scholarly journals Kinetics of fibrin clot lysis

1968 ◽  
Vol 106 (1) ◽  
pp. 101-105 ◽  
Author(s):  
R. J. Merrills ◽  
J. T. B. Shaw
Keyword(s):  
Plasminogen Activator ◽  
Experimental Studies ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Lysis Time ◽  
Kinetics Of ◽  
Fibrin Clots

The principles relating the lysis times of fibrin clots to their contents of fibrin, plasminogen and plasminogen-activator were investigated. Mathematical considerations suggested that the square of the lysis time should correlate linearly with the fibrin content, and inversely with the activator and the plasminogen contents of the system. Experimental studies, during which these parameters were independently varied, showed that the predicted relationships were valid for concentrations that gave clot-lysis times in the range normally used for studies of fibrinolysis.

Some Aspects of Fibrin Clot Lysis and Its Inhibition by Human Serum

1967 ◽  
Vol 18 (01/02) ◽  
pp. 101-113 ◽  
Author(s):  
M. J Gallimoke ◽  
J. T. B Shaw
Keyword(s):  
Sodium Chloride ◽  
Fibrin Clot ◽  
Chloride Ions ◽  
Clot Lysis ◽  
Irreversible Inhibitors ◽  
Zero Order Kinetics ◽  
Lysis Time ◽  
Kinetics Of ◽  
Clot Lysis Time ◽  
Fibrin Clots

SummaryThe lysis by plasmin of fibrin clots prepared from plasminogen-deficient fibrinogen, and by urokinase of similar clots prepared from plasminogen-rich fibrinogen has been studied. In a simple system containing no plasminogen the clot lysis time is inversely proportional to the concentration of added plasmin, and zero order kinetics are obeyed. The reciprocal of the lysis time is a measure of the fibrinolytic activity in the system, and may be used to study antiplasmins. When serum was included a reduction in reciprocal lysis time resulted, the extent of which varied linearly with the amount of serum added. These relationships persisted whether soluble or insoluble plasmin preparations were used and whether or not chloride ions were present. They indicate that serum antiplasmins behave as irreversible or pseudo-irreversible inhibitors. It was found that sodium chloride exerts a potentiating effect on fibrinolysis by plasmin, but does not influence the extent to which the enzyme is inhibited by serum antiplasmins.When fibrin clots were prepared from plasminogen-rich fibrinogen, and urokinase was included, a direct relationship was found to exist between the concentration of urokinase and the square of the reciprocal clot lysis time. When serum was added, vigorous inhibition of fibrinolysis resulted when sodium chloride was present; no inhibition was observed in its absence. It is proposed that sodium chloride weakens the interaction between plasminogen and fibrin in the clots, and renders the plasmin produced by the action of urokinase more susceptible to inhibition by antiplasmins. Evidence in support of this hypothesis is presented and the kinetics of fibrinolysis by plasmin, and its inhibition, are discussed.

scholarly journals BβArg448Lys polymorphism is associated with altered fibrin clot structure and fibrinolysis in type 2 diabetes

2017 ◽  
Vol 117 (02) ◽  
pp. 295-302 ◽  
Author(s):  
Katie A. Greenhalgh ◽  
Mark W. Strachan ◽  
Saad Alzahrani ◽  
Paul D. Baxter ◽  
Kristina F. Standeven ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Plasma Clot ◽  
Lysis Time ◽  
Increased Risk ◽  
Fibrin Network ◽  
Clot Lysis Time ◽  
Fibrin Clots

SummaryBoth type 2 diabetes (T2DM) and Bß448Lys variant of fibrinogen are associated with dense fibrin clots, impaired fibrinolysis and increased cardiovascular risk. It was our objective to investigate whether BßArg448Lys adds to vascular risk by modulating fibrin network structure and/or fibrinolysis in diabetes. The primary aim was to study effects of BßArg448Lys on fibrin network characteristics in T2DM. Secondary aims investigated interactions between gender and BßArg448Lys substitution in relation to fibrin clot properties and vascular disease. Genotyping for BßArg448Lys and dynamic clot studies were carried out on 822 T2DM patients enrolled in the Edinburgh Type 2 Diabetes Study. Turbidimetric assays of individual plasma samples analysed fibrin clot characteristics with additional experiments conducted on clots made from purified fibrinogen, further examined by confocal and electron microscopy. Plasma clot lysis time in Bß448Lys was longer than Bß448Arg variant (mean ± SD; 763 ± 322 and 719 ± 351 seconds [s], respectively; p<0.05). Clots made from plasma-purified fibrinogen of individuals with Arg/Arg, Arg/Lys and Lys/Lys genotypes showed differences in fibre thickness (46.75 ± 8.07, 38.40 ± 6.04 and 25 ± 4.99 nm, respectively; p<0.001) and clot lysis time (419 ± 64, 442 ± 87 and 517 ± 65 s, respectively; p=0.02), directly implicating the polymorphism in the observed changes. Women with Bß448Lys genotype had increased risk of cerebrovascular events and were younger compared with Bß448Arg variant (67.2 ± 4.0 and 68.2 ± 4.4 years, respectively; p=0.035). In conclusion, fibrinogen Bβ448Lys variant is associated with thrombotic fibrin clots in diabetes independently of traditional risk factors. Prospective studies are warranted to fully understand the role of BβArg448Lys in predisposition to vascular ischaemia in T2DM with the potential to develop individualised antithrombotic management strategies.

