纤溶活性与2型糖尿病及其大血管病变

组织型纤溶酶原激活剂(t-PA)和纤溶酶原激活物抑制剂-1(PAI-1)是纤溶系统的主要调控因子.2型糖尿病患者高血糖、高胰岛素血症、脂代谢紊乱、炎症反应、肥胖等多种因素可引起血浆t-PA水平降低、PAI-1水平升高.纤溶活性的降低参与了大血管病变的发生、发展.提高纤溶活性的综合治疗将对防治糖尿病大血管并发症起一定作用.     

运动负荷对不稳定性心绞痛患者纤溶活性影响的研究

对20例健康受试者和25例不稳定性心绞痛患者进行运动负荷前、后组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活剂抑制剂(PAI-1)活性的测定.结果发现运动前静息时,两组t-PA活性无显著差异,而PAI-1活性不稳定性心绞痛组明显高于对照组;运动后,不稳定性心绞痛组t-PA活性显著低于对照组(0.96±0.45IU/ml对1.89±0.68IU/ml,P<0.01),PAI-1活性下降幅度小于对照组(12.0%对31.9%),使其PAI-1活性仍显著高于对照组(8.20±2.28AU/ml对4.21±0.68AU/ml,P<0.01).提示不稳定性心绞痛患者不论是静息,还是在运动负荷激发后,均存在着纤溶活性的下降.     

急性心肌缺血氧自由基与血液高凝状态的实验研究

本文研究急性心肌缺血氧自由基及其清除剂对抗凝血酶及纤溶系统的影响。结果表明:心肌缺血4小时引起血浆丙二醛(MDA)增高,血浆抗凝血酶Ⅲ(AT-Ⅲ)及组织型纤溶酶原激活剂(t-PA)活性降低。纤溶酶原激活剂抑制物(PAI)活性增高。MDA与AT-Ⅲ呈负相关,与PAI呈正相关。自由基清除剂超氧化物歧化酶(SOD)及过氯化氢酶(CAT)可降低自由基,升高AT-Ⅲ与t-PA活性,降低PAI活性。作者认为氧自由基可能对急性心肌缺血产生高凝状态起重要作用。     

高原肺水肿患者凝血纤溶系统的检测及分析

目的　探讨高原肺水肿 (HAPE)患者血液纤溶系统的变化。方法　选择急进高原患高原肺水肿的患者 6 1例 ,采集空腹静脉血 ,检测血浆中组织纤溶酶原激活剂 (t-PA)、纤溶酶原激活剂抑制物 - 1(PAI - 1)活性和D -二聚体 (DD)、纤维蛋白原 (FG)及纤溶降解产物 (FDP)质量浓度 ,并与 2 0例高原健康人作对照研究。结果　HAPE患者DD、FG和FDP质量浓度及PAI - 1活性的变化与病情程度有关 ,且显著高于健康人 (P <0 0 1)。HAPE组t-PA活性明显高于正常对照组 (P <0 0 1或 0 0 5 ) ,但轻型HAPE与正常对照组差异无显著性 (P >0 0 5 )。结论　HAPE肿患者存在纤溶抑制功能的亢进及凝血与纤溶系统的紊乱。     

复方丹参滴丸对不稳定型心绞痛患者血小板活化及纤溶活性的影响

目的　探讨复方丹参滴丸对不稳定型心绞痛 (UA)患者血小板活化状态和纤溶活性的影响。方法　 40例 UA患者随机分为常规治疗组 (2 0例 )和复方丹参滴丸组 (2 0例 )。疗程 4周。治疗前后测定血浆中血小板 α-颗粒膜蛋白 (GMP-14 0 )、组织型纤溶酶原激活剂 (t-PA)及其抑制物 (PAI-1)水平。结果　两组 UA患者治疗后 GMP-14 0含量、PAI-1活性均明显降低 (P<0 .0 5 ;P<0 .0 1) ,t-PA活性显箸升高 (P<0 .0 5 ;P<0 .0 1)。复方丹参滴丸组降低 GMP-14 0和升高 t-PA的幅度高于常规治疗组 (P<0 .0 5 )。结论　复方丹参滴丸能有效抑制血小板活化、改善纤溶活性     

