妊娠高血压综合征患者血浆纤维蛋白溶解系统变化的初步观察

目的：观察妊高征患者血浆纤维蛋白溶解系统的变化。方法：测定20例正常孕妇及15例妊局征患者血浆中D-二聚体（D－D）、纤维蛋白降解产物（FDP）、纤维蛋白原（Fg）含量、组织型纤溶酶原激活物活性（t－PA：A）、α2－纤溶酶抑制物活性（α2－PI：A）。结果：非孕妇与正常孕妇、正常孕妇与好高征患者之间D—D含量有明显差异（P＜0．01,P＜0．001）;好高征患者FDP阳性率（100％）明显高于正常妊娠组（15％）;非孕妇与正常孕妇及好高征患者间Fg含量有明显差异（P＜0.01）;非孕妇与正常孕妇之间t－PA:A无差异,但与妊高征之间有明显差异（P＜0.001）,α2－PI：A则无组间差异。结论：正常孕妇处于高凝状态,妊高征者有血栓形成倾向。本文所检测的指标,尤其D－D、t－PA：A和α2－PI：A为纤溶系统分子标志物,可作为监测妊高征纤溶及凝血变化的重要指标。     

妊高征患者血栓前状态指标的检测及其临床意义

目的 观察妊娠高血压综合征(简称妊高征)患者的血管内皮损伤、血小板活化状态、抗凝及纤溶系统部分指标的变化，探讨其对妊高征血栓前状态(PTS)的诊断意义。方法 采用ELlSA法和全自动血凝仪分析，检测了正常非妊娠非妇女、正常晚期妊娠妇女各20例和52例妊高征患者的血管性血友病因子(vWF)、血小板o—颗粒膜蛋白(GMP—140)、抗凝血酶、蛋白C系统筛选(ProC Global)、纤维蛋白原(Fbg)、纤溶酶原(PLG)、组织纤溶酶原激活物(t—PA)及其抑制物(PAI)、D—二聚体(D—Dimer)等指标。结果 与正常非孕组及正常晚期妊娠组比较，妊高征组vWF、GMP—140水平均显著增高，并随病情加重而呈增高趋势，而AT、ProC活性均显著下降，病情越重下降越明显。纤溶系统各项指标妊高征组、正常晚期妊娠组均显著高于非孕组；而与正常晚期妊娠组比较，妊高征组Fbg、PLG、D—Dimer、PAI均显著增高．中重度患者尤其明显，而t—PA无显著性改变。结论 正常妊娠妇女存在高凝状态，而妊高征患者存在明显血栓前状态。产前测定有关凝血和纤溶功能指标，对妊高征的防治具有重要价值。     

纵向序贯研究正常妊娠高凝状态时纤溶系统活性的变化

目的探讨汉族人群正常妊娠生理性高凝状态时原发性纤溶系统活性的变化。方法采用纵向序贯研究,纳入孕期及妊娠结局均正常的孕妇(正常妊娠组)100名,以同期进行健康体检的100名育龄期妇女作为非孕对照组。检测正常孕期妇女常规纤溶指标[纤维蛋白原(Fg)、纤维蛋白原降解产物(FDP)、Fg/FDP比值]及纤溶调节指标[组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制剂-1(PAI-1)含量和t-PA/PAI-1比值]的变化,分析Fg、FDP与t-PA/PAI-1比值的相关性。结果正常妊娠组Fg、FDP水平及Fg/FDP随孕期增加逐渐升高(P0.01);与非孕对照组相比,正常妊娠组各孕期t-PA、PAI-1、t-PA/PAI-1比值均增高(P0.05)。正常妊娠组早孕时t-PA/PAI-1比值与Fg呈正相关[(r)=0.81,P0.05];t-PA/PAI-1比值在中孕时降到最低(即Fg降解率达到最低),Fg在晚孕时达到高峰。正常妊娠组孕早、晚期t-PA/PAI-1比值与FDP均呈正相关(r分别为0.75及0.79,P0.05)。结论汉族人群正常妊娠时机体并未启动凝血。机体在整个妊娠期通过增强原发性纤溶活性直接控制升高的Fg含量,在高水平上使凝血/纤溶系统保持平衡。     

