Bleeding in anticoagulated patients with atrial fibrillation : practical considerations

Major bleeding (especially intracranial hemorrhage) is the most feared adverse event observed in patients with atrial fibrillation (AF) receiving oral anticoagulation. Clinical risk factor–based scores have modest ability to predict major or clinically relevant bleeds, and blood biomarkers are increasingly implemented to improve bleeding prognostication in patients with AF on life‑long anticoagulation. To improve the safety of anticoagulation in the era of non–vitamin K antagonist oral anticoagulants (NOACs, or direct oral anticoagulants [DOACs], including dabigatran, rivaroxaban, apixaban, and edoxaban), specific demographic, clinical, and laboratory variables should be considered. The current review summarizes practical challenges in the management of oral anticoagulation with emphasis on the risk assessment tools, elderly or underweight patients, cancer patients, impact of chronic kidney disease, liver cirrhosis, and thrombocytopenia in the context of bleeding risk in patients with AF

Antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention

The management of atrial fibrillation (AF) in patients who have undergone percutaneous coronary intervention (PCI) with stent implantation is challenging. Oral anticoagulation has been shown to significantly reduce the risk of stroke in AF, whereas dual antiplatelet therapy prevents major adverse cardiovascular events, including stent thrombosis after PCI. A typical triple antithrombotic therapy, involving an anticoagulant, i.e. vitamin K antagonist (VKA), together with aspirin and P2Y12 inhibitor, usually clopidogrel, has been shown to minimize ischemic and stroke risks, but is associated with increased risk of major bleeding. The use of dabigatran, rivaroxaban, or apixaban in combination with antiplatelet agents lowers the risk of major bleeding and makes it an option preferred over triple therapy in the majority of PCI patients with AF. The consistency across randomized controlled trials on combination therapy with non-vitamin K antagonist oral anticoagulant (NOAC) and clopidogrel, including patients with acute coronary syndromes, led to changes in everyday practice. However, the use of triple and dual antithrombotic therapy at high bleeding risk should be individualized. The present review summarizes available data on the efficacy and safety of antithrombotic therapy in AF patients undergoing PCI in the era of NOAC

Prognostic significance of age in patients with acute ischaemic stroke treated with intravenous thrombolysis

Aim of the study. To assess the influence of age on long-term functional outcome in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT).Material and methods. We performed retrospective analysis of 362 AIS patients treated with IVT or IVT and subsequent mechanical thrombectomy in the University Hospital in Krakow, Poland. Patients were categorised into four subgroups by age: (I) below the age of 60, (II) 60 to 69, (III) 70 to 79, and (IV) 80 or more. The outcomes were assessed with modified Rankin scale (mRS) 90 days after stroke onset, and defined as favourable (mRS 0–2), poor (mRS 3–5), or death (mRS = 6).Results. Patients aged 80 or more compared to those below 60 were more often women (72.64% vs. 26.76%, < 0.001), more often suffered from hypertension (94.34% vs. 60.56%, p < 0.001), ischaemic heart disease (27.36% vs. 8.45%, p = 0.002), atrial fibrillation (49.06% vs. 5.63%, p < 0.001), and premorbid disability (pre-stroke mRS ≥ 1: 17.92% vs. 1.41%, p < 0.001), less often were active smokers (0% vs. 27.14%, p < 0.001), more often had cardioembolic aetiology (50.00% vs. 16.90%, p < 0.001), and less often other stroke aetiology (1.89% vs. 15.49%, < 0.008), had shorter time from stroke onset to IVT (125 [93–180] vs. 140 [110–186] min, p < 0.008), less often underwent mechanical thrombectomy (18.87% vs. 46.48%, p < 0.001), had higher CRP levels (10.3 [3.2–39.8] vs. 4.3 [2.1–9.6] mg/L, p = 0.003), higher maximal systolic blood pressure within 24 hours after IVT (153 [140–170] vs. 138 [120–145] mmHg, p < 0.001), and higher creatinine concentration (88 [68–108] vs. 77 [67–87] μmol/l, p = 0.004), less often had a favourable outcome (48.04% vs. 85.51%, odds ratio [OR] 0.16, 95%CI: 0.07–0.34, p < 0.001), and had a greater risk of death (26.47% vs. 5.80%, OR 5.85, 95%CI: 1.95–17.59, p < 0.001) within three months of stroke onset. Multivariable logistic regression analysis showed that the independent predictors of worse outcome in patients aged 80 or more were NIHSS score after IVT (OR 0.64, 95%CI: 0.53–0.78, p < 0.001), pre-stroke mRS score ≥ 1 (OR 0.10, 95%CI: 0.02–0.61, p = 0.012), and CRP levels (OR 0.96, 95%CI: 0.93–0.99, p = 0.007).Conclusions. AIS patients treated with reperfusion therapy and aged 80 or more have around a six times higher risk of an unfavourable outcome or death within three months of stroke onset compared to those aged below 60. Higher NIHSS score after IVT, any signs of disability before stroke as measured with mRS, and higher CRP levels are independent risk factors for worse prognosis in the elderly

