BACKGROUND: Despite secondary prevention with aspirin, patients with stable cardiovascular disease (CVD) remain at elevated long-term risk of major adverse cardiovascular events. The Cardiovascular Outcomes in People Using Anticoagulant Strategies (COMPASS) double-blind, randomized clinical trial demonstrated that aspirin plus low-dose rivaroxaban (COMPASS regime) significantly decreased the incidence of major adverse cardiovascular events by 24% compared with aspirin alone. However, the mechanisms underlying these potential synergistic/nonantithrombotic effects remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD. OBJECTIVES: We hypothesized that circulating EV profiles reflect the cardioprotective properties of the COMPASS regime. METHODS: A cohort of stable CVD patients (N = 40) who participated in the COMPASS trial and were previously randomized to receive aspirin were prospectively recruited and assigned a revised regimen of open-label aspirin plus rivaroxaban. Blood samples were obtained at baseline (aspirin only) and 6-month follow-up. Plasma EV concentration, size, and origin were analyzed by nanoparticle tracking analysis and flow cytometry. EVs were enriched by ultracentrifugation for proteomic analysis. RESULTS: The COMPASS regime fundamentally altered small (<200 nm) and large (200-1000 nm) EV concentration and size compared with aspirin alone. Crucially, levels of platelet-derived and myeloperoxidase-positive EVs became significantly decreased at follow-up. Comparative proteomic characterization further revealed a significant decrease in highly proinflammatory protein expression at follow-up. CONCLUSION: The observed changes in EV subpopulations, together with the differential protein expression profiles, suggest amelioration of an underlying proinflammatory and prothrombotic state upon dual therapy, which may be of clinical relevance toward understanding the fundamental mechanism underlying the reported superior cardiovascular outcomes associated with this antithrombotic regimen.

• MeSH
• Aspirin * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• extracelulární vezikuly * metabolismus   účinky léků   MeSH
• inhibitory agregace trombocytů * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• inhibitory faktoru Xa * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární nemoci * krev   prevence a kontrola   farmakoterapie   MeSH
• kombinovaná farmakoterapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• prospektivní studie MeSH
• proteomika metody   MeSH
• rivaroxaban * aplikace a dávkování   MeSH
• senioři MeSH
• trombóza krev   prevence a kontrola   farmakoterapie   MeSH
• výsledek terapie MeSH
• zánět krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

The SARS-CoV-2 infection (COVID-19) is causing an ongoing pandemic and potentially fatal disease. Development of coagulopathy with thrombotic complications such as deep vein thrombosis and pulmonary embolism are emerging as factors for progression to severe disease and death. Also, a markedly increased level of D-dimer, a protein product of fibrin degradation, has been associated to mortality. Furthermore, activation of immune response due to virus infection may led to uncontrolled severe inflammation with damage to host cells and induction of endotheliitis and cellular apoptosis and pyroptosis. The use of low molecular weight heparin in early stage of the disease could prevent vascular complications and reduce the progression to severe stage of the disease. Aim of this paper was to summarize current evidence about vascular involvement in COVID-19 disease and potential antithrombotic therapy.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• COVID-19 komplikace   epidemiologie   MeSH
• farmakoterapie COVID-19 MeSH
• kardiologie * MeSH
• konsensus * MeSH
• lidé MeSH
• pandemie * MeSH
• SARS-CoV-2 MeSH
• společnosti lékařské * MeSH
• trombóza krev   etiologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• biologické markery krev   MeSH
• hemostáza fyziologie   MeSH
• koagulopatie krev   komplikace   diagnóza   MeSH
• lidé MeSH
• mimotělní membránová oxygenace metody   MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• transplantace plic metody   MeSH
• trombocyty fyziologie   MeSH
• trombóza krev   etiologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND The aim of the study was to investigate the role of von Willebrand factor (vWF), the vWF-cleaving protease, ADAMTS13, the composition of thrombus, and patient outcome following mechanical cerebral artery thrombectomy in patients with acute ischemic stroke. MATERIAL AND METHODS A prospective cohort study included 131 patients with ischemic stroke (<6 hours) with or without intravenous thrombolysis. Interventional procedure parameters, hemocoagulation markers, vWF, ADAMTS13, and histological examination of the extracted thrombi were performed. The National Institutes of Health Stroke Scale (NIHSS) score was used on hospital admission, after 24 hours, at day 7; the three-month modified Rankin Scale score was used. RESULTS Mechanical thrombectomy resulted in a Treatment in Cerebral Ischemia (TICI) score of 2-3, with recanalization in 89% of patients. Intravenous thrombolysis was used in 101 (78%). Patients with and without intravenous thrombolysis therapy had a good clinical outcome (score 0-2) in 47% of cases (P=0.459) using the three-month modified Rankin Scale. Patients with a National Institutes of Health Stroke Scale (NIHSS) score ≥15 had significantly increased vWF levels (P=0.003), and a significantly increased vWF: ADAMTS13 ratio (P=0.038) on hospital admission. Significant correlation coefficients were found for plasma vWF and thrombo-embolus vWF (r=0.32), platelet (r=0.24), and fibrin (r=0.26) levels. In the removed thrombus, vWF levels were significantly correlated with platelet count (r=0.53), CD31-positive cells (r=0.38), and fibrin (r=0.48). CONCLUSIONS In patients with acute ischemic stroke, mechanical cerebral artery thrombectomy resulted in a good clinical outcome in 47% of cases, with and without intravenous thrombolysis therapy.

