71/293)	52.3(68/130)	10.5(34/323)	10.8(35/323)
χ²值		3.347	11.859	2.254	11.003
P值		0.067	0.001	0.133	0.001

表5 2组判断患儿脏器功能损伤情况指标的发生率比较[%(n/n′)]

组别	例数	循环系统功能损伤			消化系统功能损伤
组别	例数	乳酸>2 mmol/L	cTnI>0.034 μg/L	NTBNP>450 pg/mL	AST>基线2倍	ALT>基线2倍	TB>70 μmol/L	白蛋白<30 g/L
脓毒症组	286	38.3(41/107)	18.8(29/154)	73.7(73/99)	10.8(30/279)	7.5(21/279)	2.2(6/278)	13.7(38/278)
川崎病组	326	0(0/8)	5.5(12/218)	72.3(112/155)	8.1(26/322)	13.4(43/322)	0.3(1/320)	7.2(23/321)
χ²值		3.241^a	16.344	0.067	1.269	5.334	2.931^a	6.890
P值		0.072	<0.001	0.796	0.260	0.021	0.087	0.009
组别	例数	呼吸系统功能损伤		凝血功能异常
组别	例数	需呼吸支持^b	PaO₂/FiO₂<300 mmHg	PT延长>3 s	APTT延长>10 s	INR>1.5	Fg<200 mg/L	Fg>400 mg/L
脓毒症组	286	12.9(37/286)	27.6(79/286)	15.7(25/159)	20.8(33/159)	10.8(17/157)	16.8(26/155)	49.0(76/155)
川崎病组	326	0.3(1/326)	2.1(7/326)	1.9(4/216)	4.2(9/216)	1.0(2/205)	0.9(2/215)	83.3(179/215)
χ²值		41.732	81.862	24.697	25.338	17.354	32.323	49.247
P值		<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001
组别	例数	凝血功能异常				泌尿系统功能损害
组别	例数	DD升高	FDP升高	PLT<150×10⁹/L	PLT<100×10⁹/L	BUN>基线1.5倍	SCr>基线1.5倍
脓毒症组	286	82.2(74/90)	74.4(67/90)	13.6(39/286)	7.7(22/286)	4.3(12/276)	4.3(12/276)
川崎病组	326	92.0(126/137)	65.4(89/136)	2.1(7/326)	0.9(3/326)	0.3(1/310)	0.3(1/310)
χ²值		4.926	2.053	28.929	17.832	10.906	10.906
P值		0.026	0.152	<0.001	<0.001	0.001	0.001
组别	例数	血电解质异常				Hb<90 g/L	PLT>450×10⁹/L
组别	例数	Na^＋<130 mmol/L	K^＋<3.5 mmol/L	K^＋>5.5 mmol/L	Ca^2＋<2.1 mmol/L	Hb<90 g/L	PLT>450×10⁹/L
脓毒症组	286	10.5(29/276)	19.6(54/276)	3.3(9/276)	17.9(49/273)	21.3(61/286)	17.5(50/286)
川崎病组	326	4.8(15/311)	19.3(60/311)	0.3(1/311)	5.8(18/311)	4.6(15/326)	14.1(46/326)
χ²值		6.814	0.007	5.891^a	21.169	39.194	1.310
P值		0.009	0.934	0.015^a	<0.001	<0.001	0.252

表5 2组判断患儿脏器功能损伤情况指标的发生率比较[%(n/n′)]

组别	例数	循环系统功能损伤			消化系统功能损伤
组别	例数	乳酸>2 mmol/L	cTnI>0.034 μg/L	NTBNP>450 pg/mL	AST>基线2倍	ALT>基线2倍	TB>70 μmol/L	白蛋白<30 g/L
脓毒症组	286	38.3(41/107)	18.8(29/154)	73.7(73/99)	10.8(30/279)	7.5(21/279)	2.2(6/278)	13.7(38/278)
川崎病组	326	0(0/8)	5.5(12/218)	72.3(112/155)	8.1(26/322)	13.4(43/322)	0.3(1/320)	7.2(23/321)
χ²值		3.241^a	16.344	0.067	1.269	5.334	2.931^a	6.890
P值		0.072	<0.001	0.796	0.260	0.021	0.087	0.009
组别	例数	呼吸系统功能损伤		凝血功能异常
组别	例数	需呼吸支持^b	PaO₂/FiO₂<300 mmHg	PT延长>3 s	APTT延长>10 s	INR>1.5	Fg<200 mg/L	Fg>400 mg/L
脓毒症组	286	12.9(37/286)	27.6(79/286)	15.7(25/159)	20.8(33/159)	10.8(17/157)	16.8(26/155)	49.0(76/155)
川崎病组	326	0.3(1/326)	2.1(7/326)	1.9(4/216)	4.2(9/216)	1.0(2/205)	0.9(2/215)	83.3(179/215)
χ²值		41.732	81.862	24.697	25.338	17.354	32.323	49.247
P值		<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001
组别	例数	凝血功能异常				泌尿系统功能损害
组别	例数	DD升高	FDP升高	PLT<150×10⁹/L	PLT<100×10⁹/L	BUN>基线1.5倍	SCr>基线1.5倍
脓毒症组	286	82.2(74/90)	74.4(67/90)	13.6(39/286)	7.7(22/286)	4.3(12/276)	4.3(12/276)
川崎病组	326	92.0(126/137)	65.4(89/136)	2.1(7/326)	0.9(3/326)	0.3(1/310)	0.3(1/310)
χ²值		4.926	2.053	28.929	17.832	10.906	10.906
P值		0.026	0.152	<0.001	<0.001	0.001	0.001
组别	例数	血电解质异常				Hb<90 g/L	PLT>450×10⁹/L
组别	例数	Na^＋<130 mmol/L	K^＋<3.5 mmol/L	K^＋>5.5 mmol/L	Ca^2＋<2.1 mmol/L	Hb<90 g/L	PLT>450×10⁹/L
脓毒症组	286	10.5(29/276)	19.6(54/276)	3.3(9/276)	17.9(49/273)	21.3(61/286)	17.5(50/286)
川崎病组	326	4.8(15/311)	19.3(60/311)	0.3(1/311)	5.8(18/311)	4.6(15/326)	14.1(46/326)
χ²值		6.814	0.007	5.891^a	21.169	39.194	1.310
P值		0.009	0.934	0.015^a	<0.001	<0.001	0.252

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