Altered fibrin clot properties and fibrinolysis in patients with atrial fibrillation: practical implications

EP Europace ◽  
2019 ◽  
Author(s):  
Anetta Undas
Keyword(s):  
Atrial Fibrillation ◽  
Thrombin Generation ◽  
Stroke Risk ◽  
Vitamin K Antagonists ◽  
Fibrin Clot ◽  
Stroke Risk Factors ◽  
Cerebrovascular Events ◽  
Fibrin Monomers ◽  
Practical Implications

AbstractCompelling 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.

Embolic stroke of undetermined source correlates to atrial fibrosis without atrial fibrillation

Neurology ◽  
2019 ◽  
Vol 93 (4) ◽  
pp. e381-e387 ◽  
Author(s):  
Karman Tandon ◽  
David Tirschwell ◽  
W.T. Longstreth ◽  
Bryn Smith ◽  
Nazem Akoum
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Stroke Risk ◽  
Embolic Stroke ◽  
Cardioembolic Stroke ◽  
Healthy Controls ◽  
Atrial Fibrosis ◽  
Stroke Risk Factors ◽  
Causal Pathway

ObjectiveTo examine the hypothesis that atrial fibrosis and associated atrial cardiopathy may be in the causal pathway of cardioembolic stroke independently of atrial fibrillation (AF) by comparing atrial fibrosis burden between patients with embolic stroke of undetermined source (ESUS), patients with AF, and healthy controls.MethodsWe used late-gadolinium-enhancement MRI to compare atrial fibrosis in 10 patients with ESUS against 10 controls (no stroke, no AF) and 10 patients with AF. Fibrosis was compared between groups, controlling for stroke risk factors.ResultsMean age was 51 ± 15 years, and 43% of participants were female. Patients with ESUS had more atrial fibrosis than controls (16.8 ± 5.7% vs 10.6 ± 5.7%, p = 0.019) and similar fibrosis compared to patients with AF (17.8 ± 4.8%, p = 0.65). Odds ratios of ESUS per quartile of fibrosis were 3.22 (95% CI [CI] 1.11–9.32, p = 0.031, unadjusted) and 3.17 (95% CI 1.05–9.52, p = 0.041, CHA2DVASc score adjusted). Patients with >12% fibrosis had a higher percentage of ESUS (77.8% vs 27.3%, p = 0.02), and patients with >20% fibrosis had the highest proportion of ESUS (4 of 5).ConclusionsPatients with ESUS exhibit similar atrial fibrosis compared to patients with AF and more fibrosis than healthy controls. Fibrosis is associated with ESUS after controlling for stroke risk factors, supporting the hypothesis that fibrosis is in the causal pathway of cardioembolic stroke independently of AF. Prospective studies are needed to assess the role of anticoagulation in primary and secondary stroke prevention in patients with high atrial fibrosis.

scholarly journals Atrial Fibrillation and Stroke. A Review on the Use of Vitamin K Antagonists and Novel Oral Anticoagulants

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 617 ◽  
Author(s):  
Caturano ◽  
Galiero ◽  
Pafundi
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Stroke Risk ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Life Quality ◽  
Novel Oral Anticoagulants ◽  
New Findings ◽  
Ischemic Stroke Risk

Atrial fibrillation (AF) is the most common arrhythmia, ranging from 0.1% in patients <55 years to >9% in octogenarian patients. One important issue is represented by the 5-fold increased ischemic stroke risk in AF patients. Hence, the role of anticoagulation is central. Until a few years ago, vitamin K antagonists (VKAs) and low molecular weight heparin represented the only option to prevent thromboembolisms, though with risks. Novel oral anticoagulants (NOACs) have radically changed the management of AF patients, improving both life expectancy and life quality. This review aims to summarize the most recent literature on the use of VKAs and NOACs in AF, in light of the new findings.

scholarly journals Etiology of Ischemic Strokes of Patients with Atrial Fibrillation and Therapy with Anticoagulants

2020 ◽  
Vol 9 (9) ◽  
pp. 2938
Author(s):  
Jan C. Purrucker ◽  
Kyra Hölscher ◽  
Jennifer Kollmer ◽  
Peter A. Ringleb
Keyword(s):  
Atrial Fibrillation ◽  
Medication Errors ◽  
Stroke Risk ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Imaging Data ◽  
Stroke Risk Factors ◽  
Brain Imaging Data ◽  
Diagnostic Work ◽  
Work Up