Substrate Composition and the Effect of ε-Aminocaproic Acid on Tissue Plasminogen Activator and Urokinase-induced Fibrinolysis

1974 ◽  
Vol 32 (02/03) ◽  
pp. 306-324 ◽  
Author(s):  
Sixtus Thorsen ◽  
Tage Astrup
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Aminocaproic Acid ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Substrate Composition ◽  
Lysis Time ◽  
Biphasic Effect ◽  
Tissue Plasminogen ◽  
Inhibition Curve

SummaryThe influence of variations in substrate composition on the biphasic pattern of inhibition by e-aminocaproic acid (EACA) of urokinase-induced fibrinolysis, first observed on bovine plasminogen-rich fibrin, was studied using a fibrin clot lysis time assay. Different species of fibrinogen and plasminogen or plasmin were used. Preparations of different degrees of purification were compared at varying concentrations. The behavior of urokinase was compared with that of a porcine tissue plasminogen activator. Variations in the conditions of the assay greatly influenced the results. The concentration of fibrinogen had a particularly marked influence. At increased fibrinogen concentrations the biphasic response of urokinase was enhanced and a weak biphasic effect was also produced by the tissue activator which usually yields a uniformly increasing inhibition curve. The phase of fibrinolysis enhancement produced by urokinase with genuine plasminogen substrates occurs at substrate concentrations and EACA levels present in patients treated with EACA. The observed variations may explain discordant findings reported by various investigators.

3309Complement activation leads to C3 and C5 dependent prothrombotic alterations of fibrin clots

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K A Schutt ◽  
S Maxeiner ◽  
K Lysaja ◽  
M Berger ◽  
S Ruetten ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Complement Activation ◽  
Fibrin Clot ◽  
Complement C3 ◽  
Clot Lysis ◽  
Lysis Time ◽  
Patients With Diabetes ◽  
Clot Structure ◽  
Clot Lysis Time ◽  
Fibrin Clots

Abstract Background and aims Alterations of clot structure with thin fibres, small pores and prolonged fibrinolysis are associated with an increased cardiovascular risk. We previously demonstrated complement C3 to be incorporated into fibrin clots resulting in prolongation of fibrinolysis, an effect which was exaggerated in patients with diabetes. Patients with diabetes are known to display higher levels of complement activation. However, the role of complement activation in particular activation of C3 and C5 on clot lysis time remains unexplored. Thus, the present study seeks to determine whether activation of complement C3 and C5 by cobra venom factor (CVF) has an impact on fibrin clot structure and clot lysis. Materials and methods Fibrin clot structure and lysis were determined in a plasma pool of healthy controls in the presence and absence of the complement C3 and C5 activator CVF using a validated turbidimetric assay and scanning electron microscopy. C3 activation was inhibited by the addition of the small 14-AA-peptide Cp40, while C5 activation was blocked by the addition of the FDA approved monoclonal antibody eculizumab (Emab). Results Complement activation with CVF leads to a prothrombotic clot structure with thinner fibres (Co 0.20±0.001 au, CVF 0.13±0.001 au; p<0.0001) and prolongation of clot lysis time (Co 864±32 sec, CVF 1665±17 sec; p<0.0001), which was confirmed by electron microscopy (Co 94.7±1.44 nm, CVF 60.7±0.96 nm; p<0.0001). Inhibition of C3 activation by Cp40 improved clot structure resulting in thicker fibres (Co 0.20±0.001 au, CVF 0.13±0.001 au, CP40 0.20±0.002 au; p<0.0001) and shorter clot lysis time (Co 100%, CVF 181±8.9%, CP40 139±7.8%; p<0.0001), while scrambled protein had no effect on either clot structure or lysis time. As CVF can also activate C5 convertase we next investigated the inhibition of complement C5 activation with eculizumab. The latter improved both fibre thickness (Co 0.20±0.002 au, CVF 0.13±0.003 au, Emab 0.16±0.006 au; p<0.0001) and clot lysis time (Co 100%, CVF 192±12%, Emab 140±11%; p<0.001). The combined inhibition of C3 and C5 activation using both, Cp40 and eculizumab in combination optimized clot structure (Co 0.22±0.001 au, CVF 0.13±0.0006 au, Cp40/Emab 0.21±0.001 au; Co vs. Cp40/Emab p=0.003) and restored clot lysis time (Co 100%, CVF 226±6%, CP40/Emab 104±1%; Co vs. Cp40/Emap p=0.8). The results were confirmed by electron microscopy (fibre thickness: Co 93±1.4 nm, CVF 68±1.3 nm, Cp40 83±1.4 nm, Emab 78±1.7 nm, CP40/Emap 95±1.6 nm). Conclusions Complement activation at the level of complement C3 and C5 has a detrimental impact on clot properties. Blocking C3 and C5 activation can restore both clot density and prolongation of clot lysis time. Further studies are needed to determine the underlying binding sites on fibrin(ogen) to pave the way for molecules improving clot properties without affecting immune responses. Acknowledgement/Funding KS is supported by the German Research Foundation (DFG) (SFB/TRR219 C-07; HE 5666/1-2 to KS (née Hess)]

