急性脑卒中患者血浆t—PA,PAI—1活性变化及意义

采用发色底物显色法检测了３６例多发性脑梗塞患者、１６例脑出血患者以及２９例同期住院的非脑血管病患者血浆组织型纤溶酶原激活物（ｔ－ＰＡ）、纤溶酶原激活物抑制物（ＰＡＩ－１）活性。结果：脑梗塞组ｔ－ＰＡ活性减低，ＰＡＩ－１活性增高（均Ｐ＜０．０５）。表明脑梗塞患者有血浆纤溶功能损害。提示血浆ｔ－ＰＡ、ＰＡＩ活性变化以及两者之间的平衡失调在脑梗塞的发生、发展中起一定作用     

脑血栓形成患者血浆组织型纤溶酶原激活物及其快速抑制物的变化 …

目的 观察急性动脉硬化性脑血栓形成患者血浆组织型纤溶酶原激活物（ｔ－ＡＰ）及其快速抑制物（ＰＡＩ－１）的变化规律，探讨血浆纤溶活性在脑血栓发生，发展及转归中的作用；同时测查恢复期或后遗期脑血栓形成患者血浆ｔ－ＰＡ及ＰＡＩ－１的变化规律，了解此类患者再发生血栓的危险性。方法 采用美国Σ９６０酶标读数仪，用发色底物法对２５例急性脑血栓形成患者血浆ｔ－ＰＡ及ＰＡＩ－１活性进行动态测查（发病后１、３、７、     

脑卒中患者急性期血浆t—PA和PAI活性的研究

脑卒中患者急性期血浆ｔ－ＰＡ和ＰＡＩ活性的研究张波张秋滨何宏刘滨唐强组织型纤溶酶原激活物（ｔ－ＰＡ），其抑制物（ＰＡＩ）是纤溶系统的关键酶，两者的相互作用调节纤溶系统的功能，我们对急性脑梗塞、急性脑出血的ｔ－ＰＡ和ＰＡＩ的活性进行了研究，现报道如下。...     

脑血栓形成急性期后患者血浆t－PA、PAI活性动态变化

动态观察２０例脑血栓形成患者急性期后及随后３周的血浆ｔ－ＰＡ、ＰＡＩ活性水平，并与正常老年人对照，以了解脑血栓形成后患者纤溶活性的变化规律，并探讨其临床意义。结果发现脑血栓形成患者血浆ｔ－ＰＡ活性低于正常老年人（Ｐ＜０．００１），随后３周，ＰＡＩ活性升高（Ｐ＝０．０５９），ＰＡＩ／ｔ－ＰＡ值升高（Ｐ＜０．０５），纤溶功能低下并呈降低趋势     

脑血栓形成急性期后患者血浆t—PA,PAI活性动态变化

动态观察了２０例脑血栓形成患者急性期后及随后３周的血浆ｔ－ＰＡ、ＰＡＩ活性水平，并与正常老年人对照，以了解脑血栓形成后患者纤溶活性的变化规律，并探讨其临床意义。结果发现脑血栓形成患者血浆ｔ－ＰＡ的活性低于正常人，随后３周，ＰＡＩ活性升高ＰＡＩ／ｔ－ＰＡ值升高，纤溶功能低下半呈降低趋势。     

组织型纤溶酶原激活物及其抑制物与脑血管疾病

组织型纤溶酶原激活物 (ｔｉｓｓｕｅｐｌａｓ ｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒ ,ｔ -ＰＡ)及其抑制物(ｔｉｓｓｕｅｐｌａｓｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒｉｎｈｉｂｉｔｏｒ -1,ＰＡＩ - 1)是纤溶系统的二个重要组成部分。目前对二者的结构、特性以及与脑血管疾病的关系尚未完全阐明。缺血性脑血管病患者血浆中二者的活性、抗原含量测定甚至出现了矛盾的结果。1　ｔ -ＰＡ、ＰＡＩ- 1在纤溶系统中的作用　　纤溶酶原激活物 (ＰＡ)即组织型纤溶酶原激活物 (ｔ -ＰＡ)和尿激酶型纤溶酶原激活物 (ｕ -ＰＡ)以及它们的抑制物在纤维蛋白…     

