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Anetta Undas - One of the best experts on this subject based on the ideXlab platform.
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Effect of enoxaparin on plasma Fibrin Clot properties and Fibrin structure in patients with acute pulmonary embolism.
Vascular pharmacology, 2020Co-Authors: Michał Ząbczyk, Joanna Natorska, Krzysztof Piotr Malinowski, Anetta UndasAbstract:Abstract Background Low-molecular-weight heparins (LMWHs) influence the Fibrin network structure in in vitro models. There have been no reports on LMWH-induced modifications of Fibrin Clot characteristics and their determinants in acute pulmonary embolism (PE). Aim We investigated how enoxaparin alters Fibrin Clot properties in acute PE patients. Methods Clots were generated from plasma of 46 acute PE patients, aged47-77 years treated with enoxaparin 1 mg/kg bid. Fibrin Clot permeability (Ks) and Clot lysis time (CLT), along with coagulation and Fibrinolysis proteins were determined. Plasma Fibrin Clot nanostructure was assessed using scanning electron microscopy (SEM). Results Both Ks and CLT were associated with anti-factor (F)Xa activity (r = 0.75, p Conclusions We identified new laboratory and clinical factors contributing to prothrombotic plasma Fibrin Clot characteristics during enoxaparin treatment, which might help elucidate mechanisms underlying therapy failure in patients with acute PE.
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Plasma Fibrin Clot proteomics in healthy subjects: Relation to Clot permeability and lysis time.
Journal of proteomics, 2019Co-Authors: Michał Ząbczyk, Joanna Natorska, Aneta Stachowicz, Rafał Olszanecki, Jacek R. Wiśniewski, Anetta UndasAbstract:Abstract Background Little is known about Fibrin Clot composition in relation to its structure and lysability. We investigated plasma Clots protein composition and its associations with Clot properties. Methods We studied 20 healthy subjects aged 31–49 years in whom plasma Fibrin Clot permeability (Ks) and Clot lysis time (CLT) were determined. A proteomic analysis of plasma Fibrin Clots was based on quantitative liquid chromatography-mass spectrometry. Results Among 494 Clot-bound proteins identified in all Clots, the highest concentrations were for Fibrinogen chains (about 64% of the Clot mass) and fibronectin (13%). α2-antiplasmin (2.7%), factor XIIIA (1.2%), complement component C3 (1.2%), and histidine-rich glycoprotein (HRG, 0.61%) were present at relatively high concentrations. Proteins present in concentrations Conclusions This study is the first to show associations of two key measures of Clot properties with protein content within plasma Clots, suggesting that looser Fibrin Clots with enhanced lysability contain less Fibrinogen-γ chain, platelet-derived PF4, and HRG. Significance Our study for the first time suggests that more permeable Fibrin Clots with enhanced lysability contain less Fibrinogen-γ chain, platelet-derived factor 4, and histidine-rich glycoprotein, which is related to accelerated Clot lysis. The current findings might have functional consequences regarding Clot structure, stability, and propagation of thrombin generation, and detailed proteomic analysis of Clots in various disorders opens new perspective for coagulation and Fibrin research.
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Antithrombotic medications and their impact on Fibrin Clot structure and function.
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2018Co-Authors: Anetta Undas, Zabczyk MAbstract:Fibrin constitutes a major protein component of intravascular thrombi in all locations. Fibrin formation and its functions are essential for physiological hemostasis and the pathologic thrombosis. Formation of dense Fibrin networks which are relatively resistant to lysis is observed in patients with venous or arterial thromboembolism, including myocardial infarction, ischemic stroke and venous thromboembolism. Measures of Clot characteristics, in particular Clot permeability and Clot lysis time, may predict arterial and venous recurrent thromboembolic events. Medications, including vitamin K antagonists (VKA), direct oral anticoagulants (DOAC), and parenteral direct or indirect thrombin or activated factor X inhibitors increase Clot permeability, reflecting Fibrin network density, in association with enhanced efficiency of Fibrinolysis. These effects are only in part related to decreased thrombin generation. There is evidence that aspirin can also favorably alter Fibrin Clot properties probably through acetylation of Fibrinogen. No such effects were observed for P2Y12 inhibitors. Of note, plasma Fibrin Clot permeability has been shown to predict adverse clinical outcomes in patients receiving oral anticoagulants, which might have practical implications. The current review summarizes data on effects of antithrombotic agents on Fibrin Clot phenotype in cardiovascular disease.