高原地区妊高征患者一氧化氮水平的变化

目的：探讨高原地区妊高征与一氧化氮水平变化的关系。方法：选择高原地区妊高征患者36例,正常妊娠妇女21例,正常健康女性20例;采集空腹静脉血,应用硝酸根还原酶与Griess反应相结合的方法检测受检者血中一氧化氮含量,并进行分析。结果：高原妊高征患者血清中一氧化氮含量显著高于正常妊娠妇女及正常非妊娠妇女,妊高征患者一氧化氮含量按轻、中、重程度不同较正常妊娠组逐渐增高。结论：高原妊高征患者一氧化氮含量明显增高,且增高水平与病情有关。     

妊娠高血压综合征患者血浆纤维蛋白溶解系统变化的初步观察

目的：观察妊高征患者血浆纤维蛋白溶解系统的变化。方法：测定２０例正常孕妇１５例妊高征患者血浆中Ｄ－二聚体（Ｄ－Ｄ）、纤维蛋白降解产物（ＦＤＰ）、、纤维蛋白原（Ｆｇ）含量、组织型纤溶酶原激活物活性（ｔ－ＰＡ：ａ）、ａ２－纤溶酶抑制物活性（ａ２－ＰＩ：Ａ）。结果非孕妇与正常孕妇、正常孕妇与妊高征患者之间Ｄ－Ｄ含量有明显差异（Ｐ〈０．０１,Ｐ〈０．００１）;妊高征患者ＦＤＰ阳性率（１００％）ＪＥ ＪＯ     

血栓性疾病患者血浆中主要纤溶指标的检测及其临床意义

组织型纤溶酶原激活剂（t—PA），纤溶酶原激活剂抑制剂（PAI）是人体纤溶系统的主要指标。其检测日益受到重视。用显色底物比色法对人体血浆中t－PA、PAI活性进行了测定，结果表明该法灵敏度高，稳定性好。对照组t-PA活性为1．55±0．67IU／ml，PAI活为8.077±3．07AU／ml。心肌梗塞、脑梗塞和冠心病患者t—PA活性较正常水平下降，PAI活性则明显升高。     

冠心病患者抗凝与纤溶功能的改变及其临床意义

目的探讨冠心病患者凝血、抗凝与纤溶功能的改变及临床意义。方法应用发色底物法及胶乳增强的免疫比浊法分别测定不同类型的冠心痛患者160例（包括凝血65例,抗凝52例,纤溶功能43例）及健康对照者80例血浆抗凝血酶（autithrombin,AT）、组织型纤溶酶原激活剂（tissue type plasminogen activator,t—PA）、纤溶酶原激活抑制物-1（plasminogen activator inhibitor-1,PAI-1）及D-二聚体（D—dimer）的活性或含量水平,并进行比较分析。结果与对照组比较,冠心病患者AT、t--I,A的活性显著降低,PAI-1、D—dimer的活性或含量水平显著增高（P〈0．05或P〈0．01）;与稳定性心绞痛患者组比较．不稳定性心绞痛组及心肌梗死组AT、t—PA、PAI-1、D—dimer的活性或含量水平亦有显著性改变（P〈0．05或P〈0．01）。结论冠心病患者特别是不稳定性心绞痛及心肌梗死患者存在高凝状态及纤溶活性亢进。     

不同剂量阿托伐他汀对2型糖尿病患者纤溶活性的影响

目的研究不同剂量阿托伐他汀对2型糖尿病患者纤溶活性的影响。方法用酶联免疫吸附法(ELISA)测定2型糖尿病患者外周血中血浆纤溶酶原激活剂(t-PA)及其血浆纤溶酶原激活剂抑制物-1(PAI-1)的水平,并比较不同剂量阿托伐他汀对它们的影响。结果10 mg和20 mg阿托伐他汀治疗前后总胆固醇(TC)、PAI-1均有显著下降(P<0.05)、t-PA水平显著上升(P<0.05),20 mg组治疗后TC、t-PA及PAI-1均较10 mg组差异有统计学意义(P<0.05)。结论阿托伐他汀对2型糖尿病患者纤溶活性有积极作用,且在一定范围内随着剂量的增加而加强,同时具有良好的安全性。     