急性脑梗塞患者静脉溶栓治疗期间血浆纤溶活性和GMP—140？…

本文动态观察了１３例急性脑梗塞患者早期大剂量尿激酶静脉溶栓期间血浆纤溶活性及ＧＭＰ－１４０的变化。结果显示溶栓完毕后即刻血浆溶酶原活性和Ｄ－二聚体明显升高，纤溶酶原激活物抑制物（ＰＡＩ）明显下降，但这些变化持时间较短，血浆ｔ－ＰＡ，ＰＡＩ活性分别于２４小时，４８小时后又恢复到溶橙有水平，血浆ＧＭＰ－１４０于溶栓完毕后即刻上升，２４小时达高峰，４８小时后下降，认为急性脑梗塞早期静脉溶栓间继发性纤溶增     

急性脑梗塞患者静脉溶栓治疗期间血浆纤溶活性和GMP-140变化的研究

本文动态观察了１３例急性脑梗塞患者早期大剂量尿激酶静脉溶栓期间血浆纤溶活性及ＧＭＰ－１４０的变化。结果显示溶栓完毕后即刻血浆纤溶酶原活性（ｔ－ＰＡ）和Ｄ－二聚体明显升高（Ｐ＜０．０５），纤溶酶原激活物抑制物（ＰＡＩ）明显下降（Ｐ＜０．０５），但这些变化持续时间较短，血浆ｔ－ＰＡ、ＰＡＩ活性分别于２４小时、４８小时后又恢复到溶栓前水平，血浆ＧＭＰ－１４０于溶栓完毕后即刻上升，２４小时达高峰，４８小时后下降。认为急性脑梗塞早期静脉溶栓期间继发性纤溶增加同时伴有血小板激活，凝血活性增高     

血纤溶活性变化对颈动脉粥样硬化和急性脑梗死患者的影响和分析

目的：研究血纤溶活性变化对颈动脉粥样硬化患者和急性脑梗死患者的影响。方法：67例急性脑梗死患者（ACI组）和62名健康体检老年人（对照组），均行彩色多普勒超声诊断仪超声观察颈动脉有无斑块；同时测定血浆组织型纤溶酶原激活物（t-PA）和纤溶酶原激活物抑制物-1（PAI-1）的活性。结果：对照组中有颈动脉斑块者与无颈动脉斑块者相比，血浆t-PA降低，PAI-1升高，P／t值升高（P〈0．05）；观察组颈动脉斑块发生率明显高于对照组（P〈0．05）；观察组患者急性期血浆t-PA、PAI-1升高，P／t值减少（P〈0．05）。结论：颈动脉硬化时，机体纤溶活性处于减低状态；急性脑梗死发生时，纤溶活性处于相对亢进状态。     

急性脑梗死患者血浆纤溶酶原激活剂抑制物活性及其启动子区 …

目的 探讨纤溶酶原激活剂抑制物（ＰＡＩ－１）活性和启动子基因多态性在急性脑梗死发病过程中的作用。方法 通过等位基因特异性寡核苷酸斑点要交技术，测定１０７例急性脑梗死患者和９５名健康人的白细胞ＰＡＩ－１启动子区４Ｇ／５Ｇ多态性位点的基因型，用发色底物法测定血浆ＰＡＩ－１活性。结果 脑梗死组血浆ＰＡＩ－１活性明显高于对照组，病例组和组织中４Ｇ／４Ｇ基因型患者的ＰＡＩ－１活性水平最高，４Ｇ／５Ｇ基因型次     

Deep vein thrombosis and fibrinolysis. Defective urokinase type plasminogen activator release.

In the present study 57 consecutive patients with a first episode of venographically proven deep vein thrombosis were investigated to evaluate the release of tissue-type plasminogen activator (t-PA) and of urokinase-type plasminogen activator (u-PA) in response to DDAVP stimulation as well as the resting plasminogen activator inhibitor (PAI) concentration, comparing this to the results obtained in 66 similar patients with a clinical suspicion of thrombosis but with a normal venogram. All assays were performed without knowledge of the patient's status. Four patients in the deep vein thrombosis-group (7%) had an absent u-PA antigen response upon DDAVP infusion, while a normal response was observed in all control subjects. Patients and controls showed similar increases in t-PA antigen level upon DDAVP. High resting PAI antigen levels were encountered in 5 patients in the deep vein thrombosis-group (9%) and in 6 subjects in the control group (9%). The results from this controlled study indicate that a defective release of u-PA may occur in patients with deep vein thrombosis and may have pathogenetic significance. Furthermore it is concluded that elevation of PAI levels cannot be considered as a specific risk factor for venous thrombosis.     