• MeSH
• arteriae cerebrales metabolismus   patologie   MeSH
• cévní mozková příhoda krev   metabolismus   chirurgie   MeSH
• demografie MeSH
• hemokoagulace MeSH
• ischemie mozku krev   metabolismus   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protein ADAMTS13 metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• trombektomie * MeSH
• trombóza krev   imunologie   metabolismus   MeSH
• von Willebrandův faktor metabolismus   MeSH
• výsledek terapie MeSH
• zánět patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Aldosterone plays a key role in maintaining the homeostasis of the whole organism. Under some circumstances, aldosterone can contribute to the progression of cardiovascular diseases, including coronary artery disease. This study demonstrates that aldosterone associates negatively with some lipidogram parameters and positively with the concentration of homocysteine. These associations are characteristic for coronary artery disease and are not present in control subjects. The findings also indicate that in vitro aldosterone stimulates homocysteine production by rat adrenal glands, which may explain the associations observed with coronary artery disease. Moreover, we have found that aldosterone significantly modulates in vitro platelet reactivity to arachidonate and collagen - aldosterone increases the pro-aggregatory action of collagen, but decreases the pro-aggregatory potential of arachidonate. Therefore, the findings of these in vitro and ex vivo experiments indicate the existence of new pathways by which aldosterone modulates lipid- homocysteine- and platelet-dependent atherogenesis.

• MeSH
• agregace trombocytů účinky léků   MeSH
• aldosteron krev   farmakologie   MeSH
• cholesterol krev   MeSH
• homocystein biosyntéza   krev   MeSH
• kolagen metabolismus   MeSH
• kreatinin krev   MeSH
• krysa rodu rattus MeSH
• kyselina arachidonová metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nadledviny účinky léků   metabolismus   MeSH
• nemoci koronárních tepen krev   MeSH
• potkani Sprague-Dawley MeSH
• senioři MeSH
• sulfhydrylové sloučeniny krev   MeSH
• techniky in vitro MeSH
• trombóza krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Long-term performance of implanted cardiovascular grafts can be ensured if living endothelium overgrows their surface. Surface modifications to implants are therefore being sought that can encourage endothelialization while preventing thrombus formation until the natural endothelium is formed. In the present study, heparin was covalently attached to a fibrin mesh grown from a polyvinyl chloride (PVC) substrate surface by the catalytic action of surface immobilized thrombin on a fibrinogen solution. The coating prevented platelet activation, thrombin generation and clot formation, and reduced inflammatory reactions when exposed to fresh human whole blood circulating in a Chandler loop model. In addition, in vitro seeded human umbilical vein and human saphenous vein endothelial cells showed considerably enhanced attachment and proliferation on the coating. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2995-3005, 2017.

