噬血细胞性淋巴组织细胞增生症与脓毒症临床特征比较

doi:10.12372/jcp.2024.22e1731

摘要/Abstract

摘要：

目的比较噬血细胞性淋巴组织细胞增生症（HLH）与脓毒症的临床特征，寻找帮助鉴别诊断的实验室指标。方法回顾性分析2013年1月—2020年12月无基础疾病HLH以及发热伴外周血二系细胞减少或脾脏肿大的脓毒症患儿的临床资料。结果共106例患儿纳入研究。HLH组患儿72例，男46例、女26例，中位年龄26.5（14.3~56.8）个月；脓毒症组患儿34例，男18例、女16例，中位年龄14.0（3.8~89.0）个月。脓毒症组总住院时间和PICU入住时间均长于HLH组，差异有统计学意义（P<0.05）。与脓毒症组相比，HLH组的白细胞计数（WBC）-Min、中性粒细胞绝对值（ANC）-Min、血红蛋白（HB）-Min、血小板计数-Min、肌酐（CREA）-Max、纤维蛋白原（FIB）-Min、C反应蛋白-Max、降钙素原（PCT）-Max较低，三酰甘油-Max、血清铁蛋白（SF）-Max较高，HB减少持续时间较短，ANC减少持续时间较长，组间差异均有统计学意义（均P<0.05）。多因素logistic回归分析发现WBC-Min、FIB-Min、CREA-Max和PCT-Max水平的下降有助于诊断HLH（P<0.05）。ROC曲线分析显示，SF-Max协助判断HLH的AUC为0.72（95%CI：0.62~0.80）。经logistic回归方程拟合，获得WBC-Min、FIB-Min、CREA-Max和PCT-Max的联合预测因子，其协助判断HLH的AUC为0.95（95%CI：0.89~0.99）；联合预测因子的AUC显著大于SF-Max，差异有统计学意义（P<0.01）。结论 WBC-Min、FIB-Min、CREA-Max、PCT-Max四项指标拟合可能有助于更好鉴别HLH和脓毒症。

关键词: 噬血细胞性淋巴组织细胞增生症, 脓毒症, 血清铁蛋白, 临床特征

Abstract:

Objective To compare the clinical features of hemophagocytic lymphohistiocytosis (HLH) and sepsis, and to find laboratory markers to help differential diagnosis. Methods The clinical data of HLH children without underlying disease or sepsis children with fever and decreased peripheral blood two cell lines or splenomegaly from January 2013 to December 2020 was retrospectively analyzed. Results A total of 106 patients were enrolled in this study. There were 72 children (46 boys and 26 girls) in the HLH group, and the median age was 26.5 (14.3-56.8) months. There were 34 children (18 boys and 16 girls) in the sepsis group, and the median age was 14.0 (3.8-89.0) months. The total length of hospital stay and PICU stay in the sepsis group were longer than those in the HLH group, and the differences were statistically significant (P<0.05). Compared with the sepsis group, the white blood cell count (WBC)-Min, absolute neutrophil count (ANC)-Min, hemoglobin (HB)-Min, platelet count (PLT)-Min, creatinine (CREA)-Max, fibrinogen (FIB)-Min, C-reactive protein (CRP)-Max, and procalcitonin (PCT)-Max were lower, and triglyceride-Max and serum ferritin (SF)-Max were higher in the HLH group. The duration of HB reduction was shorter in the HLH group, while the duration of ANC reduction was longer, and the differences between the two groups were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the decreased levels of WBC-Min, FIB-Min, CREA-Max and PCT-Max were helpful for the diagnosis of HLH (P<0.05). The AUC of SF-Max to aid in the diagnosis of HLH was 0.72 (95%CI: 0.62-0.80), according to ROC curve analysis. The combined predictors of WBC-Min, FIB-Min, CREA-Max and PCT-Max were obtained by logistic regression equation fitting, and the AUC of which in the diagnosis of HLH was 0.95 (95%CI: 0.89-0.99). The AUC of the combined predictors was significantly larger than that of SF-Max, and the difference was statistically significant (P<0.01). Conclusions The fitting of WBC-Min, FIB-Min, CREA-Max and PCT-Max may help to better distinguish HLH from sepsis.

Key words: hemophagocytic lymphohistiocytosis, sepsis, serum ferritin, clinical characteristics

钟小梅, 任宏, 张建, 李璧如, 钱娟, 宁铂涛, 高怡瑾, 王莹. 噬血细胞性淋巴组织细胞增生症与脓毒症临床特征比较[J]. 临床儿科杂志, 2024, 42(6): 547-552.

ZHONG Xiaomei, REN Hong, ZHANG Jian, LI Biru, QIAN Juan, NING Botao, GAO Yijin, WANG Ying. Comparison of clinical features between hemophagocytic lymphohistiocytosis and sepsis[J]. Journal of Clinical Pediatrics, 2024, 42(6): 547-552.

