fibrin and Atrial-Fibrillation

Compelling evidence indicates that a hypercoagulable state occurs in patients with atrial fibrillation (AF) including those in sinus rhythm following paroxysmal and persistent AF. Activation of blood coagulation in AF reflects heightened thrombin generation with the subsequent increased formation of fibrin as evidenced by elevated soluble fibrin monomers and D-dimer. Formation of denser fibrin meshworks, relatively resistant to plasmin-mediated lysis has been demonstrated in patients with AF. The presence of stroke risk factors in AF, such as diabetes, heart failure, hypertension, previous myocardial infarction, or stroke, advanced age have been shown to be linked to the prothrombotic clot characteristics, including reduced clot permeability and lysability. Importantly, biomarkers, including cardiac troponins and N-terminal pro-brain natriuretic peptide, are associated with thrombin generation and fibrin-related markers in AF patients. Recently, increased fibrin clot density (low clot permeability measured in plasma-based assays) and impaired fibrinolysis measured off anticoagulation have been demonstrated to predict ischaemic cerebrovascular events in patients with AF receiving vitamin K antagonists and those on rivaroxaban. The current review summarizes evidence for a role of altered fibrin clot properties and hypofibrinolysis in AF and their prognostic value in terms of adverse events.

Topics: Atrial Fibrillation; Blood Coagulation; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Humans

A pre-thrombotic (hypercoagulable) state is observed in patients with thrombophilia, malignant diseases, pregnancy, auricular fibrillation, connective tissue diseases, prosthetic replacement arthroplasty, infection, or old age, and these states are also caused by dehydration, remaining in the same position for a long time, or estrogen drugs. Such patients have a high risk of developing thrombosis. The pre-thrombotic state is diagnosed or excluded by fibrin-related markers (FRMs), such as soluble fibrin (SF), fibrinogen and fibrin degradation products (FDP), and D-dimer. The cut-off values of FRMs are higher in patients with pregnancy or malignant diseases than in other patients. Patients with more than two of the eight underlying states and three causative factors for pre-thrombotic conditions or those with one of those conditions and high levels of FRMs are diagnosed as being in a prethrombotic state. These patients should receive treatment with anticoagulant therapy.

Topics: Anticoagulants; Atrial Fibrillation; Biomarkers; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Thrombosis

For thrombus formation, three important factors, blood flow, blood component and blood vessels, have been recognized as Virchow's triad. In cardiogenic embolism with atrial fibrillation, stagnation of blood in the left atrium causes fibrin-rich thrombus. Anticoagulation is the only effective drug for prevention of this type of thrombus. In atherothrombotic and lacunar infarction, injury of endothelium and arterial vessels and platelet play a crucial role of formation of platelet-rich thrombus. Antiplatelet drugs such as aspirin, clopidogrel and cilostazole are effective for prevention of arterial thrombus and stroke recurrence, but other drugs such as statin for plaque stabilization and improvement of endothelial function could be used to reduce the recurrence of ischemic stroke.

Topics: Anticoagulants; Atrial Fibrillation; Blood Platelets; Carotid Stenosis; Cerebral Infarction; Fibrin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Platelet Aggregation Inhibitors; Secondary Prevention; Thrombosis

Atrial fibrillation, an increasingly common arrhythmia whose prevalence will reach epidemic proportions over the next two decades, is characterized by atrial/atrial appendage inflammation, fibrosis, remodeling, and endocardial thrombosis. Biomarkers measured within the peripheral circulation reflect these pathobiologic events with evidence of heightened thrombin generation and activity, platelet activity, fibrin formation, endocardial injury, inflammatory mediator release, and reduced fibrinolytic potential Unfortunately, the correlation between traditional biomarkers and clinical events is weak at best, as is their ability to predict successful treatment (prevention of cardioembolism) with antithrombotic agents. Future efforts devoted to the investigation of cellular biomarkers will likely provide greater practical yield and insights concerning the development, diagnosis, prognosis, and management of atrial fibrillation.

Topics: Atrial Fibrillation; Biomarkers; Blood Platelets; Comorbidity; Electric Countershock; Embolism; Fibrin; Humans; Myocardium; Platelet Activation; Stroke; Thrombin

Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).. The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.. In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.. Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.. NCT00412984.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; Blood Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Risk Assessment; Stroke; Thrombin; Treatment Outcome; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin and heparins in several clinical situations. With varying modes of action, the effects of NOACs on thrombus formation, integrity, and lysis is unknown. To determine whether two techniques of thrombelastography (TEG) and a micro-plate assay (MPA) provide novel data on thrombus formation, integrity and lysis in those taking a NOACs compared to warfarin and a control group taking aspirin. We assessed thrombogenesis, clot integrity and fibrinolysis in blood (TEG) and plasma (MPA) from 182 atrial fibrillation patients-50 on aspirin, 50 on warfarin, and 82 on a NOAC (17 apixaban, 19 dabigatran and 46 rivaroxaban). Eleven of 16 TEG indices and 4 of 5 MPA indices differed (p ≤ 0.01) between those on aspirin, warfarin or a NOAC. Three TEG indices and 4 MPA indices differed (p < 0.01) between the NOACs. Time to initiation of clot formation was most rapid on apixaban, then rivaroxaban and slowest on dabigatran. The rate of clot formation was most rapid on dabigatran, then apixaban, and slowest on rivaroxaban. Clot density was greatest on rivaroxaban, then apixaban, but weakest on dabigatran. The rate of clot dissolution was most rapid in apixaban, then dabigatran, and slowest on rivaroxaban. The TEG and MPA identify major differences in thrombogenesis and fibrinolysis in different NOACs. These techniques may have value in investigating the effects of these drugs on haemostasis in a clinical setting, and in identifying those in need of targeted therapy.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Fibrin; Humans; Middle Aged; Thrombolytic Therapy; Vitamin K