辛伐他汀对冠心病患者纤溶参数的影响

目的了解冠心病患者纤溶参数的变化,并观察辛伐他汀对冠心病患者纤溶参数的影响。方法测定87例正常对照者和108例冠心病患者血浆组织型纤溶酶原激活物(t-PA)活性和纤溶酶原激活物抑制物-(1PAI-1)活性,随后108例冠心病患者被随机分成常规治疗组和常规治疗+辛伐他汀40mg每日一次(辛伐他汀组)。治疗14d后复测t-PA活性和PAI-1活性。结果与正常对照组相比较,冠心病患者纤溶参数异常,t-PA活性下降,PAI-1活性上升(P<0.01)。常规治疗组治疗后纤溶参数无显著变化(P>0.05)。辛伐他汀组纤溶参数明显改善,表现为t-PA活性上升,PAI-1活性下降(P<0.01)。结论冠心病患者纤溶参数明显异常,辛伐他汀能改善冠心病患者纤溶参数。     

纤溶活性与2型糖尿病及其大血管病变

组织型纤溶酶原激活剂(t—PA)和纤溶酶原激活物抑制剂-1(PAI-1)是纤溶系统的主要调控因子。2型糖尿病患者高血糖、高胰岛素血症、脂代谢紊乱、炎症反应、肥胖等多种因素可引起血浆t-PA水平降低、PAI-1水平升高。纤溶活性的降低参与了大血管病变的发生、发展。提高纤溶活性的综合治疗将对防治糖尿病大血管并发症起一定作用。     

急性冠脉综合征患者纤溶活性与脂蛋白（a）的关系探讨

目的 通过测定急性冠脉综合征(ACS)患者血浆中组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活剂抑制物(PAI-1)抗原含量及脂蛋白(a)[Lp(a)]的水平,探讨纤溶活性与Lp(a)对冠脉血栓形成的影响及相互关系.方法 选取54例发病1 h～8 h以内的ACS患者作为病例组,并据病情分为不稳定型心绞痛(UAP)组及急性心肌梗死(AMI)组;42名健康体检者作为对照组.用ELISA法检测研究对象血浆t-PA、PAI-1抗原含量,用免疫透射比浊法检测Lp(a)的浓度,比较两组中各指标的变化.结果 UAP组及AMI组血浆t-PA、 PAI-1含量较对照组明显升高(P<0.05或P<0.01),t-PA在UAP组与AMI患者之间无统计学意义,而AMI组PAI-1含量较UAP组明显增高.UAP组及AMI组血浆Lp(a)浓度较对照组明显升高,AMI组又较UAP组明显升高.血浆Lp(a)水平与PAI-1含量存在着显著的正相关,而与t-PA含量之间无显著的相关关系.结论 冠脉血栓疾病发生时,血浆纤溶活性下降,t-PA、PAI-1抗原含量增加,以PAI-1增加为明显;血浆Lp(a)水平增高.Lp(a)促进PAI-1的分泌,抑制t-PA的分泌,减弱t-PA活性,打破了t-PA与PAI-1的动态平衡.     

凝血因子Ⅻ活性的变化对深静脉血栓形成的影响

目的:探讨凝血因子Ⅻ活性(FⅫ:C)的变化对纤维蛋白原溶解功能与深静脉血栓形成(DVT)的影响.方法:采用一期法测定63例DVT患者和30例正常对照组的FⅫ:C,同时用发色底物法检测血浆纤溶酶原活性(PLG:A),酶联免疫法测定组织型纤溶酶原激活物抗原性(t-PA:Ag)纤溶酶原激活物抑制剂-Ⅰ抗原性(PAI-Ⅰ:Ag)及免疫比浊法测定血浆D-二聚体(D-D)含量.结果:DVT组FⅫ:C和PLG:A含量显著低于正常对照组(P＜0.01),其中5例(7.9%)年龄＜45岁的患者FⅫ:C低于正常对照组x-2S;PAI-Ⅰ:Ag,D-D含量显著高于正常组(P＜0.01);t-PA:Ag含量与正常对照组差异无统计学意义(P＞0.05).结论:FⅫ:C下降易导致纤溶酶原内激活途径受抑制,DVT的形成与FⅫ:C降低有关.     

高血压患者胰岛素抵抗与纤溶系统的关系

目的研究高血压病(EH)患者胰岛素抵抗(IR)与纤溶系统的关系.方法 EH病人71例,采用75 g葡萄糖口服负荷法(OGTT),将EH患者分为糖耐量正常组(NGT)44例和糖耐量异常组(IGT)27例,正常对照组31例.测定血浆组织型纤溶酶原激活物活性(t-PA)、纤溶酶原激活物抑制物-1活性(PAI-1)、纤溶酶原活性(PLG),在OGTT测定的同时作血胰岛素(INS)测定,并根据Cederholm公式计算出胰岛素敏感指数(ISIc).结果 NGT组和IGI组相比t-PA无明显差别(P＞0.05),但两组均较正常对照组降低(P＜0.05).NGT组和IGT组PAI-1与正常对照组比较均无明显差别(P>0.05).IGT与NGT相比PLG增高(P＜0.05),与正常对照比较PLG明显增高(P＜0.01).ISIc在NGT组和IGT组较正常对照组明显降低(P＜0.05,P＜0.01),且IGT组较NGT组更低(P＜0.01).ISIc与t-PA, PAI-1不相关.结论高血压病人存在胰岛素抵抗,当高血压病合并IGT时,胰岛素抵抗更明显.EH病人存在纤溶活性的下降,当合并IGT时,纤溶活性的降低更为明显.t-PA和PAI-1与ISIc无明显相关性.     

凝血及纤溶系统变化在急性心肌梗塞溶栓治疗中的作用

本文通过对急性心肌梗塞(AMI)早期溶栓治疗的43例患者进行凝血及纤溶系统功能的测定,分别在溶栓前、溶栓后4h、12h、24h、48h及1周测定凝血酶原时间(PT)、活化的部分凝血活酶时间(APTT)、纤溶酶原(PLG)、α_2抗纤溶酶(α_2AP)、纤维蛋白原(Fg)、D二聚体含量(D=Dimer)、组织型纤维溶酶原活化物(t-PA)、组织型纤溶酶原活化物抑制物(PAI),其结果显示,溶栓组冠脉再通26例(60.5%),溶栓前与溶栓后4h相比冠脉再通组t-PA活性明显高于未通组(P<0.01),PLG活性及Fg含量的降低幅度再通组明显高于未通组,建议溶栓中应把测定t-PA、PAI、PLG及Fg作为判断溶栓治疗效果的指标.     

老年雄激素低下患者血液凝血和纤溶系统的变化

目的探讨老年雄激素水平减低对血液凝血和纤溶活性的影响。方法先测定82例80岁以上老年血液总睾酮、游离睾酮等性激素浓度及凝血和纤溶活性变化,然后对游离睾酮减低组(观察组)及正常组(对照组)两组的凝血和纤溶系统活性变化进行对比分析。结果80岁以上老年总睾酮水平随年龄增加而降低的现象不显著,观察组总睾酮轻度降低,游离睾酮减低更显著,导致游离睾酮总睾酮显著降低;游离睾酮减低组部分凝血酶原时间、凝血酶原活动度、活化部分凝血酶时间、血小板聚集率与对照组比较无显著差异,但纤维蛋白原含量显著升高、纤溶酶原活性及α2抗纤溶酶活性显著增强,组织型纤溶酶原激活物抗原含量显著降低,抗凝血酶Ⅲ活性及组织型纤溶酶原激活物抑制剂1抗原含量无显著变化;多元相关分析显示,纤维蛋白原与长期卧床显著正相关、纤溶酶原活性与糖尿病显著正相关、组织型纤溶酶原激活物抗原浓度与游离睾酮浓度显著正相关、α2抗纤溶酶活性与游离睾酮浓度显著负相关。结论游离睾酮减低可导致血液凝血活性增强及纤溶活性抑制,凝血和纤溶活性变化的程度与游离睾酮减低的程度相关。     

无症状性脑梗死患者血清炎性因子和纤溶及抗纤溶活性的变化

目的观察无症状性脑梗死(silent cerebral infarction,SCI)患者血清炎性因子和纤溶及抗纤溶活性的变化。方法选择SCI患者53例(SCI组)和健康体检者55例(对照组),分别检测血清高敏C反应蛋白(hs-CRP)、血浆纤溶酶原活性(PLG:A)、纤溶酶活性(PLM:A)、组织型纤溶酶原激活物(t-PA)活性、D-二聚体(D-D)含量、_2α-纤溶酶抑制剂(α_2-PI)和纤溶酶原激活物抑制剂(PAI)活性。结果 SCI组hs-CRP水平明显高于对照组[(15.36±4.30)mg/L vs (10.26±2.61)mg/L,P<0.01],SCI组PLM:A、t-PA和D-D含量均明显低于对照组[(35.84±10.23)% vs (68.74±18.41)%,(0.11±0.01)U/ml vs (0.49±0.12)U/mL(0.36±0.14)mg/L vs (0.68±0.16)mg/L,P<0.01)],SCI组PLG:A与对照组比较差异无统计学意义(P>0.05),SCI组α_2-PI活性和PAI活性明显高于对照组[(128.46±23.75)% vs (96.36±19.34)%,(0.86±0.22)AU/ml vs (0.48±0.10)AU/ml.P<0.01]。结论炎症过程和纤溶及抗纤溶系统的功能失调与SCl的形成有关。     

