慢加急性肝衰竭患者血小板减少的可能原因

The potential factors contributing to thrombocytopenia in acute on chronic liver failure patients

目的：探讨引起慢加急性肝衰竭患者发生血小板减少的可能原因。方法选取南方医院肝病中心2011年12月至2014年8月住院的慢性乙型肝炎（CHB）、HBV相关肝硬化（CIR）、HBV相关慢加急性肝功能衰竭（ACLF）患者，收集患者相关临床资料，检测网织血小板比例、促血小板生成素水平、血小板活化比例（PAC‐1、CD63、CD62p）、糖蕚素、可溶性CD163、凋亡血小板比例等指标，对以上指标进行相关和多元线性回归分析。结果研究共纳入191例患者，其中慢性乙型肝炎组68例，肝硬化组48例，慢加急性肝功能衰竭组75例。慢加急性肝功能衰竭患者血小板计数98（3～253）G／L较慢性乙型肝炎组172（24～327）G／L低（P＜0．01），与肝硬化患者88（22～244）G／L相当（P＝0．913）。ACLF患者入院1周血小板计数71（4～208）G／L较入院当天97（21～267）G／L明显下降（ P＜0．01）。慢加急性肝功能衰竭组患者脾脏厚度（40．4比35．1 mm ，P＝0．002）、D‐二聚体（443．5比90 ug／L ，P＝0．002）、PT‐INR（2．14比1．26，P＜0．01）、sCD163（5．33比1．81 ln mg／mL ，P＜0．01）均高于慢性乙型肝炎组。但纤维蛋白原水平（1．24比2．25 g／L ，P＜0．01）和血小板PAC‐1（＋）阳性率（3．33比10．7，P＝0．002）均低于慢性乙型肝炎组。网织血小板比例、TPO、CD62p、CD63、糖蕚素、凋亡血小板比例在慢性乙型肝炎组与慢加急性肝功能衰竭组之间差异无统计学意义。血小板计数与脾脏厚度、PT‐INR、总胆红素水平、血小板凋亡水平呈负相关，与纤维蛋白原水平、白蛋白水平、糖萼素水平呈正相关。多元线性回归分析显示，脾脏厚度、糖萼素水平，纤维蛋白原水平是ACLF患者血小板减少的独立危险因素（R2＝0．597，P＝0．011）。入院日的血小板计数可预测28天死亡（AUROC＝0．72，P＜0．01）。结论慢加急性肝衰竭患者脾脏厚度、纤维蛋白原、糖萼素为血小板减少的独立危险因素。入院日血小板计数可预测患者的短期预后。

Objective To investigate the potential factors affecting onset of thrombocytopenia in patients with HBV‐related acute on chronic liver failure .Methods A total of 191 hospitalized patients between December 2011 and August 2014 with HBV‐related diseases including chronic hepatitis B （CHB） ,liver cirrhosis（CIR） and acute on chronic liver failure （ACLF） were enrolled .Reticulated platelet ratio ,serum thrombopoietin level ,platelet activation ratio （PAC‐1 ,CD62P , and CD63） ,glycocalicin ,and serum soluble CD163 and apoptosis ratio of platelet were measured .Factors contributing to thrombocytopenia developed in ACLF patients were assessed using multiple linear regression analysis .Results There were 191 patients in the cohort comprised of 68 CHB ,48 CIR and 75 ACLF cases .Platelet counts （G/L） were lower in ACLF （98 ,3～253 G/L） than in CHB （172 ,24～327 G/L）（P〈0 .0001） ,however comparable to CIR patients （88 ,22～244 G/L） ,（P=0 .913） .Platelet count of ALCF patients endured a rapid decrease during the first week ,from 97（21～267）G/L to 71（4～208）G/L （P〈0 .0001） .The reticulated platelet ratio ,serum TPO level ,platelet activation index CD62P and CD63 , glycocalicin and platelet apoptosis ratio in CHB patients were all comparable with those in ACLF cases .ACLF patients had greater spleen width （40 .4 vs .35 .1mm ,P=0 .002） ,D‐dimer （443 .5 vs .90ug/L ,P=0 .002） ,PT‐INR （2 .14 vs .1 .26 , P 〈0 .0001） and sCD163 lg2（5 .33vs .1 .81 mg/mL ,P〈0 .0001） than CHB patients ,however with lower fibrinogen level（1 . 24vs .2 .25 g/L ,P〈0 .0001）and PAC‐1（＋ ） ratio （3 .33 vs .10 .7 , P=0 .002） .Platelet counts were negatively correlated with spleen width ,PT‐INR ,serum total bilirubin and platelet apoptosis ratio ,while positively correlated with fibrinogen , albumin level ,alanine aminotransferase and glycocalicin level .Multiple linear regression analysis showed that spleen width , fibrinogen level and glycocalicin level had linear regression relation with platelet count ：Platelet count=137 .937＋21 .658＊fibrinogen level （g/L）‐2 .249＊ spleen width （mm） ＋ 0 .020 ＊ glycocalicin level （ln mg/ml） （R2 =0 .597 , P= 0 .011） . Platelet count at admission could predict 28‐day survival （AUROC=0 .72 , P〈0 .0001） .Conclusion Thrombocytopenia was common and severe in ACLF patients . The thickness of the spleen , fibrinogen level and glycocalicin level were independent factors associated with platelet count in HBV infection related patients .The platelet count at admission day could predict short‐term survival of patients with HBV related chronic liver disease .