Abstract 16668: The Effects of Dabigatran on Fibrin Network Structure and Lysis: A Simple Technique to Monitor Efficacy of Treatment?

Background: Thrombus formation represent the final step in the atherothrombotic process and occurs secondary to a complex interaction between platelets and coagulation factors. Increased platelet reactivity and enhanced clot formation can both determine predisposition to vascular events. Direct platelet inhibition by modern antiplatelet therapy is now effective at controlling the cellular component of coagulation but the fibrin network is not generally targeted in arterial disease. Our aim was to investigate the effects of dabigatran on fibrin network characteristics in individuals dual antiplatelet therapy (DAPT). Methods: This was a prospective, randomized, double-blind study conducted in 30 patients on maintenance (at least 30 days) DAPT with aspirin (81mg/day) and clopidogrel (75mg/day). Patients were randomized to receive either dabigatran 150mg bid or matching placebo for 7 days. Fibrin clot properties were studied using a validated turbidimetric assay and the following parameters were recorded: lag phase and time to full clot formation, both of which measure clotting potential; clot maximum absorbance, representing fibrin network density and fibre thickness; clot lysis time to assess fibrinolytic efficiency. Results: Dabigatran treatment was associated with an increase in lag phase, compared with baseline, of 1013±167 sec , whereas no difference was detected in placebo treated patients (-17±14 sec, p<0.001 for dabigatran vs placebo). Similar results were obtained for clot formation time with an increase of 240±37 sec in dabigatran treated patients with no change following placebo treatment (-24±18 sec; p<0.001 comparing the two groups). The change in clot maximum absorbance after dabigatran and placebo treatment showed no differences (-0.02±0.01 and 0.00±0.01 au, respectively; p=0.2) and clot lysis time was similar. Conclusions: In patients on DAPT with aspirin and clopidogrel, additional treatment with dabigatran delays fibrin clot formation without affecting fibrinolysis. Therefore, triple therapy with dabigatran may be one option to reduce thrombosis potential in high risk individuals. Moreover, our assay, which can be conducted on stored samples, offers the opportunity to monitor response to dabigatran therapy.

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

Thrombosis and Haemostasis ◽

10.1160/th13-11-0980 ◽

2014 ◽

Vol 112 (08) ◽

pp. 287-296 ◽

Cited By ~ 21

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.

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

Thrombosis and Haemostasis ◽

10.1160/th16-07-0554 ◽

2017 ◽

Vol 117 (02) ◽

pp. 295-302 ◽

Cited By ~ 1

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.

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The ABO Locus is Associated with Increased Fibrin Network Formation in Patients with Stable Coronary Artery Disease

Thrombosis and Haemostasis ◽

10.1055/s-0040-1713753 ◽

2020 ◽

Vol 120 (09) ◽

pp. 1248-1256

Author(s):

Anne Winther-Larsen ◽

Morten Krogh Christiansen ◽

Sanne Bøjet Larsen ◽

Mette Nyegaard ◽

Søs Neergaard-Petersen ◽

...

Keyword(s):

Risk Allele ◽

Fibrin Clot ◽

Clot Lysis ◽

Risk Variant ◽

Risk Variants ◽

Lysis Time ◽

Fibrin Network ◽

Artery Disease ◽

Stable Cad ◽

Clot Lysis Time

Abstract Background The ABO locus has been associated with increased risk of myocardial infarction (MI) in patients with coronary artery disease (CAD), but the underlying mechanisms are unknown. As altered fibrin clot structure has been demonstrated to predict MI in CAD patients, we examined the association between the ABO risk variant and fibrin clot properties, and investigated the effects of other CAD-associated risk variants. Methods We included 773 stable CAD patients. Patients were genotyped for 45 genome-wide CAD risk variants, including rs495828 at the ABO locus. We used a genetic risk score (GRS) for CAD calculated as the weighted sum of the number of risk alleles based on all 45 variants. Fibrin clot properties were evaluated using a turbidimetric assay. We studied clot maximum absorbance, a measure of clot density and fiber thickness, together with clot lysis time, an indicator of fibrinolysis potential. Results The rs495828 risk allele was present in 13.2% of patients and associated with higher clot maximum absorbance (adjusted effect size per risk allele: 1.05 [1.01 − 1.09], p = 0.01) but not with clot lysis time (p = 0.97). The rs12936587 (p = 0.04), rs4773144 (p = 0.02), and rs501120 (p = 0.04) were associated with clot lysis time; however, after Bonferroni correction, no significant associations were found between any of the remaining 44 CAD-associated variants and fibrin clot properties. The GRS was not associated with fibrin clot properties (p-values > 0.05). Conclusion The ABO risk allele was associated with a more compact fibrin network in stable CAD patients, which may represent a mechanism for increased MI risk in ABO risk variant carriers.