心绞痛患者介入术后血小板活化及纤溶功能的变化

目的 研究冠心病不稳定心绞痛患者经皮冠状动脉腔内成形术（PTCA）和冠状动脉内支架术（stent)后外周循环中血小板活化及纤溶功能的变化。方法 由外周静脉采血，采用ELISA检测PTCA和stent术前后血浆血小板表面α-颗粒膜蛋白（GMP-140），血管性假血友病因子（VWF），组织纤溶酶原激活剂（t-PA)，纤溶酶原激活剂抑制物-1（PAI-1），D-二聚体（D-D）的含量。结果 31例不稳定型心绞痛患者PTCA术后10min血浆血小板膜表面GMP-140及D-二聚体明显增高。术后24h虽明显下降，但血小板膜表面GMP-140尚未降至正常，PAI-1术后24h亦明显增高。结论 冠心病不稳定型迟缓绞痛患者PTCA和stent术后确有血小板活化和纤溶活性受损。     

老年冠心病患者血清同型半胱氨酸与纤溶酶活性

背景：同型半胱氨酸已成为动脉粥样硬化的独立危险因子，它可能通过破坏内皮细胞的结构和功能从而导致动脉粥样硬化。目的：探讨同型半胱氨酸对老年冠心病患者纤溶酶活性的影响。设计：以冠心病患者为研究对象，健康人群为对照组的病例一对照。单位：一所大学医院的综合科及心内科。对象：本研究于首都医科大学附属北京朝阳医院综合科及心内科完成。选择2001—12／2003—8本院心内科及综合科门诊及住院患者177例，根据冠状动脉造影结果分为：冠心病组91例，其中男50例，女41例，平均年龄(66&;#177;6)岁；冠状动脉造影阴性组86例，其中男43例，女43例，平均年龄(60&;#177;6)岁。正常对照组为同期于本院门诊体检的健康中年人85例，其中男43例，女42例，平均年龄(55&;#177;5)岁。方法：收集外周血，检测血浆中的组织型纤溶酶原激活剂、纤溶酶原激活物抑制剂1和血管性血友病因子的活性，用酶免疫试验法测同型半胱氨酸，并计算纤溶酶原激活物抑制剂1／组织型纤溶酶原激活剂活性比值。主要观察指标：血清同型半胱氨酸水平及血浆组织型纤溶酶原激活剂、纤溶酶原激活物抑制剂1、血管性血友病因子活性，纤溶酶原激活物抑制剂1／组织型纤溶酶原激活剂的比值。结果：冠状动脉病变组同型半胱氨酸，纤溶酶原激活物抑制剂1，纤溶酶原激活物抑制剂1／组织型纤溶酶原激活剂，血管性血友病因子均明显高于冠状动脉造影阴性组及正常对照组(P&;lt;0．01)，组织型纤溶酶原激活剂水平显著低于对照组(P&;lt;0．01)；从相关分析看，同型半胱氨酸与纤溶酶原激活物抑制剂1，纤溶酶原激活物抑制剂1／组织型纤溶酶原激活剂，血管性血友病因子呈正相关，与组织型纤溶酶原激活剂呈负相关。结论：老年冠心病患者其血清同型半胱氨酸增高的同时，纤溶酶活性受损；同型半胱氨酸与纤溶酶原激活物抑制剂1，血管性血友病因子呈正相关，与组织型纤溶酶原激活剂呈负相关；同型半胱氨酸可能是冠状动脉早期病变的预报因子，可为冠心病的一级预防和早期康复措施介入提供相关实验数据。     

Variations in fibrinolytic parameters and inhibin-A in pregnancy: related hypertensive disorders

Summary.  Background:  The mechanisms leading to pregnancy-related hypertensive disorders, and pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) in particular, are still not clear. Diagnostic criteria are clinical because specific markers of the condition are lacking. A role of the fibrinolytic system has been suggested. Objectives:  We aimed to evaluate the behavior of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), PAI-2, and the placental hormone inhibin-A in women with a normal pregnancy vs. women with pregnancies complicated by PIH or PE. Methods:  Blood samples were drawn between the 25th and 30th gestational week (GW) and between the 31st and 36th GW in order to assay t-PA, PAI-1, PAI-2 and inhibin-A; routine biochemical exams, ultrasonography umbilical artery pulsatility index (PI), placental weight and newborn weight were measured. Results:  In pregnancies complicated by hypertensive disorders, PAI-1 levels were higher than in controls and increased significantly after the 25th GW, especially in PE, as did inhibin-A. PAI-2 levels were significantly lower after the 30th GW in patients with PIH and PE. The PAI-1/PAI-2 ratio was significantly higher in PE patients than in controls as of the 25th GW, but only after the 30th GW in patients with PIH. Inhibin-A was significantly correlated with fibrinolytic parameters, and inversely with newborn weight. Receiver–operator characteristic curves for PAI-1 and inhibin-A showed a high sensitivity and specificity for PE. PAI-2 correlated with newborn and placental weight, and inversely with PI of the umbilical artery. Conclusions:  Fibrinolytic tests (especially PAI-1) and inhibin-A monitoring during pregnancy may help in the early diagnosis of pregnancy-related hypertensive disorders.     

