Anticoagulation for Patients With Concomitant Atrial Fibrillation and End-Stage Renal Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population. METHODS AND RESULTS: An updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64-0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation. CONCLUSIONS: For dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.

Reversal and resumption of anticoagulants in patients with anticoagulant-associated intracerebral hemorrhage.

The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

Clot time ratio (CTR) and treatment outcomes in Apixaban-treated atrial fibrillation patients.

There are clinical situations where information about the anticoagulant effects of Apixaban could be useful. Specialised methods for measuring Apixaban concentrations are not available at all medical laboratories while methods for measuring the functional effects of Apixaban, using clot time ratio (CTR), can be performed in most medical laboratories around the clock using well-established measurement procedures. The aim of this study was to investigate CTR in trough and peak samples during Apixaban treatment of atrial fibrillation and to correlate the findings to bleeds and thrombotic events. Three trough- and three peak samples from 61 patients (31 on Apixaban 5 mg twice daily and 30 on Apixaban 2.5 mg twice daily) were analysed with MRX PT DOAC. Patients were followed for 30 + /-15 months, and bleeds and thrombotic events were documented. The effect of Apixaban could be measured with MRX PT DOAC and there was a statistically significant difference between CTR in trough samples compared to peak samples (p < 0.001). A total of 21 patients suffered bleeds during follow-up; two patients suffered major bleeds, and 19 suffered minor bleeds. Patients with major bleeds had both mean peak- and mean trough CTR above the respective first to third quartile (Q1-Q3) range. Four patients suffered thromboembolic events. Generally, the peak CTRs were below or in the lower end of the peak Q1-Q3 for these patients. The new test MRX PT DOAC can be used to measure the effect of Apixaban during the treatment of atrial fibrillation. High mean peak- and mean trough CTR were seen in 2 patients with major bleeds, and low peak CTR was seen in 4 patients with thromboembolic events.

Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis.

OBJECTIVES: Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain. DATA SOURCES: A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome. STUDY SELECTION: Abstracts and full texts were assessed independently and in duplicate by two reviewers. DATA EXTRACTION: Data were extracted independently and in duplicate by two reviewers using predefined extraction forms. DATA SYNTHESIS: The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies. CONCLUSIONS: A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.

Risk factors and clinical impact of thrombosis during induction chemotherapy for pediatric acute lymphoblastic leukemia: A report from CYP-C.

Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to determine risk factors for TE during ALL induction (TEind ) therapy and whether TEind is associated with treatment refractoriness. This retrospective cohort study using the population-based Cancer in Young People Canada (CYP-C) registry included children <15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TEind and whether TEind predicted induction failure and ALL treatment intensification. The impact of TEind on overall and event-free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TEind . Age (<1 year and ≥10 years vs. 1-<10 years), T-cell phenotype, high-risk ALL, and central nervous system involvement were all associated with TEind in univariate analysis. Age and T-cell phenotype remained independent predictors of TEind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TEind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR [95% CI]: 0.66 [0.26-1.69]). TEind was independently associated with overall survival (adjusted HR [95% CI]: 2.54 [1.20-5.03]) but not event-free survival (adjusted HR [95% CI] 1.86 [0.98-3.51]). In this population-based study of children treated with contemporary chemotherapy protocols, TEind was associated with age and T-cell phenotype and mortality but did not predict induction failure.

An overview regarding the article 'clinical outcomes and mortality in patients with atrial fibrillation and recently diagnosed lung cancer in oncology outpatient settings'.

Cancer-related inflammation, anti-cancer treatment and other cancer-related comorbidities are proposed to affect atrial remodeling, increasing the susceptibility of lung cancer patients for developing atrial fibrillation. Moreover, cancer is assumed to modify the risk of thromboembolisms and bleeding. An association between AF and malignancy has been reported but incompletely defined. The earliest publications of cancer predisposing to AF came in the 1940s-50s with reports of neoplastic cardiac infiltration or mechanical pressure on the heart, and with oncologic thoracic surgery. Subsequently, multiple studies have reported an increased risk of AF after cancer therapy with surgery (particularly thoracic) and chemotherapy. However, the prevalence of AF appears to be higher in patients with cancer at the time of diagnosis even before undergoing therapy. The emerging field of cardio-oncology has revealed that these seemingly disparate disease processes are intertwined, owing to the cardiovascular sequelae of anticancer therapies, shared risk factors that predispose individuals to both cardiovascular disease and cancer, as well the possible potentiation of cancer growth by cardiac dysfunction. Although direct oral anticoagulants (DOAC) seem to represent a safe and effective option, compared to Vitamin K antagonists (VKA), in this population, this statement is based mainly on observational studies and sub analyses of pivotal trials of the DOAC.