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Thrombin generation and fibrin clot structure after vitamin D supplementation

Endocrine Connections ◽

10.1530/ec-19-0429 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1447-1454 ◽

Cited By ~ 1

Author(s):

Marc Blondon ◽

Emmanuel Biver ◽

Olivia Braillard ◽

Marc Righini ◽

Pierre Fontana ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Thrombin Generation ◽

Fibrin Clot ◽

Clot Lysis ◽

High Dose ◽

Severe Vitamin ◽

Lysis Time ◽

Clot Structure ◽

Clot Lysis Time

Objective Vitamin D deficiency is associated with increased risks of arterial and venous cardiovascular events. Hypothetically, supplementation with vitamin D may lead to a less prothrombotic phenotype, as measured by global coagulation assays and fibrin clot structure. Methods In this prospective cohort study, we enrolled adult outpatients attending the Primary Care Division of the Geneva University Hospitals with a severe vitamin D deficiency (25-hydroxyvitamin-D3 (25-OHD) <25 nmol/L), excluding obese patients or with a recent acute medical event. We evaluated changes in coagulation times, thrombin generation assay, clot formation and clot lysis time, 25-OHD and parathormone before and 1–3 months after cholecalciferol oral supplementation with one-time 300,000 IU then 800 IU daily. Paired t-tests with a two-sided alpha of 0.05 compared absolute mean differences. Results The 48 participants had a mean age of 43.8 ± 13.8 years. After supplementation, 25-OHD levels increased from 17.9 ± 4.6 nmol/L to 62.5 ± 20.7 nmol/L 6.4 ± 3.0 weeks after inclusion. Endogenous thrombin potential and thrombin generation peak values both decreased significantly (−95.4 nM × min (95%CI −127.9 to −62.8), P < 0.001; −15.1 nM (−23.3 to −6.8), P < 0.001). The maximum absorbance by turbidimetry decreased significantly (P = 0.001) after supplementation. There was no change in clot lysis time, coagulation times or plasminogen activator inhibitor-1 and homocysteine levels. Conclusions In severe vitamin D deficiency, a high-dose cholecalciferol supplementation was associated with a reduction in thrombin generation and an average decreased number of fibrin protofibrils per fibers and fibrin fiber size measured by turbidimetry. This suggests that severe vitamin D deficiency may be associated with a potentially reversible prothrombotic profile.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655021 ◽

1967 ◽

Vol 18 (01/02) ◽

pp. 101-113 ◽

Cited By ~ 3

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.

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FRI0232 ALTERED FIBRIN CLOT PROPERTIES IN PATIENTS WITH SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5506 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 699.2-700

Author(s):

J. Colic ◽

A. Antovic ◽

I. Pruner ◽

J. Vojinovic ◽

M. Sefik Bukilica ◽

...

Keyword(s):

