BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in critically ill patients, who often have multiple risk factors. Pharmacological thromboprophylaxis is widely applied to lower this risk, but guidelines lack dosing recommendations. OBJECTIVE: This survey aims to assess current thromboprophylaxis preferences and willingness to participate in future randomized clinical trials (RCTs) on this topic. METHOD: We conducted an international online survey between February and May 2023 among intensive care unit (ICU) physicians, including 16 questions about preferences in relation to thromboprophylaxis and preferences on topics for a future RCT. The survey was distributed through the network of the Collaboration for Research in Intensive Care. RESULTS: A total of 715 physicians from 170 ICUs in 23 countries contributed information, with a mean response rate of 36%. In most ICUs, both pharmacological (n = 166, 98%) and mechanical thromboprophylaxis (n = 143, 84%) were applied. A total of 36 pharmacological thromboprophylaxis regimens were reported. Use of low-molecular-weight heparin (LMWH) was most common (n = 149 ICUs, 87%), followed by subcutaneous unfractionated heparin (n = 44 ICUs, 26%). Seventy-five percent of physicians indicated that they used enoxaparin 40 mg (4000 IU), dalteparin 5000 IU, or tinzaparin 4500 IU once daily, whereas 25% reported the use of 16 other LMWH type and dose combinations. Dose adjustment according to weight was common (78 ICUs, 46%). Participants perceived high variation in the application of thromboprophylaxis and were willing to consider an alternative LMWH type (n = 542, 76%) or dose (n = 538, 75%) in the context of an RCT. CONCLUSION: LMWH was the preferred agent for thromboprophylaxis in critically ill patients. There was considerable variation in the application of LMWH for prophylaxis, reflected by the use of different types, doses, and dosing strategies. Most physicians would be willing to participate in an RCT on thromboprophylaxis. EDITORIAL COMMENT: This survey demonstrates current patterns in implementation preferences for critically ill patients. While there is one approach and drug that is commonly preferred, these findings show that there is some variation in practice.

• Klíčová slova
• ICU, survey, thromboprophylaxis,
• MeSH
• antikoagulancia * terapeutické užití   aplikace a dávkování   MeSH
• heparin nízkomolekulární * terapeutické užití   aplikace a dávkování   MeSH
• internacionalita MeSH
• jednotky intenzivní péče * MeSH
• kritický stav MeSH
• lékaři MeSH
• lidé MeSH
• péče o pacienty v kritickém stavu metody   MeSH
• průzkumy a dotazníky MeSH
• žilní tromboembolie * prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikoagulancia * MeSH
• heparin nízkomolekulární * MeSH

BACKGROUND: Unfractionated heparin is used as the most common anticoagulation for venovenous extracorporeal membrane oxygenation (VV ECMO) patients. However, it is accompanied by frequent bleeding and thrombotic complications. The aim of the study was to demonstrate the feasibility of Enoxaparin anticoagulation for VV ECMO patients. METHODS: This study is a retrospective analysis of VV ECMO patients on continuous intravenous Enoxaparin anticoagulation. The primary outcome was the incidence of bleeding, thrombotic, and neurological complications during ECMO support. The secondary outcome was an analysis of secondary and primary hemostasis profiles. RESULTS: Data from 38 patients were analyzed in this study. The incidence of bleeding complications was 5.3%, for thrombotic complications it was 2.6% and for neurological (bleeding/ischemic events) complications it was 10.5%. The targeted anti-Xa activity of 0.4-0.6 IU/mL was achieved and maintained during whole ECMO period in 28 patients (73.8%), not affecting the hemocoagulation profile represented by APTT-r 1.15 ± 0.2, TT 18.67 ± 3.35 s, PT/INR 1.21 ± 0.19, fibrinogen 5.39 ± 1.49 g/L, antithrombin, and platelet count. Primary hemostasis pathology was diagnosed in all patients by PFA 200 tests Col/EPI 279 ± 38 s and Col/ADP 249 ± 66 s. The running time of ECMO was 7.8 ± 3.4 days. CONCLUSIONS: Enoxaparin anticoagulation appears to be feasible for VV ECMO patients without an increase in adverse events. Further larger-sampled and comparative studies are needed in the future to support our findings.