Influence of Moderate and Strenuous Daily Physical Activity on Fibrinolytic Activity of Blood: Possibility of Plasminogen Activator Stores Depletion

1979 ◽  
Vol 41 (04) ◽  
pp. 745-755 ◽  
Author(s):  
Dušan Keber ◽  
Mojca Stegnar ◽  
Irena Keber ◽  
Bojan Accetto
Keyword(s):  
Physical Activity ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Regular Physical Activity ◽  
Clot Lysis ◽  
Moderate Activity ◽  
Lysis Time ◽  
Strenuous Activity ◽  
Activity Measurements ◽  
Clot Lysis Time

SummaryFibrinolysis was studied in 10 alpinists during regular physical activity of different intensity. Blood was sampled at rest and after exposure to submaximal workload on the treadmill on three occasions: before and after 6 months physical conditioning (moderate physical activity), and after 6 weeks of an alpinistic expedition (strenuous physical activity). Measurements included submaximal working capacity, fibrinogen, euglobulin clot lysis time (ELT), whole plasma clot lysis time, and estimations derived from ELT - percent increase in fibrinolytic activity after exercise (RFS), and absolute increase in fibrinolytic activity after exercise (PAR).Regular moderate activity increased the resting level of ELT, but strenuous activity decreased is. After each treadmill testing, a marked increase in fibrinolytic activity was observed. RFS was unaltered at all three testings. PAR increased after moderate activity, but decreased after strenuous activity.The results indicate that regular physical activity can lead from enhanced to decreased resting activity of plasminogen activator in blood. It is presumed that increased release of activator during prolonged stress causes partial depletion of endothelial stores with the consequence of decreased activator activity in the blood.

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.

scholarly journals Incorporation of α2-Plasmin Inhibitor into Fibrin Clots and Its Association with the Clinical Outcome of Acute Ischemic Stroke Patients

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 347
Author(s):  
Zsuzsa Bagoly ◽  
Barbara Baráth ◽  
Rita Orbán-Kálmándi ◽  
István Szegedi ◽  
Réka Bogáti ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Intravenous Thrombolysis ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Stroke Patients ◽  
Plasmin Inhibitor ◽  
Fibrin Clots

Cross-linking of α2-plasmin inhibitor (α2-PI) to fibrin by activated factor XIII (FXIIIa) is essential for the inhibition of fibrinolysis. Little is known about the factors modifying α2-PI incorporation into the fibrin clot and whether the extent of incorporation has clinical consequences. Herein we calculated the extent of α2-PI incorporation by measuring α2-PI antigen levels from plasma and serum obtained after clotting the plasma by thrombin and Ca2+. The modifying effect of FXIII was studied by spiking of FXIII-A-deficient plasma with purified plasma FXIII. Fibrinogen, FXIII, α2-PI incorporation, in vitro clot-lysis, soluble fibroblast activation protein and α2-PI p.Arg6Trp polymorphism were measured from samples of 57 acute ischemic stroke patients obtained before thrombolysis and of 26 healthy controls. Increasing FXIII levels even at levels above the upper limit of normal increased α2-PI incorporation into the fibrin clot. α2-PI incorporation of controls and patients with good outcomes did not differ significantly (49.4 ± 4.6% vs. 47.4 ± 6.7%, p = 1.000), however it was significantly lower in patients suffering post-lysis intracranial hemorrhage (37.3 ± 14.0%, p = 0.004). In conclusion, increased FXIII levels resulted in elevated incorporation of α2-PI into fibrin clots. In stroke patients undergoing intravenous thrombolysis treatment, α2-PI incorporation shows an association with the outcome of therapy, particularly with thrombolysis-associated intracranial hemorrhage.