Treatment doses of heparins are not recommended for acute ischemic stroke. Despite this, their use in this setting is widespread. We investigated whether subgroups of patients with acute ischemic stroke and atrial fibrillation, identified by clinical, hemostatic (d-dimer, prothombin fragments(1+2) [F(1+2)], soluble fibrin monomer), or inflammatory (C-reactive protein [CRP]) variables might have a differential response to low molecular weight heparin (LMWH) over aspirin. In addition, we sought to identify factors associated with a poor clinical outcome at 3 months.. We conducted a post hoc subgroup analysis of a randomized, placebo-controlled, double-blind trial (Heparin in Acute Embolic Stroke Trial) designed to test the hypothesis that treatment doses of LMWH (dalteparin; 100 IU/kg BID) would be superior to aspirin (160 mg per day) in patients with acute ischemic stroke and atrial fibrillation. For the current analysis, 431 participants were included. The primary outcome measure was a poor outcome at 3 months, defined as death or dependency in activities of daily living. Using regression analysis, we determined whether any of the chosen variables were associated with a differential response to dalteparin (treatment interaction) or with poor outcome.. In the multivariable logistic regression model, none of the clinical, hemostatic, or inflammatory variables were associated with a significant treatment interaction. Stroke severity (odds ratio [OR], 1.09 [95% CI, 1.07 to 1.12]), increasing age (OR, 1.09 [CI, 1.05 to 1.14]), CRP level (OR, 1.32 [CI, 1.04 to 1.66]), and F(1+2) level (OR, 1.77 [CI, 1.07 to 2.91]) were independently associated with a poor outcome at 3 months.. Our study does not support the use of treatment doses of LMWH in any of the studied subgroups of patients with acute ischemic stroke and atrial fibrillation. Age, stroke severity, CRP, and F(1+2) were predictive of poor outcome at 3 months.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; C-Reactive Protein; Double-Blind Method; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Humans; Ischemia; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Placebos; Prothrombin; Stroke; Time Factors; Treatment Outcome

Electrical cardioversion of atrial fibrillation (AF) is associated with a thromboembolic risk, and this risk can be reduced by the use of antithrombotic therapy. International guidelines recommend an effective oral anticoagulant therapy (OAT) for at least 3 weeks before, and 4 weeks after cardioversion. We studied whether electrical cardioversion in it self causes changes in the level of activity in the haemostatic system during treatment with either low-molecular-weight heparin (LMWH).. Thirty-eight patients with AF were randomised consecutively to either LMWH administered subcutaneous in a fixed daily dose, or conventional OAT. Changes in the biochemical markers prothrombin fragment 1+2 (F1+2), D-Dimer, and soluble fibrin, all reflecting the activity in the haemostatic system, were assessed at baseline, before and after electrical cardioversion in patients treated with LMWH for 3 weeks prior to cardioversion. A follow up compared the time spent on anticoagulation prior to cardioversion, and eventual complications in the two group (LMWH vs. OAT).. No significant differences between the levels of the biochemical markers measured before, and after cardioversion were seen, indicating that during anticoagulant therapy with LMWH, electrical cardioversion in itself, does not cause an increased activity in the haemostatic system. Also the level of F1+2 had declined significantly after cardioversion, when compared to baseline level in patients, whom had a normal sinus rhythm (NSR) re-established. This indicates that even in patients on a stable anticoagulant treatment, restoration of a NSR can cause a further decrease in thrombin generation. The median time spent on antithrombotic treatment prior to cardioversion, was significantly different between the LMWH (27 days) and the OAT group (138 days). Our study indicates that cardioversion in patients on LMWH does not cause a hypercoagulable state and that LMWH significantly shortens the time spent on anticoagulant therapy prior to cardioversion.