Systemic Sclerosis ◽

Activity Index ◽

Pulmonary Function Tests ◽

Inverse Correlation ◽

Fibrin Clot ◽

Clot Lysis ◽

Sem Images ◽

Plasma Clot ◽

Lysis Time ◽

Clot Lysis Time

Background:Vasculopathy in Systemic sclerosis (SSc) is connected with the activation of coagulation. However, the fibrinolytic activity still remains unclear since the most preliminary evidences are discordant (1, 2).Objectives:To assess the haemostatic function, fibrin clot density and clot lysis time in SSc patients and healthy controls (HC) to determine their relation to disease findings.Methods:Patients who fulfilled the 2013 ACR/EULAR SSc criteria and have never been treated with endothelin receptor antagonist, phosphodiesterase 5 inhibitors or prostanoids were eligibile. Our study included 58 SSc patients [36 limited (lcSSc) and 22 diffuse cutaneous SSc (dcSSc)] and 46 sex/age-matched HC. Clinical evaluation of patients was performed, including high-resolution CT (HRCT), pulmonary function tests and the revised EUSTAR activity index. The interstitial lung disease (ILD) group (n = 15) was defined as moderate or severe changes on HRCT, with a forced vital capacity (FVC) < 85% predicted, without evidence of significant pulmonary arterial hypertension. The serum concentration of ICAM1 and von Willebrand factor antigen (VWF) were measured by ELISA. Haemostatic potential parameters; including overall haemostasis (OHP), overall coagulation (OCP) and overall fibrinolysis (OFP) potential, were assessed and endogenous thrombin potential (ETP) was determined. Maximum absorbance (Cmax), reflects the fibrin clot density and clot lysis time (Lys50t0), reflects fibrinolytic susceptibility, were calculated from OHP and OCP curves (3). Fibrin structure was visualised using scanning electron microscopy (SEM).Results:The OFP value was significantly decreased, Lys50t0 prolonged (p<0.05), while OHP and ETP were increased (p<0.05) in patients. In dSSc group ETP, OHP, Cmax and Lys50t0 were higher compared to HC (p<0.05). In SSc group, a positive association was found between coagulation parameters (OCP, OHP, Cmax) and the erythrocyte sedimentation rate (ESR), fibrinogen and ICAM1 (respectively p<0.05). Lys50t0 was positively correlated with ICAM1, ESR and VWF (respectively p<0.001, p<0.05, p<0.05). An inverse correlation was found between Cmax and both the diffusing capacity of the lungs for carbon monoxide (r=-0.408, p<0.01) and FVC (r=-0.318, p<0.01). Increased Cmax was found in ILD respect to HC (p<0.01). Denser plasma clot was associated with active disease (p<0.01). Longer Lys50t0 was observed in pitting scars group (p<0.01). Prolonged Lys50t0 was independently predicted by ICAM1 (OR 1.12, 95% CI 1.03–1.2, p<0.01).Conclusion:Our results provide evidences of denser plasma fibrin clot among patients with lung involvement and impaired fibrinolysis, selectively presented among SSc patients with piting scars. Thus, these patients might be at risk for thrombotic complications. Raised ICAM-1 levels could reflect impaired fibrinolysis, giving insight the important role of this molecule in endothelial homeostasis.References:[1]Cerinic MM, et al. Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis. Semin Arthritis Rheum. 2003;32:285–95[2]Lippi G, et al. Plasma D-dimer concentration in patients with systemic sclerosis.Thromb J. 2006;4:2.[3]Carter AM, et al. Heritability of clot formation, morphology, and lysis: the EuroCLOT study. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2783-9Figure 1.SEM images of fibrin network in 1 representative sample from a SSc (A) and 1from HC sample (B).Disclosure of Interests:Jelena Colic: None declared, Aleksandra Antovic: None declared, Iva Pruner: None declared, Jelena Vojinovic Consultant of: Roche, Abbvie, Pfizer, MSD, Speakers bureau: Roche, Abbvie, Pfizer, MSD, Mirjana Sefik Bukilica: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche

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Does Fibrin Structure Contribute to the Increased Risk of Thrombosis in COVID-19 ICU Patients?

Blood ◽

10.1182/blood-2021-145307 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3208-3208

Author(s):

Judith Juliana De Vries ◽

Chantal Visser ◽

Lotte Geers ◽

Johan A. Slotman ◽

Henrik Endeman ◽

...

Keyword(s):