Background: Reducing the number of ischemic strokes in patients with atrial fibrillation despite oral anticoagulation remains an important, yet largely unsolved challenge. Therefore, we assessed the etiology of ischemic strokes despite anticoagulation with vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs). Methods: Patients with known atrial fibrillation (AF), treatment with VKA or NOAC, and acute ischemic stroke admitted between 2015 and 2018 (1st half) were identified from the hospital database. Brain imaging data were independently reviewed. An integrated etiologic classification according to the ASCOD system was made. Medication errors (admission INR <2.0 in the VKA- or NOAC-specific concentration <10 ng/mL) or dosage/dosing errors were also analyzed. Results: Of 3610 patients screened, n = 341 were included (VKA, n = 127; NOAC, n = 214). An overall increasing rate of OAC-associated stroke per year was observed. In 95.3% of patients with adequate diagnostic work-up (n = 321/337), at least one additional potential, uncertain, or unlikely non-cardiac cause of stroke was identified. More patients in the VKA than in the NOAC group had a medication error (81/127, 63.8% vs. 102/205, 49.8%; p = 0.013). Conclusions: Stroke risk factors despite atrial fibrillation were highly prevalent. Although less common with NOACs than VKAs, medication errors are still frequent.

Stroke Prophylaxis by Percutaneous Closure of Patent Foramen Ovale and Left Atrial Appendage

2011 ◽  
Vol 6 (1) ◽  
pp. 67
Author(s):  
Antonio L Bartorelli ◽  
Claudio Tondo ◽  
◽  
Keyword(s):  
Left Atrial ◽  
Patent Foramen Ovale ◽  
Stroke Risk ◽  
Left Atrial Appendage ◽  
Cryptogenic Stroke ◽  
Atrial Appendage ◽  
Foramen Ovale ◽  
Percutaneous Procedures ◽  
Cerebrovascular Events

Innovative percutaneous procedures for stroke prevention have emerged in the last two decades. Transcatheter closure of the patent foramen ovale (PFO) is performed in patients who suffered a cryptogenic stroke or a transient ischaemic attach (TIA) in order to prevent recurrence of thromboembolic events. Percutaneous occlusion of the left atrial appendage (LAA) has been introduced to reduce stroke risk in patients with atrial fibrillation (AF). The role of PFO and LAA in the occurrence of cerebrovascular events and the interventional device-based therapies to occlude the PFO and LAA are discussed.

Abstract WP333: A Simplified Score to Predict Stroke Risk in Nonvalvular Atrial Fibrillation

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Clare T Garrard ◽  
Mahesh Amin ◽  
Abdul H Hakki
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Stroke Risk ◽  
Predictive Accuracy ◽  
Myocardial Infarct ◽  
Female Gender ◽  
Arterial Disease ◽  
Nonvalvular Atrial Fibrillation ◽  
Aortic Plaque ◽  
Cerebrovascular Events

The widely used CHADS2 score has been validated to predict the annual stroke risk (SR) in patients with non-valvular atrial fibrillation (AF). The CHA2DS2-VASc score incorporates 5 more risk factors including female gender, age 65 to 74 years, and peripheral arterial disease (PAD), prior myocardial infarct or aortic plaque. The two schemes have different SR and require separate tables to calculate SR (Table 1) . Table 1 An acronym (AFIB)2S4 + PaF2 (Table 2) is presented to predict SR that increases with higher scores, simplifies memorization of the score, incorporates all known risk factors and more accurately predicts SR without the use of tables. Table 2 The SR per 100 patient-years is calculated by adding (AFIB)2S4 + PaF2 scores. For example if all are positive including age 75 years then the SR is 15%, while if all are negative, including age <65 and male gender, then the SR is 0. To determine the predictive accuracy of the three scores, we reviewed the records of 100 consecutive patients admitted with acute cerebrovascular events and AF. The results showed 83% would have been classified as moderate to high risk (score>1) by CHADS2 , 95% by CHA2DS2-VASc , and 99% by (AFIB)2S4 + PaF2. (P <0.012). Conclusion: Compared to the CHADS2 , and CHA2DS2-VASc , (AFIB)2S4 + PaF2 more accurately predicts risk of acute cerebrovascular events in patients with AF. It is easy to remember and does not require the use of tables to assess SR in AF. Further studies are needed for validation. PEN ©

Assays of fibrin network properties altered by VKAs in atrial fibrillation – importance of using an appropriate coagulation trigger

2015 ◽  
Vol 113 (04) ◽  
pp. 851-861 ◽  
Author(s):  
Michal Ząbczyk ◽  
Margareta Blombäck ◽  
Jacek Majewski ◽  
Grzegorz Karkowski ◽  
Hakan N. Wallen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Thrombin Generation ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Clot Lysis ◽  
Flow Measurements ◽  
Fibrin Networks ◽  
Fibrin Network ◽  
Long Term Treatment