Topics: Aged; Atrial Fibrillation; Biomarkers; Electric Countershock; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Hemostasis; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Peptide Fragments; Prothrombin; Thrombophilia

During commencement of oral anticoagulant therapy (OAT) a theoretical possibility of a transient hypercoagulable state emerges from the difference in plasma half-life between the vitamin K-dependent pro-coagulation factors II and X, and the vitamin K-dependent anticoagulant proteins C and S. In the present study, markers reflecting the activity in the haemostatic system (prothrombin fragment 1+2 [F1+2], D-dimer and soluble fibrin) was assessed during initiation of OAT compared to subcutaneously administered low-molecular weight heparin (LMWH) which does not cause any imbalance between the concentrations of the pro- and anticoagulation proteins.. Thirty-three patients with atrial fibrillation were randomly treated either with OAT (warfarin 10, 7.5, and 5 mg for three consecutive days) or LMWH administered in a fixed dose of 200 anti-Xa IU/kg body weight in one subcutaneous injection daily. The biochemical markers were measured at baseline, and after 12, 36 and 60 h of treatment.. After introducing antithrombotic therapy, none of the biochemical markers increased within the study period in the two treatment groups. The level of F1+2 had declined significantly at 60 h in both groups. The level of soluble fibrin showed a significant decrease within the first 60 h in the OAT group, and no significant changes were seen in the LMWH group. No significant change in the level of D-dimer was seen during the first 60 h of treatment in either group. Taken together, no transient hypercoagulable state could be identified within the first 60 h of commencing OAT in patients with atrial fibrillation.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Biomarkers; Blood Coagulation Factors; Dalteparin; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Half-Life; Humans; Male; Middle Aged; Peptide Fragments; Prothrombin; Stroke; Thrombophilia; Time Factors; Vitamin K; Warfarin

The purpose of the study was to evaluate alterations of the hemostatic system and the effect of anticoagulant therapy in nonvalvular atrial fibrillation. A set of molecular hematologic markers was measured prospectively in 69 patients with atrial fibrillation and 28 age-matched patients in sinus rhythm. Significantly elevated levels of thrombin-antithrombin III complex (8.5 +/- 1.6 vs. 2.5 +/- 0.3 micrograms/l; p < 0.001), fibrin monomers (27.1 +/- 3.2 vs. 13.4 +/- 3.7 nM; p < 0.001), D-dimers (788 +/- 76 vs. 405 +/- 46 micrograms/l; p < 0.005), and tissue-type plasminogen activator (9.6 +/- 0.5 vs. 7.2 +/- 0.5 micrograms/l; p < 0.05) were observed in patients with atrial fibrillation compared to those in sinus rhythm. In a subgroup of patients in whom anticoagulant therapy with oral coumadin or standard intravenous heparin was established after the initial study, hemostatic activation decreased significantly. In conclusion, molecular hematologic markers indicate a hypercoagulable state in atrial fibrillation which may characterized a group of patients at elevated risk of thromboembolic disease.

Topics: Aged; Anticoagulants; Antithrombin III; Aspirin; Atrial Fibrillation; Biomarkers; Blood Coagulation; Blood Proteins; Echocardiography, Transesophageal; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Male; Mitral Valve; Partial Thromboplastin Time; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Prospective Studies; Prothrombin; Risk; Thromboembolism; Tissue Plasminogen Activator; Warfarin

Topics: Atrial Fibrillation; Epstein-Barr Virus Infections; Fibrin; Herpesvirus 4, Human; Humans; In Situ Hybridization, Fluorescence; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Myxoma; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-6

Topics: Atrial Fibrillation; Biology; Fibrin; Humans; Magnetic Resonance Spectroscopy; Positron-Emission Tomography; Predictive Value of Tests; Thrombosis; Tomography, X-Ray Computed

This chapter details the generation of atrial fibrin-based engineered heart tissue (EHT) in standard 24-well format as a 3D model for the human atrium. Compared to 2D cultivation, human-induced pluripotent stem cells (hiPSCs)-derived atrial cardiomyocytes demonstrated a higher degree of maturation in 3D format. Furthermore, we have demonstrated in previous work that the model displayed atrial characteristics in terms of contraction and gene expression patterns, electrophysiology, and pharmacological response. Here, we describe how to embed atrial cardiomyocytes differentiated from hiPSCs in a fibrin hydrogel to form atrial EHT attached to elastic silicone posts, allowing auxotonic contraction. In addition, we describe how force and other contractility parameters can be derived from these beating atrial EHTs by video-optical monitoring. The presented atrial EHT model is suitable to study chamber-specific mechanisms, drug effects and to serve for disease modeling.

Topics: Atrial Fibrillation; Fibrin; Heart Atria; Humans; Myocytes, Cardiac; Tissue Engineering

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 partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dinoprost; Female; Fibrin; Hemorrhage; Humans; Risk Factors; Stroke; Thromboembolism; Thrombosis; von Willebrand Factor

Atrial fibrillation (AF), a risk factor for stroke and systemic thromboembolism, is associated with unfavorable fibrin clot properties and increased thrombus formation in peripheral blood. The left atrial appendage (LAA) is known to be the primary site of thrombus formation.. We investigated the relative differences in plasma fibrin clot features including plasma fibrin clot permeability (K. Sixteen patients with nonvalvular AF who stopped oral anticoagulant therapy at least 2 days before a LARIAT procedure participated in a single-center prospective study. We measured fibrinogen and plasminogen levels along with K. LAA clot porosity was reduced by 16.2% compared to peripheral blood (p = 0.026), also after adjustment for fibrinogen levels (p = 0.038). K. Patients with AF are characterised by a local prothrombotic state as reflected by formation of compact fibrin clots in the LAA compared to peripheral blood, which may contribute to LAA thrombus formation and device-related thrombi.

