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Introduction: Plasma protein carbonylation that reflects oxidative stress has been demonstrated to be associated with the prothrombotic fibrin clot phenotype. However, the role of protein carbonyls (PC) in predicting ischemic stroke in atrial fibrillation (AF) is largely unknown. This study aimed to investigate whether PC increase the risk of stroke in anticoagulated AF patients during follow-up. Methods: In 243 AF patients on anticoagulation (median age 69 years; median CHA2DS2-VASc of 4), we measured plasma PC using the assay by Becatti, along with plasma clot permeability (Ks), clot lysis time (CLT), thrombin generation, and fibrinolytic proteins, including plasminogen activator inhibitor type 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor (TAFI). Ischemic stroke, major bleeding, and mortality were recorded during a median follow-up of 53 months. Results: Plasma PC levels (median, 3.16 [2.54–3.99] nM/mg protein) at baseline showed positive associations with age (P < 0.001), CHA2DS2-VASc (P = 0.003), and N-terminal B-type natriuretic peptide (P = 0.001), but not with type of AF or comorbidities except for heart failure (P = 0.007). PC levels were correlated with CLT (r = 0.342, P < 0.001), endogenous thrombin potential (r = 0.217, P = 0.001) and weakly with Ks (r = -0.145, P = 0.024), but not with fibrinogen, PAI-1, or TAFI levels. Stroke was recorded in 20 patients (1.9%/year), who had at baseline 36% higher PC levels (P < 0.001). Elevated PC (P = 0.003) at baseline were independently associated with stroke risk. Conclusion: Our findings suggest that in patients with AF enhanced protein carbonylation is associated with increased "residual" risk of stroke despite anticoagulation, which is at least in part due to unfavorably altered fibrin clot phenotype. [ABSTRACT FROM AUTHOR]

Introduction: Root biomodification in periodontal therapy aims at removing the smear layer and enhances the clot stability necessary for periodontal regeneration. Citric Acid (CA), EDTA, fibronectin has been used routinely. But if used injudiciously acidic erosion of the periodontal tissues might occur. Apple Cider Vinegar (ACV) an organic acetic has been reported to possess antimicrobial, anti-inflammatory and antioxidant effects. Aim: To assess the effect of smear layer removal and fibrin clot adhesion of ACV in comparison to CA on periodontally affected teeth. Materials and Methods: This pilot study was conducted at Sri Venkateswara Dental College and Hospital, Chennai, India, for three months, starting in January 2024 and ending in March 2024. 8 Teeth extracted due to periodontal reasons were cleaned, scaled and root planed. From the extracted teeth 16 dentin block samples were obtained, of which eight underwent CA testing (Control group) and eight underwent ACV testing (test group). The SEM analysis was done to assess the efficiency of smear layer removal and fibrin clot adhesion. Results: Under qualitative Scanning Electron Microscope (SEM) analysis, though ACV (50%) and CA (50%) group exhibited significant level of smear layer removal, complete dentinal tubule opening (RMSI score 2) was observed only in ACV category. In regard to Blood Element Adhesion Index (BEAI) both the groups demonstrated moderate fibrin clot adhesion (BEA score 2) in 50% of their samples. Considering both the parameters, root conditioning effects of ACV was better than CA. Conclusion: Teeth treated with ACV had a comparable effect as the CA in terms of root biomodification. This novel agent with several medicinal effects can be considered for future studies to determine its regenerative effectiveness. [ABSTRACT FROM AUTHOR]

Introduction: Root biomodification in periodontal therapy aims at removing the smear layer and enhances the clot stability necessary for periodontal regeneration. Citric Acid (CA), EDTA, fibronectin has been used routinely. But if used injudiciously acidic erosion of the periodontal tissues might occur. Apple Cider Vinegar (ACV) an organic acetic has been reported to possess antimicrobial, anti-inflammatory and antioxidant effects. Aim: To assess the effect of smear layer removal and fibrin clot adhesion of ACV in comparison to CA on periodontally affected teeth. Materials and Methods: This pilot study was conducted at Sri Venkateswara Dental College and Hospital, Chennai, India, for three months, starting in January 2024 and ending in March 2024. 8 Teeth extracted due to periodontal reasons were cleaned, scaled and root planed. From the extracted teeth 16 dentin block samples were obtained, of which eight underwent CA testing (Control group) and eight underwent ACV testing (test group). The SEM analysis was done to assess the efficiency of smear layer removal and fibrin clot adhesion. Results: Under qualitative Scanning Electron Microscope (SEM) analysis, though ACV (50%) and CA (50%) group exhibited significant level of smear layer removal, complete dentinal tubule opening (RMSI score 2) was observed only in ACV category. In regard to Blood Element Adhesion Index (BEAI) both the groups demonstrated moderate fibrin clot adhesion (BEA score 2) in 50% of their samples. Considering both the parameters, root conditioning effects of ACV was better than CA. Conclusion: Teeth treated with ACV had a comparable effect as the CA in terms of root biomodification. This novel agent with several medicinal effects can be considered for future studies to determine its regenerative effectiveness.

Significance: Aging is a complex process associated with an increased risk of many diseases, including thrombosis. This review summarizes age-related prothrombotic mechanisms in clinical settings of thromboembolism, focusing on the role of fibrin structure and function modified by oxidative stress. Recent Advances: Aging affects blood coagulation and fibrinolysis via multiple mechanisms, including enhanced oxidative stress, with an imbalance in the oxidant/antioxidant mechanisms, leading to loss of function and accumulation of oxidized proteins, including fibrinogen. Age-related prothrombotic alterations are multifactorial involving enhanced platelet activation, endothelial dysfunction, and changes in coagulation factors and inhibitors. Formation of more compact fibrin clot networks displaying impaired susceptibility to fibrinolysis represents a novel mechanism, which might contribute to atherothrombosis and venous thrombosis. Alterations to fibrin clot structure/function are at least in part modulated by post-translational modifications of fibrinogen and other proteins involved in thrombus formation, with a major impact of carbonylation. Fibrin clot properties are also involved in the efficacy and safety of therapy with oral anticoagulants, statins, and/or aspirin. Critical Issues: Since a prothrombotic state is observed in very elderly individuals free of diseases associated with thromboembolism, the actual role of activated blood coagulation in health remains elusive. It is unclear to what extent oxidative modifications of coagulation and fibrinolytic proteins, in particular fibrinogen, contribute to a prothrombotic state in healthy aging. Future Directions: Ongoing studies will show whether novel therapies that may alter oxidative stress and fibrin characteristics are beneficial to prevent atherosclerosis and thromboembolic events associated with aging. [ABSTRACT FROM AUTHOR]

Neutrophil-activating peptide 2 (NAP-2, CXCL7), a platelet-derived neutrophil chemoattractant, is involved in inflammation. We investigated associations between NAP-2 levels, neutrophil extracellular traps (NETs) formation, and fibrin clot properties in atrial fibrillation (AF). We recruited 237 consecutive patients with AF (mean age, 68 ± 11 years; median CHA2DS2VASc score of 3 [2–4]) and 30 apparently healthy controls. Plasma NAP-2 concentrations were measured, along with plasma fibrin clot permeability (Ks) and clot lysis time (CLT), thrombin generation, citrullinated histone H3 (citH3), as a marker of NETs formation, and 3-nitrotyrosine reflecting oxidative stress. NAP-2 levels were 89% higher in AF patients than in controls (626 [448–796] vs. 331 [226–430] ng/ml; p < 0.0001). NAP-2 levels were not associated with demographics, CHA2DS2-VASc score, or the AF manifestation. Patients with NAP-2 in the top quartile (> 796 ng/ml) were characterized by higher neutrophil count (+ 31.7%), fibrinogen (+ 20.8%), citH3 (+ 86%), and 3-nitrotyrosine (+ 111%) levels, along with 20.2% reduced Ks and 8.4% prolonged CLT as compared to the remaining subjects (all p < 0.05). NAP-2 levels were positively associated with fibrinogen in AF patients (r = 0.41, p = 0.0006) and controls (r = 0.65, p < 0.01), along with citH3 (r = 0.36, p < 0.0001) and 3-nitrotyrosine (r = 0.51, p < 0.0001) in the former group. After adjustment for fibrinogen, higher citH3 (per 1 ng/ml β = -0.046, 95% CI -0.029; -0.064) and NAP-2 (per 100 ng/ml β = -0.21, 95% CI -0.14; -0.28) levels were independently associated with reduced Ks. Elevated NAP-2, associated with increased oxidative stress, has been identified as a novel modulator of prothrombotic plasma fibrin clot properties in patients with AF. [ABSTRACT FROM AUTHOR]

Fibrin, described on a single-lens microscopy for the first time by Malpighi in 1666 and named by de Fourcroy, has been extensively studied by biochemists, biophysicists, and more recently by clinicians who recognized that fibrin is the major component of most thrombi. Elucidation of key reactions leading to fibrin clot formation in the 1950s and 1960s grew interest in the clinical relevance of altered fibrin characteristics. Implementation of scanning electron microscopy to image fibrin clots in 1947 and clot permeation studies in the 1970s to evaluate an average pore size enabled plasma clot characterization in cohorts of patients. Unfavorably altered fibrin clot structure was demonstrated by Blombäck's group in coronary artery disease in 1992 and in diabetes in 1996. Fifteen years ago, similar plasma fibrin clot alterations were reported in patients following venous thromboembolism. Multiple myeloma was the first malignant disease to be found to lead to abnormal fibrin clot phenotype in the 1970s. Apart from anticoagulant agents, in 1998, aspirin was first shown to increase fibrin clot permeability in cardiovascular patients. The current review presents key data on the rich history of fibrin research, in particular, those that first documented abnormal fibrin clot properties in a variety of human disease states, as well as factors affecting fibrin phenotype. [ABSTRACT FROM AUTHOR]