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reduced plasma Fibrin Clot permeability is associated with recurrent thromboembolic events in patients with antiphospholipid syndrome
Rheumatology, 2018Co-Authors: Magdalena Celinskalowenhoff, Teresa Iwaniec, Krzysztof Plens, Jacek Musial, Michal Zabczyk, Anetta UndasAbstract:Objectives APS is associated with arterial and venous thrombosis. The unfavourable Fibrin Clot phenotype, including formation of dense and poorly lysable Clots, has been reported in thrombotic APS. We investigated whether abnormal plasma Clot properties are predictive of recurrent thromboembolism in APS. Methods We followed 126 consecutive patients with thrombotic APS and 105 control subjects, without APS, matched for thrombotic events. Plasma Fibrin Clot permeability (Ks), turbidity measurements and Clot lysis time were evaluated ⩾5 months after a thrombotic event. The primary composite end point was symptomatic recurrent venous thromboembolism, ischaemic stroke and/or myocardial infarction. Results During follow-up (median, 62 months; range 46-74 months; 1183.2 patient-years), the primary outcome was observed in 33 (26.2%) APS patients and 16 (15.2%) controls, including 25 (19.8%) and 14 (13.3%) subjects with recurrent venous thromboembolism, respectively. Reduced Ks and prolonged Clot lysis time predicted recurrent thromboembolic events in APS patients [per 1 × 10-9 cm2: hazard ratio (HR) = 0.37; 95% CI: 0.24, 0.56; and per 10 min: HR = 1.20; 95% CI: 1.01, 1.40, respectively] and in controls (per 1×10-9 cm2: HR = 0.23; 95% CI: 0.11, 0.42; and per 10 min: HR = 1.51; 95% CI: 1.08, 2.16, respectively). A multivariate analysis showed that positive IgG and IgM anti-β2 glycoprotein I antibodies, withdrawal of anticoagulation, lower platelet count and reduced Ks predicted thromboembolic events in APS patients. Conclusion Formation of denser Fibrin networks could be a novel risk factor for recurrent thromboembolism in APS, which highlights the importance of Fibrin phenotype in thrombotic disorders.
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Plasma Fibrin Clot structure and thromboembolism: clinical implications.
Polish archives of internal medicine, 2017Co-Authors: Michał Ząbczyk, Anetta UndasAbstract:Fibrin formed as a result of Fibrinogen polymerization is the main protein component of a Clot in a test tube and intravascular thrombi in vivo. Fibrin Clot structure characterized by fiber diameter and pore size differs between healthy persons and those with thromboembolic diseases, in part due to the quality and quantity of Fibrinogen and the magnitude of thrombin generation. A key measure of plasma Clot structure is its permeability, reflected by the Darcy constant (Ks). Reduced Ks is a typical feature of the prothrombotic Fibrin Clot phenotype, which is associated with faster formation of denser Fibrin mesh, relatively resistant to lysis. Low Ks has been reported in patients with prior or acute myocardial infarction (MI), stroke, or venous thromboembolism (encompassing deep vein thrombosis [DVT] and pulmonary embolism [PE]), as well as in those with prothrombotic conditions (eg, in several thrombophilic states) and in the presence of cardiovascular risk factors (eg, obesity). Antithrombotic and anticoagulant agents, along with statins, have been shown to increase Ks. Growing evidence indicates associations between the properties of plasma Fibrin Clots and morphology of intravascular thrombi in patients with MI. Recently, reduced Ks has been shown to predict recurrent thromboembolic episodes in patients with a history of stroke, PE, DVT, and their serious complications, including postthrombotic syndrome and thromboembolic pulmonary hypertension. We discuss the current evidence for the significance of Clot density measured in vitro as a prognostic marker in a number of clinical conditions associated with elevated thromboembolic risk.
Ramzi Ajjan - One of the best experts on this subject based on the ideXlab platform.
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Fibrin Clot properties independently predict adverse clinical outcome following acute coronary syndrome a plato substudy
European Heart Journal, 2018Co-Authors: Wael Sumaya, Ramzi Ajjan, Lars Wallentin, Stefan James, Agneta Siegbahn, Katja Gabrysch, Maria Bertilsson, Anders Himmelmann, Robert F StoreyAbstract:Aims: To determine whether Fibrin Clot properties are associated with clinical outcomes following acute coronary syndrome (ACS). Methods and results: Plasma samples were collected at hospital discharge from 4354 ACS patients randomized to clopidogrel or ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. A validated turbidimetric assay was employed to study plasma Clot lysis time and maximum turbidity (a measure of Clot density). One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were estimated using Cox proportional hazards models. After adjusting for CV risk factors, each 50% increase in lysis time was associated with CV death/spontaneous MI [HR 1.17, 95% confidence interval (CI) 1.05–1.31; P 0.05). Neither lysis time nor maximum turbidity was associated with major bleeding events. Conclusion: Fibrin Clots that are resistant to lysis independently predict adverse outcome in ACS patients. Novel therapies targeting Fibrin Clot properties might be a new avenue for improving prognosis in patients with ACS.