PHYSICAL ACTIVITY RELEASES TISSUE PLASMINOGEN ACTIVATOR FROM EXERCISING PARTS OF BODY

1987 ◽  
Author(s):  
I Keber ◽  
K Potisk ◽  
D Keber ◽  
M Stegnar ◽  
N Vene
Keyword(s):  
Physical Activity ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Venous Occlusion ◽  
Clot Lysis ◽  
Lysis Time ◽  
Tissue Plasminogen ◽  
Euglobulin Clot Lysis Time ◽  
The Difference

To determine the origin of tissue plasminogen activator (t-PA) release during physical activity, we studied the separate and combined effects of venous occlusion and acute physical activity on t-PA release in arm and leg. In 15 healthy volunteers 20 min venous occlusions of arm and leg were performed simultaneously before physical activity ( maximal stress testing on treadmill)(occlusion I), immediately after physical activity and 45 min later (occlusion II). Blood samples were drawn from unoccluded arm before occlusion and after physical activity, and from occluded arm and leg after occlusion. Fibrinolytic activity was measured by euglobulin clot lysis time (ECLT) and t-PA activity assay. The amount of released t-PA during different stimuli (fibrinolytic potential) was calculated as the difference between post- and prestimulation fibrinolytic activity. Before physical activity there was a great increase in fibrinolytic activity due to t-PA in the occluded arm but no increase in the occluded leg. Physical activity itself caused a similar increase of systemic fibrinolytic activity as arm occlusion locally. After physical activity arm occlusion evoked equally good response than before it. Fibrinolytic activity during leg occlusion behaved differently: there was an increase in t-PA activity in the occluded leg which persisted one hour after physical activity, when systemic fibrinolytic activity already fell to initial level.These results demonstrated that walking and running triggered t-PA release from the leg vessels. Since leg occlusion was not a stimulus for t-PA release, it served only as a method to demonstrate the effect of physical activity.

Altered fibrin clot structure/function in patients with antiphospholipid syndrome: association with thrombotic manifestation

2014 ◽  
Vol 112 (08) ◽  
pp. 287-296 ◽  
Author(s):  
Magdalena Celińska-Löwenhoff ◽  
Teresa Iwaniec ◽  
Agnieszka Padjas ◽  
Jacek Musiał ◽  
Anetta Undas
Keyword(s):  
Structure Function ◽  
Antiphospholipid Syndrome ◽  
Thrombotic Event ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Lag Phase ◽  
Lysis Time ◽  
Clot Structure ◽  
Clot Lysis Time ◽  
D Dimer

SummaryWe tested the hypothesis that plasma fibrin clot structure/function is unfavourably altered in patients with antiphospholipid syndrome (APS). Ex vivo plasma clot permeability, turbidity and susceptibility to lysis were determined in 126 consecutive patients with APS enrolled five months or more since thrombotic event vs 105 controls. Patients with both primary and secondary APS were characterised by 11% lower clot permeability (p<0.001), 4.8% shorter lag phase (p<0.001), 10% longer clot lysis time (p<0.001), and 4.7% higher maximum level of D-dimer released from clots (p=0.02) as compared to the controls. Scanning electron microscopy images confirmed denser fibrin networks composed of thinner fibres in APS. Clots from patients with “triple-antibody positivity” were formed after shorter lag phase (p=0.019) and were lysed at a slower rate (p=0.004) than in the remainder. Clots from APS patients who experienced stroke and/or myocardial infarction were 8% less permeable (p=0.01) and susceptible to lysis (10.4% longer clot lysis time [p=0.006] and 4.5% slower release of D-dimer from clots [p=0.01]) compared with those following venous thromboembolism alone. Multivariate analysis adjusted for potential confounders showed that in APS patients, lupus anticoagulant and “triple-positivity” were the independent predictors of clot permeability, while “triple-positivity” predicted lysis time. We conclude that APS is associated with prothrombotic plasma fibrin clot phenotype, with more pronounced abnormalities in arterial thrombosis. Molecular background for this novel prothrombotic mechanism in APS remains to be established.

Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban

2017 ◽  
Vol 117 (09) ◽  
pp. 1739-1749 ◽  
Author(s):  
Agnieszka Janion-Sadowska ◽  
Joanna Natorska ◽  
Jakub Siudut ◽  
Michal Zabczyk ◽  
Andrzej Stanisz ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Mutation Carriers ◽  
Lysis Time ◽  
Prothrombin Mutation ◽  
Fibrinolysis Inhibitor ◽  
Heterozygous Carriers ◽  
Mutation Group ◽  
Clot Structure

SummaryWe sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2–6 hours (h) after and 20–25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks −12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2–6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT −25 % and −25 %, CLT-TAFI −20 % and −24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks −12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20–25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.

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