继发性噬血细胞性淋巴组织细胞增多症早期死亡高危临床因素分析

Analysis of High-Risk Clinical Factors of Early Death in Secondary Hemophagocytic Lymphohistiocytosis

目的:探索继发性噬血细胞性淋巴组织细胞增多症(s HLH)患者发生早期死亡的高危临床因素,进一步识别与s HLH短期内迅速恶化进展的临床相关因素。方法:回顾性分析s HLH患者的临床表现、实验室检查及预后,连续性变量采用中位数进行分组,采用单因素及多因素Cox回归分析、Kaplan-Meier生存曲线来探讨影响s HLH早期死亡的高危临床因素,用独立危险因素建立列线图模型,Bootstrap重抽样的方法进行验证,使用一致性指数和较正曲线验证列线图,检测预测精度。结果:共纳入126例s HLH患者,中位年龄48.5(16-88)岁,男性74例,女性52例,55例(43.6%)在30 d内死亡,其中男性39例,女性16例。单因素回归分析结果显示,淋巴细胞数<0.45×10^(9)/L、血小板数<39.5×10^(9)/L、凝血酶原时间≥13.3 s、活化部分凝血活酶时间≥39.7 s、白蛋白<25.9 g/L、乳酸脱氢酶≥811U/L、肌酐≥67μmol/L及降钙素原≥0.61 ng/ml是s HLH患者30 d内死亡的危险因素。多因素回归分析结果显示,淋巴细胞数<0.45×10^(9)/L、活化部分凝血活酶时间≥39.7 s及白蛋白<25.9 g/L均为s HLH患者30 d内死亡的独立危险因素。基于以上3个危险因素建立列线图模型,模型的一致性指数为0.683,校准图显示s HLH的观测值和预测值之间有较好的一致性。结论:淋巴细胞减少、活化部分凝血活酶时间延长,低白蛋白血症是s HLH患者早期死亡的危险因素,早期识别并积极干预有望降低此类患者的早期死亡率,基于上述危险因素建立的列线图模型为临床医生评估s HLH提供了方法。

Objective:To explore the high-risk clinical factors of early death in patients with secondary hemophagocytic lymphohistiocytosis(sHLH),and further identify the clinical factors related to the rapid progression of sHLH in the short term.Methods:The clinical manifestations,laboratory examination and prognosis of sHLH patients were retrospectively analyzed.Continuous variables were grouped by median,univariate and multivariate Cox regression analysis and KaplanMeier survival curve were used to explore the risk factors affecting early death of sHLH.Then,a nomogram model was established with independent risk factors,Bootstrap resampling method was used for verification,and consistency index(C-index) and calibration curve were used to detect the prediction accuracy.Results:A total of 126 sHLH patients were enrolled,with a median age of 48.5(16-88) years,including 74 males and 52 females.Fifty-five patients(43.6%)died within 30 days,including 39 males and 16 females.Univariate regression analysis showed that lymphocyte count 0.45×10^(9)/L,platelet count(PLT) 39.5×10^(9)/L,prothrombin time(PT)≥13.3 s,activated partial thromboplastin time(APTT)≥39.7 s,albumin(ALB) 25.9 g/L,lactate dehydrogenase(LDH)≥811 U/L,creatinine(Cr) ≥67 μmol/L and procalcitonin(PCT)≥0.61 ng/ml were risk factors for death within 30 days in sHLH patients.Multivariate regression analysis showed that lymphocyte count 0.45×10^(9)/L,APTT≥39.7 s and ALB 25.9 g/L were independent risk factors for death within 30 days in sHLH patients.A nomogram model was established based on the above three risk factors,its C-index was 0.683,and the calibration chart showed good agreement between the observed and predicted values of sHLH.Conclusions:Lymphopenia,prolonged APTT,and hypoalbuminemia are risk factors for early death of sHLH patients.Early identification and positive intervention are expected to reduce early mortality in sHLH patients.The nomogram model based on the above risk factors provides a method for clinicians to evaluate sHLH.