• Klíčová slova
• anticoagulation, enoxaparin, extracorporeal membrane oxygenation, heparin, primary hemostasis,
• MeSH
• antikoagulancia aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• enoxaparin * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• inhibitory faktoru Xa aplikace a dávkování   terapeutické užití   MeSH
• intravenózní podání MeSH
• krvácení * prevence a kontrola   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace * škodlivé účinky   metody   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• studie proveditelnosti MeSH
• trombóza prevence a kontrola   etiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikoagulancia MeSH
• enoxaparin * MeSH
• inhibitory faktoru Xa MeSH

Chronic Kidney Disease (CKD) is associated with heightened risk of thrombosis. Prescription of anticoagulants is key to manage it; however, CKD patients have shown an increased risk of bleeding under anticoagulation therapy compared to non-CKD patients. We hypothesized that the sex could modify the metabolism of indoxyl sulfate (IS), a uremic toxin and Apixaban. Our intoxication model shows that higher doses of IS and apixaban accumulate in the plasma of female mice because of expression differences in efflux transporters and cytochromes in the liver, ileum and kidneys, when compared to males. Furthermore, we found that accumulation of apixaban in females contributes to increased bleeding. Transcriptional analysis of liver samples revealed elevated Sult1a1 but reduced Abcg2 and Cyp3a11 in female mice, while in the kidneys the expression rates of Oat1 and Oat3 were respectively lower and higher than those observed in males, potentially affecting drug clearance. Whole proteomics liver analysis confirmed the previous transcriptional results at the protein level and revealed that sex had a major influence in regulating both coagulation and drug metabolism pathways. Thus, our findings underline the need for inclusive clinical and preclinical trials to accurately reflect sex-specific metabolic variations, and to consider CKD-specific changes to optimize dosing, minimize side effects, and improve patient outcomes.

• MeSH
• ABC transportér z rodiny G, člen 2 metabolismus   genetika   MeSH
• antikoagulancia aplikace a dávkování   metabolismus   MeSH
• chronická renální insuficience metabolismus   farmakoterapie   MeSH
• cytochrom P-450 CYP3A metabolismus   genetika   MeSH
• indican * metabolismus   krev   MeSH
• játra * metabolismus   účinky léků   MeSH
• krvácení metabolismus   MeSH
• ledviny metabolismus   účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• přenašeče organických aniontů nezávislé na sodíku metabolismus   genetika   MeSH
• protein 1 přenášející organické anionty metabolismus   genetika   MeSH
• pyrazoly * farmakologie   MeSH
• pyridony * aplikace a dávkování   metabolismus   farmakologie   MeSH
• sexuální faktory MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABC transportér z rodiny G, člen 2 MeSH
• antikoagulancia MeSH
• apixaban MeSH Prohlížeč
• cytochrom P-450 CYP3A MeSH
• indican * MeSH
• organic anion transport protein 3 MeSH Prohlížeč
• přenašeče organických aniontů nezávislé na sodíku MeSH
• protein 1 přenášející organické anionty MeSH
• pyrazoly * MeSH
• pyridony * MeSH

UNLABELLED: Direct oral anticoagulants from the perspective of Czech pharmacists - opinions, attitudes, confidence, and patient education during dispensing in a pharmacy Introduction and Aim: Pharmacists play an important role in the management of anticoagulation therapy, therefore good knowledge and confidence in care of patients treated with anticoagulation are essential. The aim of this study was to analyse the opinions and attitudes of pharmacists in the Czech Republic towards direct oral anticoagulants (DOACs), their perception of the benefits and risks of DOACs, and the position of pharmacists in educating patients about the basic principles of DOAC treatment in the context of dispensing these medicines in pharmacies. METHODS: An online anonymous questionnaire survey conducted in 2021 among pharmacists of three specific District Pharmacists Associations of the Czech Chamber of Pharmacy. The questionnaire included 32 open- and closed-ended questions, and questions for reporting of the level of agreement using a Likert scale. Descriptive statistics, parametric and non-parametric tests were used to evaluate the data. RESULTS: A total of 162 pharmacists participated (14% return rate), 139 of whom dispensed medicines in a pharmacy in the last year. Respondents working in pharmacies located in any health centre and in hospital pharmacies reported dispensing DOACs more frequently (p < 0.001). The majority of respondents (73%) felt completely or rather confident in providing expert information regarding DOACs. Higher confidence was associated with respondents working in hospital pharmacies or pharmacies located in health centres (p < 0.05), working in clinical pharmacy wards (p < 0.05) and being more likely to dispense DOACs in the pharmacy (p < 0.001). Higher confidence was related to the areas pharmacists discussed with patients during DOAC dispensing, e.g., reasons for using DOACs or how to administer. CONCLUSION: The frequency of dispensing DOACs, type of pharmacy, and working as clinical pharmacist influenced respondents' confidence towards DOACs. Confidence may have influenced the course of DOAC dispensing in the pharmacy. Consolidating the pharmacist's position in patient education during DOAC treatment and strengthening pharmacists' confidence in dispensing DOACs should be therefore considered.