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abstract 14539 adverse Fibrin Clot properties are associated with worse outcome following acute coronary syndrome a plato substudy
Circulation, 2017Co-Authors: Wael Sumaya, Ramzi Ajjan, Lars Wallentin, Stefan James, Agneta Siegbahn, Katja Gabrysch, Maria Bertilsson, Anders Himmelmann, Robert F StoreyAbstract:Introduction: Compact Fibrin Clots that resist lysis have been implicated in thrombotic conditions but large studies are lacking. We investigated Fibrin Clot properties and clinical outcomes in pat...
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The influence of type 2 diabetes on Fibrin Clot properties in patients with coronary artery disease
Thrombosis and haemostasis, 2014Co-Authors: Søs Neergaard-petersen, Anne-mette Hvas, Sanne Bøjet Larsen, Steen Dalby Kristensen, Erik Lerkevang Grove, Fladia Phoenix, Zeyad Kurdee, Peter J. Grant, Ramzi AjjanAbstract:Type 2 diabetes mellitus (T2DM) increases the risk of coronary thrombosis and both conditions are associated with altered Fibrin Clot properties. However, the influence of T2DM on Fibrin Clot properties in patients with coronary artery disease (CAD) remains unclear. We aimed to investigate the influence of T2DM on Fibrin Clot properties in patients with CAD. Fibrin Clot structure and Fibrinolysis were investigated in 581 CAD patients (148 with T2DM) using turbidimetric assays, confocal and scanning electron microscopy. Clots made from plasma and plasma-purified Fibrinogen were studied, and plasma levels of inflammatory markers were analysed. T2DM patients had increased Clot maximum absorbance compared with non-diabetic patients (0.36 ± 0.1 vs 0.33 ± 0.1 au; p=0.01), displayed longer lysis time (804 [618;1002] vs 750 [624;906] seconds; p=0.03) and showed more compact Fibrin structure assessed by confocal and electron microscopy. Fibrinogen levels were elevated in T2DM (p
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Fibrin Clot structure and platelet aggregation in patients with aspirin treatment failure.
PloS one, 2013Co-Authors: Søs Neergaard-petersen, Ramzi Ajjan, Anne-mette Hvas, Katharina Hess, Sanne Bøjet Larsen, Steen Dalby Kristensen, Erik Lerkevang GroveAbstract:Background Aspirin is a cornerstone in prevention of cardiovascular events and modulates both platelet aggregation and Fibrin Clot formation. Some patients experience cardiovascular events whilst on aspirin, often termed aspirin treatment failure (ATF). This study evaluated both platelet aggregation and Fibrin Clot structure in patients with ATF.
Rolf P. Kreutz - One of the best experts on this subject based on the ideXlab platform.
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Fibrin Clot Strength in Patients with Diabetes Mellitus Measured by Thrombelastography
Journal of diabetes research, 2018Co-Authors: Benjamin Maatman, Glen Schmeisser, Rolf P. KreutzAbstract:Background Patients with diabetes mellitus (DM) exhibit increased risk of recurrent myocardial infarction. Maximal Clot strength measured by thrombelastography (TEG) is a risk factor for recurrent ischemic events. We hypothesized that diabetic subjects exhibit increased Fibrin Clot strength in platelet-poor plasma and that glycemic control correlates with maximal Fibrin Clot strength. Methods We collected plasma samples from subjects with known or suspected coronary artery disease undergoing cardiac catheterization (n = 354). We measured kaolin-activated TEG in platelet-poor citrate plasma. Time to Fibrin formation (R), Clot formation time (K), and maximal Fibrin Clot strength (MA) were recorded. Results Plasma Fibrin MA was increased among subjects with DM (n = 152) as compared to non-DM (n = 202) (37.0 ± 8 versus 34.1 ± 8 mm; p < 0.001). Hemoglobin A1c (HbA1c) (ρ = 0.22; p = 0.001) and Fibrinogen (ρ = 0.29; p < 0.001) correlated with Fibrin MA. In multivariable regression analysis, DM remained significantly associated with plasma MA after adjustment for Fibrinogen level (p = 0.003). Conclusions Subjects with diabetes mellitus exhibit increased maximal Fibrin Clot strength measured by TEG in platelet-poor plasma.