Impaired fibrinolysis in obstructive jaundice--evidence from clinical and experimental studies

Microvascular thrombosis is considered an important pathogenetic factor in renal failure associated with obstructive jaundice but the mechanisms leading to fibrin deposition are still unknown. The plasma levels of plasminogen activator inhibitor (PAI) in 29 patients with obstructive jaundice were found significantly increased as compared to 20 nonjaundiced patients. Fibrin autography of plasma supplemented with tissue plasminogen activator (t-PA) revealed that in icteric samples most of the added activator migrated with an apparent Mr of 100 kDa, corresponding to t-PA-PAI complex, whereas in control samples virtually all t-PA migrated as free enzyme. PAI activity detected in icteric samples is similar to the endothelial type PAI since it is neutralized by a monoclonal antibody against PAI-1. Venous stasis in jaundiced patients was neither associated with an increase in blood fibrinolytic activity nor with a decrease in PAI activity. Immunologic assay showed that t-PA release was impaired in 3 out of 4 patients. In controls, venous occlusion induced an increase in both fibrinolytic activity and t-PA antigen and a reduction in PAI activity. Bile duct recanalization in jaundiced patients subjected to surgery was accompanied by a decrease in plasma PAI activity which paralleled the decrease in serum bilirubin levels. In nonjaundiced patients, surgical treatment did not cause significant changes in either parameter. Rabbits made icteric by bile duct ligation showed an early and progressive increase in plasma PAI activity indicating that obstructive jaundice itself causes the elevation of circulating PAI. it is concluded that obstructive jaundice is associated with a severe impairment of fibrinolysis which might contribute to microvascular thrombosis and renal failure.     

Effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator and plasminogen activator inhibitor

Short-term effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were studied in two age groups of volunteers (20-30 and 45-55 years), each consisting of eight healthy males. The alcohol (30 g in red port and wine) was consumed during a standard dinner. Two blood samples were drawn: one in the postprandial phase, and one the next morning after fasting overnight. Alcohol consumption tended to increase platelet aggregation and production of hydroxy fatty acids, reduced plasma t-PA activity and increased PAI activity in the postprandial phase. After the overnight fast the effects on t-PA and PAI had disappeared whereas at that time alcohol consumption tended to decrease platelet function. The effects of alcohol on t-PA and PAI activity appeared mainly in the older age group, whereas the t-PA activity in this group was already much lower, irrespective of alcohol consumption.     

急性脑梗死患者血浆纤溶酶原激活物及其抑制剂-1水平的动态变化及其与梗死面积的关系

目的 探讨急性脑梗死患者血浆组织型纤溶酶原激活物(t-PA)及其抑制剂-1(PAI-1)水平的动态变化及其与梗死面积的关系.方法 急性脑梗死患者100例,其中大面积脑梗死22例、小面积脑梗死36例、腔隙性脑梗死42例,采用发色底物显色法检测脑梗死患者病后24 h、2 d、14 d、21 d的血浆t-PA、PAI-1水平,与正常对照组比较;并比较不同面积脑梗死患者血桨t-PA、PAI-1水平.结果 与正常对照组比较,急性脑梗死患者病后24 h、2 d、14 d血浆t-PA水平显著降低,血浆PAI-1水平明显升高(均P＜0.01);病后21 d两者与正常对照组差异无统计学意义(均P＞0.05);大面积脑梗死患者t-PA水平明显低于小面积和腔隙性脑梗死患者,小面积脑梗死患者又明显低于腔隙性脑梗死患者(均P＜0.01);不同面积脑梗死组之间PAI-1水平未见明显差异(均P＞0.05).结论 脑梗死患者急性期血浆t-PA水平降低及PAI水平升高;脑梗死面积越大的患者血浆t-PA水平降低程度越明显,而血浆PAI-1水平与梗死面积无关.     

