Recent advances in understanding endogenous fibrinolysis: implications for molecular-based treatment of vascular disorders

2002 ◽  
Vol 4 (7) ◽  
pp. 1-10 ◽  
Author(s):  
Peter F. Bodary ◽  
Kevin J. Wickenheiser ◽  
Daniel T. Eitzman
Keyword(s):  
Animal Models ◽  
Thrombus Formation ◽  
Plasminogen Activator Inhibitor ◽  
Coagulation Cascade ◽  
Clot Lysis ◽  
Plasmin Activity ◽  
Plasminogen Activator Inhibitor 1 ◽  
Fibrinolysis Inhibitor ◽  
Activator Inhibitor

The fate of a forming thrombus is determined through the delicate balance between the coagulation cascade, favouring clot formation, and the fibrinolytic system, favouring clot lysis. These processes occur simultaneously, and enhancement of fibrinolysis has been shown to reduce occlusive thrombus formation in animal models. This review examines the roles of the major fibrinolytic factors involved in clot lysis. The regulation of plasmin activity by plasminogen activators, α-2-antiplasmin, plasminogen activator inhibitor 1, and thrombin-activatable fibrinolysis inhibitor, and their effects on thrombus formation in vivo are discussed. Since alterations in fibrinolytic capacity appear to affect thrombus formation in animal models, there is considerable interest in the pharmacological manipulation of fibrinolysis.

The Roles of α2-Antiplasmin and Plasminogen Activator Inhibitor 1 (PAI-1) in the Inhibition of Clot Lysis

1993 ◽  
Vol 70 (02) ◽  
pp. 301-306 ◽  
Author(s):  
Linda A Robbie ◽  
Nuala A Booth ◽  
Alison M Croll ◽  
Bruce Bennett
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Dependent Inhibition ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe relative importance of the two major inhibitors of fibrinolysis, α2-antiplasmin (α2-AP) and plasminogen activator inhibitor (PAI-1), were investigated using a simple microtitre plate system to study fibrin clot lysis in vitro. Cross-linked fibrin clots contained plasminogen and tissue plasminogen activator (t-PA) at concentrations close to physiological. Purified α2-AP and PAI-1 caused dose-dependent inhibition. All the inhibition due to normal plasma, either platelet-rich or poor, was neutralised only by antibodies to α2-AP. Isolated platelets, at a final concentration similar to that in blood, 2.5 × 108/ml, markedly inhibited clot lysis. This inhibition was neutralised only by antibodies to PAI-1. At the normal circulating ratio of plasma to platelets, α2-AP was the dominant inhibitor. When the platelet:plasma ratio was raised some 20-fold, platelet PAI-1 provided a significant contribution. High local concentrations of PAI-1 do occur in thrombi in vivo, indicating a role for PAI-1, complementary to that of α2-AP, in such situations.

Reactivated Recombinant Plasminogen Activator Inhibitor-1 (rPAI-1) Effectively Prevents Thrombolysis In Vivo

1992 ◽  
Vol 68 (01) ◽  
pp. 060-063 ◽  
Author(s):  
Douglas E Vaughan ◽  
Paul J Declerck ◽  
Elizabeth Van Houtte ◽  
Maria De Mol ◽  
Désiré Collen
Keyword(s):  
Plasminogen Activator ◽  
Rabbit Model ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Jugular Vein Thrombosis ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe effects of human recombinant plasminogen activator inhibitor (rPAI-1) on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) were studied in a rabbit model of jugular vein thrombosis. Two functionally distinct rPAI-1 preparations were used in these experiments, including latent rPAI-1 (~2 units of t-PA neutralizing activity per µg protein) and reactivated rPAI-1 (~150 units/µg).Simultaneous intravenous infusion over 4 h of 1.7 mg/kg of reactivated rPAI-1 (inhibitory capacity ~0.5 mg/kg rt-PA) with 0.5 mg/kg of rt-PA completely prevented lysis of a jugular venous thrombus, whereas an equivalent amount of latent PAI-1 did not significantly influence clot lysis. These findings demonstrate that reactivated human rPAI-1 efficiently neutralizes thrombolysis with rt-PA in vivo. Since previous studies have suggested that elevated endogenous levels of PAI-1 do not attenuate the thrombolytic potency of rt-PA in the endotoxin-treated model, we compared the stability of complexes formed by 125I-rt-PA with reactivated human rPAI-1 and with rabbit PAI-1 in vitro. Our findings indicate that both forms of PAI-1 form SDS-stable complexes following incubation with 125I-rt-PA. Thus, it seems likely that elevated levels of active PAI-1 can negate the thrombolytic effects of rt-PA in vivo and argues against the possibility that t-PA can dissociate from PAI-1 and have its activity restored in the presence of a thrombus. We propose that the present model may be a valuable tool in monitoring and evaluating the in vivo thrombolytic efficacy of various t-PA mutants designed to be less sensitive to the inhibitory effects of PAI-1.