SAMe-TT2R2 to Predict Clinical Outcomes and Time in Therapeutic Range in Patients on Vitamin K Antagonists: A Systematic Review and Meta-Analysis.

BACKGROUND: The SAMe-TT2R2 score identifies patients on vitamin K antagonists (VKAs) who are more likely to have poor time in therapeutic range (TTR); however, the association between SAMe-TT2R2 and clinical outcomes remains controversial. OBJECTIVES: The objective is to assess the association of SAMe-TT2R2 score with clinical outcomes and poor TTR in patients on VKAs. METHODS: We searched using the term "SAMe-TT2R2." Original articles reporting clinical outcomes and SAMe-TT2R2 scores before October 2021 were included. Odds ratios (ORs) of clinical outcomes, diagnostic accuracy parameters of poor TTR (<60%-70%), and mean TTR were extracted. Meta-analysis was performed using random-effects models. RESULTS: Ten studies were included (N = 22 894); 4 showed pooled changes in TTR of -3.61% (95% CI:-4.88% to -2.35%) and -3.98% (95% CI: -6.08% to -1.87%) at SAMe-TT2R2 scores ≥2 and ≥3, respectively, compared with lower scores. The diagnostic accuracy parameters for poor TTR were too heterogeneous to conclude. SAMe-TT2R2 ≥3 significantly correlated with all adverse events (OR = 1.43 [95% CI: 1.29-1.54; P < 0.001]), composite thromboembolism (OR = 1.53 [95% CI: 1.19-1.97; P = 0.001]), and composite bleeding (OR = 1.33 [95% CI: 1.12-1.59; P = 0.001] regardless of the indication, while an SAMe-TT2R2 ≥2 significantly correlated with mortality (OR = 1.32 [95% CI: 1.02-1.70; P = 0.033]). We found no relationship between an SAMe-TT2R2 ≥3 and mortality or between a score ≥2 and clinical outcomes. CONCLUSIONS AND RELEVANCE: Patients on VKAs with SAMe-TT2R2 ≥3 experienced more adverse events, bleeding, and thromboembolism compared with patients who had an SAMe-TT2R2 <3. However, the score had limited and inconclusive predictability for poor TTR in the study.

Between a rock and a hard place: resumption of oral anticoagulant therapy after intracranial hemorrhage.

Intracranial hemorrhage (ICH) is the most feared and lethal complication of oral anticoagulant (OAC) therapy. Resumption of OAC after ICH has long posed a challenge for clinicians, complicated by the expanding range of anticoagulant agents available in modern clinical practice, including direct OACs and, more recently, factor XI and XII inhibitors. A review of the current literature found support for resuming OAC in the majority of patients after ICH based on pooled retrospective data showing that resumption is associated with a lower risk of mortality and thromboembolism without a significantly increased risk of recurrent hemorrhage. The optimal time to resume OAC is less clear; however, the available evidence suggests that the composite risk of both recurrent hemorrhage and thromboembolism is likely minimized, somewhere between 4 and 6 weeks, after ICH in most patients. Specific considerations to guide the optimal resumption time in the individual patient include ICH location, mechanism, and anticoagulant class. Patients with mechanical heart valves and intracerebral malignancy represent high-risk groups who require more nuanced decision making. Here, we appraise the literature with the aim of providing a practical guide for clinicians while also discussing priorities for future investigation.

Tranexamic acid for percutaneous nephrolithotomy: an abridged Cochrane review.

OBJECTIVE: To assess the effects of tranexamic acid (TXA) in individuals with kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We performed a literature search of Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, grey literature, and conference proceedings. We included randomised controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients aged ≥18 years. Two review authors independently classified studies and abstracted data. Primary outcomes were blood transfusion, stone-free rate (SFR), thromboembolic events (TEE). We rated the certainty of evidence (CoE) according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach using a minimally contextualised approach with pre-defined thresholds for minimally clinically important differences (MCID). RESULTS: We included 10 RCTs assessing the effect of systemic TXA in PCNL vs placebo (or no TXA). Eight studies were published as full text. Based on an adjusted baseline risk of blood transfusion of 5.7%, systemic TXA may reduce blood transfusions (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.27-0.76). Based on an adjusted baseline SFR of 75.7%, systemic TXA may increase SFR (RR 1.11, 95% CI 0.98-1.27). There is probably no difference in TEEs (risk difference 0.001, 95% CI -0.01 to 0.01). Systemic TXA may increase adverse events (AEs) (RR 5.22, 95% CI 0.52-52.72). Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84-1.57). The CoE for most outcomes was assessed as low or very low. CONCLUSIONS: Based on a body of evidence of 10 RCTs, we found that systemic TXA in PCNL may reduce blood transfusions, major surgical complications, and hospital length of stay, as well as improve the SFR; however, it may increase AEs. These findings should inform urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.

