Affiliation:
1. Clinical Department of Interventional Cardiology John Paul II Hospital Krakow Poland
2. Department of Thromboembolic Disorders, Institute of Cardiology Jagiellonian University Medical College Krakow Poland
3. Department of Bioinformatics and Telemedicine, Faculty of Medicine Jagiellonian University Medical College Krakow Poland
4. Center for Digital Medicine and Robotics Jagiellonian University Medical College Krakow Poland
5. Krakow Center for Medical Research and Technologies John Paul II Hospital Krakow Poland
6. Department of Biochemistry University of Vermont Burlington Vermont USA
Abstract
AbstractIntroductionPatients 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.MethodsIn 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.ResultsCirculating 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.ConclusionsTo 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.
Funder
Uniwersytet Jagielloński Collegium Medicum
Subject
Clinical Biochemistry,Biochemistry,General Medicine
Cited by
2 articles.
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