Fibrin presence within aortic valves in patients with aortic stenosis: association with in vivo thrombin generation and fibrin clot properties.
A role of coagulation in the pathogenesis of aortic stenosis (AS) is unknown. The aim of this study was to investigate the fibrin (Fn) presence and its determinants in calcified stenotic aortic valve leaflets. Twenty-one patients with dominant AS and 17 well-matched patients with dominant aortic insufficiency (AI) undergoing aortic valve replacement were studied. Immunofluorescence analysis was performed on decalcified leaflets using antibodies against human Fn and tissue factor (TF). Fn-positive (41.4%) and TF-positive (25.3%) areas were increased in AS valves compared with AI valves (7.9% and 5.9%, respectively, both p<0.001). Patients with AS had elevated plasma D-dimer (236.4 ± 28 ng/ml, p=0.002) and prothrombin fragment 1+2 (F1.2) (261.7 ± 27.1 pM, p=0.005) compared to AI subjects (142.8 ± 10 ng/ml and 131.2 ± 1.3 pM, respectively). In AS patients Fn-positive areas correlated with TF-positive areas (r=0.68, p=0.0005), D-dimer (r=0.45, p=0.018), F1.2 (r=0.64, p=0.002), the time required for plasma fibrin clot formation (r=0.44, p=0.015) and maximum absorbance of fibrin clots (r=-0.38, p<0.0001), but not with clot permeability or lysis time. Thickness of Fn layer within AS valves was associated with maximum transvalvular gradient (r =0.41, p=0.048). Patients with maximal gradient above 75 mmHg (n=11) showed significant associations between Fn-positive area and both maximal (r =0.63) and mean (r =0.67) transvalvular gradients. Large fibrin amounts, mostly co-localised with TF, are present within the valve leaflets of patients with advanced AS. In vivo thrombin generation and fibrin clot formation are associated with the extent of Fn presence within leaflets, which might contribute to the AS progression.
Institute of Cardiology, Jagiellonian University School of Medicine, 80 Pradnicka St., 31-202 Krakow, Poland. mmundas@cyf-kr.edu.pl
Joanna
J
Natorska
Grzegorz
G
Marek
Marta
M
Hlawaty
Jerzy
J
Sadowski
Wieslawa
W
Tracz
Anetta
A
Undas
D000368:Aged; D001021:Aortic Valve / Q000737:chemistry* / Q000000981:diagnostic imaging; D001022:Aortic Valve Insufficiency / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D001024:Aortic Valve Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D002114:Calcinosis / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D016009:Chi-Square Distribution; D005260:Female; D005337:Fibrin / Q000032:analysis*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011044:Poland; D011516:Prothrombin; D012720:Severity of Illness Index; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000032:analysis; D014463:Ultrasonography
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D005337:Fibrin; D013925:Thromboplastin; D013917:Thrombin