Summary
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 vivothrombin generation and fibrin clot formation are associated with the extent of Fn
presence within leaflets, which might contribute to the AS progression.
Keywords
Aortic stenosis - fibrin - clot structure - transvalvular gradient