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参考文献 19

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项目	HLH组(n=72)	脓毒症组(n=34)	统计量	P
男性[n(%)]	46(63.9)	18(52.9)	χ²=1.16	0.282
年龄[M(P₂₅~P₇₅)]/月	26.5(14.3~56.8)	14.0(3.8~89.0)	Z=1.47	0.143
总住院时间[M(P₂₅~P₇₅)]/d	15.5(9.5~26.8)	31.0(14.3~39.5)	Z=2.65	0.008
PICU入住时间[M(P₂₅~P₇₅)]/d	3.5(0~10.0)	14.5(5.0~25.5)	Z=4.73	<0.001
治疗结局[n(%)]
存活	48(66.7)	22(64.7)	χ²=0.04	0.842
死亡	24(33.3)	12(35.3)

实验室指标	HLH组(n=72)	脓毒症组(n=34)	统计量	P
WBC-Min[M(P₂₅~P₇₅)]/×10⁹·L^-1	1.1(0.6~2.0)	3.5(2.0~4.4)	Z=5.30	<0.001
ANC-Min[M(P₂₅~P₇₅)]/×10⁹·L^-1	0.3(0.1~1.1)	1.1(0.6~2.9)	Z=4.49	<0.001
ANC减少持续时间[M(P₂₅~P₇₅)]/d	4.5(0~10.5)	0(0~2.0)	Z=4.44	<0.001
HB-Min[M(P₂₅~P₇₅)]/g·L^-1	61.5(55.5~74.5)	69.0(63.0~78.0)	Z=2.36	0.018
HB减少持续时间[M(P₂₅~P₇₅)]/d	5.5(2.0~12.0)	8.0(5.0~18.0)	Z=2.30	0.021
PLT-Min[M(P₂₅~P₇₅)]/×10⁹·L^-1	18.0(9.0~47.5)	44.0(12.0~101.0)	Z=2.38	0.017
PLT减少持续时间[M(P₂₅~P₇₅)]/d	6.0(3.0~12.5)	4.0(2.0~9.0)	Z=1.59	0.111
脏器功能指标
TBIL-Max[M(P₂₅~P₇₅)]/μmol·L^-1	49.6(18.0~97.4)	31.9(17.0~84.9)	Z=0.62	0.533
ALT-Max[M(P₂₅~P₇₅)]/U·L^-1	228.5(126.5~441.5)	153.5(57.0~451.0)	Z=1.30	0.194
AST-Max[M(P₂₅~P₇₅)]/U·L^-1	452.0(184.5~781.0)	248.5(103.0~471.0)	Z=1.56	0.118
TG-Max[M(P₂₅~P₇₅)]/mmol·L^-1	3.5(2.9~4.1)	1.9(1.3~3.6)	Z=3.65	<0.001
ALB-Min(x±s)/g·L^-1	26.1±6.4	26.8±7.3	t=0.48	0.632
CREA-Max[M(P₂₅~P₇₅)]/μmol·L^-1	28.0(21.0~39.5)	51.5(33.0~72.0)	Z=4.19	<0.001
凝血指标[M(P₂₅~P₇₅)]
APTT-Max/s	50.8(41.2~63.2)	54.0(44.0~107.6)	Z=1.13	0.257
PT-Max/s	15.2(13.2~22.1)	19.3(14.3~23.6)	Z=1.51	0.130
FIB-Min/g·L^-1	0.9(0.6~1.3)	1.7(1.0~2.4)	Z=3.82	<0.001
D二聚体-Max/mg·L^-1	5.1(2.1~11.4)	3.0(1.0~6.0)	Z=1.41	0.158
炎症指标[M(P₂₅~P₇₅)]
CRP-Max/mg·L^-1	32.5(11.0~101.0)	144.5(81.0~200.0)	Z=4.23	<0.001
PCT-Max/ng·mL^-1	1.1(0.4~4.1)	8.7(4.1~84.8)	Z=5.39	<0.001
SF-Max/ng·mL^-1	4 500.0(1 589.4~4 500.0)	1 133.7(391.8~4 500.0)	Z=3.80	<0.001
LDH-Max/U·L^-1	2 738.0(1 732.5~5 297.5)	2 126.0(1 141.0~5 140.0)	Z=1.47	0.143

变量	偏回归系数	标准误	χ²值	P	OR(95%CI)
WBC-Min	-0.84	0.29	8.66	0.003	0.43(0.25~0.76)
CREA-Max	-0.02	0.01	4.86	0.028	0.98(0.96~0.998)
FIB-Min	-1.11	0.47	5.53	0.019	0.33(0.13~0.83)
PCT-Max	-0.08	0.03	6.43	0.011	0.92(0.87~0.98)
常量	6.31	1.49	17.87	<0.001	－

指标	AUC(95%CI)	P	截断值	灵敏度/%	特异度/%
SF-Max/ng·mL^-1	0.72 (0.62~0.80)	<0.001	1 739.60	73.6	67.6
联合指标	0.95(0.89~0.99)	<0.001	0.77	87.0	90.9