Prosthetic heart valve (PHV) replacement has increased the survival rate and quality of life for heart valve-diseased patients. However, PHV thrombosis remains a critical problem associated with these procedures. To better understand the PHV flow-related thrombosis problem, appropriate experimental models need to be developed. In this study, we present an in vitro fibrin clot model that mimics clot accumulation in PHVs under relevant hydrodynamic conditions while allowing real-time imaging. We created 3D-printed mechanical aortic valve models that were inserted into a transparent glass aorta model and connected to a system that simulates human aortic flow pulse and pressures. Thrombin was gradually injected into a circulating fibrinogen solution to induce fibrin clot formation, and clot accumulation was quantified via image analysis. The results of valves positioned in a normal versus a tilted configuration showed that clot accumulation correlated with the local flow features and was mainly present in areas of low shear and high residence time, where recirculating flows are dominant, as supported by computational fluid dynamic simulations. Overall, our work suggests that the developed method may provide data on flow-related clot accumulation in PHVs and may contribute to exploring new approaches and valve designs to reduce valve thrombosis. [ABSTRACT FROM AUTHOR]

Fibrin clots are crucial for hemostasis and the healing of wounds; nevertheless, excessive blood clotting plays an important role in many chronic diseases, including cardiovascular disease. In this study, we demonstrated the effect of the prepared AuNPs@PANI core/shell on the formed fibrin network. The synthesis of nanoparticles combining electrically conducting polymers polyaniline (PANI) and gold nanoparticles (AuNPs) is an appealing field of research currently because of their physical features and prospective applications in biochemistry. AuNPs showed surface plasmonic resonance (SPR) properties in the visible region at 520 nm then, after coating with PANI, there was a dramatic red shift to 610 nm. The morphological conformation was confirmed by characterization at the microscopic (TEM, SEM, EDX). The PANI shell plays a crucial role in this system, first enhances the stability of AuNPs core; also, the surface of the PANI shell has positive charges (zeta potential = +17.8 mV), leading to electrostatic interactions with fibrin clots that have negatively charged surfaces. The synthesized core/shell AuNPs@PANI showed good efficiency for degrading fibrin networks under 1:30 h of irradiation by an external source of laser light, which is a result of AuNPs’ ability to absorb light at 520 nm. The degradation of fibrin was observed using a scanning electron microscope (SEM), which showed a clear change in the shape of the network. The appearance of fibrous endings and gaping indicates the beginning of the degradation and melting of the fibrin network in different sites of the clot. Overall, this method could have a major influence on disease states, for example, deep vein thrombosis, through a localized, catheter-based approach.

Background: The menisci are critical for knee stability and cushioning and tears of the menisci have been linked to the acceleration of osteoarthritis. Horizontal cleavage tears split the meniscus into a top and bottom portion and are notoriously difficult to repair due to their localization in the avascular zone of the meniscus. Repair augmentation techniques, including fibrin clot and bone marrow venting, have been reported to increase meniscus healing. Indications: The use of a fibrin clot is indicated when there is a complex horizontal cleavage tear of the meniscus. There must be a clear separation of the top and bottom leaflets that can hold the fibrin clot inside. Technique Description: The horizontal cleavage tear is first identified, and a shaver with the suction left off is used to roughen between the upper and lower leaflets of the meniscus tear. A rasp is used inside the horizontal tear to roughen up the edges and expose the entire tear. Inside-out sutures are used in a hay bale technique to surround the tear. Thirty milliliters of blood are stirred until a fibrin clot is formed. This clot is stabilized with a circumferential Vicryl stitch and shuttled in between the leaflets of horizontal tear using a suture tied around the fibrin clot. The previously placed hay bale sutures are loosened to allow for placement of the fibrin clot. All sutures are tied at the end of the procedure. Results: A study by Nakayama et al reported a clinical success rate of 18 of 24 patients undergoing medial meniscus horizontal cleavage tear repair with fibrin clot augmentation. All patients with failures were in significant varus alignment. Another study by Kamimura et al with 10 patients reported increases in postoperative patient reported outcomes and a healing rate of 70% on second-look arthroscopy. Discussion: This fibrin clot interposition technique augments the repair of a horizontal cleavage tears. Due to horizontal cleavage tears being localized in the white-white avascular zone, augmentation including using a fibrin clot can help induce healing. This repair can help restore the stability and cushioning of the meniscus to slow the progression of osteoarthritis. [ABSTRACT FROM AUTHOR]

Formation of denser and resistant to lysis fibrin clot networks has been shown in chronic kidney disease (CKD) and atrial fibrillation (AF). We investigated whether such prothrombotic fibrin clot properties are associated with faster progression of CKD in AF patients. We recruited 265 AF patients (men 49.1 %, median age of 64.0 years, median estimated glomerular filtration rate [eGFR] of 77.0 ml/min/1.73 m2), including 137 patients on non-vitamin K antagonist oral anticoagulants (NOACs) (51.7 %) and 109 patients (41.1 %) on vitamin K antagonists (VKAs). At baseline while off anticoagulation, we determined fibrin clot permeability (K s), and clot lysis time (CLT), along with plasminogen activator inhibitor-1 (PAI-1), endogenous thrombin potential (ETP), and von Willebrand factor (vWF). The kidney function was assessed at baseline and after a median follow-up of 50.0 months. During follow-up, a median eGFR decreased by 8.0 (5.0–11.0) ml/min/1.73 m2, 1.8 ml/min/1.73 m2/year and this change correlated with age (R = 0.19, P = 0.002), K s (R = 0.46, P < 0.0001), and CLT (R = -0.17, P = 0.005), but not ETP, fibrinogen, PAI-1 or vWF. A decrease in eGFR was lower in patients who used NOACs at baseline but not in those who started NOACs during follow-up (n = 101) as compared to the remaining patients. On multiple linear regression analysis, adjusted for age and fibrinogen, baseline K s , eGFR, hypertension, and NOACs use independently predicted a decrease in eGFR. This study is the first to show that more compact fibrin clot networks may contribute to faster progression of CKD in AF, indicating novel kidney-related harmful effects of prothrombotic clot properties in humans. • Denser and resistant to lysis fibrin clot networks have been shown in chronic kidney disease and atrial fibrillation. • The magnitude of the decrease in eGFR is related to fibrin clot permeability and clot lysis time. • The decrease in eGFR is lower in patients who used non-vitamin K antagonist oral anticoagulants. • In atrial fibrillation the prothrombotic fibrin clot properties are associated with faster deterioration of kidney function. [ABSTRACT FROM AUTHOR]

Cancer is associated with a high risk of venous thromboembolism (VTE) and its recurrence. There is evidence that the prothrombotic fibrin clot phenotype, involving the formation of denser and stiffer clots relatively resistant to lysis, occurs in cancer patients, which is in part related to enhanced inflammation, oxidative stress, and coagulation activation, along with the release of neutrophil extracellular traps, indicating that fibrin-related mechanisms might contribute to cancer-associated thrombosis (CAT). Multiple myeloma and its therapy have been most widely explored in terms of altered fibrin characteristics, but prothrombotic fibrin clot features have also been reported in patients with active solid cancer, including lung cancer and gastrointestinal cancer. Patient-related factors such as advanced age, smoking, and comorbidities might also affect fibrin clot characteristics and the risk of CAT. Prothrombotic fibrin clot features have been shown to predict the detection of cancer in patients following VTE during follow-up. Cancer-specific therapies and anticoagulation can favorably modify the phenotype of a fibrin clot, which may alter the course of CAT. It is unclear whether the fibrin clot phenotype might help identify patients with CAT who are more likely to experience recurrent events. This narrative review summarizes the current knowledge on the role of fibrin clot structure and function in cancer patients in the context of CAT. [ABSTRACT FROM AUTHOR]

