Kinetics of fibrin clot lysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Merrills RJ
PROVIDER: S-EPMC1198474 | biostudies-other | 1968 Jan
REPOSITORIES: biostudies-other
Similar Datasets
Project description:ObjectiveKlinefelter syndrome (KS) is associated with increased risk of thrombosis. Hypogonadism and accumulating body fat in KS have a potential impact on fibrinolysis. In this study, we assessed the fibrinolytic system and the association with testosterone levels in KS.DesignThis study is a cross-sectional comparison of men with KS and age-matched male controls.MethodsFibrin clot lysis was evaluated by turbidity measurements and by measuring levels of individual fibrinolytic proteins in plasma samples. Fibrin clot structure was evaluated by scanning electron microscopy. Total testosterone was measured by liquid chromatography-tandem mass spectrometry. Body fat was evaluated by dual-energy X-ray absorptiometry.ResultsIn this study, 45 men with KS and 45 age- and education-matched controls were included. Men with KS had a 24% reduction in fibrin clot lysis compared with controls (46.2 ± 17.1 vs 60.6 ± 18.8 %/h, P = 0.0003) and higher levels of fibrinogen, factor XIII (P ≤ 0.01), and plasminogen activator inhibitor type 1 (P = 0.04). Men with KS had lower total testosterone (P = 0.008) and higher body fat (P = 0.001). In KS, reduced fibrin clot lysability was associated with higher fibrinogen and body fat related to decreasing total testosterone and hypogonadism among men with KS. Fibrin clot structure was not different compared to KS and controls.ConclusionsFibrin clot lysis in KS was markedly reduced, potentially contributing to a prothrombotic state and increasing thrombotic risk. Hypogonadism in KS was associated with increased fibrinogen and total body fat, predicting reduced fibrin clot lysis.
| S-EPMC9175611 | biostudies-literature
Project description:It has been observed in vitro that complete clot lysis is generally preceded by a slow phase of lysis during which the degradation seems to be inefficient. However, this slow regime was merely noticed, but not yet quantitatively discussed. In our experiments, we observed that the lysis ubiquitously occurred in two distinct regimes, a slow and a fast lysis regime. We quantified extensively the duration of these regimes for a wide spectrum of experimental conditions and found that on average, the slow regime lasts longer than the fast one, meaning that during most of the process, the lysis is ineffective. We proposed a computational model in which the properties of the binding of the proteins change during the lysis: first, the biochemical reactions take place at the surface of the fibrin fibers, then in the bulk, resulting in the observed fast lysis regime. This simple hypothesis appeared to be sufficient to reproduce with a great accuracy the lysis profiles obtained experimentally.
| S-EPMC8510862 | biostudies-literature
Project description:BackgroundPlatelet-fibrin clot contraction is critical for wound closure and maintenance of vessel patency, yet a molecular understanding of the process has lagged because of a lack of flexible quantitative assay systems capable of assaying multiple samples simultaneously.ObjectivesWe devised a sensitive and inexpensive method to assess clot contraction kinetics under multiple conditions.MethodsClot contraction was measured using time-lapse digital photography, automated image processing with customized software, and detailed kinetic analysis using available commercial programs.ResultsOur system was responsive to alterations in platelet counts and calcium, fibrinogen, and thrombin concentrations, and our analysis detected and defined three phases of platelet-fibrin clot formation: initiation, contraction, and stabilization. Lag time, average contraction velocity, contraction extent, and area under the curve were readily calculated from the data. Using pharmacological agents (blebbistatin and eptifibatide), we confirmed the importance of myosin IIA and the interactions of integrin αIIbβ3-fibrinogen/fibrin in clot contraction. As further proof of our system's utility, we showed how 2-deoxyglucose affects contraction, demonstrating the importance of platelet bioenergetics, specifically glycolysis.ConclusionsOur system is an adaptable platform for assessing the effects of multiple conditions and interventions on clot contraction kinetics in a regular laboratory setting, using readily available materials. The automated image processing software we developed will be made freely available for noncommercial uses. This assay system can be used to directly compare and define the effects of different treatments or genetic manipulations on platelet function and should provide a robust tool for future hemostasis/thrombosis research and therapeutic development.
| S-EPMC9301529 | biostudies-literature
Project description:Polyphosphate, a linear polymer of inorganic phosphate, is present in platelet dense granules and is secreted on platelet activation. We recently reported that polyphosphate is a potent hemostatic regulator, serving to activate the contact pathway of blood clotting and accelerate factor V activation. Because polyphosphate did not alter thrombin clotting times, it appeared to exert all its procoagulant actions upstream of thrombin. We now report that polyphosphate enhances fibrin clot structure in a calcium-dependent manner. Fibrin clots formed in the presence of polyphosphate had up to 3-fold higher turbidity, had higher mass-length ratios, and exhibited thicker fibers in scanning electron micrographs. The ability of polyphosphate to enhance fibrin clot turbidity was independent of factor XIIIa activity. When plasmin or a combination of plasminogen and tissue plasminogen activators were included in clotting reactions, fibrin clots formed in the presence of polyphosphate exhibited prolonged clot lysis times. Release of polyphosphate from activated platelets or infectious microorganisms may play an important role in modulating fibrin clot structure and increasing its resistance to fibrinolysis. Polyphosphate may also be useful in enhancing the structure of surgical fibrin sealants.