Flow cytometric assessment of endothelial and platelet microparticles in patients with atrial fibrillation treated with dabigatran

The prothrombotic state in patients with atrial fibrillation (AF) is related to endothelial injury, the activation of platelets and the coagulation cascade. We evaluated the levels of platelet- (CD42b) and endothelial-derived (CD144) microparticles in the plasma patients with non-valvular AF treated with dabigatran at the time of expected minimum and maximum drug plasma concentrations. Following that, we determined the peak dabigatran plasma concentration (cpeak ). CD42b increased after taking dabigatran (median [IQR] 36.7 [29.4-53.3] vs. 45.6 [32.3-59.5] cells/mL; p ¼ 0.025). The concentration of dabigatran correlated negatively with the post-dabigatran change in CD42b (DCD42b, r ¼ -0.47, p ¼ 0.021). In the multivariate model, the independent predictors of DCD42b were: cpeak (HR -0.55; with a 95% confidence interval, CI [-0.93, -0.16]; p ¼ 0.007), coronary artery disease (CAD) (HR -0.41; 95% CI [-0.79, -0.02]; p ¼ 0.037) and peripheral artery disease (PAD) (HR 0.42; 95% CI [0.07, 0.74]; p ¼ 0.019). CD144 did not increase after dabigatran administration. These data suggest that low concentrations of dabigatran may be associated with platelet activation. PAD and CAD have distinct effects on CD42b levels during dabigatran treatment

Course of fatigue among patients previously hospitalised due to COVID-19

Introduction. Discrepancies exist regarding the clinical course and prognostic factors for post-COVID fatigue. Therefore, our aim was to assess the timely course of fatigue and its possible predictors in patients previously hospitalised due to SARS-CoV-2 infection. Material and methods. Patients and employees of the University Hospital in Krakow were assessed with the use of a validated neuropsychological questionnaire. Included were participants aged 18 or more, previously hospitalised due to COVID-19, who completed questionnaires only once > 3 months after the onset of infection. Individuals were retrospectively asked about the presence of eight symptoms of chronic fatigue syndrome at four timepoints: before COVID-19, within 0–4 weeks, 4–12 weeks, and > 12 weeks post-infection. Results. We enrolled 204 patients [40.2% women, median age 58 (46–66) years] evaluated after a median of 187 (156–220) days from the first positive nasal swab test for SARS-CoV-2. The most common comorbidities were hypertension (44.61%), obesity (36.27%), smoking (28.43%), and hypercholesterolemia (21.08%); none of the patients required mechanical ventilation during hospitalisation. Before COVID-19, 43.62% of patients reported at least one symptom of chronic fatigue. Within 4, 4–12, and > 12 weeks after COVID-19, the prevalence of chronic fatigue was 76.96%, 75.49%, and 66.17%, respectively (all p < 0.001). The frequency of chronic fatigue symptoms decreased within > 12 weeks following the onset of infection but did not return to baseline values, except for self-reported lymph node enlargement. In a multivariable linear regression model, the number of fatigue symptoms was predicted by female sex [β 0.25 (0.12; 0.39), p < 0.001 and 0.26 (0.13; 0.39), p < 0.001 for weeks 0–12 and > 12, respectively], and age [for < 4 weeks, β –0.12 (–0.28; –0.01), p = 0.029]. Conclusions. Most patients previously hospitalised due to COVID-19 suffer from fatigue > 12 weeks after infection onset. The presence of fatigue is predicted by female sex and – only for the acute phase — age