Fibrin clot is a vital class of fibrous materials, governing the mechanical response of blood clots. Fracture behavior of fibrin clots under complex physiological load is relevant for hemostasis and thrombosis. But how they fracture under cyclic and variable rate loading has not been reported. Here we conduct cyclic fatigue and monotonic variable rate loading tests on fibrin clots to characterize their fracture properties in terms of fatigue threshold and rate-dependent fracture toughness. We demonstrate that the fracture behavior of fibrin clots is sensitive to the amplitude of cyclic load and the loading rate. The cyclic fatigue tests show the fatigue threshold of fibrin clots at 1.66 J/m2, compared to the overall fracture toughness 15.8 J/m2. Furthermore, we rationalize the fatigue threshold using a semi-empirical model parameterized by 3D morphometric quantification to account for the hierarchical molecular structure of fibrin fibers. The variable loading tests reveal rate dependence of the overall fracture toughness of fibrin clots. Our analysis with a viscoelastic fracture model suggests the viscoelastic origin of the rate-dependent fracture toughness. The toughening mechanism of fibrin clots is further compared with biological tissues and hydrogels. This study advances the understanding and modeling of fatigue and fracture of blood clots and would motivate further investigation on the mechanics of fibrous materials. Fibrin clot is a soft fibrous gel, exhibiting nonlinear mechanical responses under complex physiological loads. It is the main load-bearing constituent of blood clots where red blood cells, platelets and other cells are trapped. How the fibrin clot fractures under complex mechanical loads is critical for hemostasis and thrombosis. We study the fracture behavior of fibrin clots under cyclic fatigue and monotonic variable rate loads. We characterize the fatigue-threshold and viscous energy dissipation of fibrin clots. We compare the toughness enhancement of fibrin clots with hydrogels. The findings offer new insights into the fatigue and fracture of blood clots and fibrous materials, which could improve design guidelines for bioengineered materials. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Residual pulmonary vascular obstruction (RPVO) is common following pulmonary embolism (PE) but its association with fibrin clot properties is poorly understood. We investigated whether prothrombotic state and hypofibrinolysis markers can identify patients with RPVO. Methods: In 79 normotensive noncancer patients (aged 56 ± 13.3 years) with acute PE, we determined fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), fibrinolysis proteins, oxidative stress markers, and E-selectin on admission before initiation of anticoagulant therapy, after 5–7 days, and 3 months of anticoagulation. RPVO was diagnosed using computed tomography angiography 3–6 months since PE. Results: Patients with RPVO (n = 23, 29.1%) had at baseline higher simplified Pulmonary Embolism Severity Index (sPESI) (P = 0.004), higher N-terminal brain natriuretic propeptide (P = 0.006) and higher D-dimer (P = 0.044). Patients with versus without RPVO had lower Ks (P < 0.001) and longer CLT (P < 0.05), both at baseline and 5–7 days since admission, but not at 3 months. Patients with RPVO showed 40.6% higher E-selectin (P < 0.001) solely at 3 months. By multivariable logistic regression, baseline Ks (odds ratio [OR] 0.010, 95% confidence interval [CI] 0.001–0.837, P = 0.042, per 10− 9 cm2), baseline D-dimer (OR 1.105, 95% CI 1.000-1.221, P = 0.049, per 100 ng/ml), and E-selectin levels after 3 months (OR 3.874, 95% CI 1.239–12.116, P = 0.020, per 1 ng/ml) were associated with RPVO. Conclusions: RPVO patients despite anticoagulation characterize with the formation of denser fibrin clots on admission and higher E-selectin at 3 months. Those parameters could be the potential novel RPVO risk factors that warrant further evaluation in an independent cohort. Key points: RPVO occurs in a large proportion of acute PE patients despite anticoagulation. Plasma fibrin clot permeability and lysability on admission and after 5–7 days are potential novel RPVO risk factors. Elevated E-selectin after 3 months since PE was observed in RPVO patients. E-selectin inhibitors are potentially attractive in the RPVO prevention in PE patients. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) can traverse the intestinal barrier and enter bloodstream, causing endotoxemia and triggering inflammation. Increased circulating LPS was reported in arterial thromboembolism. We investigated whether increased LPS levels occur in acute pulmonary embolism (PE) and if it is associated with a prothrombotic state. We studied 120 normotensive PE patients (aged 59 [48–68] years) on admission, after 5–7 days, and after a 3-month anticoagulation. Serum LPS levels, along with zonulin, a marker of gut permeability, endogenous thrombin potential (ETP), fibrin clot permeability (K s), clot lysis time (CLT), fibrinolysis proteins, and platelet markers were assessed. Median LPS concentration on admission was 70.5 (61.5–82) pg/mL (min-max, 34–134 pg/mL), in association with C-reactive protein (r = 0.22, p = 0.018), but not with fibrinogen, D-dimer or platelet markers. Patients with more severe PE had higher LPS levels compared with the remainder. Median zonulin level was 3.26 (2.74–4.08) ng/mL and correlated with LPS (r = 0.66, p < 0.0001). Patients with baseline LPS levels in the top quartile (≥82 pg/mL; n = 29) compared to lower quartiles had 18.6 % increased ETP, 14.5 % reduced K s , and 25.3 % prolonged CLT, related to higher plasminogen activator inhibitor type 1 (PAI-1) levels. LPS decreased by 23.4 % after 5–7 days and by 40.4 % after 3-month anticoagulation together with reduced zonulin by 18.4 % and 22.3 %, respectively, compared to baseline (all p < 0.001). LPS levels were not related with fibrin characteristics and other variables assessed at 3 months. Low-grade endotoxemia is detectable in patients with acute PE and may contribute to increased thrombin generation and PAI-1-mediated hypofibrinolysis. • LPS traverse the intestinal barrier, enter bloodstream, causing endotoxemia. • Low-grade endotoxemia was detectable in patients with acute PE. • Time since PE was associated with decreased LPS levels. • LPS correlated with increased thrombin generation and hypofibrinolysis. [ABSTRACT FROM AUTHOR]

Background: Failure rate of meniscal repair can reach 25%. Multiple techniques have been used to increase meniscal healing, notably biological augmentation techniques. One of them is fibrin clot-augmented meniscal repair, which will be described in this video. Indications: This technique is indicated mainly for the lesions with a high failure rate. This includes large, horizontal, and radial tears and even for meniscal cysts, especially in a stable knee. This technique can also be used in revision meniscal suture when failure is no longer an option. Surgical Technique: Fibrin clot is prepared from sterile peripheral venous blood from the patient. A plastic syringe is used to stir the blood in a sterile glass container. The fibrin clot is then formed and washed rigorously with saline solution. Rolling the fibrin clot which is fixed to the syringe allows to give the fibrillar aspect of the clot. The formed fibrin clot is now solid enough to be manipulated and can be fixed to a vicryl suture thread allowing it to enter the knee and be fixed inside the meniscal lesion. The clot is wrapped inside the meniscal lesion with inside-out or outside-in suture technique. Results: We used this technique for multiple types of lesions, like bucket handle meniscal tear, horizontal meniscal cleavage, parrot beak tear, and even in lesions within white-white zone. The postoperative protocol is the same as standard inside-out meniscal repair. This technique has been used in the literature with promising results. Conclusion: The fibrin clot-augmented meniscal repair is a demanding but promising technique. We need further follow-up to confirm its effectiveness. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. [ABSTRACT FROM AUTHOR]

Introduction: Patients with coronary artery disease (CAD) display a prothrombotic fibrin clot phenotype, involving low permeability and resistance to lysis. The determinants of this phenotype remain elusive. Circulating tissue factor (TF) and activated factor XI (FXIa) are linked to arterial thromboembolism. We investigated whether detectable active TF and FXIa influence fibrin clot properties in CAD. Methods: In 118 CAD patients (median age 65 years, 78% men), we assessed Ks, an indicator of clot permeability, and clot lysis time (CLT) in plasma‐based assays, along with the presence of active TF and FXIa. We also analysed proteins involved in clotting and thrombolysis, including fibrinogen, plasminogen activator inhibitor‐1 (PAI‐1) and thrombin activatable thrombolysis inhibitor (TAFI). During a median 106 month (interquartile range 95–119) follow‐up, myocardial infarction (MI), stroke, systemic thromboembolism (SE) and cardiovascular (CV) death were recorded. Results: Circulating TF and FXIa, detected in 20.3% and 39.8% of patients, respectively, were associated with low Ks and prolonged CLT. Solely FXIa remained an independent predictor of low Ks and high CLT on multivariable analysis. Additionally, fibrinogen and PAI‐1 were associated with low Ks, while PAI‐1 and TAFI—with prolonged CLT. During follow‐up low Ks and prolonged CLT increased the risk of MI and the latter also a composite endpoint of MI, stroke/SE or CV death. Conclusions: To our knowledge, this study is the first to show that circulating FXIa is associated with prothrombotic fibrin clot properties in CAD, suggesting additional mechanisms through which FXIa inhibitors could act as novel antithrombotic agents in CAD. [ABSTRACT FROM AUTHOR]

Abstract Background In knee arthroscopic surgery, fibrin clot (FC) and leukocyte-rich platelet-rich fibrin (L-PRF) may be used in augmentation for meniscal repair. Studies have investigated growth factors released from FC and L-PRF; however, it is difficult to compare FC and L-PRF between different studies. Direct comparison of growth factors that may support meniscal healing released from FC and L-PRF may be beneficial in deciding whether to use FC or L-PRF. If no significant difference is seen, the surgeon may decide to use FC which is easier to prepare compared to L-PRF. The purpose of this pilot study is to investigate the release amount and pattern of basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1) from FC and L-PRF. Method Twenty milliliters (ml) of whole blood was collected from each of the four volunteers. Ten milliliters of whole blood was allocated for preparation of FC and 10 ml for L-PRF. FC and L-PRF were separately placed in 5 ml of culture media. Five milliliters of the culture media was sampled and refilled at 15 min, 1 day, 3 days, 1 week and 2 weeks. The collected culture was used to quantify bFGF, PDGF-AB, TGF-β1, VEGF, and SDF-1 release by Enzyme-linked immune-sorbent assay (ELISA). Mann–Whitney U test was performed to assess significance of differences in amount of each growth factor released between FC and L-PRF. Significance was accepted at P value less than 0.05. Results At two weeks, the cumulative release of TGF-β1 was the highest among all the growth factors in both FC and L-PRF (FC:19,738.21 pg/ml, L-PRF: 16,229.79 pg/ml). PDGF-AB (FC: 2328 pg/ml, L-PRF 1513.57 pg/ml) had the second largest amount, followed by VEGF (FC: 702.06 pg/ml, L-PRF 595.99 pg/ml) and bFGF (FC: 23.48 pg/ml, L-PRF 18.2 pg/ml), which order was also common in both FC and L-PRF. No significant difference in final release amount and pattern was seen between FC and L-PRF. Conclusion The current pilot study showed that cumulative release amount and release pattern of PDGF-AB, VEGF, TGF-β1, and bFGF did not significantly differ between FC and L-PRF during the two weeks of observation.