Topics: Aged; Atrial Appendage; Atrial Fibrillation; Blood Coagulation Factors; Cohort Studies; Female; Fibrin; Fibrin Clot Lysis Time; Heart Diseases; Humans; Male; Middle Aged; Thrombosis

Topics: Aged; Atrial Fibrillation; Female; Fibrin; Heart Neoplasms; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Myxoma

A foreign body left in left atrium after catheter ablation of atrial fibrillation is a very rare complication. Nevertheless, there are no reports so far about a large newly emerged structure only giving the impression of being a foreign body left in the heart after catheter ablation.. This report presents a case of a patient after catheter ablation for persistent atrial fibrillation. Because of atrial tachycardia during follow-up, patient was indicated for reablation. Imaging methods including intracardiac echocardiography showed a straw-like foreign body with the character of a transseptal sheath in left atrium. A cardiac surgery was performed with extraction of the foreign body. We found a fibrous chord-like material in the left atrium, microscopy showed myocardial tissue with continuous transition to fibrinous elastic vessel. No signs of foreign material were found.. We have found a newly emerged body giving the impression of being of foreign origin in left atrium after catheter ablation of atrial fibrillation. Microscopy of the extracted material showed myocardial tissue with continuous transition to fibrinous elastic vessel and a fibrinous tissue with focal dystrophic calcification. Its origin remains unknown.

Topics: Aged; Atrial Fibrillation; Blood Vessels; Catheter Ablation; Diagnostic Errors; Echocardiography, Transesophageal; Fibrin; Foreign Bodies; Heart Atria; Humans; Magnetic Resonance Imaging; Male; Myocardium; Tomography, X-Ray Computed

Dense fibrin clot formation and hypofibrinolysis have been reported in atrial fibrillation (AF). It is unclear which factors affect fibrin clot properties in AF.. We investigated plasma fibrin clot permeability (K. In AF patients prothrombotic fibrin clot properties assessed ex vivo are determined by PAI-1 and NT-proBNP and this phenotype is associated with prior ischemic stroke.

Topics: Aged; Atrial Fibrillation; Biomarkers; Female; Fibrin; Fibrin Clot Lysis Time; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Thrombosis

Formation of denser fiber networks has been reported in atrial fibrillation and ischemic stroke. In this longitudinal cohort study, we evaluated whether fibrin clot density may predict thromboembolic and bleeding risk in patients with atrial fibrillation on vitamin K antagonists.. In 236 patients with atrial fibrillation receiving vitamin K antagonists treatment, we measured ex vivo plasma clot permeability (K. During a median follow-up of 4.3 (interquartile range, 3.7-4.8) years, annual rates of ischemic stroke or transient ischemic attack and major bleeds were 2.96% and 3.45%, respectively. In multivariate Cox regression analysis, patients with lower K. This study is the first to show that unfavorable fibrin properties reflected by formation of denser fibrin networks determine, in part, the efficacy and safety of anticoagulation with vitamin K antagonists in patients with atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Capillary Permeability; Cohort Studies; Female; Fibrin; Follow-Up Studies; Hemorrhage; Humans; Longitudinal Studies; Male; Middle Aged; Predictive Value of Tests; Stroke; Thrombosis

Atrial fibrillation (AF) is the most common cardiac arrhythmia for both men and women. The embolic cardiovascular events represent serious complications of AF, and apparently women are affected more seriously than men. Little is known about prothrombotic factors and possible gender differences. The present study aimed to characterize fibrin polymerization, fibrinolysis, and fibrin fiber properties in men and in women with AF.. Forty-six female and 101 male patients with AF and without previous stroke were included. Polymerization kinetics, lysis of preformed clot, and fibrin fiber properties were determined by turbidimetric methods.. Women were slightly older than men (P < .01), and the male group had a higher systolic blood pressure (P < .01) and a higher incidence of peripheral arterial disease (P < .01) than the female group. Compared with men, women had a higher Vmax during fibrin polymerization (P < .04) and a lower lysability of fibrin, when recombinant tissue plasminogen activator (rt-PA) was added during clot formation (P < .01), while external lysis (rt-PA added after clot formation), plasma fibrinolytic activity, d-dimer, and fibrin fiber properties did not differ between men and women. A significantly higher number of men received acetylsalicylic acid (ASA) compared with women (P < .004). Subgroup analyses on subjects not receiving ASA demonstrated that women still had higher Vmax (P < .04) and a lower rt-PA-induced fibrinolysis (P < .03).. Women with AF have a higher velocity of lateral aggregation of fibrin fiber protofibrils and a lower lysis of fibrin clots than men.