• MeSH
• aktivace trombocytů účinky léků   MeSH
• antikoagulancia chemie   farmakologie   MeSH
• biokompatibilní potahované materiály chemie   farmakologie   MeSH
• buněčná adheze účinky léků   MeSH
• cévní protézy škodlivé účinky   MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• endoteliální buňky cytologie   účinky léků   MeSH
• fibrin chemie   MeSH
• hematokrit MeSH
• hemokoagulace účinky léků   MeSH
• heparin chemie   farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• trombóza krev   etiologie   prevence a kontrola   MeSH
• vena saphena cytologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• inhibitory faktoru Xa terapeutické užití   MeSH
• koagulační faktory metabolismus   MeSH
• krvácení chemicky indukované   krev   MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• trombóza * farmakoterapie   krev   MeSH
• žilní tromboembolie * farmakoterapie   krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• biologické markery MeSH
• dospělí MeSH
• exprese genu * MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa genetika   metabolismus   MeSH
• hodnocení rizik MeSH
• hypoxie genetika   metabolismus   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorový supresorový protein VHL genetika   MeSH
• následné studie MeSH
• polycytemie komplikace   genetika   metabolismus   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• thrombospondin 1 genetika   MeSH
• trombóza krev   diagnóza   epidemiologie   etiologie   MeSH
• zárodečné mutace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• aldosteron metabolismus   MeSH
• antagonisté mineralokortikoidních receptorů škodlivé účinky   terapeutické užití   MeSH
• hemostáza účinky léků   MeSH
• hyperaldosteronismus krev   komplikace   farmakoterapie   mortalita   MeSH
• kardiovaskulární nemoci krev   chemicky indukované   komplikace   mortalita   MeSH
• krvácení krev   chemicky indukované   komplikace   mortalita   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• riziko MeSH
• trombóza krev   chemicky indukované   komplikace   mortalita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH

Controversies still exist regarding definition of the thrombotic risks in Ph- (BCR/ABL1-) myeloproliferative disorders with thrombocythemia (MPD-T). Platelet counts at diagnosis are currently not taken as a risk factor of thrombosis. In our cohort of 1179 patients with MPD-T, prospectively registered for anagrelide treatment, we found that the median platelet count prior to the thrombotic event was significantly higher than at time points without any ensuing thrombosis (453 vs. 400 × 10(9)/L, P < 0.001), albeit higher platelet counts at diagnosis tended to be connected with fewer thrombotic events (in contrast to WBC counts at diagnosis). The JAK2(V617F) mutation predicted both arterial and venous events, while age >65 yr, hypertension, diabetes mellitus, smoking, elevated triglyceride and homocysteine levels predicted arterial events only. For venous events, the specific thrombophilic risk factors (factor V 'Leiden' and others), antiphospholipid antibodies, and elevated factor VIII levels played a major role. During anagrelide treatment (± aspirin), we documented a decrease in both venous (6.7-fold) and arterial events (1.8-fold), while bleeding (mostly minor events) increased twofold compared to history. Our results suggest that keeping platelet counts at low levels may be a meaningful therapeutic measure to prevent thrombosis, although their counts at diagnosis lack any prognostic value.

• MeSH
• Aspirin aplikace a dávkování   MeSH
• bcr-abl fúzní proteiny MeSH
• chinazoliny aplikace a dávkování   MeSH
• filadelfský chromozom * MeSH
• Janus kinasa 2 genetika   MeSH
• lidé MeSH
• missense mutace MeSH
• počet trombocytů MeSH
• prospektivní studie MeSH
• registrace * MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• substituce aminokyselin MeSH
• trombocytóza * krev   komplikace   farmakoterapie   genetika   MeSH
• trombóza * krev   farmakoterapie   etiologie   genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH