Direct Oral Anticoagulants versus Warfarin in Octogenarians with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis

Direct oral anticoagulants (DOACs) have been demonstrated to be more effective and safer than vitamin-K antagonist (VKA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). This meta-analysis aims to assess the effect of DOACS vs. VKA in patients ≥ 80 and AF. Primary endpoints were stroke or systemic embolism and all-cause death. Secondary endpoints included major bleeding, intracranial bleeding, and gastrointestinal bleeding. A random-effects model was selected due to significant heterogeneity. A total of 147,067 patients from 16 studies were included, 71,913 (48.90%) treated with DOACs and 75,154 with VKA (51.10%). The stroke rate was significantly lower in DOACs group compared with warfarin group (Relative risk (RR): 0.72; 95% confidence interval (CI): 0.63–0.82; p < 0.001). All-cause mortality was significantly lower in DOACs group compared with warfarin group (RR: 0.82; 95% CI: 0.70–0.96; p = 0.012). Compared to warfarin, DOACs were not associated with reductions in major bleeding (RR: 0.85, 95% CI 0.69–1.04; p = 0.108) or gastrointestinal bleeding risk (RR: 1.08, 95% CI 0.76–1.53; p = 0.678) but a 43% reduction of intracranial bleeding (RR: 0.47, IC 95% 0.36–0.60; p < 0.001) was observed. Our meta-analysis demonstrates that DOACs are effective and safe with statistical superiority when compared with warfarin in octogenarians with AF.

Serotonergic Antidepressants and Risk for Traumatic Intracranial Bleeding

Background: Serotonergic antidepressants may predispose to bleeding but the effect on traumatic intracranial bleeding is unknown.Methods: The rate of intracranial bleeding in patients with antidepressant medication was compared to patients not antidepressants in a cohort of patients with acute head injury. This association was examined by using a consecutive cohort of head trauma patients from a Finnish tertiary center emergency department (Tampere University Hospital, Tampere, Finland). All consecutive (2010–2012) adult patients (n = 2,890; median age = 58; male = 56%, CT-positive = 22%, antithrombotic medication users = 25%, antidepressant users = 10%) who underwent head CT due to head trauma in the emergency department were included.Results: Male gender, GCS &lt;15, older age, and anticoagulation were associated with an increased risk for traumatic intracranial bleeding. There were 17.8% of patients not taking antidepressants and 18.3% of patients on an antidepressant who had traumatic intracranial bleeding (p = 0.830). Among patients who were taking antithrombotic medication, 16.6% of the patients not taking antidepressant medication, and 22.5% of the patients taking antidepressant medication, had bleeding (p = 0.239). In a regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use.Conclusions: Serotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage.

Clinical case of an infant with severe hemophilia A on emicizumab

Hemophilia A is an X-linked congenital bleeding disorder caused by a deficiency or absence of coagulation factor VIII. In children who are in the first year of life, bleeding into the head accounts for 12.8–17.7 % of cases, and up to 45.5 % of them are intracranial bleeding in contrast to adult patients, in whom joints are the most frequent localization of bleeding. The first 2 years of life are the most dangerous in relation tointracranial bleeding for a child with hemophilia and the provision of full preventive treatment is extremely important for this time.Aim of the study – present the first experience of using emicizumab as primary prophylaxis in a child of the first year of life with hemophilia A. A patient born in 2020 with a severe hemophilia A had two post-traumatic bleeding that required hospitalization and replacement therapy. We decided to start primary prophylaxis with emicizumab at the age of 10 months.There were not spontaneous bleedings during 8 months of emicizumab usage. Post-traumatic bleeding did not require hospitalization and additional therapy.The clinical case demonstrates that emicizumab is effective and safe in infant who have not previously received prophylactic treatment.