Clot Lysis ◽

Healthy Controls ◽

Similar Time ◽

Icu Patients ◽

Lysis Time ◽

Increased Risk ◽

Fibrin Network ◽

Fibrin Fiber ◽

Clot Lysis Time ◽

Time Point

Abstract Introduction: SARS-CoV-2 is responsible for a global pandemic, with almost 200 million confirmed cases. SARS-CoV-2 infection can lead to various disease states, from only mild symptoms in the majority of cases to severe disease, which is associated with an increased incidence of venous thromboembolism (VTE). We hypothesized that an altered fibrin network structure contributes to VTE in COVID-19 patients by affecting thrombus stability and fibrinolysis sensitivity. By studying the fibrin network of COVID-19 patients, we aimed to unravel the mechanisms that contribute to the increased risk of VTE in COVID-19 patients. Methods: Between April 2020 and December 2020, we collected plasma samples from patients with COVID-19 admitted to the intensive care unit (ICU) of the Erasmus Medical Center. We included patients with confirmed VTE diagnosed on CT-angiography, and COVID-19 patients without confirmed VTE during ICU admission. Samples were collected on admission to the ICU and after confirmed VTE or at similar time points in ICU patients without confirmed VTE. In addition, we collected plasma from COVID-19 patients at admission to general wards without confirmed VTE and from healthy controls. Clots were formed by mixing citrated plasma with thrombin (final concentration 1 U/ml) and calcium (17 mM). We imaged the clots using stimulated emission depletion (STED) microscopy, a super-resolution technique in which a depletion laser is used to selectively switch off fluorophores surrounding the focal point, thereby increasing the resolution. In these images, fibrin fiber diameters were measured using the Local Thickness plugin of ImageJ. Fiber density was quantified as percentage of area in Z-stacks of confocal microscopy images. Finally, a clot lysis assay based on turbidity was used to determine sensitivity to fibrinolysis (clot lysis time) and clot density (difference between maximum and baseline absorbance). Differences in fibrin network properties between groups were tested using One-Way ANOVA with Bonferroni post-hoc tests and linear regression with and without adjustment for fibrinogen levels. Results: We included 21 COVID-19 ICU patients with confirmed VTE, 20 COVID-19 ICU patients without confirmed VTE, 10 COVID-19 ward patients and 7 healthy controls. Mean age was comparable between the groups, while BMI was higher in COVID-19 patients than in healthy controls (Table 1). Levels of fibrinogen, D-dimer and anti-Xa were significantly higher in COVID-19 ICU patients than in COVID-19 ward patients and healthy controls. FVIII levels were significantly higher in COVID-19 ICU patients than in healthy controls, while FXIII levels were significantly lower. On admission to the ICU, clot density was significantly higher in COVID-19 ICU patients with and without confirmed VTE than in healthy controls (Figure 1 and Table 2). However, after adjustment for fibrinogen levels, this difference disappears. Clot lysis time was significantly longer in clots from COVID-19 ICU patients than in clots from healthy controls, regardless of fibrinogen levels (Table 2). COVID-19 ICU patients with confirmed VTE also showed a significant longer clot lysis time than COVID-19 ward patients. Interestingly, in the clot lysis assay, fibrinolysis did not occur in 25% of COVID-19 ICU patients with VTE versus 9.5% of COVID-19 ICU patients without VTE (Figure 2). This fibrinolysis shutdown was never observed in clots from healthy controls and COVID-19 ward patients. Fibrin fiber diameters were comparable between the groups. In the clots from plasma samples collected at admission to the ICU, there were no differences between COVID-19 ICU patients with and without VTE (Figure 2). However, when comparing clots prepared from plasma collected at the second time point (after VTE or at a similar time point for patients without VTE), we observed significant longer clot lysis times in patients with confirmed VTE (97.4 [88.5-158.8] min) than in patients without confirmed VTE (80.0 [76.0-97.8] min) (p=0.03). Finally, there were no significant changes between clots from plasma before and after VTE or between the two time points in patients without VTE, except for a decreased clot lysis time over time for COVID-19 ICU patients without confirmed VTE. Conclusion: Our results suggest that SARS-CoV-2 infection increases clot density and decreases clot susceptibility to fibrinolysis, and that these changes relate to the severity of the disease. Figure 1 Figure 1. Disclosures Kruip: Daiichi Sankyo: Research Funding; Bayer: Honoraria, Research Funding.