scholarly journals Targeted Disruption of the Mouse Rho-Associated Kinase 2 Gene Results in Intrauterine Growth Retardation and Fetal Death

2003 ◽  
Vol 23 (14) ◽  
pp. 5043-5055 ◽  
Author(s):  
Dean Thumkeo ◽  
Jeongsin Keel ◽  
Toshimasa Ishizaki ◽  
Masaya Hirose ◽  
Kimiko Nonomura ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Intrauterine Growth Retardation ◽  
Fetal Death ◽  
Thrombus Formation ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Intrauterine Growth ◽  
Elevated Expression ◽  
Activator Inhibitor

ABSTRACT Rho-associated kinase (ROCK), including the ROCK-I and ROCK-II isoforms, is a protein kinase involved in signaling from Rho to actin cytoskeleton. However, in vivo functions of each ROCK isoform remain largely unknown. We generated mice deficient in ROCK-II by gene targeting. ROCK-II−/− embryos were found at the expected Mendelian frequency until 13.5 days postcoitum, but approximately 90% died thereafter in utero. ROCK-II−/− mice of both genders that survived were born runts, subsequently developed without gross abnormality, and were fertile. Whole-mount staining for a knocked-in lacZ reporter gene revealed that ROCK-II was highly expressed in the labyrinth layer of the placenta. Disruption of architecture and extensive thrombus formation were found in the labyrinth layer of ROCK-II−/− mice. While no obvious alteration in actin filament structures was found in the labyrinth layer of ROCK-II−/− placenta and stress fibers were formed in cultured ROCK-II−/− trophoblasts, elevated expression of plasminogen activator inhibitor 1 was found in ROCK-II−/− placenta. These results suggest that ROCK-II is essential in inhibiting blood coagulation and maintaining blood flow in the endothelium-free labyrinth layer and that loss of ROCK-II leads to thrombus formation, placental dysfunction, intrauterine growth retardation, and fetal death.

A long-acting PAI-1 inhibitor reduces thrombus formation

2017 ◽  
Vol 117 (07) ◽  
pp. 1338-1347 ◽  
Author(s):  
Shuangzhou Peng ◽  
Guangpu Xue ◽  
Lihu Gong ◽  
Chao Fang ◽  
Jingfei Chen ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Plasminogen Activator Inhibitor ◽  
Fibrin Clot ◽  
Computational Method ◽  
Tissue Type ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Long Acting ◽  
Pai 1

SummaryPlasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activators (t/uPA) and plays an important role in fibrinolysis. Inhibition of PAI-1 activity prevents thrombosis and accelerates fibrinolysis, indicating that PAI-1 inhibitors may be used as effective antithrombotic agents. We previously designed a PAI-1 inhibitor (PAItrap) which is a variant of inactivated urokinase protease domain. In the present study, we fused PAItrap with human serum albumin (HSA) to develop a long-acting PAI-1 inhibitor. Unfortunately, the fusion protein PAItrap-HSA lost some potency compared to PAItrap (33 nM vs 10 nM). Guided by computational method, we carried out further optimisation to enhance inhibitory potency for PAI-1. The new PAItrap, denominated PAItrap(H37R)-HSA, which was the H37R variant of PAItrap fused to HSA, gave a six-fold improvement of IC50 (5 nM) for human active PAI-1 compared to PAItrap-HSA, and showed much longer plasma half-life (200-fold) compared to PAItrap. We further demonstrated that the PAItrap(H37R)-HSA inhibited exogenous or endogenous PAI-1 to promote fibrinolysis in fibrin-clot lysis assay. PAItrap(H37R)-HSA inhibits murine PAI-1 with IC50 value of 12 nM, allowing the inhibitor to be evaluated in murine models. Using an intravital microscopy, we demonstrated that PAItrap(H37R)-HSA blocks thrombus formation and platelet accumulation in vivo in a laser-induced vascular injury mouse model. Additionally, mouse tail bleeding assay showed that PAItrap(H37R)-HSA did not affect the global haemostasis. These results suggest that PAItrap(H37R)-HSA have the potential benefit to prevent thrombosis and accelerates fibrinolysis.