• Klíčová slova
• pharmacists, DOACs, attitude, opinions, education,
• MeSH
• antikoagulancia * terapeutické užití   MeSH
• aplikace orální MeSH
• farmaceuti * MeSH
• lidé MeSH
• postoj zdravotnického personálu * MeSH
• průzkumy a dotazníky MeSH
• vzdělávání pacientů jako téma * MeSH
• zdraví - znalosti, postoje, praxe MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antikoagulancia * MeSH

BACKGROUND: Anticoagulation during extracorporeal membrane oxygenation (ECMO) might still lead to severe bleeding complications. Heparin is the most frequently used anticoagulant, but novel drugs could be promising. Argatroban is a new alternative to heparin. To date, no robust studies have confirmed the clear superiority of argatroban (AG) over heparin, although it has some advantages and may be safer. STUDY DESIGN AND METHODS: An observational study was conducted in all adult veno-venous ECMO patients with COVID-19-associated acute respiratory distress syndrome admitted to the University Hospital Ostrava (n = 63). They were anticoagulated with heparin in the first period and with AG in the second period, targeting the same activated partial thromboplastin time (aPTT; 45-60 s). Bleeding complications requiring transfusion and life-threatening bleeding events were evaluated. The primary objective was to compare heparin and AG in terms of bleeding, transfusion requirements and mortality-related bleeding. RESULTS: The total time on ECMO per patient was 16 days with an in-hospital mortality of 55.6%. The red blood cell consumption in the AG group (median 2.7 transfusions/week) was significantly lower than in the heparin group (median 4.2 transfusions/week, p = 0.011). Life-threatening bleeding complications were higher in the heparin group compared to the AG group (35.7% vs. 10.2%, p = 0.035), and mortality-related bleeding complications were also higher in the heparin group (21.4% vs. 2.0%, p = 0.032). DISCUSSION: Argatroban is an interesting alternative to heparin with less bleeding, less need for red blood cell transfusions and improved safety of ECMO with less mortality-related bleeding.

• Klíčová slova
• anticoagulation, argatroban, bleeding, extracorporeal membrane oxygenation (ECMO), heparin,
• MeSH
• antikoagulancia * škodlivé účinky   terapeutické užití   MeSH
• arginin * analogy a deriváty   MeSH
• COVID-19 komplikace   MeSH
• dospělí MeSH
• heparin * škodlivé účinky   MeSH
• krvácení * chemicky indukované   terapie   MeSH
• kyseliny pipekolové * terapeutické užití   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace * MeSH
• mortalita v nemocnicích MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• sulfonamidy * MeSH
• syndrom dechové tísně terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH
• Názvy látek
• antikoagulancia * MeSH
• argatroban MeSH Prohlížeč
• arginin * MeSH
• heparin * MeSH
• kyseliny pipekolové * MeSH
• sulfonamidy * MeSH

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.

