血栓弹力图法评估凝血紊乱与儿童脓毒症严重程度及预后的相关性

目的 通过血栓弹力图(thromboelastography,TEG)结果分析凝血紊乱与脓毒症严重程度、器官功能障碍和预后的关系.方法 收集2014年2月至2015年1月我院PICU诊断脓毒症和严重脓毒症患儿(n=62)的临床资料,于诊断脓毒症当天(D1)、第2天(D2)、第3天(D3)检测患儿血常规、炎症指标(C-反应蛋白、降钙素原)、器官功能指标(ALT、TBiL、ALB、Cr、BUN、PaO2/FiO2)、乳酸、传统凝血功能检测指标(APTT、PT、INR、Fib、D-dimers)、TEG指标(R、K、α、MA、LY30、CI).(1)比较脓毒症、严重脓毒症组组间D1～3 TEG结果;比较低凝、高凝组组间D1炎症指标、D1危重评分.(2)比较低凝、高凝组组间D1器官功能指标(ALT、TBiL、ALB、Cr、BUN、PaO2/FiO2)、D1～3儿童多器官功能障碍评分和器官功能障碍数目.(3)比较存活、死亡组组间D1～3 TEG结果;采用Kaplan-Meier生存曲线、Log Rank检验分析D1CI和APTT、PT结果与脓毒症28d生存率的关系.结果 (1)凝血紊乱与脓毒症严重程度的关系:严重脓毒症组(n=21)较脓毒症组(n=41) D1～3TEG结果呈持续低凝状态:D1～2R及D1、D3K延长,D1～3α减小,D1～3MA、CI降低(P＜0.05);低凝组(n=16)D1PRISM Ⅲ高于高凝组(n=26) (P＜0.05);低凝组D1中性粒细胞计数低于高凝组(P＜0.05).(2)凝血紊乱与多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)的关系:低凝组D1器官功能损害重于高凝组:D1Cr、BUN、ALT升高(P＜0.05);低凝组D1儿童多器官功能障碍评分、D1～3器官功能障碍累积数目高于高凝组(P＜0.05).(3)凝血紊乱与脓毒症预后的关系:低凝组病死率高于高凝组(62.5％ vs.15.4％,P=0.002);死亡组(n=18)较存活组(n=44) D1～3TEG结果呈持续低凝状态:D1～2R及D1、D3K延长,D1～3α减小,D1～3MA、CI降低(P＜0.05);Kaplan-Meier生存分析显示低凝、高凝、正常组28d生存曲线分布差异有统计学意义(P＜0.05).结论 TEG结果呈持续低凝状态可反映患儿脓毒症和MODS严重程度,TEG对预测脓毒症28d预后有参考价值.TEG对于综合判断脓毒症严重程度、MODS和预测脓毒症转归具有重要意义.

Correlation analysis of coagulation disorders and the severity and outcome of pediatric sepsis: Thromboelastography method

Objective To assess the association between coagulation disorders and the severity as well as the outcome of pediatric sepsis by thromboelastography (TEG) method.Methods Total of 62 patients suffering from sepsis or severe sepsis in PICU in our hospital from February 2014 to January 2015 were included in this study.All patients had routine blood tests,inflammatory biomarkers (CRP,PCT) tests,organ function parameters(ALT,TBiL,ALB,Cr,BUN,PaO2/FiO2) tests,lactic acid,classical coagulation laboratory test (platelets count,APTT,PT,INR,Fib,D-dimers) and TEG (R,K,α,MA,LY30,CI) everyday for the first 3 days of diagnosis of sepsis or severe sepsis (D1,D2,D3).(1)D1～3 TEG results between Sepsis and Severe sepsis groups were investigated;D1 inflammatory biomarkers and D1～3 critical scores between hypocoagulation and hypercoagulation groups were investigated.(2)D1 organ function parameters(ALT,TBiL,ALB,Cr,BUN,PaO2/FiO2) and D1～3 Pediatric multiple organ dysfunction score (P-MODS) between hypocoagulation and hypercoagulation groups were investigated.(3)D1～3 TEG results between sepsis and severe sepsis groups were compared; Dependence of 28 day survival on normal or pathological D1CI,APTT,PT were evaluated using Kaplan-Meier plots and Log Rank test.Results (1) Coagulation disorders and the severity of sepsis:Compared with sepsis group(n=41),severe sepsis group(n=21) presented persistent hypocoagulability:D1～2R and D1,D3K were significantly prolonged,D1～3 α,MA,CI were significantly reduced (P＜0.05);Compared with hypercoagulation group (n=26),hypocoagulation group (n=16) had significantly higher D1 PRISM Ⅲ scores (P＜0.05),lower D1 neutrophils counts (P＜0.05).(2) Coagulation disorders and multiple organ dysfunction syndrome:Compared with hypercoagulation group,hypocoagulation group had more severe organ dysfunctions:Cr,BUN,ALT were increased (P＜0.05);higher D1 P-MODS scores(P＜0.05) and D1～3 organ failure index (P＜0.05) were found in hypocoagulation group.(3) Coagulation disorders and outcome of sepsis:hypocoagulation group had a higher mortality than hypercoagulation group(62.5％ vs.15.4％,P＜0.05) ; Non-survival group (n=18) presented persistent hypocoagulability compared with survival group(n =44) according to D1～3TEG results[D1～2R,D1 and D3K were prolonged,D1～3 α,MA,CI were reduced (P＜0.05)] ; Kaplan-Meier plots demonstrated that normal or pathological D1CI were associated with 28-day survival (P＜0.05).Conclusion TEG assays present that persistent hypocoagulability can reveal the severity and 28 day prognosis of sepsis.TEG may be a valuable tool in assessing whole blood coagulation disorders in pediatric sepsis with a comprehensive evaluation of the severity as well as the outcome of sepsis.