Topics: Aged; Atrial Fibrillation; Blood Pressure; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Peripheral Arterial Disease; Polymerization; Sex Characteristics

Atrial fibrillation (AF) brings a risk of thrombosis, requiring oral coagulation, and is associated with renal impairment. The two processes may be linked, as altered fibrin clot structure is present in end-stage renal failure. We hypothesised that progressively deteriorating renal function is linked to altered whole blood and fibrin clot properties and fibrinolysis.. Thrombogenesis and fibrinolysis in 200 warfarinised AF patients was assessed by thromboelastography (TEG), a micro-plate assay (MPA) and the international normalized ratio (INR). Renal function was determined by creatinine clearance and two versions of the estimated glomerular filtration rate (eGFR).. Two TEG indices independently reflecting thrombogenesis were linked to creatinine clearance (p < 0.01), whilst a third, reflecting clot strength, was linked to the eGFR (p < 0.001). MPA indices of thrombogenesis and clot density (p < 0.001), and an index of fibrinolysis (p < 0.001) were linked to the eGFR. The time for 50% of the fibrin clot to lyse was linked to creatinine clearance (p = 0.001). The INR was unrelated to any renal function index, and the CHA2DS2VASc score was unrelated to any index.. In warfarinised AF patients, renal function is linked to whole blood clot and fibrin clot formation, structure and dissolution, but has no effect on the INR. Key messages Despite oral anticoagulation, patients with atrial fibrillation (AF) still suffer from stroke and venous thromboembolism. The effect of renal function in warfarinised patients with AF is unknown and may account for excess thrombosis and/or haemorrhage. Using two different laboratory methods, our data point to an effect of renal function on clot structure and function that is independent of an effect of warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Tests; Female; Fibrin; Fibrinolysis; Humans; International Normalized Ratio; Kidney Function Tests; Male; Middle Aged; Stroke; Thrombelastography; Thrombosis; Warfarin

An experimental in vitro model of the hemodynamics that occur in atrial fibrillation (AFib) in the left atrial appendage (LAA) was developed to study changes in human endothelial cell thrombotic potential. We applied human-derived sinus rhythm and AFib hemodynamic shear stress patterns to primary human endothelial cells (ECs) in culture. We found that ECs exposed to AFib hemodynamics have increased thrombotic potential as measured by increased expression of pro-thrombotic gene markers and fibrin deposition on the endothelium. Treatment with the factor Xa inhibitor, apixaban, attenuated fibrin deposition thickness while increasing fibrin density at the endothelial cell surface. This study suggests that altered hemodynamics associated with AFib play a key role in driving the thrombotic potential of the LAA endothelium.

Topics: Atrial Appendage; Atrial Fibrillation; Cells, Cultured; Endothelial Cells; Fibrin; Hemodynamics; Humans; Thrombosis

Topics: Atrial Fibrillation; Blood Coagulation; Fibrin; Humans; Microscopy, Electron, Scanning; Renal Insufficiency, Chronic

Rivaroxaban is currently used to prevent stroke in patients with atrial fibrillation. Measuring coagulation function may help clinicians to understand the effects of this drug and the associated risk of bleeding.. Rivaroxaban was given to 136 patients with non-valvular atrial fibrillation. Mean age was 74.5±9.0 years (men: 63.2%) and mean CHADS2 score (±SD) was 1.8±1.2. Prothrombin times (PTs) and plasma soluble fibrin (SF) levels were examined in 84 out of 136 patients at baseline and at least 2 weeks thereafter. In 48 patients we were able to collect blood at exact times, namely just before and 3h after rivaroxaban administration, corresponding to the trough and peak concentrations. Mean peak PT in 48 patients was 17.1±3.6s and median peak SF level was 1.46μg/mL. Multiple regression analysis showed that female sex, high brain natriuretic peptide, and high dose were independent factors prolonging the peak PT. Patients with peak PTs ≥20s experienced significantly more bleeding events. Among 29 of 46 patients newly treated with rivaroxaban without any previous anticoagulant, we examined coagulation function at the exact trough and peak times. In 29 patients, peak PT was significantly more prolonged than the baseline or trough PT (p<0.001 for both), whereas trough PT was comparable to the baseline PT. In contrast, both trough and peak SF levels in these newly treated patients were significantly reduced than at baseline (p=0.003 and p<0.001, respectively).. In Japanese patients with non-valvular atrial fibrillation receiving rivaroxaban, a prolonged peak PT (≥20s) could indicate increased risk of bleeding, and both trough and peak SF levels were reduced relative to baseline. PT and SF are both valuable measures of coagulation status in patients receiving rivaroxaban, regardless of prior anticoagulant history.