• Klíčová slova
• aspirin, cardiovascular disease, extracellular vesicles, proteomics, rivaroxaban,
• 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
• Názvy látek
• Aspirin * MeSH
• inhibitory agregace trombocytů * MeSH
• inhibitory faktoru Xa * MeSH
• mediátory zánětu MeSH
• rivaroxaban * MeSH

BACKGROUND: Randomized clinical trials demonstrated similar efficacy and improved safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation (AF). Long-term data in routine clinical practice are needed. HYPOTHESIS: Patients with AF receiving edoxaban at baseline continue to have low annualized effectiveness and safety event rates in the second year of follow-up, with regional variations observed. METHODS: The Global ETNA-AF program is a prospective, noninterventional study of patients with AF receiving edoxaban. Patient characteristics and annualized clinical event rates were assessed overall and by region across the 2-year follow-up. Annualized event rates of bleeding and thromboembolic events were assessed within the first year and conditionally in patients who were event-free up to 12 months in the second year. RESULTS: This analysis comprised 26 805 patients from Europe (n = 13 164), Japan (n = 10 342), and non-Japanese Asian regions (n = 3299). Patients from Europe had the highest burden of comorbidities. The annualized event rates for major bleeding, any stroke, all-cause death, and cardiovascular death varied by region. The global annualized event rates in the first and second year were 1.31%/year and 0.86%/year for major bleeding, 1.06%/year and 0.65%/year for any stroke, 0.84%/year and 0.73%/year for cardiovascular death, and 3.05%/year and 3.18%/year for all-cause death. CONCLUSION: Annualized event rates for any stroke and major bleeding remained low through 2-year follow-up for patients with AF receiving edoxaban at baseline. Differences in annualized event rates for all-cause and cardiovascular mortality between Europe, Japan, and non-Japanese Asian regions may reflect variations in baseline characteristics. TRIAL REGISTRATION: Europe, NCT02944019; Japan, UMIN000017011; Korea/Taiwan, NCT02951039; Hong Kong, NCT03247582; and Thailand, NCT03247569.

• Klíčová slova
• anticoagulation, atrial fibrillation, direct oral anticoagulant (DOAC), edoxaban, major bleeding, oral anticoagulants, stroke prevention,
• MeSH
• časové faktory MeSH
• cévní mozková příhoda prevence a kontrola   epidemiologie   etiologie   MeSH
• fibrilace síní * farmakoterapie   komplikace   MeSH
• incidence MeSH
• inhibitory faktoru Xa * terapeutické užití   škodlivé účinky   MeSH
• krvácení * chemicky indukované   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prospektivní studie MeSH
• pyridiny * terapeutické užití   škodlivé účinky   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thiazoly * terapeutické užití   škodlivé účinky   MeSH
• tromboembolie prevence a kontrola   epidemiologie   etiologie   MeSH
• výsledek terapie 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
• multicentrická studie MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• edoxaban MeSH Prohlížeč
• inhibitory faktoru Xa * MeSH
• pyridiny * MeSH
• thiazoly * MeSH

BACKGROUND: Abelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown. METHODS: Patients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion. The primary end point was major or clinically relevant nonmajor bleeding. RESULTS: A total of 1287 patients underwent randomization; the median age was 74 years, and 44% were women. At 3 months, the median reduction in free factor XI levels with abelacimab at a dose of 150 mg was 99% (interquartile range, 98 to 99) and with abelacimab at a dose of 90 mg was 97% (interquartile range, 51 to 99). The trial was stopped early on the recommendation of the independent data monitoring committee because of a greater-than-anticipated reduction in bleeding events with abelacimab. The incidence rate of major or clinically relevant nonmajor bleeding was 3.2 events per 100 person-years with 150-mg abelacimab and 2.6 events per 100 person-years with 90-mg abelacimab, as compared with 8.4 events per 100 person-years with rivaroxaban (hazard ratio for 150-mg abelacimab vs. rivaroxaban, 0.38 [95% confidence interval {CI}, 0.24 to 0.60]; hazard ratio for 90-mg abelacimab vs. rivaroxaban, 0.31 [95% CI, 0.19 to 0.51]; P<0.001 for both comparisons). The incidence and severity of adverse events appeared to be similar in the three groups. CONCLUSIONS: Among patients with atrial fibrillation who were at moderate-to-high risk for stroke, treatment with abelacimab resulted in markedly lower levels of free factor XI and fewer bleeding events than treatment with rivaroxaban. (Funded by Anthos Therapeutics; AZALEA-TIMI 71 ClinicalTrials.gov number, NCT04755283.).

• MeSH
• antikoagulancia škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• aplikace orální MeSH
• cévní mozková příhoda * prevence a kontrola   MeSH
• dvojitá slepá metoda MeSH
• faktor XI antagonisté a inhibitory   MeSH
• fibrilace síní * farmakoterapie   komplikace   MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• inhibitory faktoru Xa * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• injekce subkutánní MeSH
• krvácení * chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rivaroxaban * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři 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
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• antikoagulancia MeSH
• faktor XI MeSH
• humanizované monoklonální protilátky * MeSH
• inhibitory faktoru Xa * MeSH
• rivaroxaban * MeSH

Despite the widespread use of anticoagulant rodenticides in baits for controlling commensal rodent pests, their application is problematic due to secondary intoxication and increasing resistance. In contrast to studies on Western European house mice (Mus musculus domesticus), few resistance studies have focused on Eastern European house mice (M. musculus musculus), which have a western distribution boundary in the Czech Republic. This study newly analysed the VKORC1 gene in M. m. musculus field populations from Czech farms and grain stores and identified a nonsynonymous mutation Tyr139Phe. This mutation was common throughout the Czech Republic and was present in 80.2% of the 86 individuals sampled. Additionally, all individuals exhibited a genotype with three synonymous mutations specific to the subspecies M. m. musculus. The functional (mortality-survival) response of the Tyr139Phe mutation was validated in a laboratory choice feeding test using bromadiolone-based bait, where all resistant homozygous individuals survived, while all susceptible mice died, with a mean survival of 6.9 days.

• Klíčová slova
• Mus musculus musculus, VKORC1, Anticoagulant rodenticides, Resistance, Rodent pests,
• MeSH
• 4-hydroxykumariny MeSH
• antikoagulancia * farmakologie   MeSH
• genotyp MeSH
• léková rezistence genetika   MeSH
• mutace * MeSH
• myši MeSH
• rodenticidy * MeSH
• vitamin K - epoxid reduktázy * genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• 4-hydroxykumariny MeSH
• antikoagulancia * MeSH
• bromadiolone MeSH Prohlížeč
• rodenticidy * MeSH
• vitamin K - epoxid reduktázy * MeSH

OBJECTIVES: To determine whether selected single nucleotide polymorphisms (SNPs) of genes encoding proteins responsible for the activation, transport, or metabolism of dabigatran and apixaban might be associated with a risk of gastrointestinal bleeding in a cohort of adult patients treated with these drugs. No previous study has focused specifically on the association with gastrointestinal bleeding. MATERIALS AND METHODS: Ninety-one patients treated with dabigatran or apixaban were genotyped for selected polymorphisms. The following polymorphisms were studied: ABCB1 gene rs1045642, rs4148738, rs1128503 and rs2032582; CES1 gene rs2244613, rs8192935 and rs2244614; and SULT1A1 gene rs9282861 and SULT1A2 gene rs1136703. Two groups divided by particular drugs and genotypes were compared in terms of the presence (bleeding group) or absence (nonbleeding group) of gastrointestinal bleeding. The genotype distribution was expressed via dominant and recessive models. RESULTS: In patients treated either with dabigatran or with apixaban, no evidence was found to support the association of gastrointestinal bleeding with any genotype for any of the studied SNPs. CONCLUSION: In both dabigatran- and apixaban-treated patients, no associations between the selected polymorphisms and gastrointestinal bleeding risk were found, however the results should be interpreted with caution because of the small cohort size.

• MeSH
• antithrombiny škodlivé účinky   terapeutické užití   MeSH
• dabigatran * škodlivé účinky   MeSH
• dospělí MeSH
• farmakogenetika MeSH
• gastrointestinální krvácení * genetika   chemicky indukované   MeSH
• genotyp MeSH
• inhibitory faktoru Xa škodlivé účinky   terapeutické užití   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• P-glykoproteiny MeSH
• pyrazoly * škodlivé účinky   terapeutické užití   MeSH
• pyridony * škodlivé účinky   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři 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
• časopisecké články MeSH
• Názvy látek
• ABCB1 protein, human MeSH Prohlížeč
• antithrombiny MeSH
• apixaban MeSH Prohlížeč
• dabigatran * MeSH
• inhibitory faktoru Xa MeSH
• P-glykoproteiny MeSH
• pyrazoly * MeSH
• pyridony * MeSH