Anti-thrombotic Effect of a PAI-1 Inhibitor in Rats Given Endotoxin

1996 ◽  
Vol 75 (01) ◽  
pp. 118-126 ◽  
Author(s):  
T Abrahamsson ◽  
V Nerme ◽  
M Strömqvist ◽  
B Åkerblom ◽  
A Legnehed ◽  
...  
Keyword(s):  
Plasminogen Activator Inhibitor ◽  
Rat Plasma ◽  
Clot Lysis ◽  
Fibrin Deposition ◽  
Plasminogen Activator Inhibitor 1 ◽  
Fab Fragment ◽  
Dose Dependent Decrease ◽  
Pai 1

SummaryThe aim of this study was to investigate the anti-thrombotic effects of an inhibitor of the plasminogen activator inhibitor-1 (PAI-1) in rats given endotoxin. In studies in vitro, PRAP-1, a Fab-fragment of a polyclonal antibody against human PAI-1, was shown to inhibit PAI-1 activity in rat plasma as well as to stimulate clot-lysis of the euglobulin fraction derived from rat plasma. Endotoxin administered to anaesthetised rats produced a marked increase in plasma PAI-1 activity. To study fibrin formation and lysis in vivo after intravenous (i. v.) injection of the coagulant enzyme batroxobin, 125I-fibrinogen was administered to the animals. The thrombi formed by batroxobin were rapidly lysed in control animals, while the rate of lysis was markedly attenuated in rats given endotoxin. PRAP-1 was administered i.v. (bolus + infusion) to rats given endotoxin and batroxobin and the PAI-1 inhibitor caused a dose-dependent decrease in the 125I-fibrin deposition in the lungs. An immunohistochemical technique was used to confirm this decrease in density of fibrin clots in the tissue. Furthermore, PRAP-1 decreased plasma PAI-1 activity in the rats and this reduction was correlated to the decrease in lung 125I-fibrin deposition at the corresponding time point. It is concluded that in this experimental model the PAI-1 antibody PRAP-1 may indeed inhibit thrombosis in animals exposed to endotoxin.

scholarly journals Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zuo ◽  
Mark Warnock ◽  
Alyssa Harbaugh ◽  
Srilakshmi Yalavarthi ◽  
Kelsey Gockman ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Ex Vivo ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Bleeding Complications ◽  
Clot Lysis ◽  
Thrombosis Prophylaxis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

AbstractPatients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.

scholarly journals The interaction of plasminogen activator inhibitor 1 with plasminogen activators (tissue-type and urokinase-type) and fibrin: localization of interaction sites and physiologic relevance

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 401-409 ◽  
Author(s):  
J Keijer ◽  
M Linders ◽  
AJ van Zonneveld ◽  
HJ Ehrlich ◽  
JP de Boer ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Regulatory Protein ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activators ◽  
Tissue Type ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Interaction Sites ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Plasminogen activator inhibitor 1 (PAI-1), an essential regulatory protein of the fibrinolytic system, harbors interaction sites for plasminogen activators (tissue-type [t-PA] and urokinase-type [u-PA]) and for fibrin. In this study, anti-PAI-1 monoclonal antibodies (MoAbs) were used to identify interaction sites of PAI-1 with these components. The binding sites of 18 different MoAbs were established and are located on five distinct “linear” areas of PAI-1. MoAbs, binding to two distinct areas of PAI-1, are able to prevent the inhibition of t-PA by PAI-1. In addition, two interaction sites for fibrin were identified on PAI-1. The area located between amino acids 110 and 145 of PAI-1 contains a binding site for both components and its significance is discussed in the context of the t-PA inhibition by fibrin-bound PAI-1. Subsequently, the MoAbs were used to assess the role of platelet-PAI-1 in clot-lysis. An in vitro clot-lysis system was used to demonstrate that clot-lysis resistance is dependent on the presence of activated platelets and that PAI-1 is a major determinant for lysis-resistance. We propose that, upon activation of platelets, PAI-1 is fixed within the clot by binding to fibrin and retains its full capacity to inhibit t-PA and u-PA.