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Plasma Fibrin Clot Properties Are Unfavorably Altered in Women following Venous Thromboembolism Associated with Combined Hormonal Contraception

Disease Markers ◽

10.1155/2019/4923535 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Magdalena Piróg ◽

Sławomir Piwowarczyk ◽

Anetta Undas

Keyword(s):

Venous Thromboembolism ◽

Thrombin Generation ◽

Hormonal Contraception ◽

Fibrin Clot ◽

Clot Formation ◽

Clot Lysis ◽

Lag Phase ◽

Plasminogen Activator Inhibitor 1 ◽

Rate Of Increase ◽

Increased Risk

The use of hormonal contraception is associated with an increased risk of venous thromboembolism (VTE). Unfavorably altered fibrin clot phenotype has been reported in patients following unprovoked VTE who are at risk of recurrences. It remains unknown whether fibrin clot characteristics in women with contraception-related VTE differ from those in unprovoked VTE. We studied three age-matched groups of women: (1) after contraception-related VTE, (n=48) (2) after unprovoked VTE (n=48), and (3) controls (n=48). Plasma fibrin clot permeability (Ks), turbidity of clot formation, efficiency of fibrinolysis using clot lysis time (CLT), and rate of increase in D-dimer during lytic clot degradation (D-Drate), along with thrombin generation and fibrinolysis proteins were determined. Compared with the controls, patients following contraception-related and unprovoked VTE formed faster (lag phase, -8.8% and -20.4%, respectively) fibrin clots of increased density (Ks, -8.6% and -13.4%, respectively) displaying impaired fibrinolysis as evidenced by prolonged CLT (+11.5% and +14.5%, respectively) and lower D-Drate (-7.1% and -5.6%, respectively), accompanied with higher plasminogen activator inhibitor-1 (PAI-1, +14.9% and +17.8%, respectively) and elevated peak thrombin generation (+63.8% and +36.7%, respectively). The only differences between women with unprovoked and contraception-related VTE were lower fibrin mass in plasma clots (D-Dmax, -8.6%), along with higher peak thrombin generation (+19.8%) and shorter lag phase (-6.8%) in the latter group. This study suggests that women after contraception-related VTE, similar to those following unprovoked VTE, have denser fibrin clot formation and impaired clot lysis. These findings might imply higher risk of VTE recurrence in women with the prothrombotic clot phenotype.

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Inhibition of Tissue Activator by Urokinase Inhibitor

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654286 ◽

1971 ◽

Vol 25 (01) ◽

pp. 129-133 ◽

Cited By ~ 2

Author(s):

T Kawano ◽

Y Uemura

Keyword(s):

Human Placenta ◽

Human Heart ◽

Fibrin Clot ◽

Clot Lysis ◽

Plate Method ◽

Urokinase Inhibitor ◽

Lysis Time ◽

Fibrin Plate ◽

Clot Lysis Time

SummaryInhibition of tissue activator purified from human heart by urokinase inhibitor purified from human placenta was observed by both the fibrin plate method and fibrin clot lysis time method. It was shown to be of much less on extent in comparison with urokinase, that is, 20 Ploug units of urokinase were completely inhibited by approximately 100 or 200 u of urokinase inhibitor in the respective methods but 6 Ploug units of tissue activator were inhibited only 25% to 50% even though 1,000 u of urokinase inhibitor were used.

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The Role of Complement and Platelets in the Dissolution of Thrombin-Induced Clots

10.1055/s-0039-1680482 ◽

1977 ◽

Author(s):

Fletcher B. Taylor

Keyword(s):

Blood Clot ◽

Fibrin Clot ◽

Clot Formation ◽

Clot Lysis ◽

Temperature Sensitive ◽

Clot Retraction ◽

Clinical Value ◽

Fibrin Network ◽

Deep Vein

The dilute whole blood clot lysis assay has been used in diagnosis of patients with deep vein thrombophlebitis and pulmonary embolism. Because of its clinical value it has also been the subject of biochemical and physiologic studies of clot lysis of normal diluted blood. This assay reflects the behavior of platelets in that clot lysis as well as clot retraction are platelet dependent. Further, this contribution of platelets is temperature sensitive whereas the rate of fibrin clot formation is not. Thus, this assay offers a convenient model for functional and morphologic studies of temperature induced discontinuity of platelet-fibrin assembly and the interaction of platelet and fibrin in clot formation, retraction and lysis. In these studies the release of serotonin from platelets was correlated with clot formation, retraction, lysis, and clot morphology at 1) 37°, 4° and 4°−37° at 5, 15, 30 and 60 minute intervals. The results suggest that both platelets and fibrinogen are influenced by thrombin used in the assay and that under certain temperature conditions the platelets will release their contents out of phase with the assembly of the fibrin network. In cases where this discontinuity exists, the diluted clots will not retract or lyse normally.

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