[Massive pulmonary thromboembolism in a patient with Crohn's disease and latent tuberculosis treated with ustekinumab]. / Tromboembolia pulmonar masiva en un paciente con enfermedad de Crohn y tuberculosis latente tratada con ustekinumab.

Inflammatory bowel disease (IBD) is a spectrum of chronic immune-mediated diseases that affect the gastrointestinal tract and other extraintestinal systems, behaving as a systemic disease. Thromboembolic phenomena are a frequent complication in IBD, because of hypercoagulability states associated with disease activity, and their presence has a negative impact on prognosis and patient survival. Due to this, the control of the inflammatory activity of IBD is one of the pillars in the control of thromboembolic events. Biological drugs are associated with rapid control of the inflammatory process, however, the security profile for the reactivation of latent infections, particularly tuberculosis, is always discussed. We present the case of a 37-year-old patient who presented with deep vein thrombosis in the left lower limb and later with massive pulmonary thromboembolism. During his evaluation, he was diagnosed with Crohn's disease (CD). When carrying out the studies prior to the use of biologics, PPD and quantiferon tests were positive. After discussing the case, we decided to start treatment with ustekinumab.

Local thrombolytics via balloon-assisted intra-arterial infusion as rescue therapy for thromboembolism during endovascular coil embolisation.

Thromboembolism is the most frequent complication of coil embolisation for intracranial aneurysm. Complications of thromboembolism can lead to stroke and have a serious impact on sequelae and mortality, necessitating appropriate rescue therapy. Here, we succeeded in recanalisation of an occluded stent by balloon-assisted local infusion of a thrombolytic agent following stent-assisted coil embolisation of an unruptured posterior communicating artery aneurysm. This method involves inflating a microballoon just distal to the occluded vessel and then administering a thrombolytic agent through a microcatheter. This technique may increase the rate of vessel reopening by maximising the local drug concentration. This method can be applied to any type of thrombolytic agent and helps reduce the dose of systemic drugs, which might decrease the incidence of haemorrhagic complications. Balloon-assisted intra-arterial thrombolytic infusion for an occluded vessel during endovascular coil embolisation could offer an alternative rescue therapy when conventional thrombolytic agent administration fails to improve thromboembolism.

Efficacy and Safety of Activated Prothrombin Complex Concentrate for Reversal of the Anticoagulant Effect of Apixaban and Rivaroxaban in Patients with Major Bleeding.

BACKGROUND: The use of activated prothrombin complex concentrate (aPCC) to treat direct oral anticoagulant (DOAC)-associated bleeding is off-label and clinical experience is limited. OBJECTIVES: We aimed to assess the efficacy and safety of aPCC in reversing the anticoagulant effect of apixaban and rivaroxaban in patients presenting with major bleeding. METHODS: A retrospective cohort study of adult non-randomized patients was conducted at a tertiary referral medical center in the United States (US) to investigate the use of aPCC for the reversal of the anticoagulant effect of apixaban and rivaroxaban in patients presenting with major bleeding. The primary outcome was achieving clinical hemostasis according to prespecified criteria. Safety outcomes included the occurrence of thrombotic events during hospitalization. RESULTS: A total of 217 patients were included in the study. Intracranial hemorrhage (ICH) was the most common site of bleeding (n = 100, 46.1%), followed by gastrointestinal bleed (n = 87, 40.1%). Clinical hemostasis was achieved in 170 patients (78.3%), and the risk of not achieving hemostasis with ICH-related bleeding was significantly higher than that of non-ICH-related bleeding (2.5, 95% confidence interval [CI] 1.44-4.34; p < 0.001). Eight patients not achieving hemostasis died during hospitalization, all of whom were suffering from ICH, and mortality associated with non-ICH-related bleeding was significantly lower compared with ICH-related bleeding (0.91, 95% CI 0.86-0.97; p < 0.001). Thromboembolic events during hospitalization occurred in one patient (0.5%). CONCLUSIONS: The use of aPCC for the management of apixaban- or rivaroxaban-related major bleeding is effective in most cases and is associated with a low risk of thromboembolism.