Prostacyclin (PGI2) analogues (epoprostenol, treprostonil, iloprost) are the cornerstone of pulmonary arterial hypertension (PAH) treatment. PGI2 analogues inhibit platelet reactivity, but their impact on coagulation and fibrinolysis parameters has not been elucidated. We compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in patients with PAH treated with PGI2 analogues (n = 20) and those not receiving PGI2 analogues (n = 20). Platelet reactivity was lower in patients treated with PGI2 analogues, compared to the control group, as evaluated with arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor-activating peptide-6 (TRAP) tests (p = .009, p = .02, p = .007, respectively). In the subgroup analysis, both treprostinil and epoprostenol decreased platelet reactivity to the similar extent. There were no differences regarding thrombin generation, clot permeation, and lysis parameters in patients receiving and not receiving PGI2 analogues (p ≥ .60 for all). In the subgroup analysis, there were no differences regarding coagulation and fibrinolysis parameters between treprostinil, epoprostenol, and no PGI2 analogues. To conclude, patients with PAH treated with PGI2 analogues have reduced platelet reactivity, but similar clot formation and lysis parameters, compared to patients not receiving PGI2 analogues. Further randomized clinical trials are required to confirm these findings.

Background: Atrial fibrillation (AF) is associated with cardiac remodelling and prothrombotic state. Enhanced neutrophil extracellular traps (NETs) formation has been reported in AF, contributing to thromboembolism. Purpose: We investigated whether increased left atrium (LA) diameter and reduced left ventricular ejection fraction (LVEF) affect NETs formation and prothrombotic state in AF patients. Methods: In 243 AF patients (median CHA2DS2‐VASc = 4) we measured LA diameter and LVEF, 123 of them with LVEF<50%. Moreover, we determined 3 markers of NETosis: circulating citrullinated histone H3 (H3cit), myeloperoxidase (MPO) and peptidylarginine deiminase 4 (PAD4), along with prothrombotic markers, including endogenous thrombin potential, plasma fibrin clot permeability (Ks) and clot lysis time (CLT). Ischaemic cerebrovascular events, major bleeding and death were recorded during a median follow‐up of 53 months, on anticoagulation. Results: LA diameter correlated positively with H3cit, MPO and PAD4, while LVEF was inversely associated with the same NETosis markers. After adjustment for age and body mass index, concentrations of MPO (per 10 units; β = −1.9, 95%CI −3.40;−0.42) and H3cit (per 10 units; β = 2.02, 95%CI 0.61–3.42) were independently associated with LVEF and LA diameter. LA diameter, but not LVEF, correlated inversely with Ks and positively with CLT. The Cox regression analysis revealed that H3cit >6.16 ng/mL (HR = 21.76, 95%CI 2.85–166.28, p =.003) and LA diameter > 46 mm (HR = 2.89, 95%CI 1.04–8.03, p =.043) independently predicted cerebrovascular ischaemic events (1.9%/year). Conclusions: This hypothesis‐generating study suggests that in AF enlarged LA diameter and reduced LVEF are associated with enhanced NETs formation, which might have clinical importance and contribute to thromboembolic events despite anticoagulation. [ABSTRACT FROM AUTHOR]

Background: In knee arthroscopic surgery, fibrin clot (FC) and leukocyte-rich platelet-rich fibrin (L-PRF) may be used in augmentation for meniscal repair. Studies have investigated growth factors released from FC and L-PRF; however, it is difficult to compare FC and L-PRF between different studies. Direct comparison of growth factors that may support meniscal healing released from FC and L-PRF may be beneficial in deciding whether to use FC or L-PRF. If no significant difference is seen, the surgeon may decide to use FC which is easier to prepare compared to L-PRF. The purpose of this pilot study is to investigate the release amount and pattern of basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1) from FC and L-PRF. Method: Twenty milliliters (ml) of whole blood was collected from each of the four volunteers. Ten milliliters of whole blood was allocated for preparation of FC and 10 ml for L-PRF. FC and L-PRF were separately placed in 5 ml of culture media. Five milliliters of the culture media was sampled and refilled at 15 min, 1 day, 3 days, 1 week and 2 weeks. The collected culture was used to quantify bFGF, PDGF-AB, TGF-β1, VEGF, and SDF-1 release by Enzyme-linked immune-sorbent assay (ELISA). Mann–Whitney U test was performed to assess significance of differences in amount of each growth factor released between FC and L-PRF. Significance was accepted at P value less than 0.05. Results: At two weeks, the cumulative release of TGF-β1 was the highest among all the growth factors in both FC and L-PRF (FC:19,738.21 pg/ml, L-PRF: 16,229.79 pg/ml). PDGF-AB (FC: 2328 pg/ml, L-PRF 1513.57 pg/ml) had the second largest amount, followed by VEGF (FC: 702.06 pg/ml, L-PRF 595.99 pg/ml) and bFGF (FC: 23.48 pg/ml, L-PRF 18.2 pg/ml), which order was also common in both FC and L-PRF. No significant difference in final release amount and pattern was seen between FC and L-PRF. Conclusion: The current pilot study showed that cumulative release amount and release pattern of PDGF-AB, VEGF, TGF-β1, and bFGF did not significantly differ between FC and L-PRF during the two weeks of observation. [ABSTRACT FROM AUTHOR]

Studies on the effect of statins on platelets in patients with coronary artery disease (CAD) yielded inconsistent results. We sought to investigate whether high-dose statin therapy reduces plasma concentrations of soluble P-selectin (sP-selectin), a well-established platelet activation marker and if such changes can affect fibrin clot properties, which are unfavorably altered in CAD patients. We studied 130 consecutive patients with advanced CAD who did not achieve the target LDL cholesterol on statins. At baseline and after 6–12 months of treatment with atorvastatin 80 mg/day or rosuvastatin 40 mg/day, soluble plasma sP-selectin, along with plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation and fibrinolysis proteins were determined. Before high-intensity statin treatment, lower Ks and longer CLT values were associated with increased sP-selectin (β −0.27 [95% CI -0.44 to −0.10] and β 0.21 [95% CI 0.01 to 0.41]; both p < 0.05, respectively) also after adjustment for potential confounders. sP-selectin, alongside fibrin features and other variables at baseline showed no association with lipid profile. On high-dose statin therapy, there was 32% reduction in sP-selectin levels (p < 0.001). On-treatment change (Δ) in sP-selectin correlated with ΔKs and ΔCLT (r = −0.32, p < 0.001 and r = 0.22, p = 0.011, respectively), but not with cholesterol and C-reactive protein lowering. We did not observe any associations between post-treatment sP-selectin levels and lipids, fibrin clot properties or thrombin generation. High-dose statin therapy reduces markedly sP-selectin levels in association with improved fibrin clot phenotype, which highlights the contribution of platelet-derived proteins to a prothrombotic state in hypercholesterolemia and statin-induced antithrombotic effects. • High-dose statin therapy reduce plasma sP-selectin concentrations in CAD patients. • Decrease of sP-selectin is associated with the improvement in fibrin clot properties. • Platelet-related statin effect is independent from cholesterol lowering. [ABSTRACT FROM AUTHOR]

BACKGROUND: Meniscus plays a key role in the biomechanics and cartilage protection of knee joint, and has multiple functions such as shock absorption, maintaining the stability of the knee joint force line, and reducing the wear and tear of articular cartilage. So far, the effect of surgical repair of meniscal nonblood supply area injury has been poor. If only meniscectomy is performed, the change of the overall mechanical structure of knee joint is easy to accelerate the progress of knee osteoarthritis. Therefore, in recent years, scholars are trying to use different ways to assist the repair of meniscus injury, in order to improve the prognostic effect of meniscal non-blood supply area injuries suture and slow down the progress of knee osteoarthritis. OBJECTIVE: To summarize the repair treatment of meniscus injury for non-blood supply area in recent years, and look forward to the future development prospect and challenges in this field. METHODS: CNKI, Wanfang, PubMed, and FMRS databases were used for literature retrieval. The retrieval range was from 2005 to 2021. All articles related to meniscus injury repair, including clinical research and tissue engineering research, were included. Finally, 60 articles were included for analysis. RESULTS AND CONCLUSION: (1) Due to the special anatomical structure of the meniscus, there is a problem of poor blood supply in two-thirds of the medial area of the meniscus, which is difficult to heal after injury. The current methods of auxiliary meniscus injury repair include: microfracture, subpatellar fat pad crushing, mesenchymal stem cells, platelet-rich plasma, and fibrin clot. (2) Different repair methods have their own advantages and disadvantages. As clinical application methods, microfracture and comminution of subpatellar fat pad are easy to operate, but they may cause iatrogenic injury, postoperative pain, and osteoarthritis. Further fine operation to avoid injury is an inevitable topic in clinic. Although mesenchymal stem cells and platelet-rich plasma have shown good effects in basic research, their preparation methods are diverse, their application methods are not fixed, and platelet-rich plasma even has completely opposite clinical effects in clinical application. Therefore, further studying the mechanism of mesenchymal stem cells and platelet-rich plasma to improve meniscus repair potential and standardizing its preparation process and application method are still the next research direction. (3) Fibrin clot has shown good results in clinical application, but there is still a lack of more relevant research. (4) In conclusion, there are still few research contents on fibrin clot technology and comminution of subpatellar fat pad, while platelet-rich plasma has appeared polarization in clinical manifestations. Microfracture and clinical application of synovial mesenchymal stem cells are stable, which is a good supplementary method at present. [ABSTRACT FROM AUTHOR]

