摘要
目的研究肝脏合成的促抗凝因子、纤维蛋白原降解产物、肝外组织合成的凝血相关蛋白等成分在慢性乙型肝炎、肝硬化、肝衰竭患者中的变化特点，探讨肝脏疾病凝血与出血之间的平衡关系，寻找肝病初期的敏感指标。方法收集我院慢性乙型肝炎、肝硬化、肝衰竭患者、健康者资料，并分为慢陛乙型肝炎组、肝硬化组、肝衰竭组，正常对照组。用真空管抽取患者肘静脉血2．7ml，真空管内含109mmol／L的构橼酸钠抗凝剂，其与血液的比例为1：9。取血后1h内3000×g离心15min，分装冻存于-70℃。凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ活性检测用一期凝固法检测凝血象活化部分凝血酶原时间、凝血酶时间、凝血酶原时间、纤维蛋白原用凝固法检测；蛋白质C、AT-Ⅲ用发色底物法检测；纤维蛋白原降解产物（FDP）、D-二聚体（D—D）浓度检测用免疫比浊法；组织因子途径抑制物（TFPI）、血栓调节蛋白（TM）、血管性血友病因子（vWF）及组织因子（TF）含量测定用酶联免疫吸附法。数据均进行正态性及方差齐性检验。不同程度的肝脏疾病之间用方差分析，并进行组间的多重比较及非参数秩和检验。结果肝硬化组患者20例；慢性乙型肝炎组患者10例，肝衰竭组患者18例，正常对照组10例。除凝血因子Ⅷ外，由肝实质细胞合成的凝血因子、抗凝蛋白活性均降低t凝血象延长，FDP，D—D含量升高，TFPI、TM、vWF及TF检测值在慢性乙型肝炎组开始升高，至肝衰竭组明显升高。TFPI：Ag检测值（慢性乙型肝炎组：239．3±206．4；肝硬化组：315．0±258．6；肝衰竭组：319．5±298．1I均高于正常对照组的104．0±87．1；F：5．453，P〈0．05）；vWF：Ag检测值（慢性乙型肝炎组：70．3±29．5；肝硬化组：105．5±57．9；肝衰竭组：179．3±61．7；均高于正常对照组的21．9±7．2；，=20．104，P〈0．05），TF检测值（慢性乙型肝炎组：86．0±85．7；肝硬化组：234．2±202．9；肝衰竭组：344．7±214．6；均高于正常对照组的12．9±8．11F=8．619，P〈0．05）IFVlll：C检测值（慢性乙型肝炎组：157．2±53．4；肝硬化组：206．9±86．9；肝衰竭组：335．7±117．7l均高于正常对照组的105．5±46．2；F=13．418，P〈0．05）。结论肝脏疾病随着病情发展，由肝实质细胞合成的促抗凝成分伴发平行减少、纤溶活性增强、肝外合成凝血相关蛋白TFPI、TM、vWF及TF释放入血增多。终末期肝病患者凝血与抗凝平衡失调，可能与以上原因有关。TFPI、TM、vWF及TF在肝病轻度阶段即发生明显变化，可作为早期监测血管内皮细胞损伤敏感指标。
Objective To investigate the correlation between procoagulation factors and anticoagulation factors synthesized by the liver, and the correlation between fibrin degradation products （FDP） and D-dimer （D-D） concentration and coagulation proteins synthesized by extra-hepatic tissues, in different liver diseases; to explore the relationship between coagulation and bleeding in hepatic diseases. Methods Chronic hepatitis B （CHB） patients, CHB-related liver cirrhosis patients, CHB-related liver failure patients and healthy （normal） controls were selected for study and provided blood samples for analysis. The activity of coagulation factors （F）Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ was detected using the one-stage clotting method. Coagulogram analysis, including activated partial thromboplastia time （APTT）, thrombin time （TT）, and prothrombin time （PT）, was conducted by the solidification method. Antithrombin III （AT-Ⅲ） and protein C （PC） activities were measured by chromogenic substrate assay. FDP concentration was detected using immunoturbidimetry. Tissue factor pathway inhibitor （TFPI）, thrombomodulin （TM）, von Willebrand factor （vWF）, and tissue factor （TF） concentrations were measured by enzyme-linkod immunosorbent assay （ELISA）. Results With the exception of FVIII, coagulation factors and anticoagulant proteins synthesized by the liver were decreased and the coagulogram was extended for all patients. Likewise, the FDP and D-D concentrations Were increased in blood. CHB patients, however, presented with increased levels of FVIII, TFPI, TM, vWF, and TF. Pairwise comparison indicated statistical differences existed among CHB, CHB-realted liver cirrhosis, and liver failure patients： TFPI： 239.3± 206.4, 315.0 ± 258.6, and 319.5 ± 298.1 - higher than normal control： 104.0 ± 87.1, F = 5.453, P 〈 0.05; vWF： 70.3 ± 29.5, 105.5 ± 58.0, and 179.3 ± 61.7 - higher than normal control： 21.9 ± 7.2, F= 20.104, P 〈 0.05; TF： 85.9 ± 85.7, 234.2 ± 202.9, and 344.7 ± 214.6 - higher than normal control： 12.8 ± 8.1, F = 8.619, P 〈 0.05; FVIII： 157.2 ± 53.4, 206.9 ± 86.9, and 335.7 ± 117.7 - higher than normal control： 105.5 ± 46.2,F= 13.418,P 〈 0.05. Conclusion In parallel to the progression of liver diseases, procoagulation and anti-coagulation elements synthesized by the liver were reduced. In contrast, fibrinolysis activity was enhanced, which is expected to lead to an imbalance between blood clotting and anti-clotting factors. This may be an important cause for the bleeding that occurs in end-stage liver disease. Expressions of TFPI, TM, vWF, and TF significantly change in the early stage of liver diseases, as compared to normal （healthy） levels, and may represent a sensitive indicator of vascular injury. [Key words] Hepatitis B, chronic; Liver failure; Coagulation factors
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2012年第3期206-210,共5页
Chinese Journal of Hepatology
关键词
肝炎
乙型
慢性
肝功能衰竭
凝血因子
Hepatitis B, chronic
Liver failure
Coagulation factors