tPA和PAI-1活性与自然流产的相关性

【目的】探讨组织型纤溶酶原激活剂（tPA）和纤溶酶原激活剂抑制剂-1（PAI-1）活性与自然流产的相关性。【方法】选择2003年10月至2004年3月中南大学湘雅二医院门诊有自然流产史患者71例（非孕50例．孕妇21侧）和对照组41例（非孕20侧,孕妇21例）进行研究,运用发色底物法测定血浆tPA和PAI-1活性。【结果】非孕有自然流产史的研究组tPA活性比对照组低（t=2．226,P=0．029〈0．05）,早孕研究组tPA活性比对照组低（t=2．166,P=0．036〈0．05）,差别均有统计学意义;研究组中,tPA活性早孕高于非孕（t=-2．937,P=0．005）,PAI-1活性早孕低于非孕（t=2．428,P=0．018）;在对照组中,tPA活性早孕也高于非孕（t=2．597,P=0．013）,PAI-1活性早孕也低于非孕者（t=2．653,P=0．012）。差别均有统计学意义。【结论】妊娠后tPA活性增高和PAI-1活性下降。有自然流产史者在非孕状态时tPA活性明显下降,且妊娠后呈低增长水平。tPA活性下降与引起自然流产的发病机制有关。     

Pregnancy outcome and fibrinolytic, endothelial and coagulation markers in women undergoing uterine artery Doppler screening at 23 weeks

Summary.  Background:  Pre-eclampsia (PET) and/or fetal growth restriction (FGR) remain a major cause of maternal and fetal morbidity and mortality. In pregnancy, fibrinolysis is controlled by the maternal endothelium and placenta, both of which are central to the pathogenesis of PET/FGR. Clinically, uterine artery Doppler screening at 23 weeks is used to predict PET/FGR. An abnormal uterine artery Doppler finding is defined as early diastolic bilateral uterine artery notching (BN) in the waveform. However, about 50% of mothers with BN do not develop PET/FGR. Objectives:  We investigated fibrinolytic changes and uterine artery Doppler findings in the second trimester, and related them to pregnancy outcome; in particular assessing whether fibrinolytic markers could discriminate between normal and abnormal outcome in mothers with BN. Patients/methods:  Plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor-2 (PAI-2), plasmin-α₂ antiplasmin (PAP), D-dimers and markers of endothelial dysfunction were measured with Doppler ultrasound at 23 weeks. Results:  Those with BN had decreased PAP and D-dimer levels, and raised PAI-1 and thrombomodulin levels. Mothers with BN and PET/FGR had significantly increased t-PA levels and reduced PAI-2 levels. Conclusions:  BN at 23 weeks of gestation is associated with increased PAI-1 levels. Within the BN group, mothers who developed PET/FGR had increased t-PA levels and decreased PAI-2 levels, although there was no net change in fibrinolysis as measured by D-dimer levels. No single fibrinolytic marker is helpful in determining pregnancy outcome in those with BN, but t-PA and PAI-2 are worthy of study in a multifactorial algorithm.     

The hyperfibrinolytic state of liver cirrhosis: possible pathogenetic role of ascites

We evaluated coagulation and fibrinolytic parameters in both plasma and ascitic fluid of 39 patients with ascites secondary to liver cirrhosis and in 14 cirrhotic patients without ascites, in order to verify if the peritoneal compartment could be involved in the pathogenesis of the hyperfibrinolytic state of the disease. An activation of fibrinolysis, as suggested by increased levels of FDP, D-dimer and tissue plasminogen activator (t-PA) was demonstrated in both ascitic fluid and to a lesser extent in plasma. A positive correlation was also observed between plasma and ascitic fluid plasminogen, antiplasmin and fibrinogen, while a negative correlation was found between plasma and ascitic fluid plasminogen activator inhibitor-1 (PAI-1). Moreover, plasma PAI-1 was significantly lower in patients with ascites than in those without ascites and among ascitic patients in those who had bleeding into soft tissues when compared to those who did not present haemorrhagic events. Finally, a significant association was also shown between positivity for plasma D-dimer (> 200 ng/ml) and the presence of ascites. Taken together, our data suggest an exchange of some coagulation and fibrinolytic proteins between plasma and ascitic fluid and point out the key role of PAI-1 in regulating plasma fibrinolytic potential and in bleeding complications in cirrhotic patients.     