Fibrinogen conversion into insoluble fibrin and the formation of a stable clot is the final step of the coagulation cascade. Fibrin clot porosity and its susceptibility to plasmin-mediated lysis are the key fibrin measures, describing the properties of clots prepared ex vivo from citrated plasma. Cardiovascular disease (CVD), referring to coronary heart disease, heart failure, stroke, and hypertension, has been shown to be associated with the formation of dense fibrin networks that are relatively resistant to lysis. Denser fibrin mesh characterized acute patients at the onset of myocardial infarction or ischaemic stroke, while hypofibrinolysis has been identified as a persistent fibrin feature in patients following thrombotic events or in those with stable coronary artery disease. Traditional cardiovascular risk factors, such as smoking, diabetes mellitus, hyperlipidaemia, obesity, and hypertension, have also been linked with unfavourably altered fibrin clot properties, while some lifestyle modifications and pharmacological treatment, in particular statins and anticoagulants, may improve fibrin structure and function. Prospective studies have suggested that prothrombotic fibrin clot phenotype can predict cardiovascular events in short- and long-term follow-ups. Mutations and splice variants of the fibrinogen molecule that have been proved to be associated with thrombophilia or increased cardiovascular risk, along with fibrinogen post-translational modifications, prothrombotic state, inflammation, platelet activation, and neutrophil extracellular traps formation, contribute also to prothrombotic fibrin clot phenotype. Moreover, about 500 clot-bound proteins have been identified within plasma fibrin clots, including fibronectin, α2-antiplasmin, factor XIII, complement component C3, and histidine-rich glycoprotein. This review summarizes the current knowledge on the mechanisms underlying unfavourable fibrin clot properties and their implications in CVD and its thrombo-embolic manifestations. [ABSTRACT FROM AUTHOR]

Changes in coagulation and fibrinolysis have been reported in women undergoing controlled ovarian hyperstimulation (COH) supporting a potential hypercoagulable condition related to this treatment. This study aimed at evaluating the changes in fibrin clot properties and thrombin generation induced by two different COH protocols: long with gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant). Primary outcomes included determination of plasma fibrin clot properties, including clot permeability (Ks) and efficiency of fibrinolysis using clot lysis time (CLT), along with thrombin generation (prothrombin fragments 1 + 2) and endogenous thrombin potential (ETP) and fibrinolysis inhibitor levels. One hundred twenty-nine infertile women were included in the final analysis. The GnRH-ant protocol resulted in increased ETP (+ 9.8%) and reduced Ks (− 2.4%). Conversely, COH with the GnRH-a protocol reduced thrombin generation by decreasing both ETP (− 6.6%) and F1 + 2 (− 30.8%) together with favorably altered fibrin clot properties represented by increased Ks (+ 21.7%) and reduced CLT (− 13.8%) as well as decreased PAI-1 levels (by 2.5 times). The GnRH-ant compared to the GnRH-a protocol increased PAI-1 levels (+ 77.3%), thrombin generation (9.3% higher ETP), and Ks (+ 13.7%). In the GnRH-a group, post-COH Ks was 14.3% higher (Ks ≥ 7.92 × 10−9 cm2) in women with positive vs. negative pregnancy outcomes. Our results show that the GnRH-ant protocol enhanced thrombin generation and slightly decreased fibrin clot density. COH with the GnRH-a reduced thrombin generation and improved fibrin clot features. This trial was registered (NCT04166825). Clinical Trial Registration Number: NCT04166825. [ABSTRACT FROM AUTHOR]

[Display omitted] Fibrin clots are crucial for hemostasis and the healing of wounds; nevertheless, excessive blood clotting plays an important role in many chronic diseases, including cardiovascular disease. In this study, we demonstrated the effect of the prepared AuNPs@PANI core/shell on the formed fibrin network. The synthesis of nanoparticles combining electrically conducting polymers polyaniline (PANI) and gold nanoparticles (AuNPs) is an appealing field of research currently because of their physical features and prospective applications in biochemistry. AuNPs showed surface plasmonic resonance (SPR) properties in the visible region at 520 nm then, after coating with PANI, there was a dramatic red shift to 610 nm. The morphological conformation was confirmed by characterization at the microscopic (TEM, SEM, EDX). The PANI shell plays a crucial role in this system, first enhances the stability of AuNPs core; also, the surface of the PANI shell has positive charges (zeta potential = +17.8 mV), leading to electrostatic interactions with fibrin clots that have negatively charged surfaces. The synthesized core/shell AuNPs@PANI showed good efficiency for degrading fibrin networks under 1:30 h of irradiation by an external source of laser light, which is a result of AuNPs' ability to absorb light at 520 nm. The degradation of fibrin was observed using a scanning electron microscope (SEM), which showed a clear change in the shape of the network. The appearance of fibrous endings and gaping indicates the beginning of the degradation and melting of the fibrin network in different sites of the clot. Overall, this method could have a major influence on disease states, for example, deep vein thrombosis, through a localized, catheter-based approach. [ABSTRACT FROM AUTHOR]

Postthrombotic syndrome (PTS), a common complication of deep vein thrombosis (DVT), is largely inflammatory by nature with contribution of prothrombotic mechanisms. The role of factor (F)XI in PTS has not been explored yet. We investigated whether elevated FXI is associated with PTS occurrence. We enrolled 180 consecutive patients (aged 43 ± 13 years) with first-ever DVT. After 3 months FXI levels were measured, along with inflammatory markers, thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis proteins. We assessed PTS using the Villalta score and recorded symptomatic venous thromboembolism (VTE) at a 1-year and venous ulcers at a median 53 months follow-up. Baseline median FXI was 102 % [IQR 92–113 %] and showed positive association with Villalta score (R = 0.474, P < 0.001). Patients with PTS (n = 48, 26.7 %) had 16.1 % higher FXI (P < 0.001) and FXI ≥120 % occurred more often in PTS patients (odds ratio [OR] 5.55, 95 % confidence interval [CI] 2.28–13.47). There were associations of baseline FXI with Ks and CLT along with thrombin activatable fibrinolysis inhibitor (TAFI) activity, C-reactive protein, and interleukin-6, but not with fibrinogen, or thrombin generation. After age adjustment higher FXI was independently associated with PTS occurrence (OR per 1 % 1.06, 95 % CI 1.02–1.09) and VTE recurrence (OR 1.03, 95 % CI 1.01–1.06). At long-term follow-up, patients with venous ulcers had 13.6 % higher baseline FXI (P = 0.002). Elevated FXI in association with inflammation and prothrombotic fibrin clot properties may contribute to the development of PTS following DVT. • Elevated FXI 3 months after deep vein thrombosis predisposes to PTS occurrence. • Higher FXI is associated with VTE recurrence and venous ulcers development. • Higher FXI is correlated with denser fibrin clot structure and impaired fibrinolysis. [ABSTRACT FROM AUTHOR]

Directly acting fibrinolytic enzyme is found to be superior therapy for treatment of cardiovascular diseases. Hence, there is a need of a novel and highly potent fibrinolytic agent which can directly degrade fibrin clot in lesser time with improved specificity and overcome shortcomings of haemorrhage. Amongst various sources, microbial fibrinolytic enzymes have attracted attention of research community so the present study aimed to isolate fibrinolytic enzymeproducing bacteria from different soil samples. Caseinolytic activity and clot lyses activity of the crude enzyme produced by these isolates were determined. All together six caseinolytic organisms were isolated, 3 of them produced fibrinolytic protease which would lyse fibrin and whole blood clot. Caseinolytic activity in the crude enzyme preparation from Colony C4 was detected to be 78.2 U/ml and was able to lyse 85.54% of whole blood clot in 90 mins. Colony 4 may be of potential interest for biotechnological use as it produces fibrinolytic proteases that degraded fibrin clot and the whole blood clot, to the maximum. [ABSTRACT FROM AUTHOR]

Enhanced oxidative stress occurs in atrial fibrillation (AF), however its impact on the efficacy and safety of anticoagulation is unknown. We sought to evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels are associated with clinical outcomes in anticoagulated AF patients. In a study involving 243 AF patients (median age 69 years), we measured serum 8-isoprostane, along with prothrombotic markers, including plasma fibrin clot permeability, clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolytic proteins. Ischemic cerebrovascular events, major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, largely on non-vitamin K antagonist oral anticoagulants (NOACs). Increased 8-isoprostane levels were observed in women, in patients with arterial hypertension, and those with paroxysmal or persistent AF. Patients with 8-isoprostane levels ≥559 pg/mL (the top quartile) compared with those with 8-isoprostane <250 pg/mL (the bottom quartile) had higher fibrinogen, lower VWF, higher plasminogen activator inhibitor 1 , along with lower fibrin clot permeability with no difference in CHA 2 DS 2 -VASc score, CLT or ETP. Patients who experienced thromboembolic events (n = 20, 1.9%/year) had 48.6% higher 8-isoprostane concentrations compared to the remainder (P <0.01). Levels of 8-isoprostane >459 pg/mL based on the optimal cut-off value were associated with thromboembolic events during follow-up (hazard ratio 2.87, 95% confidence interval 1.17–7.03, P = 0.02). There were no associations between 8-isoprostane and major bleeding (2.0%/year) or all-cause mortality (1.9%/year). Increased 8-isoprostane levels partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients. • Increased 8-isoprostane levels, associated with prothrombotic fibrin clot phenotype, characterized anticoagulated AF patients • Increased 8-isoprostane levels are independently predicted thromboembolic events during long-term follow-up • 8-isoprostane levels were not associated with major bleeding or all-cause mortality [ABSTRACT FROM AUTHOR]