| S-EPMC2556616 | biostudies-literature
Project description:Fluorogenic thrombin generation (TG) assays and turbidity-based fibrin generation (FG)- and fibrinolysis (FL)-resistance assays have been sought to assess bleeding and clotting disorders. Theoretically, TG, FG and FL tests should provide overlapping information because thrombin is responsible for FG and induces protection from FL. The relationships between TG, FG and FL parameters remain poorly investigated, partly because existing experimental systems do not permit simultaneous detection of both TG and FG in the same sample of plasma, and are instead tested in separate experiments.We evaluated the potential benefits of a combined TG/FG/FL assay by testing responses of normal plasma to a wide range of tissue factor (TF) and tissue plasminogen activator (tPA) concentrations. Correlations between multiple parameters extracted from the TG and FG/FL curves were also compared.Rate of FG correlated well with TG peak height at all TF concentrations, but correlations between TG and FL parameters depended on the TF concentration. Without thrombomodulin, all FG/FL parameters at high TF could be predicted from TG parameters and no FL protection was observed. With thrombomodulin and high TF, TF-dependent FL protection did not correlate with TF-dependent TG. The fluorogenic thrombin substrate did not interfere with optical density readings, and meaningful tPA concentrations did not interfere with TG readings.In normal plasma, TG, FG and FL parameters may provide interchangeable information. Evaluation of FL-resistance may provide additional data under special assay conditions, but the value of this information should be studied under disease conditions.
| S-EPMC4821761 | biostudies-literature
Project description:Meniscal injuries and meniscal loss are associated with changes in knee kinematics and loading, ultimately leading to poor functional outcomes and increased risk of progression to osteoarthritis. Biomechanical studies have shown restored knee function, and clinical studies have reported improved outcomes and decreased risk of osteoarthritis after meniscal repair. This has led orthopaedic surgeons to try and save the meniscus by repair whenever possible, as shown by increasing incidence of meniscal repair surgeries. Historically, meniscal lesions, particularly those greater in size and located in the white-white region of the meniscus, have been shown to have poor healing. In recent years, there has been an increasing interest in the use of biologic agents to help stimulate and expedite healing in traditionally more avascular tissue. Preliminary results for biologic therapeutic agents, such as platelet rich plasma and bone marrow aspirate concentrate, have been encouraging. However, these options are more demanding in regard to time, financial burden, resources, and regulations than some more classic agents such as fibrin clots. Fibrin clot is readily available, easy to use, affordable, and minimally invasive. This Technical Note describes a step-by-step and reproducible technique for harvesting, preparation, and using a fibrin clot to augment healing of meniscal repairs.
| S-EPMC5766256 | biostudies-literature
Project description:ObjectiveAcute hyperglycemia on admission for acute coronary syndrome worsens the prognosis in patients with and without known diabetes. Postulated mechanisms of this observation include prothrombotic effects. The aim of this study was to evaluate the effect of elevated glucose levels on blood clotting in acute coronary syndrome patients.Research design and methodsWe studied 60 acute coronary syndrome patients within the first 12 h after pain onset, including 20 subjects with type 2 diabetes, 20 subjects with no diagnosed diabetes but with glucose levels >7.0 mmol/l, and 20 subjects with glucose levels <7.0 mmol/l. We determined generation of thrombin-antithrombin complexes (TATs) and soluble CD40 ligand (sCD40L), a platelet activation marker, at the site of microvascular injury, together with ex vivo plasma fibrin clot permeability and lysis time.ResultsThe acute coronary syndrome patients with no prior diabetes but elevated glucose levels had increased maximum rates of formation and total production of TATs (by 42.9%, P < 0.0001, and by 25%, P < 0.0001, respectively) as well as sCD40L release (by 16.2%, P = 0.0011, and by 16.3%, P < 0.0001, respectively) compared with those with normoglycemia, whereas diabetic patients had the highest values of TATs and sCD40L variables (P < 0.0001 for all comparisons). Patients with hyperglycemia, with no previously diagnosed diabetes, had longer clot lysis time (by approximately 18%, P < 0.0001) similar to that in diabetic subjects, but not lower clot permeability compared with that in normoglycemic subjects.ConclusionsHyperglycemia in acute coronary syndrome is associated with enhanced local thrombin generation and platelet activation, as well as unfavorably altered clot features in patients with and without a previous history of diabetes.
| S-EPMC2494657 | biostudies-literature
Project description:The formation and dissolution of blood clots is both a biochemical and a biomechanical process. While much of the chemistry has been worked out for both processes, the influence of biophysical properties is less well understood. This review considers the impact of several structural and mechanical parameters on lytic rates of fibrin fibers. The influences of fiber and network architecture, fiber strain, FXIIIa cross-linking, and particle transport phenomena will be assessed. The importance of the mechanical aspects of fibrinolysis is emphasized, and future research avenues are discussed.
| S-EPMC5467299 | biostudies-literature
Project description:Despite recent technical advances, rotator cuff repair continues to have a high retear rate. Recent research focused on biologic augmentation of rotator cuff repair with platelet-rich plasma has shown mixed results, and use of an endogenous fibrin clot from either peripheral blood or bone marrow may have advantages over the use of platelet-rich plasma. This technique describes a method to make an endogenous fibrin clot and arthroscopically apply the fibrin clot to the superior surface of the rotator cuff repair site.
| S-EPMC3678671 | biostudies-literature
Project description:Repair of meniscus injuries always posed a significant problem, especially in relatively avascular zones. Several methods to augment the repair were devised, but only a few had convincing results. Fibrin clot augmentation is one of the augmentation procedures that shows good promise in this premise. The major hurdle to it is difficulty in delivering into the meniscus tear under constant irrigation during arthroscopic procedures. This article presents a simple and unique way to prepare and transfer a fibrin clot into a meniscal tear in a step-by-step manner.
| S-EPMC8626618 | biostudies-literature