凝血异常在HBV相关慢加急性肝衰竭患者血栓形成中的作用

Role of coagulation abnormalities in thrombosis in patients with hepatitis B virus-associated acute-on-chronic liver failure

目的观察传统凝血功能和血小板相关指标对HBV相关慢加急性肝衰竭(HBV-ACLF)患者血栓形成事件的作用。方法选取2015年1月—2019年12月在苏州大学附属第一医院住院的HBV-ACLF患者56例,分为发生血栓组(n=24)与未发生血栓组(n=32)。回顾性分析两组患者入院时的一般临床资料,观察入院后第1~7天的凝血功能,血小板计数和血小板功能相关指标平均血小板体积(MPV)的变化。符合正态分布的计量资料两组间比较采用t检验,不符合正态分布的计量资料两组间比较采用Mann-Whitney U秩和检验;计数资料两组间比较采用χ2检验。采用重复测量资料方差分析比较组内及组间不同时间凝血指标的差异。结果HBV-ACLF患者在入院时,发生血栓组年龄31.5(29.0~34.0)岁,较未发生血栓组年龄48.5(36.0~50.7)岁小,差异有统计学意义(Z=-2.637,P=0.008);在入院当天,MPV在发生血栓组与未发生血栓组间差异无统计学意义(P>0.05)。在入院后第2~7天,MPV值发生血栓组与未发生血栓组间差异均有统计学意义(t值分别为-2.696、-2.742、-2.894、-4.174、-3.945、-4.716,P值均<0.01)。发生血栓组MPV的峰值为入院第5天,均值为(13.90±1.12)fl,高于正常值范围。所有纳入患者在入院时,PT均值为(28.8±7.2)s、APTT均值(50.5±8.7)s、INR均值(2.6±0.7),均高于正常值;Fb均值为(1.16±0.3)g/L、血小板计数均值为(107.7±26.5)×109/L,均低于正常值。而PT、APTT、Fbg、INR及血小板计数在发生血栓组与未发生血栓组间差异均无统计学意义(P值均>0.05)。结论肝衰竭患者凝血功能障碍,更多是一种低平衡状态,是复杂与异质性的,需要个体化处理。HBV-ACLF患者中,易发生血栓事件者可能与血小板的功能有关,而与血小板计数及凝血常规指标关系不大。

Objective To investigate the role of coagulation function parameters and platelet indices in thrombotic events in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF).Methods A total of 56 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2019 were enrolled and divided into thrombotic complication(TC)group with 24 patients and non-thrombotic complication(NTC)group with 32 patients.A retrospective analysis was performed for their general clinical data on admission,and the patients were observed in terms of the changes in coagulation function,platelet count(PLT),and the platelet function-related index mean platelet volume(MPV)on days 1-7 after admission.The t-test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.A repeated measures analysis of variance was used to compare coagulation markers within and between groups at different time points.Results On admission,the TC group had a significantly younger age than the NTC group[31.5(29.0-34.0)years vs 48.5(36.0-50.7)years,Z=-2.637,P=0.008].On the day of admission,there was no significant difference in MPV between the TC group and the NTC group(P>0.05),while on days 2-7 after admission,there was a significant difference in MPV between the two groups(t=-2.696、-2.742、-2.894、-4.174、-3.945、-4.716,all P<0.01).In the TC group,MPV reached the peak value on day 5 of admission,with a mean value of 13.90±1.12 fl,which was higher than the range of normal values.On admission,all patients had a mean prothrombin time(PT)of 28.8±7.2 s,a mean activated partial thromboplastin time(APTT)of 50.5±8.7 s,and a mean international normalized ratio(INR)of 2.6±0.7,which were higher than normal values;all patients had a mean fibrinogen(Fb)level of 1.16±0.3 g/L and a mean PLT of(107.7±26.5)×109/L,which were lower than normal values.There were no significant differences in PT,APTT,Fb,INR,and PLT between the TC group and the NTC group(all P>0.05).Conclusion Coagulation disorder in patients with liver failure is more of a low-equilibrium state,which is complex and heterogeneous and requires individualized treatment.For patients with HBV-ACLF,the development of thrombotic events may be more associated with platelet function than PLT or conventional coagulation markers.