CAJ | 학술논문

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,并分为慢性乙型肝炎组、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109 mmol/L的枸橼酸钠抗凝剂,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;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±298.1;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 ;F=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±8.1;F=8.619,P＜0.05)；FⅧ∶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±117.7;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. 目的研究肝髒閤成的促抗凝因子、纖維蛋白原降解產物、肝外組織閤成的凝血相關蛋白等成分在慢性乙型肝炎、肝硬化、肝衰竭患者中的變化特點,探討肝髒疾病凝血與齣血之間的平衡關繫,尋找肝病初期的敏感指標. 方法收集我院慢性乙型肝炎、肝硬化、肝衰竭患者、健康者資料,併分為慢性乙型肝炎組、肝硬化組、肝衰竭組,正常對照組.用真空管抽取患者肘靜脈血2.7ml,真空管內含109 mmol/L的枸櫞痠鈉抗凝劑,其與血液的比例為1∶9.取血後1h內3000 ×g離心15min,分裝凍存于-70℃.凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ活性檢測用一期凝固法檢測；凝血象活化部分凝血酶原時間、凝血酶時間、凝血酶原時間、纖維蛋白原用凝固法檢測；蛋白質C、AT-Ⅲ用髮色底物法檢測；纖維蛋白原降解產物(FDP)、D-二聚體(D-D)濃度檢測用免疫比濁法；組織因子途徑抑製物(TFPI)、血栓調節蛋白(TM)、血管性血友病因子(vWF)及組織因子(TF)含量測定用酶聯免疫吸附法.數據均進行正態性及方差齊性檢驗.不同程度的肝髒疾病之間用方差分析,併進行組間的多重比較及非參數秩和檢驗. 結果肝硬化組患者20例；慢性乙型肝炎組患者10例；肝衰竭組患者18例,正常對照組10例.除凝血因子Ⅷ外,由肝實質細胞閤成的凝血因子、抗凝蛋白活性均降低;凝血象延長,FDP,D-D含量升高,TFPI、TM、vWF及TF檢測值在慢性乙型肝炎組開始升高,至肝衰竭組明顯升高.TFPI∶Ag檢測值(慢性乙型肝炎組:239.3±206.4；肝硬化組:315.0±258.6;肝衰竭組:319.5±298.1;均高于正常對照組的104.0±87.1；F=5.453,P＜ 0.05)；vWF∶Ag檢測值(慢性乙型肝炎組:70.3±29.5;肝硬化組:105.5±57.9；肝衰竭組:179.3±61.7；均高于正常對照組的21.9±7.2 ;F=20.104,P＜ 0.05)；TF檢測值(慢性乙型肝炎組:86.0±85.7;肝硬化組:234.2±202.9;肝衰竭組:344.7±214.6；均高于正常對照組的12.9±8.1;F=8.619,P＜0.05)；FⅧ∶C檢測值(慢性乙型肝炎組:157.2±53.4；肝硬化組:206.9±86.9;肝衰竭組:335.7±117.7;均高于正常對照組的105.5±46.2;F=13.418,P＜0.05).結論肝髒疾病隨著病情髮展,由肝實質細胞閤成的促抗凝成分伴髮平行減少、纖溶活性增彊、肝外閤成凝血相關蛋白TFPI、TM、vWF及TF釋放入血增多.終末期肝病患者凝血與抗凝平衡失調,可能與以上原因有關.TFPI、TM、vWF及TF在肝病輕度階段即髮生明顯變化,可作為早期鑑測血管內皮細胞損傷敏感指標.
목적 연구간장합성적촉항응인자、섬유단백원강해산물、간외조직합성적응혈상관단백등성분재만성을형간염、간경화、간쇠갈환자중적변화특점,탐토간장질병응혈여출혈지간적평형관계,심조간병초기적민감지표. 방법 수집아원만성을형간염、간경화、간쇠갈환자、건강자자료,병분위만성을형간염조、간경화조、간쇠갈조,정상대조조.용진공관추취환자주정맥혈2.7ml,진공관내함109 mmol/L적구연산납항응제,기여혈액적비례위1∶9.취혈후1h내3000 ×g리심15min,분장동존우-70℃.응혈인자Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ활성검측용일기응고법검측；응혈상활화부분응혈매원시간、응혈매시간、응혈매원시간、섬유단백원용응고법검측；단백질C、AT-Ⅲ용발색저물법검측；섬유단백원강해산물(FDP)、D-이취체(D-D)농도검측용면역비탁법；조직인자도경억제물(TFPI)、혈전조절단백(TM)、혈관성혈우병인자(vWF)급조직인자(TF)함량측정용매련면역흡부법.수거균진행정태성급방차제성검험.불동정도적간장질병지간용방차분석,병진행조간적다중비교급비삼수질화검험. 결과 간경화조환자20례；만성을형간염조환자10례；간쇠갈조환자18례,정상대조조10례.제응혈인자Ⅷ외,유간실질세포합성적응혈인자、항응단백활성균강저;응혈상연장,FDP,D-D함량승고,TFPI、TM、vWF급TF검측치재만성을형간염조개시승고,지간쇠갈조명현승고.TFPI∶Ag검측치(만성을형간염조:239.3±206.4；간경화조:315.0±258.6;간쇠갈조:319.5±298.1;균고우정상대조조적104.0±87.1；F=5.453,P＜ 0.05)；vWF∶Ag검측치(만성을형간염조:70.3±29.5;간경화조:105.5±57.9；간쇠갈조:179.3±61.7；균고우정상대조조적21.9±7.2 ;F=20.104,P＜ 0.05)；TF검측치(만성을형간염조:86.0±85.7;간경화조:234.2±202.9;간쇠갈조:344.7±214.6；균고우정상대조조적12.9±8.1;F=8.619,P＜0.05)；FⅧ∶C검측치(만성을형간염조:157.2±53.4；간경화조:206.9±86.9;간쇠갈조:335.7±117.7;균고우정상대조조적105.5±46.2;F=13.418,P＜0.05).결론 간장질병수착병정발전,유간실질세포합성적촉항응성분반발평행감소、섬용활성증강、간외합성응혈상관단백TFPI、TM、vWF급TF석방입혈증다.종말기간병환자응혈여항응평형실조,가능여이상원인유관.TFPI、TM、vWF급TF재간병경도계단즉발생명현변화,가작위조기감측혈관내피세포손상민감지표.
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,and 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-linked immunosorbent assay (ELISA).Results With the exception of FⅧ ,coagulation factors and anticoagulant proteins synthesized by the liver were decreased and the coagulograrn 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.