Examining the safety profile of a standard dose tranexamic acid regimen in spine surgery.

OBJECTIVE: Perioperative blood loss during spinal surgery is associated with complications and in-hospital mortality. Weight-based administration of tranexamic acid (TXA) has the potential to reduce blood loss and related complications in spinal surgery; however, evidence for standardized dosing is lacking. The purpose of this study was to evaluate the impact of a standardized preoperative 2 g bolus TXA dosing regimen on perioperative transfusion, blood loss, thromboembolic events, and postoperative outcomes in spine surgery patients. METHODS: An institutional review board approved this retrospective review of prospectively enrolled adult spine patients (> 18 years of age). Patients were included who underwent elective and emergency spine surgery between September 2018 and July 2021. Patients who received a standardized 2 g dose of TXA were compared to patients who did not receive TXA. The primary outcome measure was perioperative transfusion. Secondary outcomes included estimated blood loss and thromboembolic or other perioperative complications. Descriptive statistics were calculated, and continuous variables were analyzed with the two-tailed independent t-test, while categorical variables were analyzed with the Fisher's exact test or chi-square test. Stepwise multivariate regression analysis was performed to examine independent risk factors for perioperative outcomes. RESULTS: TXA was administered to 353 of 453 (78%) patients, and there were no demographic differences between groups. Although the TXA group had more operative levels and a longer operative time, the transfusion rate was not different between the TXA and no-TXA groups (7.4% vs 8%, p = 0.83). Stepwise multivariate regression found that the number of operative levels was an independent predictor of perioperative transfusion and that both operative levels and operative time were correlated with estimated blood loss. TXA was not identified as an independent predictor of any postoperative complication. CONCLUSIONS: A standardized preoperative 2 g bolus TXA dosing regimen was associated with an excellent safety profile, and despite increased case complexity in terms of number of operative levels and operative time, patients treated with TXA did not require more blood transfusions than patients not treated with TXA.

Systematic review and meta-analysis of topical tranexamic acid in spine surgery.

OBJECTIVE: Tranexamic acid (TXA) is an antifibrinolytic drug associated with reduced blood loss in a range of surgical specialties, including neurosurgery, orthopedic surgery, and cardiac surgery. Concerns about venous thromboembolism and seizures from intravenous (IV) TXA have led to increased use of topical TXA. Given the relative scarcity of the literature on topical TXA compared with that on IV TXA within neurosurgery, the authors aimed to conduct a systematic review and meta-analysis on the safety, efficacy, and optimal administration of topical TXA in a wide range of spinal procedures and pathologies. METHODS: The PRISMA guidelines, Cochrane risk of bias tool, and Newcastle-Ottawa Scale were used to extract randomized controlled trials and high-quality case-control and cross-sectional/cohort studies (adult studies only) from PubMed, Web of Science, Cochrane Library, and Embase published between 2016 and 2023. Studies were analyzed by two independent reviewers for variables including dosage, TXA administration route, type of spine procedure, blood loss, adverse events including thromboembolism and infection, postoperative hemoglobin level, and hospitalization length. Pooled analysis comparing intraoperative and postoperative blood loss, postoperative hemoglobin levels, and hospitalization length of stay on the basis of route of TXA administration was conducted. RESULTS: Four cohort studies, 1 cross-sectional study, 1 case-control study, and 12 randomized controlled trials, together involving 2045 patients, were included. The most common route of topical TXA administration was via TXA in saline solution. Other routes of topical TXA included retrograde injection and TXA-soaked Gelfoam. In pooled analysis, topical TXA significantly reduced visible blood loss (standardized mean difference [SMD] -0.22, 95% CI -0.45 to -0.00001), postoperative blood loss (SMD -1.63, 95% CI -2.03 to -1.22), and length of hospital stay (SMD -1.02, 95% CI -1.42 to -0.61), as well as higher postoperative hemoglobin (SMD 0.59, 95% CI 0.34-0.83), compared with non-TXA controls. No significant differences in outcomes were found between topical and IV TXA or between combined (topical and IV) and IV TXA. Thromboembolism and infection rates did not significantly differ between any TXA administration group and non-TXA controls. CONCLUSIONS: In pooled analyses, topical TXA was associated with decreased perioperative blood loss in a wide range of scenarios, including cervical spine surgery and thoracolumbar trauma, as well as in patients with a thromboembolic history.