In Vivo Stimulation of Vascular Plasminogen Activator Inhibitor-1 Production by very Low-Density Lipoprotein Involves Transcription Factor Binding to a VLDL-Responsive Element

2000 ◽  
Vol 84 (10) ◽  
pp. 706-711 ◽  
Author(s):  
Mikko Ares ◽  
Maria Stollenwerk ◽  
Cecilia Giachelli ◽  
Marta Scatena ◽  
Anders Hamsten ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasminogen Activator Inhibitor ◽  
High Plasma ◽  
Plasminogen Activator Inhibitor 1 ◽  
Mrna And Protein Expression ◽  
Responsive Element ◽  
Activator Inhibitor ◽  
Pai 1

SummaryHigh plasma levels of plasminogen activator inhibitor-1 (PAI-1) are associated with an increased risk of cardiovascular disease. There is also a close relation between high plasma levels of PAI-1 and hypertriglyceridemia. Cell culture studies have shown that very low density lipoprotein (VLDL) increases the production and secretion of PAI-1 in endothelial cells and hepatocytes, suggesting a possible mechanism for this association. To determine whether VLDL stimulates PAI-1 production in vascular cells also in vivo, Sprague-Dawley rats were injected intravenously with 6 mg/kg of VLDL (derived from human subjects with type IV hyperlipidemia). Previous studies have demonstrated that this results in an accumulation of human VLDL in the aorta and other arteries followed by increased nuclear factor-kappa B (NF-κB) activation. Endothelial, but not smooth muscle cells, showed a basal PAI-1 mRNA and protein expression as assessed by in situ hybridization and immunohistochemistry, respectively. Six to twenty-four hours after the VLDL injection, lipoprotein particle accumulation was seen in the aortic wall, which was accompanied by increasing PAI-1 mRNA and protein expression in endothelial and smooth muscle cells. Within the rat PAI-1 promoter we identified a sequence located at −589 to −571 with 74% homology with the recently described VLDL responsive element in the human PAI-1 promoter and located adjacent to a 4-guanosine motif presumably corresponding to the human 4G/5G polymorphism. Transient transfection studies showed that VLDL exerts its stimulatory effects on rat PAI-1 gene expression in vascular cells by interaction with promoter sequences located within bp −656 and −505. Electrophoretic mobility shift assays showed that VLDL increases the binding of as yet incompletely characterized factors to this response element. Taken together these observations support a direct influence of VLDL on vascular PAI-1 gene expression in vivo. This stimulation is exerted on the level of PAI-1 gene transcription, and involves transcription factor binding to a VLDL responsive element adjacent to a 4G motif within the PAI-1 promoter.

Biological Rational for the Use of Heparin in Septic Shock: Translational Data from the Halo Pilot RCT

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2336-2336
Author(s):  
Brett L. Houston ◽  
Dhruva J. Dwivedi ◽  
Peter Grin ◽  
Michelle Kwong ◽  
Enrico Rullo ◽  
...  
Keyword(s):  
Septic Shock ◽  
Protein C ◽  
Thrombin Generation ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Lysis Time ◽  
Activator Inhibitor ◽  
Clot Lysis Time