Topics: Aged; Atrial Fibrillation; Factor Xa Inhibitors; Female; Fibrin; Hemorrhage; Humans; Japan; Male; Middle Aged; Prothrombin Time; Risk; Rivaroxaban; Stroke

Atrial fibrillation (AF) is a prothrombotic condition, involving increased thrombin generation and fibrinogen concentrations. Vitamin K antagonists (VKAs) prevent arterial thromboembolism if optimal anticoagulation is achieved by individualised drug doses, assessed by determining the Prothrombin time-related International Normalized Ratio (Pt-INR). There is evidence that formation of tight-laced fibrin networks is pathogenic in prothrombotic diseases. This study was performed among AF patients, to test whether long-term treatment with VKAs affects the structure of fibrin networks, and whether the effect is altered by employing different coagulation triggers: exogenous thrombin (1 IU/ml), 10 pM tissue factor (TF) or a commercial Pt-INR reagent (containing 400-fold more TF). In the thrombin-based method, fibrin network porosity (scanning electron microscopy) and liquid permeability (flow measurements) correlated inversely to fibrinogen concentrations, while positive correlations to the degree of anticoagulation were shown with the Pt-INR reagent. In the method with 10 pM TF, the two above relationships were detected, though the influence of Pt-INR was more profound than that of fibrinogen concentrations. Moreover, greater shortening of clot lysis time (CLT) arose from more permeable clots. As a coagulation trigger, 10 pM TF vs exogenous thrombin or the Pt-INR reagent is more informative in reflecting the in vivo process from thrombin generation to fibrin formation. Since fibrin network permeability rose in parallel to elevations of INR and shortening of CLT in AF patients, antithrombotic effects on prevention of thrombotic complications may be achieved from impairment of thrombin generation, resulting in formation of permeable clots susceptible to fibrinolysis.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Case-Control Studies; Fibrin; Fibrin Clot Lysis Time; Humans; International Normalized Ratio; Microscopy, Electron, Scanning; Poland; Porosity; Protein Conformation; Sweden; Thrombin; Thrombosis; Vitamin K; Warfarin

Formation of compact and poorly lysable fibrin clots have been demonstrated in patients following ischemic stroke. Recently, it has been shown that denser fibrin networks and impaired fibrinolysis occurs in subjects with permanent atrial fibrillation (AF). Fibrin clot phenotype in other types of AF remains to be established. We evaluated fibrin clot properties in paroxysmal (PAF) and persistent AF (PsAF).. We studied 88 non-anticoagulated patients with AF on sinus rhythm and free of stroke (41 with PAF, 47 with PsAF) versus 50 controls. Ex-vivo plasma fibrin clot permeability (Ks) and clot lysis time (CLT) were evaluated along with von Willebrand factor (vWF), peak thrombin generation (TG), platelet factor 4 (PF4) and fibrinolytic proteins.. Compared with control subjects, clots obtained from plasma of patients with PAF and PsAF had similarly lower Ks (-7.7%, P=0.01; -8.6%, P=0.005, respectively) and prolonged CLT (+10.8%, P=0.006; +7.8% P=0.04, respectively). No associations of Ks and CLT with CHA2DS2-VASc and HAS-BLED score were observed. Patients with AF had higher TG, vWF, PF4 and plasminogen activator inhibitor-1 (PAI-1) antigen compared with controls. Multiple linear regression adjusted for age, gender, body mass index and fibrinogen showed that TG (β=-0.41), vWF (β=-0.29) and PF4 (β=-0.28) are the independent predictors of Ks (R(2)=0.78), while CLT was independently predicted by TG (β=0.37), PAI-1 antigen (β=0.29) and vWF (β=0.26) in the AF group (R(2)=0.39).. Patients with PAF and PsAF while on sinus rhythm display unfavorably altered fibrin clot properties, which might contribute to thromboembolic complications.

Topics: Atrial Fibrillation; Blood Coagulation; Chronic Disease; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Platelet Activation; Thrombin; Thromboembolism; Ventricular Dysfunction, Left

Atrial fibrillation (AF) increases the risk of thromboembolism that is reduced by vitamin K antagonists (VKAs). We sought to investigate changes in plasma fibrin clot phenotype at the onset of oral anticoagulation.. Forty consecutive AF patients (aged 45-83 years, CHA2DS2-VASc score 3.0±1.5) who started therapy with warfarin or acenocoumarol were studied. Plasma fibrin clot permeability (Ks), clot lysis time (CLT), along with clotting factors (F), thrombin generation (TG) profiles and protein C (PC) levels were determined on days 3, 5, 7, 28 and 56±1 since the first dose.. AF patients had 16% higher median of Ks and 15% lower median of CLT as early as on day 3 of VKA therapy compared with the baseline (both p<0.001), reaching the plateau values on day 7 and 5, respectively. Higher Ks values on days 1 and 3 were found in AF patients with further stable anticoagulation (both p<0.05). Moreover, FIX explained 32% of the total variability in Ks. Multivariate analysis adjusted for potential confounders including time as a predictor showed that vitamin K-dependent (VKD) factors, PC and TG parameters were the predictors of Ks (all p<0.0001), while only the lag phase of TG and thrombin peak predicted CLT (both p<0.05) in AF patients. Regression analysis of time-series showed however, that CLT was also predicted by VKD factors and PC (all p<0.05).. Plasma fibrin clot properties in AF patients are favourably modified as early as after 3days of VKA administration, which might contribute to antithrombotic effectiveness.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Blood Coagulation Factors; Female; Fibrin; Fibrin Clot Lysis Time; Humans; Male; Middle Aged; Thrombin; Vitamin K

