Low bleeding acceptance is associated with increased death risk in patients with atrial fibrillation on oral anticoagulation.

Bleeding is the most feared complication of anticoagulation. We sought to investigate whether the bleeding risk acceptance has a prognostic value during long-term follow-up in the era of direct oral anticoagulants (DOACs) among patients with atrial fibrillation (AF). We studied 167 consecutive AF outpatients [aged 68.8 SD 10.6 years; 141 (84.4%) on DOACs]. The bleeding acceptance was assessed based on the Bleeding Ratio defined as the declared maximum number of major bleedings that a patient would be willing to accept to prevent one major stroke. We recorded cerebrovascular ischemic events, major or clinically relevant non-major bleeds (CRNMB), and mortality. A median Bleeding Ratio was 4 (IQR 2-5). During follow-up of 946 patient-years, cerebrovascular ischemic events and/or death were observed in 28 patients (3.3%/ year) and major bleeding or CRNMB in 33 (4.6%/ year). The Bleeding Ratio was lower in patients who experienced cerebrovascular events or death (p = 0.004), but not bleeding. Patients with the Bleeding Ratio 0-3 were more often non-persistent to the OAC therapy, and more likely to have cerebrovascular event or die than those with higher bleeding acceptance (odds ratio 2.55; 0.95% CI 1.08-6.02) which was driven by the impact on mortality. The multiple Cox proportional hazards model showed that lower Bleeding Ratio, higher CHA2DS2-VASc score, and older age predicted cerebrovascular events or death during follow-up. AF patients who are willing to accept fewer serious bleedings to avoid major stroke during anticoagulation are more likely to experience death and/or cerebrovascular ischemic events, but not bleeding, what might be related to non-persistence.

Factors affecting self-reported bleeding acceptance in acute ischemic stroke survivors on various types of antithrombotic therapy.

OBJECTIVES: Prior ischemic cerebrovascular event and younger age have been shown to increase bleeding acceptance among anticoagulated outpatients with atrial fibrillation (AF). We sought to determine factors affecting bleeding acceptance in acute ischemic stroke (AIS) survivors on various types of antithrombotic therapy. MATERIALS AND METHODS: We enrolled 173 consecutive patients hospitalized for AIS (aged 68.2±11.7 years, 54.9% male), including 54 (31.2%) with AF, who had favorable functional outcome. On discharge, the Bleeding ratio, defined as the declared maximum number of major bleedings that a patient is willing to accept to prevent one major stroke, was evaluated. We assessed the predicted bleeding risk in non-cardioembolic and cardioembolic stroke survivors using S2TOP-BLEED and HAS-BLED scores, respectively. RESULTS: Patients with the low Bleeding ratio, defined as 5 (median) or less accepted bleeds (n=92; 53.2%), were older and more likely to receive thrombolysis and/or thrombectomy, with no impact of previous stroke. Prior major bleed (odds ratio [OR] 4.67; 95% confidence interval [CI] 0.92-23.72), AF with use of oral anticoagulants (OR 2.35, 95% CI 1.12-4.93), reperfusion treatment (OR 1.95, 95% CI 1.02-3.76), and hospitalization ≤10 days (OR 4.56; 95% CI 1.50-13.87) were associated with the low Bleeding Ratio. Prior use of anticoagulants or aspirin as well as HAS-BLED and S2TOP-BLEED scores did not affect the bleeding acceptance. CONCLUSIONS: Lower bleeding acceptance declared on discharge by AIS survivors is determined by prior bleeding, anticoagulation in AF, reperfusion treatment, and duration of hospitalization, which might affect medication adherence. The results might help optimize post-discharge management and educational efforts in patients on antithrombotic therapy.

Transcranial Magnetic Stimulation as a Diagnostic and Therapeutic Tool in Various Types of Dementia.

Dementia is recognized as a healthcare and social burden and remains challenging in terms of proper diagnosis and treatment. Transcranial magnetic stimulation (TMS) is a diagnostic and therapeutic tool in various neurological diseases that noninvasively investigates cortical excitability and connectivity and can induce brain plasticity. This article reviews findings on TMS in common dementia types as well as therapeutic results. Alzheimer's disease (AD) is characterized by increased cortical excitability and reduced cortical inhibition, especially as mediated by cholinergic neurons and as documented by impairment of short latency inhibition (SAI). In vascular dementia, excitability is also increased. SAI may have various outcomes, which probably reflects its frequent overlap with AD. Dementia with Lewy bodies (DLB) is associated with SAI decrease. Motor cortical excitability is usually normal, reflecting the lack of corticospinal tract involvement. DLB and other dementia types are also characterized by impairment of short interval intracortical inhibition. In frontotemporal dementia, cortical excitability is increased, but SAI is normal. Repetitive transcranial magnetic stimulation has the potential to improve cognitive function. It has been extensively studied in AD, showing promising results after multisite stimulation. TMS with electroencephalography recording opens new possibilities for improving diagnostic accuracy; however, more studies are needed to support the existing data.

Bleeding Tolerance Among Patients With Atrial Fibrillation on Oral Anticoagulation.

BACKGROUND: Oral anticoagulation increases the bleeding risk. We investigated how clinical factors and the level of atrial fibrillation (AF) knowledge affect the bleeding acceptance in patients with AF. METHODS: In 173 consecutive anticoagulated outpatients with AF (aged 68.7 ± 10.7 years, 39.3% male), the bleeding ratio was assessed based on the declared maximum number of major bleeds the people were willing to endure to avert 1 stroke. The Jessa AF Knowledge Questionnaire was used to assess the knowledge of AF. RESULTS: Compared with patients with the high bleeding ratio (≥ 4 accepted bleedings, n = 88, 50.9%), subjects with the low bleeding ratio (0-3 accepted bleedings, n = 85, 49.1%) were older, with longer duration of AF, suffered more commonly from heart failure, and were free of cerebrovascular events. Patients after major bleeding (n = 33, 19.1%) and those reporting minor bleeds on anticoagulation (n = 77, 44.5%) had lower bleeding ratio. The independent predictors of the low bleeding ratio were older age (odds ratio [OR], 2.50; 95% confidence interval [CI], 1.69-3.70), major bleeds on anticoagulation (OR, 3.33; 95% CI, 1.16-10.0), minor bleeds on anticoagulation (OR, 3.45; 95% CI, 1.67-7.14), and prior stroke/transient ischemic attack (OR, 0.47; 95% CI, 0.22-0.99). The level of knowledge of AF did not affect the bleeding ratio. CONCLUSIONS: The key determinants of the bleeding ratio among anticoagulated patients with AF are age, and prior thromboembolic and bleeding episodes. The study could support identification of patients with AF who need additional effort to increase their acceptance of a life-long oral anticoagulation therapy.

Direct oral anticoagulants in the treatment of cerebral venous sinus thrombosis: a single institution's experience.

AIM OF THE STUDY: Oral anticoagulants, preferentially vitamin K antagonists (VKA), are recommended for 3-12 months in patients with cerebral venous sinus thrombosis (CVST). We present a series of patients with CVST treated with direct oral anticoagulants (DOAC). MATERIALS AND METHODS: We prospectively recruited 36 patients with CVST (aged 40.3 ± 9.2 years, 58.3% female) treated with DOAC based on the physician's or patient's preferences. Functional outcome was assessed with modified Rankin Scale. Recanalisation was assessed on imaging at 3-6 months post the event. Patients were followed for a median of 30 [interquartile range (IQR) 25-37] months. RESULTS: After use of heparin (median: 6 days; IQR 5-8.75), patients received dabigatran (150 mg bid, n = 16 or 110 mg bid, n = 2), rivaroxaban (20 mg qd, n = 10) or apixaban (5 mg bid, n = 8) for a median of 8.5 months (IQR 6.25-12). Complete or partial recanalisation was observed in 34 cases (94.4%). Three patients (8.3%) experienced major bleeding: menorrhagia on rivaroxaban (n = 2) and gastrointestinal bleeding on dabigatran (n = 1). A favourable functional outcome was observed in 24 (66.7%) patients, without any fatality. CSVT recurred in two patients (5.6%) and two venous thromboses developed in two other patients with inherited thrombophilia after anticoagulation withdrawal. CONCLUSIONS AND CLINICAL IMPLICATIONS: DOACs could be an alternative to VKA in CVST patients.

Prevalence of CCR5-delta32 mutation in asthmatic and non-asthmatic subjects from department of medicine, JUCM, Cracow.

C-C chemokine receptor type 5 (CCR5) is chemokine receptor encoded by CCR5 gene located on the short arm of chromosome 3. Asthma is a chronic bronchial inflammatory disease of either allergic or idiopathic etiology. CCR5 Δ32 mutation is a common deletion of 32 nucleotides resulting in a frameshift and non-functional receptor. Its prevalence in European population ranges between 4 and 16% (frequency of homozygotes is 1%). The current study was aimed to assess frequency of this mutation in asthmatics and its possible impact on asthma. The study was conducted on 254 subjects (125 diagnosed with asthma and 129 in control group). Isolated DNA was analysed by PCR. Primers were designed to flank the deletion region, thus PCR products could be genotyped by mere agarose gel electrophoresis. The variant alleles were represented as bands of 270 and 238 pb lengths. The shorter amplification product was diagnostic for the presence of CCR5-delta32 deletion. Visualisation of agarose gel revealed non-mutated, mutated homozygotes as well as heterozygotes. In the control group there were 37 women and 92 men, whereas the study group comprised 87 women and 38 men. In the control group genotypes distribution was: 105 non-mutated homozygotes, 21 hetezygotes and 3 mutated homozygotes, whereas in the study group 103, 21 and 1 respectively. No statistically significant differences between these groups were detected. Prevalence of homozygotes was 1,6%. Current study revealed no association between CCR5 Δ32 mutation and incidence of asthma. It may be assumed that CCR5 Δ32 deletion is neutral as a risk factor of asthma.