Plasminogen activator inhibitor activity in bacterial infection

It has been experimentally shown that endotoxin induces a marked increase in the levels of a fast-acting inhibitor of plasminogen activator (PAI). The plasma PAI activity and tissue-type plasminogen activator (t-PA) concentrations were measured in 61 patients with human septicaemia and results were compared with those observed in healthy controls. There was a markedly significant increase of PAI in plasma and platelet extracts of patients with septicaemia as compared to controls (p less than 0.0001). No correlation between PAI and endotoxin concentration was observed. Fibrin autography of plasma samples confirmed that activator inhibition was associated with the formation of an enzyme-inhibitor complex. t-PA activity was similar in patients and controls, whereas t-PA Ag showed a significant increase in patients (p less than 0.0001). A significant inverse correlation between t-PA activity and PAI was observed (p less than 0.05). PAI activity was higher in patients with positive blood cultures (p less than 0.0001) and gram-negative septicaemia (p less than 0.0001). There was also a significant increase of PAI levels in patients with disseminated intravascular coagulation (DIC) as compared with patients without DIC (p less than 0.001). We conclude that there is a marked increase of PAI in patients with sepsis. Increased PAI activity may contribute to the pathogenesis of DIC associated with septicaemia.     

Different types of plasminogen activator activity in human brain tumours: relation with peritumoral oedema?

In 20 tissue samples from human brain tumours the concentrations were measured of (1) total plasminogen activator activity, (2) tissue-type plasminogen activator (t-PA) activity, (3) urokinase-type plasminogen activator (u-PA) activity and (4) t-PA antigen. Most tumours contained a considerable amount of t-PA, but a high interindividual and in a few cases even an intra-individual variability was observed. A weak but significant negative correlation was found between t-PA concentration and the oedema/tumour ratio, as calculated from the preoperative computerized tomography (CT) brain scanning. No correlation was found with u-PA activity. It is concluded that t-PA and u-PA are probably not important factors in the production of peritumoral cerebral oedema, but a correlation between locally different amounts of t-PA or u-PA and the locally different extent of surrounding oedema has not yet been excluded.     

Altered fibrinolysis in DVT: influence of site of sampling

Alteration of the fibrinolytic system is considered to be important in the development of deep venous thrombosis (DVT). Using specific assays for tissue plasminogen activator (t-PA) activity, t-PA inhibitor (PAI) and t-PA antigen, we measured these activities in 16 women who developed DVT during their pregnancies. A group of 24 healthy females of comparable age was studied as controls. PAI was increased in 87% of these patients compared to the healthy controls. In some of these patients a defect in release of t-PA from vascular endothelium was found as well. The site at which blood was sampled for analysis appeared to be an important criterion in the ex vivo assessment of functional t-PA reserve and PAI levels, though relatively less so for the latter measurement. The unaffected lower limbs, relative to the unaffected upper limbs, showed an increase in PAI and a demonstrable decrease in t-PA release, both representing increased risk factors for rethrombosis. The affected lower limbs showed similar but more accentuated changes in these parameters.     

Fibrinolytic response in normal subjects to venous occlusion and DDAVP infusion

A set of fibrinolytic parameters was measured in 40 healthy subjects before and after a venous occlusion (VO) test lasting 10 min. After VO, plasma levels of tissue-type plasminogen activator (t-PA) antigen increased in all subjects, t-PA activity increased only in 25 subjects who were considered responders and remained unchanged in 15 (non-responders). High levels of plasminogen activator inhibitor (PAI) in the non-responder group explain this discrepancy. The non-responders had basal levels of PAI activity and t-PA antigen higher than responders (p less than 0.0001) and their basal levels of t-PA activity were lower (p less than 0.001). DDAVP infusion elicited good responses in 7 of 9 non-responders to VO with a fall of PAI activity to 0. Our data indicate that a high proportion of healthy subjects do not have a fibrinolytic response after VO, that a lack of fibrinolytic response to VO is due to high plasma levels of PAI and that DDAVP infusion appear to be more selective than VO for detecting non-responders.     

Effects of defibrotide on fibrinolytic activity in diabetic patients with stable angina pectoris.

18 type II diabetes mellitus patients with coronary artery disease (CAD) have been studied. Tissue plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) antigen and activity, thrombin-antithrombin III (TAT) complexes were determined in blood samples. Diabetic CAD patients showed higher TAT levels with clearly increased PAI levels whereas t-PA levels levels were similar in patients and controls. Long term defibrotide treatment induced marked changes in fibrinolytic parameters of these diabetic patients with CAD with increased t-PA activity, that could be related to an evident reduction of PAI antigen and activity. Drugs able to modulate PAI activity may be useful in clinical conditions at high risk of thrombotic vascular complications like diabetics with stable angina.