SummaryAtrial 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.

scholarly journals CHA2DS2-VASc score, left atrial size and atrial fibrillation as stroke risk factors in the Tromsø Study

Open Heart ◽  
2016 ◽  
Vol 3 (2) ◽  
pp. e000439 ◽  
Author(s):  
Sweta Tiwari ◽  
Maja-Lisa Løchen ◽  
Bjarne K Jacobsen ◽  
Laila A Hopstock ◽  
Audhild Nyrnes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Left Atrial ◽  
Stroke Risk ◽  
Left Atrial Size ◽  
Stroke Risk Factors ◽  
Atrial Size

A Proof of Concept for Computational Fluid Dynamic Analysis of the Left Atrium in Atrial Fibrillation on a Patient-Specific Basis

2019 ◽  
Vol 142 (1) ◽  
Author(s):  
Alessandro Masci ◽  
Martino Alessandrini ◽  
Davide Forti ◽  
Filippo Menghini ◽  
Luca Dedé ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Stratification ◽  
Left Atrium ◽  
Stroke Risk ◽  
Fluid Dynamic ◽  
Blood Stasis ◽  
Patient Specific ◽  
Computational Fluid Dynamic Analysis ◽  
Cerebrovascular Events ◽  
Hemodynamic Information

Abstract Atrial fibrillation (AF) is associated with a fivefold increase in the risk of cerebrovascular events, being responsible of 15–18% of all strokes. The morphological and functional remodeling of the left atrium (LA) caused by AF favors blood stasis and, consequently, stroke risk. In this context, several clinical studies suggest that the stroke risk stratification could be improved by using hemodynamic information on the LA and the left atrial appendage (LAA). The goal of this study was to develop a personalized computational fluid dynamics (CFD) model of the LA which could clarify the hemodynamic implications of AF on a patient-specific basis. In this paper, we present the developed model and its application to two AF patients as a preliminary advancement toward an optimized stroke risk stratification pipeline.

scholarly journals Role of Biological Markers for Cerebral Bleeding Risk STRATification in Patients with Atrial Fibrillation on Oral Anticoagulants for Primary or Secondary Prevention of Ischemic Stroke (Strat-AF Study): Study Design and Methodology

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 626 ◽  
Author(s):  
Anna Poggesi ◽  
Carmen Barbato ◽  
Francesco Galmozzi ◽  
Eleonora Camilleri ◽  
Francesca Cesari ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Biological Markers ◽  
Oral Anticoagulant ◽  
Stroke Risk ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Circulating Biomarkers ◽  
Cerebral Mri

Background and Objectives: In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. Cerebral small vessel disease (SVD) represents the pathologic substrate for primary intracerebral hemorrhage and ischemic stroke. We hypothesize that biological markers—both circulating and imaging-based—and their possible interaction, might improve the prediction of bleeding risk in AF patients under treatment with any type of oral anticoagulant. Materials and Methods: The Strat-AF study is an observational, prospective, single-center hospital-based study enrolling patients with AF, aged 65 years or older, and with no contraindications to magnetic resonance imaging (MRI), referring to Center of Thrombosis outpatient clinic of our University Hospital for the management of oral anticoagulation therapy. Recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral MRI, and circulating biomarkers assessment at baseline and after 18 months. The main outcome is SVD progression—particularly microbleeds—as a selective surrogate marker of hemorrhagic complication. Stroke occurrence (ischemic or hemorrhagic) and the progression of functional, cognitive, and motor status will be evaluated as secondary outcomes. Circulating biomarkers may further improve predictive potentials. Results: Starting from September 2017, 194 patients (mean age 78.1 ± 6.7, range 65–97; 61% males) were enrolled. The type of AF was paroxysmal in 93 patients (48%), and persistent or permanent in the remaining patients. Concerning the type of oral anticoagulant, 57 patients (29%) were on vitamin K antagonists, and 137 (71%) were on direct oral anticoagulants. Follow-up clinical evaluation and brain MRI are ongoing. Conclusions: The Strat-AF study may be an essential step towards the exploration of the role of a combined clinical biomarker or multiple biomarker models in predicting stroke risk in AF, and might sustain the incorporation of such new markers in the existing stroke prediction schemes by the demonstration of a greater incremental value in predicting stroke risk and improvement in clinical outcomes in a cost-effective fashion.

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