Atrial fibrillation increases the risk of ischemic stroke, but the risk depends on other factors as well. Present risk stratification schemes use age and co-morbidities, but not biochemical markers. We investigated the hypothesis that the formation, structure and lysability of fibrin clots are potential determinants of stroke risk in patients with atrial fibrillation.. A total of 179 patients with atrial fibrillation in stable anticoagulant treatment were included. Thirty-two had a previous ischemic stroke. We measured thrombin generation, plasma concentrations of fibrinogen and C-reactive protein and analysed fibrin structure and lysability by turbidity. Fibrinolytic capacity was measured using the euglobulin fraction of plasma expressed in terms of t-PA equivalents (IU/ml).. The patients with previous stroke had a slightly higher burden of co-morbidities compared with the remaining patients as indicated by the CHA2DS2-VASc score, but no significant differences were found regarding age, fibrinogen concentration, C-reactive protein, thrombin generation or fibrinolytic capacity. Furthermore, the patients with previous stroke had a higher mass/length ratio of fibrin fibers (5.5 vs. 5.1 x10(12) Da/cm, p=0.044) and an increased lysability (79.3 vs. 55.3%, p<0.01).. The higher lysability of fibrin clots in atrial fibrillation patients with previous stroke is most likely a result of a difference in fibrin fiber properties. An increased lysability may increase the risk of embolization of clots formed in the atria, and therefore fibrin clot structure seems to be a determinant of stroke risk in atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Comorbidity; Cross-Sectional Studies; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Risk Factors; Stroke; Thrombin

An 85 year old male suffered vision loss in both eyes due to ruptured bilateral retinal arterial macroaneurysms.. We report this unusual case and show the importance of studying these types of patients in order to detect associated systemic diseases.

Topics: Aged, 80 and over; Aneurysm; Aneurysm, Ruptured; Atrial Fibrillation; Fibrin; Humans; Hypertension; Laser Therapy; Male; Retinal Artery; Retinal Hemorrhage; Tomography, Optical Coherence; Vision Disorders

Atrial fibrillation (AF) is associated with a prothrombotic state.. We evaluated associations of previous thromboembolic events with fibrinolytic parameters in patients with AF.. We studied 62 consecutive patients with permanent AF (27 men, 35 women, aged 46-89 years [median, 78 years]). Patients receiving warfarin or acenocoumarol on a long-term basis were eligible. We determined plasma fibrin clot lysis time (CLT), plasminogen activator inhibitor-1 (PAI-1) antigen, thrombin-activatable fibrinolysis inhibitor (TAFI) activity and antigen, plasminogen, α2-antiplasmin (α2AP), and soluble thrombomodulin (sTM).. There were 19 subjects (30.6%) with a history of thrombotic events (stroke in 11, myocardial infarction in 8, and pulmonary embolism in 3 patients). They had longer CLT (P = 0.0035 for patients with previous stroke and P = 0.001 for patients with any previous thrombotic event), together with higher PAI-1 (P = 0.025 and P = 0.016, respectively), TAFI activity (P = 0.002 and P = 0.011, respectively), sTM (P = 0.0023 and P = 0.012, respectively), and α2AP (P = 0.007 and P = 0.0006, respectively) than the remaining subjects. AF patients with previous stroke had also higher TAFI antigen than the remainder (P = 0.04). CLT (P = 0.024), PAI-1 (P = 0.022), TAFI activity (P = 0.048), and sTM (P = 0.032, all P for trend) increased with higher CHA2DS2-VASc scores. CLT was not associated with time from thrombotic event to enrollment. Patients taking oral anticoagulants (n = 46) had only slightly higher sTM levels (3.6 [2.9-6.3] vs. 2.9 [2.2-4.1] ng/ml, P = 0.049) than the remaining subjects.. Stroke or other thromboembolic event in AF patients is associated with impaired lysability of fibrin clots combined with elevated PAI-1, TAFI, sTM, and α2AP.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Carboxypeptidase B2; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Thromboembolism; Thrombolytic Therapy; Tissue Plasminogen Activator; Warfarin

The incidence of stroke in patients suffering atrial fibrillation (AF) is increased when left atrial enlargement occurs. Recently, the platelet adhesive molecule, von Willebrand factor (vWF), located in the atrial endocardium, has been shown to be increased in patients with a variety of heart diseases compared with patients who have no cardiac problems.. We investigated the expression of vWF mRNA and protein in the endocardium as a possible prothrombotic alteration of AF in association with atrial structural remodeling. Atrial appendage specimens were obtained during either heart surgery or at an autopsy from AF patients with and without underlying heart disease. The immunohistochemical and in situ hybridization signals for vWF in the endocardium were well correlated and varied widely among the individual atrial appendages examined. The increased expression of vWF in the endocardium was associated with enlarged left atrial dimensions in mitral valvular disease or increased myocyte diameters in the underlying myocardium. Platelet adhesion/aggregation on the endocardium was always found under the fresh thrombi and was colocalized with strong vWF staining, but not necessarily with fibrinogen and/or fibrin staining.. Endocardial overexpression of vWF may occur during the process of atrial structural remodeling contributing to the thrombotic predilection of AF in association with underlying heart disease.