Prostacyclin (PGI2) analogues (epoprostenol, treprostonil, iloprost) are the cornerstone of pulmonary arterial hypertension (PAH) treatment. PGI2 analogues inhibit platelet reactivity, but their impact on coagulation and fibrinolysis parameters has not been elucidated. We compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in patients with PAH treated with PGI2 analogues (n = 20) and those not receiving PGI2 analogues (n = 20). Platelet reactivity was lower in patients treated with PGI2 analogues, compared to the control group, as evaluated with arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor-activating peptide-6 (TRAP) tests (p =.009, p =.02, p =.007, respectively). In the subgroup analysis, both treprostinil and epoprostenol decreased platelet reactivity to the similar extent. There were no differences regarding thrombin generation, clot permeation, and lysis parameters in patients receiving and not receiving PGI2 analogues (p ≥.60 for all). In the subgroup analysis, there were no differences regarding coagulation and fibrinolysis parameters between treprostinil, epoprostenol, and no PGI2 analogues. To conclude, patients with PAH treated with PGI2 analogues have reduced platelet reactivity, but similar clot formation and lysis parameters, compared to patients not receiving PGI2 analogues. Further randomized clinical trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Three per cent hydrogen peroxide (H2O2) is widely used to irrigate acute and chronic wounds in the surgical setting and clinical experience tells us that it is more effective at removing dried-on blood than normal saline alone. We hypothesise that this is due to the effect of H2O2 on fibrin clot architecture via fibrinolysis. We investigate the mechanisms and discuss the clinical implications using an in vitro model. Coagulation assays with normal saline (NaCl), 1% and 3% concentrations of H2O2 were performed to determine the effect on fibrin clot formation. These effects were confirmed by spectrophotometry. The effects of 1%, 3% and 10% H2O2 on the macroscopic and microscopic features of fibrin clots were assessed at set time intervals and compared to a NaCl control. Quantitative analysis of fibrin networks was undertaken to determine the fibre length, diameter, branch point density and pore size. Fibrin clots immersed in 1%, 3% and 10% H2O2 demonstrated volume losses of 0.09-0.25mm3/min, whereas those immersed in the normal saline gained in volume by 0.02±0.13 mm3/min. Quantitative analysis showed that H2O2 affects the structure of the fibrin clot in a concentration-dependent manner, with the increase in fibre length, diameter and consequently pore sizes. Our results support our hypothesis that the efficacy of H2O2 in cleaning blood from wounds is enhanced by its effects on fibrin clot architecture in a concentration- and time-dependent manner. The observed changes in fibre size and branch point density suggest that H2O2 is acting on the quaternary structure of the fibrin clot, most likely via its effect on cross-linking of the fibrin monomers and may therefore be of benefit for the removal of other fibrin-dependent structures such as wound slough.

Fungi fibrinolytic compound 1 (FGFC1) is a rare pyran-isoindolone derivative with fibrinolytic activity. The aim of this study was to further determine the effect of FGFC1 on fibrin clots lysis in vitro. We constructed a fibrinolytic system containing single-chain urokinase-type plasminogen activator (scu-PA) and plasminogen to measure the fibrinolytic activity of FGFC1 using the chromogenic substrate method. After FITC-fibrin was incubated with increasing concentrations of FGFC1, the changes in the fluorescence intensity and D-dimer in the lysate were measured using a fluorescence microplate reader. The fibrin clot structure induced by FGFC1 was observed and analyzed using a scanning electron microscope and laser confocal microscope. We found that the chromogenic reaction rate of the mixture system increased from (15.9 ± 1.51) × 10−3 min−1 in the control group to (29.7 ± 1.25) × 10−3 min−1 for 12.8 μM FGFC1(p < 0.01). FGFC1 also significantly increased the fluorescence intensity and d-dimer concentration in FITC fibrin lysate. Image analysis showed that FGFC1 significantly reduced the fiber density and increased the fiber diameter and the distance between protofibrils. These results show that FGFC1 can effectively promote fibrin lysis in vitro and may represent a novel candidate agent for thrombolytic therapy. [ABSTRACT FROM AUTHOR]

The general anticoagulant evaluation requires high expense equipment, reagents, and space. Therefore, not all laboratories can perform research related to anticoagulant. In this study, we propose a novel simple method "in vitro thrombus-growth model" that can evaluate anticoagulant ability by measuring weight. The in vitro thrombus-growth model is prepared by creating a "growthclot" with citrate plasma, calcium chloride, and thrombin, and then pouring new citrate plasma onto it. The prepared growth-clots were increased in volume in citrated human plasma, including surpluses calcium chloride, which was released slowly, leading to clot coagulation around the plasma. As a result of evaluating the anticoagulant ability of direct thrombin inhibitor using this in vitro thrombus-growth model, it was confirmed that clot growth was suppressed in a concentrationdependent manner. Therefore, this thrombus-growth model is useful as a primary anticoagulant test that can to discover compounds with anticoagulant activity perform in any laboratory. [ABSTRACT FROM AUTHOR]

Purpose: Orthopedic literature remains divided on the utility of biologic augmentation to optimize outcomes after isolated meniscal repair. The aim of this systematic review is to analyze the clinical outcomes and re-operation rates of biologically augmented meniscal repairs.Methods: PubMed, CINAHL, Cochrane, and EMBASE databases were queried in October 2020 for published literature on isolated meniscal repair with biological augmentation. Studies were assessed for quality and risk of bias by two appraisal tools. Patient demographics, meniscal tear characteristics, surgical procedure, augmentation type, post-operative rehabilitation, patient reported outcome measures, and length of follow-up were recorded, reviewed, and analyzed by two independent reviewers.Results: Of 3794 articles, 18 met inclusion criteria and yielded 537 patients who underwent biologic augmentation of meniscal repair. The biologically augmented repair rates were 5.8-27.0% with PRP augmentation, 0.0-28.5% with fibrin clot augmentation, 0.0-12.9% with marrow stimulation, and 0.0% with stem cell augmentation. One of seven studies showed lower revision rates with augmented meniscal repair compared to standard repair techniques, whereas five of seven found no benefit. Three of ten studies found significant functional improvement of biologically augmented repair versus standard repair techniques and six of ten studies found no difference. There was significant heterogeneity in methods for biologic preparation, delivery, and post-operative rehabilitation protocols.Conclusion: Patients reported significant improvements in functional outcomes scores after repair with biological augmentation, though the benefit over standard repair controls is questionable. Revision rates after biologically augmented meniscal repair also appear similar to standard repair techniques. Clinicians should bear this in mind when considering biologic augmentation in the setting of meniscal repair.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

Obesity is associated with increased serum fibrinogen level. Myostatin (MSTN), a strong inhibitor of skeletal muscle growth, is recognized as a potential target for obesity. However, the effect of MSTN inhibition on fibrinogen is not largely known. The objective of the present study was to explore fibrinogen levels after MSTN inhibition. Fibrinogen levels and the fibrin clot structure of MSTN homozygous knockout (KO) and wild‐type (WT) pigs (n = 4 in each group) were investigated. The protein expression of fibrinogen in the serum and liver of KO pigs decreased greatly (1.6‐fold loss for serum and 2.5‐fold loss for liver). KO pigs showed significantly decreased gene expression of fibrinogen chains: FGA (fibrinogen‐α; 11‐fold), FGB (fibrinogen‐β; 8‐fold) and FGG (fibrinogen‐γ; 7.4‐fold). The basal transcriptional regulators of fibrinogen, HNF1 (hepatocyte nuclear factor 1) and CEBP‐α (CCAAT/Enhancing‐binding protein‐alpha) were remarkably down‐regulated after interruption of MSTN expression by siRNA (small interfering RNA) in cultured hepatocytes (about 2‐ and 4‐fold, respectively). Compared with WT pigs, KO pigs displayed altered fibrin clot structure with thinner fibers, decreased turbidity and increased permeability. The findings indicate that the inhibition of MSTN could affect fibrinogen levels and the fibrin clot structure. [ABSTRACT FROM AUTHOR]

Spontaneous echo contrast (SEC) and left atrial appendage thrombus (LAAT) increase the risk of stroke and its severity in patients with atrial fibrillation (AF). Formation of denser fibrin networks and impaired fibrinolysis are associated with stroke risk in AF. This study investigated whether the prothrombotic fibrin clot phenotype characterizes patients with SEC/LAAT. We studied 139 anticoagulated patients with AF (median age, 70 years), who underwent transesophageal echocardiography (TEE). SEC and LAAT were recorded. We assessed plasma fibrin clot properties, i.e. permeability (K s) and clot lysis time (CLT), von Willebrand Factor (vWF) antigen, endogenous thrombin potential (ETP), proteins involved in thrombosis and fibrinolysis, as well as plasma carbonylated protein content (PC). SEC/LAAT was identified in 36 subjects (25.9 %) and was associated with heart failure (HF), AF duration, higher CHA 2 DS 2 VASc score, N-terminal prohormone of brain natriuretic peptide, and growth differentiation factor 15. Patients with SEC/LAAT had lower K s (−15 %) and prolonged CLT (+19 %), along with higher fibrinogen (+24 %), ETP (+3 %), and plasminogen activator inhibitor-1 antigen (+16 %) compared with the remainder. Thrombin-activatable fibrinolysis inhibitor antigen, plasminogen, α 2 − antiplasmin, and tissue plasminogen activator antigen were similar between the two groups. PC content was 50 % higher in SEC/LAAT and correlated with Ks (r = −0.47, p < 0.001) and CLT (r = 0.40, p < 0.001). On multivariate analysis, Ks, CLT, and PC levels, along with HF, remained independently associated with SEC/LAAT. We demonstrated a formation of denser and poorly lysable fibrin networks in AF patients with SEC/LAAT despite anticoagulation. We suggest that this phenomenon is in part related to enhanced oxidative stress. • Mechanisms behind spontaneous echo contrast/left atrial appendage thrombus (SEC/LAAT) are unclear. • SEC/LAAT in atrial fibrillation (AF) is associated with formation of denser, lysis-resistant fibrin clots. • Enhanced protein carbonylation occurs in patients with SEC/LAAT. • A prothrombotic fibrin clot phenotype, linked to oxidative stress, predisposes to SEC/LAAT in AF despite anticoagulation. [ABSTRACT FROM AUTHOR]