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Fibrin Clot strength measured by thrombelastography and outcomes after percutaneous coronary intervention
Thrombosis and Haemostasis, 2016Co-Authors: Rolf P. Kreutz, Benjamin Maatman, Glen Schmeisser, Andrea Schaffter, Anjan Sinha, Elisabeth Von Der Lohe, Jeffrey A BreallAbstract:Fibrin Clot strength measured by thrombelastography and outcomes after percutaneous coronary intervention -
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C-reactive protein and Fibrin Clot strength measured by thrombelastography after coronary stenting
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 2013Co-Authors: Rolf P. Kreutz, Anjan Sinha, Elisabeth Von Der Lohe, Jeffrey A Breall, Janelle Owens, Islam A. Bolad, David A. FlockhartAbstract:Inflammation is implicated in the progression of coronary artery disease and the molecular processes of inflammation and thrombosis are closely intertwined. Elevated levels of C-reactive protein (CRP) have been associated with an elevated risk of adverse ischaemic events after coronary stenting and hypercoagulability. Heightened whole blood Clot strength measured by thrombelastography (TEG) has been associated with adverse ischaemic events after stenting. We intended to examine the relationship of CRP to plasma Fibrin Clot strength in patients after coronary stenting. Plasma Fibrin Clot strength was measured by TEG in 54 patients 16-24 h after undergoing elective percutaneous coronary intervention (PCI). Coagulation was induced in citrated plasma by addition of kaolin and CaCl2. Plasma levels of CRP and Fibrinogen were measured by enzyme-linked immunoassay. Increasing quartiles of CRP were associated with increasing levels of maximal plasma Fibrin Clot strength measured by TEG (P
Aleksandra Antovic - One of the best experts on this subject based on the ideXlab platform.
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Fibrin Clot properties and haemostatic function in men and women with type 1 diabetes.
Thrombosis and haemostasis, 2014Co-Authors: Sara Tehrani, Gun Jörneskog, Anna Ågren, Per-eric Lins, Håkan Wallén, Aleksandra AntovicAbstract:The increased risk of vascular complications in type 1 diabetes may in part be explained by changes in haemostatic function. In the present study, we investigated the Fibrin Clot properties in patients with type 1 diabetes in relation to sex and microvascular complications. The study included 236 patients (107 women) aged between 20–70 years and without any history of cardiovascular disease. Fibrin Clot properties, assessed by determination of the permeability coefficient (Ks) and turbidimetric Clotting and lysis assays, did not differ between men and women. Compared with men, women had worse glycaemic control as well as higher levels of prothrombin fragment 1+2 and peak thrombin generation in vitro, indicating increased thrombin generation both in vivo and in vitro. Subgroup analyses of patients younger than 30 years revealed less permeable Fibrin Clots and prolonged lysis time in females compared with age-matched men. Patients with microvascular complications had higher Fibrinogen concentrations and denser and less permeable Fibrin Clots. Thus, we conclude that in vitro Fibrin Clot properties in patients with type 1 diabetes without cardiovascular disease are not different between the sexes, but associate with prevalence of microvascular complications. Tighter Fibrin Clot formation in younger women, as suggested by our results, may affect their future cardiovascular risk and should be investigated in a larger population.
Søs Neergaard-petersen - One of the best experts on this subject based on the ideXlab platform.
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The influence of type 2 diabetes on Fibrin Clot properties in patients with coronary artery disease
Thrombosis and haemostasis, 2014Co-Authors: Søs Neergaard-petersen, Anne-mette Hvas, Sanne Bøjet Larsen, Steen Dalby Kristensen, Erik Lerkevang Grove, Fladia Phoenix, Zeyad Kurdee, Peter J. Grant, Ramzi AjjanAbstract:Type 2 diabetes mellitus (T2DM) increases the risk of coronary thrombosis and both conditions are associated with altered Fibrin Clot properties. However, the influence of T2DM on Fibrin Clot properties in patients with coronary artery disease (CAD) remains unclear. We aimed to investigate the influence of T2DM on Fibrin Clot properties in patients with CAD. Fibrin Clot structure and Fibrinolysis were investigated in 581 CAD patients (148 with T2DM) using turbidimetric assays, confocal and scanning electron microscopy. Clots made from plasma and plasma-purified Fibrinogen were studied, and plasma levels of inflammatory markers were analysed. T2DM patients had increased Clot maximum absorbance compared with non-diabetic patients (0.36 ± 0.1 vs 0.33 ± 0.1 au; p=0.01), displayed longer lysis time (804 [618;1002] vs 750 [624;906] seconds; p=0.03) and showed more compact Fibrin structure assessed by confocal and electron microscopy. Fibrinogen levels were elevated in T2DM (p
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Fibrin Clot structure and platelet aggregation in patients with aspirin treatment failure.
PloS one, 2013Co-Authors: Søs Neergaard-petersen, Ramzi Ajjan, Anne-mette Hvas, Katharina Hess, Sanne Bøjet Larsen, Steen Dalby Kristensen, Erik Lerkevang GroveAbstract:Background Aspirin is a cornerstone in prevention of cardiovascular events and modulates both platelet aggregation and Fibrin Clot formation. Some patients experience cardiovascular events whilst on aspirin, often termed aspirin treatment failure (ATF). This study evaluated both platelet aggregation and Fibrin Clot structure in patients with ATF.