Topics: Adult; Aged; Aged, 80 and over; Atrial Appendage; Atrial Fibrillation; Atrial Function; Endocardium; Female; Fibrin; Fibrinogen; Gene Expression; Heart Atria; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve; Platelet Endothelial Cell Adhesion Molecule-1; RNA, Messenger; Thrombophilia; von Willebrand Factor

Thromboembolism secondary to atrial fibrillation accounts for approximately one-fourth of all strokes. Although considerable resources have been targeted to pharmacologic prophylaxis, neither the cellular nor the biochemical composition of atrial thrombi is known. Quantitative immunohistochemistry was undertaken to define the composition of atrial thrombi and to explore morphological differences between atrial appendage thrombi and those that embolize.. Serial sections of thrombi obtained during valve replacement surgery or embolectomy from 22 patients with atrial fibrillation were stained with antibodies against fibrin, integrin beta3, or tissue factor and analyzed with NIH-image.. Thrombi showed distinct regions staining for either fibrin or platelets and on average, the fibrin-rich regions predominated (P < 0.0001). The platelet content of embolized thrombi was nearly twice that of atrial thrombi (P = 0.02). Non-staining amorphous material comprised nearly half of atrial thrombi in situ, but was rare in embolized thrombi (P < 0.001). Tissue factor colocalized to areas rich in platelets and granulocytes.. The abundance of fibrin relative to platelets underscores the enhanced efficacy of warfarin prophylaxis in clinical trials. The finding of tissue factor localized to platelet-leukocyte clusters suggests its blood-borne origin. Compositional differences between in situ and embolized thrombi suggest directions for investigating propensity for embolization.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Platelets; Female; Fibrin; Heart Valve Prosthesis; Humans; Immunohistochemistry; Integrin beta3; Male; Thromboembolism; Thromboplastin; Thrombosis; Warfarin

Systemic thromboembolism is a major complication in patients with mitral stenosis, especially in those who have atrial fibrillation (AF). It has been suggested that there may be increased regional left atrial coagulation activity in such patients, despite normal systemic coagulation activity on peripheral blood sampling. Our aim was to investigate whether there were significant differences between intracardiac versus peripheral indexes of hypercoagulability in 25 patients (5 men; mean age 60 years) with mitral stenosis who were undergoing percutaneous balloon mitral valvuloplasty and who were all in chronic AF. Two days after halting warfarin therapy, intracardiac (right and left atria) and peripheral (venous and arterial) blood samples from patients were obtained and compared with levels in matched healthy controls in sinus rhythm. Thrombogenicity was assessed by levels of fibrin D-dimer, fibrinogen, indexes of platelet activation (soluble P-selectin and beta thromboglobulin [betaTG]) and indexes of endothelial dysfunction (soluble thrombomodulin [sTM] and von Willebrand factor [vWF]). There were no statistically significant differences in the various markers between the femoral vein and artery, left and right atria, and between the femoral vein and both atria (all p = NS). Plasma fibrinogen, vWf (both p <0.005), and D-dimer (p = 0.011) were significantly higher and levels of sP-selectin and sTM were lower (both p <0.005) in patients when compared with controls. There was no significant difference in plasma betaTG levels. Our results suggest that there is no significant variation in indexes of thrombogenesis, platelet activation, and endothelial dysfunction between left atrium, right atrium, and the peripheral artery or vein. Peripheral samples therefore do reflect atrial coagulation, platelet, and endothelial activities.

Topics: Atrial Fibrillation; beta-Thromboglobulin; Biomarkers; Blood Coagulation Factors; Blood Vessels; Catheterization; Female; Fibrin; Fibrinogen; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Mitral Valve Stenosis; P-Selectin; Platelet Activation; Prognosis; Retrospective Studies; Risk Factors; Thrombophilia

Topics: Atrial Fibrillation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Heart Atria; Humans; Mitral Valve Stenosis; Predictive Value of Tests; Thrombin; Thrombosis

Patients with mitral stenosis in sinus rhythm are in a prothrombotic state and have fibrinolytic dysfunction, shown by an increase in levels of the inhibitor of tissue plasminogen activator, D-dimer, and modified antithrombin III. This state may be observed even in patients without dilated left atria (diameter < or =45 mm).

Topics: Atrial Fibrillation; Echocardiography; Female; Fibrin; Humans; Immunoenzyme Techniques; Male; Middle Aged; Mitral Valve Stenosis; Plasminogen Activator Inhibitor 1; Statistics, Nonparametric; Thrombin; Tissue Plasminogen Activator

Progression of intermittent partial or total impaction of the poppet from a prosthetic mitral valve may be difficult to evaluate in patients with chronic obstructive pulmonary disease and atrial fibrillation. Heart sounds may be distant; opening and closing clicks of the poppet are muffled and irregular. Echocardiography provides a noninvasive method to detect early prosthetic malfunction at a time when the patient is clinically asymptomatic.

Topics: Atrial Fibrillation; Blood Coagulation Disorders; Echocardiography; Fibrin; Heart Valve Prosthesis; Hemodynamics; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Mitral Valve