The role of glucagon-like peptide 1-receptor gene in type 2 diabetes

WSTĘP. Celem badania było poszukiwanie związku między polimorfizmami Gly168Ser i Leu260Phe genu receptora glukagonopodobnego peptydu-1 z cukrzycą typu 2 w populacji polskiej. MATERIAŁ I METODY. Analizowano materiał genetyczny 462 chorych na cukrzycę typu 2 i 428 zdrowych ochotników. Genotypowanie polimorfizmów wykonywano, namnażając odpowiednie fragmenty DNA za pomocą reakcji łańcuchowej polimerazy, tnąc namnożone fragmenty enzymami restrykcyjnymi i uwidaczniając produkty cięcia na żelu agarozowym z dodatkiem bromku etydyny. Analiza statystyczna obejmowała test c2 dla zbadania zależności genotypów z chorobą i regresję logistyczną dla zbadania zależności haplotypów z chorobą. WYNIKI. Częstość homozygot Ser/Ser była znamiennie wyższa w grupie chorych na cukrzycę (15,7%) niż w grupie kontrolnej (9,8%), p = 0,03. Iloraz szans rozwoju cukrzycy u tych pacjentów wskazywał na niemal 2-krotnie wyższe ryzyko niż u pacjentów niebędących homozygotami Ser/Ser. Polimorfizm w pozycji 260 oraz haplotypy utworzone przez dwa badane polimorfizmy nie były związane z występowaniem cukrzycy typu 2. WNIOSKI. Wyniki badania sugerują, że polimorfizm Gly168Ser jest potencjalnym czynnikiem ryzyka cukrzycy typu 2 w populacji polskiej. Obserwacja ta wymaga potwierdzenia w innych grupach etnicznych.INTRODUCTION. The aim of the study was to search for the association between Gly168Ser and Leu260Phe amino acid variants of the glucagon-like peptide 1 receptor gene and type 2 diabetes in a Polish population. METHODS. 462 patients with type 2 diabetes and 428 healthy volunteers were genotyped by restriction fragments length polymorphism method after amplification of examined genome fragment by polymerase chain reaction technique. The digestion products were separated and visualized by electrophoresis on agarose gel containing ethidium bromide. Statistical analysis involved chi-square test for genotype-phenotype association and logistic regression for association of phenotype with haplotypes. RESULTS. Ser/Ser homozygotes frequency in diabetic patients group was significantly higher than in control group (15.7% vs. 9.8%, p = 0,03). Odds ratio of having type 2 diabetes in Ser/Ser carriers group versus other genotype carriers showed almost two fold risk increase associated with this genotype. Polymorphism in 260 amino acid position and haplotypes of the analyzed polymorphisms were not associated with type 2 diabetes. CONCLUSIONS. The results of the study suggest that polymorphism Gly168Ser may be potentially a risk factor of the type 2 diabetes in Polish population. This observation should be evaluated in other ethnic groups

Sex-related patient-reported brain fog symptoms in non-hospitalised COVID-19 patients

Introduction. Previous studies on the prognostic role of sex in post-COVID-associated brain fog have yielded divergent results. Moreover, limited evidence exists regarding the evolution of brain fog symptoms over time, especially in ambulatory patients and separately for women and men. Therefore, the aim of the current study was to assess brain fog symptoms in nonhospitalised patients with COVID-19, according to their sex. Material and methods. We created a neuropsychological questionnaire including eight questions on the presence of brain fog symptoms in the following four time periods: before COVID-19, and 0–4, 4–12, and > 12 weeks post-infection. The validity and reliability of the questionnaire were assessed. In this cross-sectional study, questionnaires were filled out anonymously and retrospectively once only by patients or through a survey link posted online. Included were patients ≥ 18 years, with > 3 months since the SARS-CoV-2 infection onset confirmed by RT-PCR from a nasopharyngeal swab. Results. The study included 303 patients (79.53% women, 47.52% medical personnel). Median time between COVID-19 onset and questionnaire completion was 208 (IQR 161–248) days. Women, compared to men, reported a higher prevalence of problems with writing, reading, and counting (< 4 weeks, OR 3.05, 95% CI: 1.38–6.72; 4–12 weeks, OR 2.51, 95% CI: 1.02–6.14; > 12 weeks, OR 3.74, 95% CI: 1.12–12.56) and thoughts communication (< 4 weeks, OR 2.53, 95% CI: 1.41–4.54; 4–12 weeks, OR 3.74, 95% CI: 1.93–7.24; > 12 weeks, OR 2.00, 95% CI: 1.01–3.99). The difference between the two sexes in answering questions in an understandable/unambiguous manner was statistically significant between four and 12 weeks after infection (OR 2.63, 95% CI: 1.36–5.10), while a sex difference in recalling new information was found below 12 weeks (OR 2.54, 95% CI: 1.44–4.48 and OR 2.43, 95% CI: 1.37–4.31 for < 4 and 4–12 weeks, respectively). No sex differences in reporting problems with multitasking, remembering information from the past, determining the current date, or field orientation were noted. Conclusions. Non-hospitalised women and men retrospectively report a different course of COVID-19-associated brain fog