Leszek Drabik

Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: Association with thrombin generation, endothelial injury and platelet activation

INTRODUCTION Formation of compact and poorly lysable fibrin clots have been demonstrated in patients following ischemic stroke. Recently, it has been shown that denser fibrin networks and impaired fibrinolysis occurs in subjects with permanent atrial fibrillation (AF). Fibrin clot phenotype in other types of AF remains to be established. We evaluated fibrin clot properties in paroxysmal (PAF) and persistent AF (PsAF). MATERIAL AND METHODS We studied 88 non-anticoagulated patients with AF on sinus rhythm and free of stroke (41 with PAF, 47 with PsAF) versus 50 controls. Ex-vivo plasma fibrin clot permeability (Ks) and clot lysis time (CLT) were evaluated along with von Willebrand factor (vWF), peak thrombin generation (TG), platelet factor 4 (PF4) and fibrinolytic proteins. RESULTS Compared with control subjects, clots obtained from plasma of patients with PAF and PsAF had similarly lower Ks (-7.7%, P=0.01; -8.6%, P=0.005, respectively) and prolonged CLT (+10.8%, P=0.006; +7.8% P=0.04, respectively). No associations of Ks and CLT with CHA2DS2-VASc and HAS-BLED score were observed. Patients with AF had higher TG, vWF, PF4 and plasminogen activator inhibitor-1 (PAI-1) antigen compared with controls. Multiple linear regression adjusted for age, gender, body mass index and fibrinogen showed that TG (β=-0.41), vWF (β=-0.29) and PF4 (β=-0.28) are the independent predictors of Ks (R(2)=0.78), while CLT was independently predicted by TG (β=0.37), PAI-1 antigen (β=0.29) and vWF (β=0.26) in the AF group (R(2)=0.39). CONCLUSIONS Patients with PAF and PsAF while on sinus rhythm display unfavorably altered fibrin clot properties, which might contribute to thromboembolic complications.

Fibrin Clot Permeability as a Predictor of Stroke and Bleeding in Anticoagulated Patients With Atrial Fibrillation

Background and Purpose— Formation of denser fiber networks has been reported in atrial fibrillation and ischemic stroke. In this longitudinal cohort study, we evaluated whether fibrin clot density may predict thromboembolic and bleeding risk in patients with atrial fibrillation on vitamin K antagonists. Methods— In 236 patients with atrial fibrillation receiving vitamin K antagonists treatment, we measured ex vivo plasma clot permeability (Ks), a measure of the pore size in fibrin networks. Results— During a median follow-up of 4.3 (interquartile range, 3.7–4.8) years, annual rates of ischemic stroke or transient ischemic attack and major bleeds were 2.96% and 3.45%, respectively. In multivariate Cox regression analysis, patients with lower Ks (<6.8 cm2×10−9, median) had increased risk of ischemic stroke or transient ischemic attack (hazard ratio [HR], 6.55; 95% confidence interval [CI], 2.17–19.82) and major bleeds (HR, 10.65; 95% CI, 3.52–32.22). Patients with elevated Ks (≥6.8 cm2×10−9) had an increased rate of minor bleeding compared with the remainder (11.63% per year versus 3.55% per year; P<0.0001). The independent predictors of stroke or transient ischemic attack were low Ks (<6.8 cm2×10−9; HR, 7.24; 95% CI, 2.53–20.76), age (HR, 1.05; 95% CI, 1.01–1.10), and treatment with angiotensin-converting enzyme inhibitors (HR, 2.27; 95% CI, 1.08–4.77). Major bleeds were predicted by low Ks (<6.8 cm2×10−9; HR, 8.48; 95% CI, 2.99–24.1) and HAS-BLED score ≥3 (HR, 2.22; 95% CI, 1.12–4.38). Conclusions— This study is the first to show that unfavorable fibrin properties reflected by formation of denser fibrin networks determine, in part, the efficacy and safety of anticoagulation with vitamin K antagonists in patients with atrial fibrillation.

Left atrial myxoma as a cause of multiple cerebral microembolization (RCD code: VI‐1A.1)

2017; 3(5): 168‐170; doi: https://doi.org/10.20418/jrcd.vol3no5.287 Conflict of interest: none declared. Submitted: May 4, 2017. Accepted: November 13, 2017. * Corresponding author: Department of Cardiac and Vascular Diseases, John Paul II Hospital, Krakow, Poland, ul. Prądnicka 80, 31‐202 Krakow, Poland; tel. 0048 12 614 22 87, fax 0048 12 423 43 76; e‐mail: wplazak@szpitaljp2.krakow.pl Copyright