The kinetics of fibrin clot destruction under catheter-delivered 32- to 45-kHz ultrasound (US) has been studied at 36°C-38°C in isotonic saline solution. A pseudo-first-order rate constant increased linearly from 0.06/min to 0.57/min with increasing US intensity I0 from 21.6 to 51.2 W/cm2. At I0 = 4.4 and 11.4 W/cm2, the degree of clot destruction did not exceed 11%-15% regardless of the time of US exposure. Starting from I0 = 21.6 W/cm2, the maximum achievable level of clot destruction increased linearly with US intensity, reaching 68% at I0 = 51.2 W/cm2 after 3 min of US exposure. Thus, US intensity is a key parameter determining the maximum achievable level of clot destruction. However, an increase in US intensity above 30 W/cm2 is limited by the intensified negative sonochemical effect on the enzymatic system of hemostasis caused by an increase in inertial cavitation. The best effect can be achieved with ultrasound of a sufficiently high intensity that ensures a large contribution of stable cavitation, generating microstreaming flows, and a minimum contribution of inertial cavitation, generating microjets and shock waves. [ABSTRACT FROM AUTHOR]

Background: Prothrombotic fibrin clot properties, including increased clot density, are in part genetically determined. We investigated whether fibrinogen alpha‐chain gene (FGA) c.991A>G (rs6050), fibrinogen beta chain gene (FGB) −455G>A (rs1800790) and factor XIII gene (F13) c.103G>T (rs5985) polymorphisms affect plasma fibrin clot properties in patients with acute pulmonary embolism (PE). Methods: As many as 126 normotensive patients with PE, free of cancer, were genotyped by TaqMan assay. Fibrin clot permeability (Ks), clot lysis time (CLT) and endogenous thrombin potential (ETP) were assessed on admission. Results: The minor allele frequencies were as follows: FGA rs6050 (n = 62, 0.31), FGB rs1800790 (n = 40, 0.17) and F13 rs5985 (n = 49, 0.23). There were no differences related to any of the polymorphisms with regard to demographic, clinical and laboratory data, except for fibrinogen concentration, which was higher in carriers of F13 rs5985 polymorphism (p =.024), and PE combined with deep‐vein thrombosis, which was less prevalent in FGB rs1800790 polymorphism carriers (p =.004). Carriers of FGB rs1800790 A allele and F13 rs5985 T allele had lower Ks, prolonged CLT and higher ETP compared with major homozygotes (all p <.05). After adjustment for fibrinogen, all differences remained significant (all p <.01). There were no associations between the FGA rs6050 polymorphism and Ks, CLT or ETP. Conclusion: Our study showed that FGB rs1800790 and F13 rs5985 polymorphisms contribute to the prothrombotic fibrin clot phenotype and these effects are strong enough to be observed in the acute phase of PE. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with type 2 diabetes mellitus (T2DM) are at high risk of cardiovascular mortality, but the mechanisms behind this remain unclear. Prothrombotic fibrin clot properties have been shown in T2DM and cardiovascular disease. We hypothesized that formation of denser clots, which are resistant to fibrinolysis, has a negative impact on cardiovascular mortality in T2DM. Methods We studied 133 T2DM patients aged 43–83 years. Plasma fibrin clot turbidity, permeation, compaction, and efficiency of clot lysis using 3 assays including the determination of maximum concentration (D-Dmax) and rate of increase in D-dimer concentration (D-Drate) released during tissue plasminogen activator-induced degradation, were evaluated at the time of enrollment, along with thrombin generation and fibrinolytic proteins. During a median follow-up period of 72 months, cardiovascular mortality was recorded. Results Cardiovascular deaths (n = 16, 12%) occurred more frequently in patients with increased D-Dmax (> 4.26 mg/l, hazard ratio [HR] 5.43, 95% confidence interval [CI] 1.99–14.79), or decreased D-Drate ( 283.5 nM, HR 5.65, 95% CI 2.07–15.51). These predictors had an even more potent impact on cardiovascular mortality in patients with prior cardiovascular disease (64.7%) and with corresponding risks as follows: HR 6.18, 95% CI 2.02–18.96; HR 8.98, 95% CI 2.99–26.96; and HR 5.35, 95% CI 1.62–17.72, respectively. Other investigated fibrin variables and fibrinolytic proteins did not associate with cardiovascular mortality. In multivariable analysis, cardiovascular mortality was predicted by D-Dmax > 4.26 mg/l, age > 65 years, prior cardiovascular disease, and C-reactive protein > 3 mg/l. Conclusions This study is the first to show that formation of denser fibrin clots resistant to fibrinolysis could be a risk factor for long-term cardiovascular mortality in T2DM.

Abstract Background In the fibrin‐forming process, thrombin cleaves fibrinogen to fibrin, which form fibrils and then fibers, producing a gel‐like clot. Thrombin also activates coagulation factor XIII (FXIII), which crosslinks fibrin γ‐chains and α‐chains, stabilizing the clot. Many proteins bind to fibrin, including FXIII, an established regulation of clot structure, and platelet glycoprotein VI (GPVI), whose contribution to clot function is largely unknown. FXIII is present in plasma, but the abundant FXIII in platelet cytosol becomes exposed to the surface of strongly activated platelets. Objectives We determined if GPVI interacts with FXIII and how this might modulate clot formation. Methods We measured interactions between recombinant proteins of the GPVI extracellular domain: GPVI‐dimer (GPVI‐Fc2) or monomer (GPVIex) and FXIII proteins (nonactivated and thrombin‐activated FXIII, FXIII subunits A and B) by ELISA. Binding to fibrin clots and fibrin γ‐chain crosslinking were analyzed by immunoblotting. Results GPVI‐dimer, but not GPVI‐monomer, bound to FXIII. GPVI‐dimer selectively bound to the FXIII A‐subunit, but not to the B‐subunit, an interaction that was decreased or abrogated by the GPVI‐dimer–specific antibody mFab‐F. The GPVI‐dimer–FXIII interaction decreased the extent of γ‐chain crosslinking, indicating a role in the regulation of clot formation. Conclusions This is the first report of the specific interaction between GPVI‐dimer and the A‐subunit of FXIII, as determined in an in vitro system with defined components. GPVI‐dimer–FXIII binding was inhibitory toward FXIII‐catalyzed crosslinking of fibrin γ‐chains in fibrin clots. This raises the possibility that GPVI‐dimer may negatively modulate fibrin crosslinking induced by FXIII, lessening clot stability.

Background: Post–pulmonary embolism (PE) syndrome occurs in up to 50% of PE patients. The pathophysiology of this syndrome is obscure. Objective: We investigated whether enhanced oxidative stress and prothrombotic state may be involved in post‐PE syndrome. Methods: We studied 101 normotensive noncancer PE patients (aged 56.5 ± 13.9 years) on admission, after 5‐7 days and after a 3‐month anticoagulation, mostly with rivaroxaban. A marker of oxidative stress, 8‐isoprostane, endogenous thrombin potential, fibrinolysis proteins, clot lysis time (CLT) and fibrin clot permeability (Ks), along with PE biomarkers, were determined. Results: Patients who developed the post‐PE syndrome (n = 31, 30.7%) had at baseline 77.6% higher N‐terminal brain natriuretic propeptide and 46.8% higher growth differentiation factor 15, along with 14.1% longer CLT associated with 34.4% higher plasminogen activator inhibitor‐1 as compared to subjects without post‐PE syndrome (all P <.05). After 5‐7 days, only hypofibrinolysis was noted in post‐PE syndrome patients. When measured at 3 months, prolonged CLT and reduced Ks were observed in post‐PE syndrome patients, accompanied by 23.8% higher growth differentiation factor 15 and 35.8% higher plasminogen activator inhibitor‐1 (all P <.05). 8‐isoprostane levels ≥108 pg/ml (odds ratio=4.36; 95% confidence interval 1.63‐12.27) and growth differentiation factor 15 ≥ 1529 pg/ml (odds ratio=3.89; 95% confidence interval 1.29‐12.16) measured at 3 months were associated with higher risk of developing post‐PE syndrome. Conclusions: Enhanced oxidative stress and prothrombotic fibrin clot properties could be involved in the pathogenesis of the post‐PE syndrome. Elevated growth differentiation factor 15 assessed at 3 months might be a new biomarker of this syndrome. [ABSTRACT FROM AUTHOR]

Background and Aim: Smear layer removal and formation of a stable bond between the blood clot and root surface are desirable for periodontal healing, which can be achieved by root biomodifiers. The objective of this in-vitro study was to evaluate the root surface changes in terms of fibrin clot adhesion subsequent to the application of MTAD (mixture of doxycycline (a tetracycline isomer), citric acid, and polysorbate-80 (a detergent) and normal saline. Materials and Methods: Twenty human single-rooted teeth were collected and grouped into Saline (Group I) and MTAD Biopure (Group II) treatment groups containing 10 teeth in each group. After root conditioning, fresh human blood was applied to each root specimen and was allowed to clot, and subsequently, samples were dehydrated in a graded series of ethanol and visualized under scanning electron microscope. Results: The highest blood clot attachment score was observed with roots treated with MTAD and the least results were observed with control group saline. Conclusion: Specimens treated with MTAD best supported the fibrin clot attachment. Saline was least effective of all the samples, showing the presence of the smear layer.