DOAC versus warfarin in patients with atrial fibrillation and stage IV-V chronic kideny disease including patients on dialysis

Introduction Patients with atrial fibrillation (AF) and severe chronic kidney disease (CKD) were excluded from most phase III randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs). Evidence of warfarin versus DOAC in the AF population with stage IV-V CKD is therefore limited. Aim To evaluate the effectiveness and safety of DOAC compared with warfarin on this population including dialysis patients. Methods A systematic review and meta-analysis of RCTs and observational studies involving AF patients with stage IV-V CKD treated with warfarin versus DOACs were conducted to evaluate the following outcomes: stroke (ischemic and hemorrhagic) or systemic embolism (SE), all-cause mortality, major bleeding, gastrointestinal (GI) bleeding, and intracranial bleeding. If the heterogeneity between studies was moderate to high calculated as the I2 ≥50%, a meta regression was undertaken between baseline characteristics and the study outcomes. We conducted a literature search using key words related to AF, severe CKD, DOAC and warfarin in PubMed, Embase and Cochrane Library. Results Nine studies were included in the meta-analysis. Compared to warfarin, DOAC was significantly associated with a reduced risk of stroke or systemic embolism (SE) (risk ratio [RR] = 0.69; 95% confidence interval [CI] 0.50–0.95) (Figure 1), intracranial bleeding (RR=0.54; 95% CI 0.35–0.84) and hemorrhagic stroke (RR=0.39; 95% CI 0.16–0.95). There was no significant difference between DOACs and warfarin in the risk of all-cause mortality (RR=0.80; 95% CI 0.57–1.13), major bleeding (RR = 0.70; 95% CI 0.44–1.11) (Figure 2) and GI bleeding (RR=0.76; 95% CI 0.56–1.02). For the outcome stroke or SE, dabigatran (compared with apixaban) significantly eliminated the net effect of DOAC as compared with warfarin (coefficient, 0.8; P=0.003). Regarding major bleeding, rivaroxaban and dabigatran both eliminated the DOAC effect from the meta-analysis as compared to apixaban (P=0.01 & P&lt;0.0001). Dabigatran significantly increased the risk of GI bleeding in comparison to apixaban (coefficient, 0.48; P=0.002) in comparison with the overall similar effect of warfarin in the meta-analysis. Conclusion Among patients with AF and stage IV or V CKD including dialysis patients, DOAC appears to have similar or better effectiveness and safety compared to warfarin. FUNDunding Acknowledgement Type of funding sources: None. Stroke or systemic embolism

Tranexamic acid in non-traumatic intracranial bleeding: a systematic review and meta-analysis

Non-traumatic intracranial bleeding (NTIB), comprising subarachnoid hemorrhage (SAH) and intra-cranial bleeding (ICH) is a significant public health concern. Tranexamic acid (TXA) is a promising treatment with benefits yet to be fully demonstrated. We conducted a systematic review and meta-analysis on the impact of TXA on mortality in NTIB. We searched the PubMed, Cochrane Library, Google Scholar and ScienceDirect databases for studies reporting mortality data following the use of TXA in NTIB for comparisons with a control group. We computed random-effect meta-analysis on estimates of risk and sensitivity analyses. We computed meta-regression to examine the putative effects of the severity of NTIB, sociodemographic data (age, sex), and publication date. Among potentially 10,008 articles, we included 15 studies representing a total of 4883 patients: 2455 receiving TXA and 2428 controls; 1110 died (23%) during the follow-up. The meta-analysis demonstrated a potential of 22% decrease in mortality for patients treated by TXA (RR = 0.78, 95%CI 0.58–0.98, p = 0.002). Meta-regression did not demonstrate any influence of the severity of NTIB, age, sex, length of treatment or date of publication. Sensitivity analyses confirmed benefits of TXA on mortality. TXA appears to be a therapeutic option to reduce non-traumatic intracranial bleeding mortality, particularly in patients with SAH.

Severe Brain Damage in a Moderate Preterm Infant as Complication of Post-COVID-19 Response during Pregnancy

Current evidence from the COVID-19 pandemic suggests that neonatal SARS-coronavirus-2 infections usually have a mild course. Data on how maternal infection during pregnancy affects fetal development are scarce. We present the unique case of a moderate preterm infant with intracranial bleeding and periventricular leukomalacia as a potential consequence of post-COVID-19 hyperinflammation during pregnancy.