妊娠期肝内胆汁淤积症患者凝血功能相关指标的临床意义

Clinical significance of coagulation related indexes in patients with intrahepatic cholestasis of pregnancy

目的探讨临产妊娠期肝内胆汁淤积症(ICP)孕妇凝血4项、D-二聚体及抗磷脂抗体检测的临床意义。方法选择80例ICP孕妇为病例组,另选取80例健康孕妇为对照组。根据疾病严重程度将病例组分为轻度ICP组(n=51)和重度ICP组(n=29)。比较各组血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、D-二聚体、血清抗心磷脂抗体(ACA)、抗β2糖蛋白Ⅰ抗体(抗β2GPⅠ)、狼疮抗凝物(LA)标准化比值。采用受试者工作特征(ROC)曲线评价FIB、D-二聚体、ACA、抗β2GPⅠ及LA标准化比值对不良妊娠结局的预测价值。结果临产前,轻度及重度ICP组孕妇血浆FIB、D-二聚体水平高于对照组,重度ICP组孕妇血浆FIB、D-二聚体水平高于轻度ICP组,差异有统计学意义(P<0.05)。临产前,轻度及重度ICP组孕妇血清ACA、抗β2GPⅠ、LA标准化比值高于对照组,重度ICP组上述指标高于轻度ICP组,差异均有统计学意义(P<0.05)。病例组孕妇剖宫产率、胎儿宫内生长受限发生率高于对照组,差异有统计学意义(P<0.05);80例ICP孕妇中,共有32例出现不良妊娠结局,不良妊娠组血浆FIB、D-二聚体水平及血清ACA、抗β2GPⅠ、LA标准化比值均高于良好妊娠组,差异有统计学意义(P<0.05)。当血浆FIB>4.520 g/L时,预测ICP孕妇不良妊娠结局的曲线下面积(AUC)为0.757,敏感度为71.9%,特异度为84.4%;当血浆D-二聚体>1.860 mg/L时,AUC为0.828,敏感度为78.1%,特异度为81.3%;当血清ACA>7.915 mU/mL时,AUC为0.774,敏感度为81.3%,特异度为75.0%;当血清抗β2GPⅠ>6.085 mU/mL时,AUC为0.875,敏感度为87.5%,特异度为68.8%;当LA标准化比值>1.305时,AUC为0.809,敏感度为84.4%,特异度为71.3%。结论临产ICP孕妇体内存在凝血、纤溶及免疫的异常状态,且异常程度与ICP严重程度相关。FIB、D-二聚体及抗磷脂抗体检测对于ICP孕妇妊娠结局的预测具有积极意义。

Objective To investigate the clinical significance of four coagulation parameters,the D-dimer and antiphospholipid antibody detection in pregnant women with intrahepatic cholestasis of pregnancy(ICP).Methods Eighty pregnant women with ICP were selected as case group,and another 80 healthy pregnant women were selected as control group.The case group was divided into mild ICP group(n=51) and severe ICP group(n=29) according to the severity of the disease.Plasma prothrombin time(PT),activated partial thrombin time(APTT),thrombin time(TT),fibrinogen(FIB),D-dimer,serum anticardiolipin antibody(ACA),antibody against β2 glycoprotein I(anti-β2 GP I) and normalized ratio of lupus anticoagulant(LA) were compared among different groups.Values of FIB,D-dimer,ACA,anti-(32 GP I and normalized ratio of LA in predicating adverse pregnancy outcomes were evaluated by receiver operating characteristic(ROC) curve.Results Before delivery,the plasma FIB and D-dimer levels in the mild ICP group and the severe ICP group were significantly higher than those in the control group,and these indexes in the severe ICP group were also significantly higher than those in the mild ICP group(P <0.05).Before delivery,the serum ACA,anti-β2 GP I and normalized ratio of LA in the mild ICP group and the severe ICP group were significantly higher than those in the control group,and these indexes in the severe ICP group were also significantly higher than those in the mild ICP group(P <0.05).The cesarean section rate and the incidence rate of fetal intrauterine growth restriction in the case group were significantly higher than those in the control group(P <0.05);among the 80 pregnant women with ICP,32 cases had adverse pregnancy outcomes,and the levels of plasma FIB,D-dimes,serum ACA,anti-β2 GP Ⅰand normalized ratio of LA in the bad pregnancy group were significantly higher than those in the good pregnancy group(P <0.05).When plasma FIB was greater than 4.520 g/L,the area under the curve(AUC) for predicting adverse pregnancy outcomes in the ICP pregnant women was 0.757,with a sensitivity of 71.9% and a specificity of 84.4%;when plasma D-dimer was greater than1.860 mg/L,the AUC was 0.828,with a sensitivity of 78.1% and a specificity of 81.3%;when serum AC A was greater than 7.915 mU/mL,the AUC was 0.774,with a sensitivity of 81.3% and a specificity of 75.0%;when serum anti-β2 GP Ⅰ was greater than 6.085 mU/mL,the AUC was0.875,with a sensitivity of 87.5% and a specificity of 68.8%;when normalized ratio of LA was greater than 1.305,the AUC was 0.809,with a sensitivity of 84.4% and a specificity of 71.3%.Conclusions There are abnormal conditions of coagulation,fibrinolysis and immunity in pregnant women with ICP during delivery,and the degree of abnormality is related to the severity of ICP.The detection of FIB,D-dimer and antiphospholipid antibody has positive significance for predicting the pregnancy outcomes of the pregnant women with ICP.