Background: This study aimed to determine the histological, biochemical, and biomechanical efficacy of fibrin clot and vitamin C in the healing of Achilles tendon ruptures (ATR) in a rat model.Methods: 52 adult Wistar-Albino rats (300-450 g) were used in the study. 12 rats were divided into four groups as Monitor (Group I), Control (Group II), Fibrin Clot (Group III), Fibrin Clot with vitamin C (Group IV). Four rats were used for fibrin clot preparation. Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) were measured on the 3rd, 7th, 14th, and 21st days. Four rats were sacrificed on the 21st day from each group for histological evaluation. The rest of the rats were sacrificed at 42nd day, half for biomechanical and a half for histological evaluation.Results: The 42nd-day HSS score of group IV was significantly lower than those of group I, group II and group III (p = 0.036, p = 0.019, and p = 0.036, respectively). Group IV showed a significantly higher Maximum force N value than those of group I, group II and group III (p = 0.034, p = 0.034 and, p = 0.025, respectively). The blood FGF and VEGF levels of group III and group IV on the 3rd, 7th, 14th, and 21st days were higher than those of group I and group II (p < 0.05).Conclusion: Fibrin clot and vitamin C produced a stronger tendon structure in terms of biomechanics while providing histological and biochemically better quality tendon healing in the surgical treatment of ATR. This model can be used to accelerate high-quality tendon healing after ATR.Level Of Evidence: Level II, experimental study. [ABSTRACT FROM AUTHOR]

Is there a difference in fibrin clot phenotype in women with endometriosis before and after ovarian stimulation? Prospective study including 73 infertile women in two age-matched groups: (i) with confirmed endometriosis (n = 29); (ii) without endometriosis (n = 44). Assessments of plasma fibrin clot permeability (K s), efficiency of fibrinolysis using clot lysis time (CLT), along with thrombin generation (prothrombin fragments 1+2 [F1+2] and endogenous thrombin potential [ETP]) and fibrinolysis inhibitors were performed together with clinical pregnancy rate. Endometriosis was associated with increased thrombin generation, reflected by both higher F1+2 (+96.1%, P = 0.005) and ETP (+14.2%, P = 0.014) along with unfavourably altered fibrin clot properties represented by lower K s (–31%, P < 0.001) and prolonged CLT (+13.5%, P = 0.02), compared with the non-endometriosis group. Moreover, women with endometriosis had higher plasminogen activator inhibitor-1 (PAI-1; +272%, P = 0.004) concentrations and alpha-2-antiplasmin activity (+39.9%, P < 0.001) in contrast to the other group. Ovarian stimulation led to reduction in F1+2 (–48.1%, P < 0.001), improvement of fibrin clot phenotype reflected by higher K s (+25.9%, P < 0.001) and shortened CLT (–11.9%, P < 0.001), along with lower PAI-1 (–54%, P = 0.016) compared with the baseline in women with endometriosis. Endometriosis is associated with the prothrombotic fibrin clot phenotype and increased thrombin generation. Ovarian stimulation favourably alters fibrin clot properties and leads to comparable pregnancy outcomes to those in women without endometriosis. [ABSTRACT FROM AUTHOR]

In acute pulmonary embolism (PE) right ventricular (RV) pressure overload negatively affects prognosis. Recently we have shown that RV dilatation is associated with a prothrombotic state in PE. We investigated which RV echocardiographic parameters best indicate prothrombotic alterations in acute PE. In 121 normotensive, noncancer PE patients, markers of RV dilatation and dysfunction were evaluated on admission using transthoracic echocardiography, along with prothrombotic state markers, i.e. increased endogenous thrombin generation (ETP), low fibrin clot permeability (K s , a measure of clot density), and prolonged clot lysis time (CLT). RV parasternal long axis (RVOT PLAX) >30 mm was associated with ETP (OR 3.86; 95% CI 1.55–9.62; p = 0.004) and CLT (OR 4.08; 95% CI 1.58–10.54; p = 0.004) in the top quartiles, but not with K s. RV short parasternal axis (RVOT PSAX) >27 mm showed similar associations with higher ETP (OR 3.54; 95% CI 1.50–8.37; p = 0.004) and prolonged CLT (OR 2.78; 95% CI 1.17–6.62; p = 0.021). RV basal diameter >41 mm solely predicted prolonged CLT (OR 2.93; 95% CI 1.23–6.99; p = 0.016). The right atrium area, pulmonary trunk diameter, and tricuspid regurgitation maximum velocity were not related to prothrombotic markers, except for tricuspid annular plane systolic excursion weakly associated with ETP. Multivariable analysis showed that RVOT PSAX is independently associated with prolonged CLT (OR 1.16; 95% CI 1.04–1.30; p = 0.007), low K s (OR 1.21; 95% CI 1.02–1.44; p = 0.029), and higher ETP (OR 1.14; 95% CI 1.03–1.26; p = 0.009). Among RV echocardiographic parameters, the RVOT dilatation measured in PSAX best predicts prothrombotic alterations in PE patients. • Association between RV echocardiographic parameters and markers of hypercoagulability in patients with acute PE were evaluated. • RV dilatation measured in PSAX and PLAX, but not TAPSE, can predict a prothrombotic state in normotensive PE patients. • RV basal diameter measured in the A4C view was related only to impaired clot lysability. • The current findings extended available data on the factors affecting prothrombotic features detected in acute PE. [ABSTRACT FROM AUTHOR]

The results of the ultrasound follow-up investigation of clotting process are presented. Phase shift between probing signal and signal passed through the sample was measured as function of time when the internal and external ways of blood coagulation were activated.

Abstract Background Type 2 diabetes mellitus (T2DM) is associated with a hypercoagulable state and increased neutrophil extracellular traps formation (NETosis). We investigated predictors of NETosis and cell death markers in circulating blood and their association with a prothrombotic state in T2DM. Methods In a cross-sectional study involving 113 T2DM patients aged 63.7 ± 8.2 years, we investigated citrullinated histone H3 (H3Cit), cell-free deoxyribonucleic acid (cfDNA), myeloperoxidase, neutrophil elastase, and inflammation markers, along with thrombin generation (TG), plasma clot lysis time (CLT), clot permeability (Ks) and fibrinolysis inhibitors. Results On multivariate logistic regression analysis adjusted for age and gender, predictors of high H3Cit (≥ 7.36 ng/mL, upper quartile) were: glycated hemoglobin (HbA1c) ≥ 7.0% and interleukin-6. Interleukin-6 was also found to be a predictor of high cfDNA (≥ 2.84 µg/mL, upper quartile) along with glucose. Citrullinated histone H3 and cfDNA correlated positively with CLT and inversely with Ks, while TG associated solely with cfDNA. These associations were not seen with myeloperoxidase and neutrophil elastase. Patients with previous myocardial infarction (n = 21, 18.6%) had higher H3Cit (+108%, p

Fungi fibrinolytic compound 1 (FGFC1) is a rare pyran-isoindolone derivative with fibrinolytic activity. The aim of this study was to further determine the effect of FGFC1 on fibrin clots lysis in vitro. We constructed a fibrinolytic system containing single-chain urokinase-type plasminogen activator (scu-PA) and plasminogen to measure the fibrinolytic activity of FGFC1 using the chromogenic substrate method. After FITC-fibrin was incubated with increasing concentrations of FGFC1, the changes in the fluorescence intensity and D-dimer in the lysate were measured using a fluorescence microplate reader. The fibrin clot structure induced by FGFC1 was observed and analyzed using a scanning electron microscope and laser confocal microscope. We found that the chromogenic reaction rate of the mixture system increased from (15.9 ± 1.51) × 10−3 min−1 in the control group to (29.7 ± 1.25) × 10−3 min−1 for 12.8 μM FGFC1(p < 0.01). FGFC1 also significantly increased the fluorescence intensity and d-dimer concentration in FITC fibrin lysate. Image analysis showed that FGFC1 significantly reduced the fiber density and increased the fiber diameter and the distance between protofibrils. These results show that FGFC1 can effectively promote fibrin lysis in vitro and may represent a novel candidate agent for thrombolytic therapy.

Chronic kidney disease patients experience not only more frequent arterial and venous thrombosis but also hemorrhagic episodes. Tranexamic acid is an anti-fibrinolytic molecule that inhibits plasmin activation. It is used in hemorrhage cases (post-traumatic, gynecologic, or gastrointestinal bleeding). We report on an original case of tranexamic acid (Exacyl®) use in a peritoneal dialysis patient for gastrointestinal bleeding of unknown origin. The use of tranexamic acid led to the Tenckhoff catheter dysfunction because of fibrin clots in the dialysate. The emergence of fibrin clots a few days after the start of tranexamic acid treatment, which never occurred again after the end of the treatment, and the anti-fibrinolytic function of tranexamic acid favors this treatment’s role in fibrin clot occurrence.