Home Treatment of Patients with Pulmonary Embolism: A Single Center 10-Year Experience from Ljubljana Registry.

Current guidelines suggest careful risk stratification using a structured clinical approach when selecting patients with pulmonary embolism (PE) for home treatment. The aim of our study was to assess whether PE patients referred to home treatment are appropriately risk-stratified according to guidelines prior to referral and what the real-life course of the disease in these patients is. We included patients with confirmed PE referred to outpatient management and treated with anticoagulants between 2010 and 2019, whose data were collected in a prospective management registry. Using simplified PE severity index and/or signs of right ventricular strain, we classified patients to either appropriate or inappropriate low-risk classes for outpatient management. We compared 30-day mortality, overall mortality, and rates of recurrent thromboembolism or major bleeding between both classes. Among 278 patients, 188 (67.6%) and 90 (32.4%) were classified as appropriate or inappropriate class, respectively. In total, 30-day mortality was low in both groups: 0% in appropriate class and 1.1% in inappropriate class. The overall mortality rate was higher in the inappropriate than in the appropriate class (12.1 vs 0.9/100 patient-years, respectively, P < .001). Rates of recurrent thromboembolism and major bleeding were similar for both classes. We conclude that in real-life, a significant proportion of inappropriate low-risk class PE patients are referred to outpatient management. However, with careful follow-up, early mortality is low, even in home-treated patients inappropriately classified as low-risk.

Thromboembolic and bleeding complications during interruptions and after discontinuation of anticoagulant treatment in patients with atrial fibrillation and active cancer: A daily practice evaluation.

BACKGROUND AND AIMS: Cancer provides challenges to the continuity of anticoagulant treatment in patients with atrial fibrillation (AF), e.g. through cancer-related surgery or complications. We aimed to provide data on the incidence and reasons for interrupting and discontinuing anticoagulant treatment in AF patients with cancer and to assess its contribution to the risk of thromboembolism (TE) and major bleeding (MB). METHODS: This retrospective study identified AF patients with cancer in two hospitals between 2012 and 2017. Data on anticoagulant treatment, TE and MB were collected during two-year follow-up. Incidence rates (IR) per 100 patient-years and adjusted hazard ratios (aHR) were obtained for TE and MB occurring during on- and off-anticoagulant treatment, during interruption and after resumption, and after permanent discontinuation. RESULTS: 1213 AF patients with cancer were identified, of which 140 patients permanently discontinued anticoagulants and 426 patients experienced one or more interruptions. Anticoagulation was most often interrupted or discontinued due to cancer-related treatment (n = 441, 62 %), bleeding (n = 129, 18 %) or end of life (n = 36, 5 %). The risk of TE was highest off-anticoagulation and during interruptions, with IRs of 19 (14-25)) and 105 (64-13), and aHRs of 3.1 (1.9-5.0) and 4.6 (2.4-9.0), respectively. Major bleeding risk were not only increased during an interruption, but also in the first 30 days after resumption, with IRs of 33 (12-72) and 30 (17-48), and aHRs of 3.3 (1.1-9.8) and 2.4 (1.2-4.6), respectively. CONCLUSIONS: Interruption of anticoagulation therapy harbors high TE and MB risk in AF patients with cancer. The high incidence rates call for better (periprocedural) anticoagulant management strategies tailored to the cancer setting.

Prescribing practices of tranexamic acid for melasma: Delphi consensus from the Pigmentary Disorders Society.

Introduction There is ambiguity regarding usage of tranexamic acid for melasma in India, be it in its pre-administration evaluation, administration route, dosing or monitoring. Hence, we conducted this study to understand various tranexamic-acid prescribing patterns and provide practical guidelines. Materials and methods A Google-form-based questionnaire (25-questions) was prepared based on the key areas identified by experts from the Pigmentary Disorders Society, India and circulated to practicing dermatologists across the country. In rounds 2 and 3, the questionnaire was re-presented to the same group of experts and their opinions were sought. The results of the practitioners' survey were denoted graphically alongside, to guide them. Consensus was deemed when at least 80% of respondents chose an option. Results The members agreed that history pertaining to risk factors for thromboembolism, cardiovascular and menstrual disorders should be sought in patients being started on oral tranexamic-acid. Baseline coagulation profile should be ordered in all patients prior to tranexamic-acid and more exhaustive investigations such as complete blood count, liver function test, protein C and S in patients with high risk of thromboembolism. The preferred oral dose was 250 mg orally twice daily, which can be used alone or in combination with topical hydroquinone, kojic acid and sunscreen. Repeated dosing of tranexamic-acid may be required for those relapsing with melasma following initial tranexamic-acid discontinuation. Coagulation profile should ideally be repeated at three monthly intervals during follow-up, especially in patients with clinically higher risk of thromboembolism. Treatment can be stopped abruptly post improvement and no tapering is required. Limitation This study is limited by the fact that open-ended questions were limited to the first general survey round. Conclusion Oral tranexamic-acid provides a valuable treatment option for melasma. Frequent courses of therapy may be required to sustain results and a vigilant watch is recommended for hypercoagulable states during the course of therapy.