纤溶系统与纤维蛋白原在不稳定型心绞痛患者发病中的临床意义

目的：探讨并研究纤溶系统与纤维蛋白原在不稳定型心绞痛（UA）患者发病中的临床价值。方法：对108例不稳定型心绞痛患者和42稳定型心绞痛（SA）患者体内纤溶酶原激活物抑制剂-1（PAI-1）、组织型纤溶酶原激活剂（t—PA）、纤维蛋白原（FIB）水平进行检测,并与20例正常对照者进行对照,探讨其临床意义。结果：UA患者体内PAI-1、FIB水平明显高于SA患者和正常对照者,UA患者中有心血管事件发生者也明显高于无心血管事件发生者;UA患者体内t—PA水平明显低于SA患者和正常对照者,UA患者中有心血管事件发生者也明显低于无心血管事件发生者。结论：UA患者纤溶系统功能异常和FIB水平升高程度较SA患者更加明显,并且UA患者的心血管事件发生可能与溶系统功能异常和FIB水平升高相关。     

Bleeding diathesis due to decreased functional activity of type 1 plasminogen activator inhibitor.

We evaluated an elderly patient with a lifelong history of severe bleeding after surgery or trauma and with evidence of persistent hyperfibrinolysis. Routine coagulation studies were normal. Serum plasminogen (40%, normal 72-128%) and alpha 2-antiplasmin (55%, normal 70-145%) activities were decreased. Euglobulin clot lysis was abnormally shortened (50 min) and normalized in vitro with epsilon-aminocaproic acid (EACA). The patient was treated with EACA with prompt cessation of bleeding. Patient tissue-plasminogen activator (t-PA) levels in serum were normal (4.7 ng/ml, control 3.5-7.2) as detected by a two-site immunoradiometric assay (IRMA). Patient fibrinolytic inhibitor activities were assessed by incubating 125I-labeled t-PA with either whole blood or serum followed by SDS-PAGE and autoradiography to identify the resultant protease/protease inhibitor complexes. In comparison to blood samples obtained from normal donors, patient plasma and serum demonstrated reduced binding of a fast-acting plasminogen activator inhibitor to 125I-labeled t-PA. Immunoprecipitation experiments indicated diminished complex formation between type 1 plasminogen activator inhibitor (PAI-1) in patient serum and 125I-labeled t-PA. Low patient PAI-1 activity was confirmed in serum (0.36 U/ml, control 0.87-1.81; n = 3) and in platelet lysates using a functional IRMA to quantitate PAI-1 binding to immobilized t-PA. However, patient serum PAI-1 antigen was within the normal range when analyzed by IRMA (31.8 ng/ml, control 19.6-42.2); this result was confirmed in both serum and platelets by Western blot (n = 3). Mixing experiments using purified PAI-1 as well as patient and control sera did not show evidence for an inhibitor against PAI-1. We conclude that this patient's bleeding diathesis was due to hyperfibrinolysis and defective PAI-1. This patient provides the first demonstration of a link between decreased in vivo PAI-1 activity and disordered hemostasis, and supports a role for PAI-1 in control of vivo fibrinolysis.     

Blood coagulation and fibrinolysis during normal pregnancy

Fifty-six pregnant women (gestational age 6-40 weeks) were evaluated for their coagulation activation (fibrin monomers and thrombin-antithrombin III complex) and for their fibrinolysis profile by determining tissue plasminogen activator, plasminogen activator inhibitor, plasminogen, alpha 2-antiplasmin and D-dimer. Fibrin monomers and thrombin-antithrombin III complexes were found to be significantly increasing with gestational age. All the fibrinolytic parameters showed a steady growth with the progress of the pregnancy, with the exception of tissue plasminogen activator which showed a significant decrease with gestational age, but mainly within the reference range. These results suggest a stimulation of the coagulation system and an activation of fibrinolysis with ongoing pregnancy, although the increasing alpha 2-antiplasmin and plasminogen levels and the decreasing tissue plasminogen activator concentrations do not conform to this trend.