Abstract BACKGROUND: Sepsis is a leading cause of mortality among critically ill patients and is associated with both systemic inflammation and up-regulation of coagulation. In the translational sub-study of the HALO (Heparin AnticoaguLation to improve Outcomes in septic shock) pilot trial, we evaluated the mechanisms by which unfractionated heparin (UFH) may reduce inflammation and coagulation in patients with septic shock. METHODS: In this multicenter pilot randomized trial of 69 patients diagnosed with septic shock, we evaluated the feasibility of administering therapeutic dose intravenous UFH (18 IU/kg/hr) compared to thromboprophylactic subcutaneous dalteparin (5000 IU daily). Blood samples were collected on days 1 (baseline prior to study infusion), 2, 3, 5, and 7. We evaluated coagulation using assays for protein C, activated protein C, thrombin-antithrombin (TAT), thrombin generation, clot lysis, plasminogen activator inhibitor-1 (PAI-1) and cell-free DNA (cf-DNA). Systematic inflammation was evaluated by measuring inflammatory cytokines (interleukin (IL)-6, IL-8, IL-10, and IL-17). RESULTS: The mean age of the study population was 61 years, of whom 43% were male. Thirty two patients (46%) were randomized to receive unfractionated heparin while 37 (54%) received dalteparin. The baseline mean aggregate Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 25 ± 7.8, and Multiple Organ Dysfunction Score (MODS) 5.6 ± 2.38. Baseline laboratory testing (coagulation assays and inflammatory cytokines) was not statistically different between UFH vs. LMWH treated patients. On day 2, the median clot lysis time in UFH-treated patients compared to those receiving dalteparin was significantly decreased [6630 (IQR 0 - 14156) seconds vs. 9615 (IQR 8209 - 11018) seconds; p = 0.008] (Figure 1). UFH administration was associated with increased protein C levels [66.4% of normal (IQR 9.9 - 122.9) vs. 41.1% of normal (IQR 4.8 - 77.4); p = 0.02], and reduced thrombin generation of 0 (IQR 0 - 1725) units/min vs. 3393 (IQR 0 - 8519) units/min; p<0.001]. On day 2, we observed no differences between thrombin-antithrombin complex (TAT), activated protein C, plasminogen activator inhibitor-1 (PAI-1) or cell-free DNA (cf-DNA). Similarly, there were no differences between treatment groups in inflammatory markers, including IL-6, IL-8, IL-10 or IL-17. Analysis thus far is limited to samples collected on days 1 and 2; day 3-7 analyses are ongoing. CONCLUSION: In patients diagnosed with septic shock, IV UFH reduces thrombin generation, shortens clot lysis time and improves endogenous protein C levels compared to dalteparin administered for thromboprophylaxis. Analyses for samples obtained on days 3, 5 and 7 are ongoing. These preliminary data provide a biologic rational for the use of heparin in sepsis. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Disclosures No relevant conflicts of interest to declare.

Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during acute arterial thrombosis in mice

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 153-160
Author(s):  
Tomihisa Kawasaki ◽  
Mieke Dewerchin ◽  
Henri R. Lijnen ◽  
Jos Vermylen ◽  
Marc F. Hoylaerts
Keyword(s):  
Carotid Artery ◽  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
Plasma Concentrations ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Deficient Mice ◽  
Activator Inhibitor ◽  
Pai 1

The role of plasminogen activator inhibitor-1 (PAI-1) in the plasma, blood platelets, and vessel wall during acute arterial thrombus formation was investigated in gene-deficient mice. Photochemically induced thrombosis in the carotid artery was analyzed via transillumination. In comparison to thrombosis in C57BL/6J wild-type (wt) mice (113 ± 19 × 106 arbitrary light units [AU] n = 15, mean ± SEM), thrombosis in PAI-1−/− mice (40 ± 10 × 106 AU, n = 13) was inhibited (P < .01), indicating that PAI-1 controls fibrinolysis during thrombus formation. Systemic administration of murine PAI-1 into PAI-1−/− mice led to a full recovery of thrombotic response. Occurrence of fibrinolytic activity was confirmed in 2-antiplasmin (2-AP)–deficient mice. The sizes of thrombi developing in wt mice, in 2-AP+/− and 2-AP−/− mice were 102 ± 35, 65 ± 8.1, and 13 ± 6.1 × 106 AU, respectively (n = 6 each) (P < .05), compatible with functional plasmin inhibition by 2-AP. In contrast, thrombi in wt mice, t-PA−/− and u-PA−/−mice were comparable, substantiating efficient inhibition of fibrinolysis by the combined PAI-1/2-AP action. Platelet depletion and reconstitution confirmed a normal thrombotic response in wt mice, reconstituted with PAI-1−/− platelets, but weak thrombosis in PAI-1−/− mice reconstituted with wt platelets. Accordingly, murine (wt) PAI-1 levels in platelet lysates and releasates were 0.43 ± 0.09 ng/109 platelets and plasma concentrations equaled 0.73 ± 0.13 ng/mL. After photochemical injury, plasma PAI-1 rose to 2.9 ± 0.7 ng/mL (n = 9, P < .01). The plasma rise was prevented by ligating the carotid artery. Hence, during acute thrombosis, fibrinolysis is efficiently prevented by plasma 2-AP, but also by vascular PAI-1, locally released into the circulation after endothelial injury.

Sign in / Sign up

Export Citation Format

Share Document