血清学指标对噬血细胞综合征患儿死亡预测价值的临床研究

Clinical study on the early prediction of death for serum markers in infants with hemophagocytic syndrome

目的 探讨噬血细胞综合征（hemophagocytic syndrome,HPS）患儿诊断时的血清学指标与死亡的关系及对死亡的早期预测价值.方法 采用回顾性病例对照研究方法,对2005年7月至2012年7月广州市妇女儿童医疗中心收治的108例HPS患儿血清学、病理学改变及预后资料进行系统分析.按随访患儿的生存情况分为存活组和死亡组,应用COX模型对可能与HPS死亡相关的危险因素进行分析；应用决策树探讨各指标对HPS死亡的预测价值.结果 108例HPS患儿中,死亡33例,病死率30.6％,且90.3％在发病后8周内死亡.多因素分析显示白细胞＜5×109/L（HR =9.08,95％ CI3.07 ～26.87）、血红蛋白＜80 g/L（HR =6.15,95％ CI 1.68 ～ 22.49）、白蛋白＜28g/L（HR=4.63,95％CI 1.12 ～7.39）、铁蛋白＞1 100 μg/L（HR =3.05,95％ CI 1.28 ～ 16.75）、甘油三酯≥4 mmol/L（HR=2.88,95％CI 1.51 ～8.60）、凝血酶原时间≥16s（HR=3.60,95％CI 1.28 ～7.24）和发热持续2周以上（HR =5.39,95％CI 1.97～14.66）是造成HPS患儿死亡的独立危险因子.决策树分析显示白细胞＜5×109/L合并血红蛋白＜80 g/L的情况下患儿死亡概率达100％;即使在白细胞≥5×109/L的情况下,若合并发热持续2周以上且总胆固醇≥4 mmol/L,死亡概率亦达66.7％.结论 发病后最初8周是治疗HPS的关键期,HPS患儿死亡与多种因素相关,合并白细胞＜5×109/L且血红蛋白＜80 g/L时,病情极其凶险,及早诊断并采取有针对性的治疗对降低HPS患儿病死率至关重要.

Objective To investigate the association with death for serum parameters at the time of diagnosis and its value in predicting the death in infants with hemophagocytic syndrome （HPS）.Methods A retrospective case-control study was conducted on 108 children with HPS who were admitted to our center between July 2005 and July 2012.For each patient,demographic,laboratory data and outcome information were collected.The patients were divided into death and surviving groups based on the follow-up results.The relation between serum markers and death was examined using the COX proportional hazards model and decision tree.Results Of 108 infants with HPS,33 died corresponding to a fatality rate of 30.6% and 90.3% of deaths occurred within 8 weeks after diagnosis.Following features were significantly associated with death：white blood cells （WBC） 〈5 x 109/L （HR =9.08,95% CI 3.07 ～ 26.87）,hemoglobin 〈80 g/L （HR =6.15,95% CI 1.68 ～ 22.49）,albumin 〈 28 g/L （HR =4.63,95% CI 1.12 ～ 7.39）,serum ferritin 〉 1 100 μg/L （HR =3.05,95% CI 1.28 ～ 16.75）,trigeminal ganglion ≥4 mmol/L （HR =2.88,95% CI 1.51 ～ 8.60）,and prothromin time ≥ 16 s （HR =3.60,95 % CI 1.28 ～ 7.24）,and fever for more than 2 weeks （HR =5.39,95% CI 1.97 ～ 14.66）.Decision tree demonstrated that the probability of death was as high as 100% for infants with WBC 〈5 x 109/L and hemoglobin 〈 80 g/L.The odds of dying was still 66.7% for infants who had WBC≥5 × 109/L but reported trigeminal ganglion ≥4 mmol/L after having fever for more than 2 weeks.Conclusion The first 8 weeks after the onset of HPS is the critical period of treatment.There are several easily available serum predictors of early mortality in HPS infants,particularly the WBC and hemoglobin level,which may help guide treatment decisions.