Aortic stenosis (AS) has been associated with impaired fibrinolysis and increased oxidative stress. This study aimed to investigate whether oxidative stress could alter fibrin clot properties in AS. We studied 173 non-diabetic patients, aged 51–79 years, with isolated AS. We measured plasma protein carbonylation (PC) and thiobarbituric acid reactive substances (TBARS), along with plasma clot permeability (K_s), thrombin generation, and fibrinolytic efficiency, which were evaluated by two assays: clot lysis time (CLT) and lysis time (Lys50). Coagulation factors and fibrinolytic proteins were also determined. Plasma PC showed an association with AS severity, reflected by the aortic valve area and the mean and maximum aortic gradients. Plasma PC was positively correlated with CLT, Lys50, plasminogen activator inhibitor-1 (PAI-1), and tissue factor (TF) antigens. TBARS were positively correlated with maximum aortic gradient, Lys50, and TF antigen. Regression analysis showed that PC predicted prolonged CLT (>104 min; odds ratio (OR) 6.41, 95% confidence interval (CI) 2.58–17.83, p < 0.001) and Lys50 (>565 s; OR 5.83, 95% CI 2.23–15.21, p < 0.001). Multivariate regression analysis showed that mean aortic gradient, PC, α2-antiplasmin, PAI-1, and triglycerides were predictors of prolonged CLT, while PC, α2-antiplasmin, and fibrinogen were predictors of Lys50. Our findings suggest that elevated oxidative stress contributes to impaired fibrinolysis in AS and is associated with AS severity.

The relationship between circulating fibrosis-related molecules and magnetic resonance-assessed cardiac fibrosis in dilated cardiomyopathy (DCM) is poorly understood. To compare circulating biomarkers between DCM patients with high and low fibrosis burdens, we performed a prospective, single-center, observational study. The study population was composed of 100 DCM patients (87 male, mean age 45.2 ± 11.8 years, mean ejection fraction 29.7% ± 10.1%). Replacement fibrosis was quantified by means of late gadolinium enhancement (LGE), whereas interstitial fibrosis was assessed via extracellular volume (ECV). Plasma concentrations of cardiotrophin-1, growth differentiation factor-15, platelet-derived growth factor, procollagen I C-terminal propeptide, procollagen III N-terminal propeptide, and C-terminal telopeptide of type I collagen were measured. There were 44% patients with LGE and the median ECV was 27.7%. None of analyzed fibrosis serum biomarkers were associated with the LGE or ECV, whereas NT-proBNP was independently associated with both LGE and ECV, and troponin T was associated with ECV. None of the circulating fibrosis markers differentiated between DCM patients with and without replacement fibrosis, or patients stratified according to median ECV. However, cardiac-specific markers, such as NT-proBNP and hs-TnT, were associated with fibrosis. Levels of circulating markers of fibrosis seem to have no utility in the diagnosis and monitoring of cardiac fibrosis in DCM.

Objectives: Protein C (PC) deficiency is an inherited thrombophilia with a prevalence of 0.5% in the general population and 3% in subjects with a first-time deep vein thrombosis (DVT). Here we report a series of 14 PC-deficient Polish patients with comprehensive clinical and molecular characteristics, including long-term follow-up data and a deep mutational analysis of the PROC gene. Patients and Methods: Fourteen unrelated probands (mean ± SD age 43.8 ± 13.0 years) with suspicion of PC deficiency, who experienced thromboembolic events and a majority of whom received anticoagulants (92.8%), were screened for PROC mutations by sequencing the nine PROC exons and their flanking intron regions. Results: Ten probands (71.4%) had missense mutations, two patients (14.3%) carried nonsense variants, and the other two subjects (14.3%) had splice-site mutations, the latter including the c.401-1G>A variant, reported here for the very first time. The proband carrying the c.401-1A allele had a hepatic artery aneurysm with a highly positive family history of aneurysms and the absence of any mutations known to predispose to this vascular anomaly. Conclusion: A novel detrimental PROC mutation was identified in a family with aneurysms, which might suggest yet unclear links of thrombophilia to vascular anomalies, including aneurysms at atypical locations in women. The present case series also supports data indicating that novel oral anticoagulants (NOACs) are effective in PC deficient patients.