凝血和抗凝及纤溶功能改变在进展型脑梗死患者中的临床意义

目的研究进展型脑梗死患者凝血、抗凝和纤溶系统功能指标的变化,探讨进展型脑梗死的发病机制,为其临床早期诊断和治疗提供依据。方法对比检测了209例进展型脑梗死患者与209例完全型脑梗死患者血浆凝血酶原时间、凝血酶时间、部分凝血活酶时间、纤维蛋白原、血小板聚集率、血管性血友病因子含量、抗凝血酶、组织型纤溶酶原激活物及纤溶酶原激活物抑制剂-1活性水平。结果与完全型脑梗死患者比较,进展型脑梗死患者的血浆凝血酶原时间、凝血酶时间、部分凝血活酶时间显著缩短,抗凝血酶、组织型纤溶酶原激活物水平显著降低,而纤维蛋白原、血小板聚集率、血管性血友病因子、纤溶酶原激活物抑制剂-1水平显著升高(P<0.01)。结论进展型脑梗死患者存在着明显的高凝血和较低的抗凝和纤溶活性。     

心力衰竭患者血浆纤溶活性指标的变化及福辛普利的干预作用

目的:探讨心力衰竭患者血浆纤溶活性指标的变化以及血管紧张素转换酶抑制剂福辛普利干预的影响。方法:58例心力衰竭患者随机分成福辛普利组30例和常规治疗组28例,福辛普利组在常规治疗基础上加用福辛普利10mg/d,入院后当天和治疗后2周采血检测血浆纤溶酶原激活剂抑制物1(PAI1)含量与活性、组织纤溶酶原激活剂(tPA)活性。选择20例健康体检者作为正常对照。结果:与健康体检者比较,心力衰竭患者血浆PAI1含量与活性升高,tPA活性降低(P均<0.01);治疗后2周福辛普利组较常规治疗组血浆PAI1含量与活性明显降低(P均<0.01),tPA活性明显升高(P均<0.01)。结论:心力衰竭时血浆纤溶活性降低,福辛普利治疗可改善其纤溶活性,对降低心力衰竭患者血栓栓塞性疾病的发生可能有重要意义。     

2级高血压患者血栓前状态分子标志物的变化

目的 探讨2级高血压患者血栓前状态相关指标的改变及其临床意义.方法 采用流式细胞仪、酶联免疫吸附双抗体夹心法(ELISA)、全自动血凝分析仪等检测2级高血压血小板表面P-选择素(P-selectin,CD62P)、血浆组织型纤溶酶原激活剂(t-PA)、抑制剂(PAI-1)和凝血四项即血浆纤维蛋白原(FIB)水平、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT).结果 2级高血压组CD62P的表达、血浆PAI-1、FIB三项指标均较正常组增高(P＜0.05),而t-PA水平较正常组降低(P＜0.05);2级高血压APTT和PT时间明显缩短(P＜0.05);正常组与2级高血压组TT时间比较无统计学意义(P＞0.05).结论 2级高血压患者血小板活化、凝血功能增强、纤溶功能减退,存在明显的血栓前状态;测定血小板表面CD62P的表达、血浆t-PA和PAI-1和凝血四项有助于早期发现2级高血压患者血栓前状态并有助于导临床早期干预治疗.     

Intra- and postoperative fibrinolysis in patients undergoing cardiopulmonary bypass surgery

The influence of cardiopulmonary bypass (CPB) on fibrinolytic activity was assessed in 100 patients with valvular heart disease or atrial septal defects. Euglobulin fibrinolytic activity (EFA), tissue type plasminogen activator (t-PA) activity, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen, alpha 2-antiplasmin (alpha 2-AP), fibrinogen degradation products (FDP), and D-dimer were measured pre-, intra-, and postoperatively. There were significant increases in EFA and t-PA activity (p less than 0.002), and decreases in plasminogen and alpha 2-AP (p less than 0.0001) intraoperatively with respect to baseline values. t-PA activity decreased significantly after surgery (p less than 0.002), whereas PAI-1 activity showed a marked increase shortly after operation and on postoperative day 1 (p less than 0.0001). FDP and D-dimer levels were significantly increased both intra- and postoperatively, the latter showing higher values (p less than 0.01 and p less than 0.0001, respectively). This study shows that there is an activation of the fibrinolytic system, as a result of the increased activation of plasminogen and decreased levels of plasmin inhibitors, during CPB surgery followed by a postoperative fibrinolytic shutdown.     

Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1)

Previous studies have shown that overall fibrinolytic activity in blood follows a diurnal rhythm with a peak in the morning and a trough in the evening. The purpose of this study was to determine which fibrinolytic factor(s) was responsible for this diurnal rhythm. Resting and postvenous occlusion tissue-type plasminogen activator (t-PA) activity, resting t-PA antigen, and resting plasminogen activator inhibitor 1 (PAI-1) activity were measured in the morning and evening in 33 healthy men (mean age, 31 years) and in 15 patients (mean age, 57 years) with previous myocardial infarction or unstable angina. PAI-1 activity and t-PA antigen were significantly higher (p less than 0.01) in the morning compared with the evening in controls and patients. In contrast, resting t-PA activity was significantly lower in the morning (p less than 0.01) in both groups and was inversely correlated with PAI-1 activity (r = -0.57, p less than 0.0001). Postvenous occlusion t-PA activity and t-PA capacity were not significantly different between morning and evening in either group. Because t-PA antigen levels and PAI-1 activity were highest in the morning, the variation in t-PA activity was probably not due to decreased secretion of t-PA but instead to changes in the secretion of PAI-1. Our findings indicate that diurnal variations in PAI-1 activity may reduce fibrinolytic activity in the morning in healthy individuals and in patients with coronary artery disease.     

The effects of rosiglitazone treatment on the fibrinolytic system in patients with type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus (DM) are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the hemostatic and fibrinolytic systems. The effects of rosiglitazone treatment on the fibrinolytic system and insulin sensitivity in patients with type 2 DM were assessed. Twenty-four patients with type 2 DM and 28 healthy subjects were enrolled in the study. Plasma global fibrinolytic capacity (GFC), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured. Insulin resistance was calculated by hoemostasis model assessment. Patients with type 2 DM then were placed on rosiglitazone (4 mg/day, for 12 weeks) in addition coexistent medication, and baseline tests were repeated. There was no difference between mean t-PA levels of the two groups. PAI-1 levels were higher in diabetic patients than control subjects (p < 0.01). Diabetic patients had lower GFC and t-PA/PAI-1 levels than control subjects (p < 0.05, p < 0.05). PAI-1 levels were positively correlated with waist circumference in diabetic group (r = 0.4, p < 0.05). After rosiglitazone treatment, there was no difference in mean plasma levels of GFC, t-PA, PAI-1 and t-PA/PAI-1 in diabetics. Insulin sensitivity significantly improved after the addition of rosiglitazone treatment in diabetic patients (p < 0.01). The short-term and low-dose treatment with rosiglitazone in type 2 diabetic patients has no effects on the fibrinolytic system, although it improves insulin sensitivity.     

Blood coagulation and fibrinolysis in patients with hyperthyroidism

Several papers concerning abnormalities of blood coagulation and fibrinolysis during hyperthyroidism, have been published. Increased von Willebrand Factor (vWF) activity and high fibrinogen levels have been reported. However, there is controversy concerning the presence of a hypercoagulable state in hyperthyroidism. We investigated various hemostatic parameters in 41 hyperthyroid patients and compared them to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with control subjects, fibrinogen, factor IX, vWF, AT III and PAI-1 were significantly increased in patients (p<0.05, p<0.0001, p<0.05, p<0.01 and p<0.0001; respectively), whereas factor X and t-PA were decreased (p<0.05). We showed that free T4 (FT3) levels were correlated with factor VIII activity (r=0.35, p<0.05). FT4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. AT III was inversely correlated with factor VII activity (r=-0.48, p<0.01). Protein C and S were correlated with vWF levels (r=0.58, p<0.0001; r=0.55, p<0.0001, respectively). Protein C was inversely correlated with t-PA (r=-0.39, p<0.01). There was a negative correlation between triglycerides, LDL-C and F X (r=-0.45, p<0.05; r=-64, p<0.01, respectively). Mean platelet volume (MPV) was correlated with anti-thyroid peroxidase (TPO) antibodies (in Graves'disease) and F IX activity (r=0.57, p<0.05 and r=0.39, p<0.05; respectively). We found important differences in the coagulatory /fibrinolytic parameters between the hyperthyroid patients and healthy controls. Hyperthyroid patients may experience vascular endothelial dysfunction and decreased fibrinolytic activity in blood. This endothelial activation may represent a situation with a higher thromboembolic potential.