Trial sequential analysis of efficacy and safety of direct oral anticoagulants and vitamin K antagonists against left ventricular thrombus.

Meta-analysis may increase the risk of random errors. Trial sequential analysis (TSA) has been developed to adjust for these random errors. We conducted TSA on the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in left ventricular thrombus (LVT) patients in order to estimate how many additional patients should be required to draw definite conclusions. PubMed, Scopus, and Cochrane Library databases were searched for articles directly comparing DOACs and VKAs for LVT in LV thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, and all-cause death. TSA was conducted with a cumulative Z-curve, monitoring boundaries, and required sample size. A simulated trial was run and TSA estimated the sample sizes of trials needed to draw definite conclusions. Of 4749 articles, 25 studies were used for the analysis. TSA revealed the current sample size already demonstrated superiority of DOACs in LV thrombus resolution and stroke, and futility in any thromboembolism and all-cause death. Two other outcomes did not achieve the required sample size. The sample size of new trials needed to demonstrate the superiority of DOACs over VKAs was estimated 400 for any bleeding. Corresponding trials needed to demonstrate no significant differences could be estimated for major bleeding and any bleeding (n = 200 and n = 2000, respectively). Current results show that the sample size required to draw definite conclusions was not reached for two outcomes, and there was a risk of random error. Further randomized controlled trials with sample sizes estimated by TSA will work effectively to obtain valid conclusions.

Sex-related differences in benefits of anticoagulation therapy in elderly patients with atrial fibrillation: a subanalysis of the EMERG-AF study. / Diferencias de sexo en los beneficios de la anticoagulación en pacientes ancianos con fibrilación auricular: un subanálisis del estudio EMERG-AF.

OBJECTIVES: To analyze the long-term benefits and safety of oral anticoagulation therapy prescribed in emergency departments for elderly patients with atrial fibrillation, and to detect any sex-related differences present. MATERIAL AND METHODS: Post-hoc analysis of data compiled by the EMERG-AF group (Spanish acronym for Emergency Department Stroke Prophylaxis and Guidelines Implementation in Atrial Fibrillation). Consecutive patients aged 75 years or older with atrial fibrillation who were treated in 62 EDs were included. We recorded clinical data and anticoagulants prescribed. Patients were followed for 1 year. The main outcome variable was a composite of death, thromboembolism, or major bleeding within 1 year. RESULTS: Data for 690 patients were registered; 386 (55.9%) were women. At discharge, 575 patients (83.3%) were on anticoagulants; therapy was started in the ED for 96 of them. A total of 158 patients (22.9%) had experienced at least 1 component of the main outcome within 1 year: 118 (17.1%) died, 22 (2.7%) had thromboembolic complications, and 34 (4.9%) had major bleeding. After adjustment for main clinical characteristics, hazard ratios (HRs) showed that anticoagulation therapy was associated with a reduction in the composite outcome (HR, 0.372; 95% CI, 0.236-0.587; P .001) but not specifically with major bleeding overall. When data for women were analyzed separately, anticoagulant therapy was again associated with a reduction in the composite outcome (HR, 0.372; 95% CI, 0.236-0.587; P .001) and also with death (HR, 0.281; 95% CI, 0.168-0.469; P .001), even in patients with anticoagulant prescriptions initiated on discharge from the ED. These associations did not reach statistical significance in men. CONCLUSION: ED anticoagulant prescription for elderly patients with atrial fibrillation is safe and contributes to a reduction in mortality. Women in this age group benefited more than men from starting anticoagulation during the acute phase in the ED.

OBJETIVO: Analizar los beneficios y seguridad a largo plazo de la anticoagulación oral (ACO) prescrita en los servicios de urgencias (SU) a pacientes mayores con fibrilación auricular (FA) y las diferencias en función del sexo. METODO: Se trata de un análisis post-hoc del estudio EMERG-AF. Se incluyeron pacientes consecutivos $ 75 años, que consultaron en 62 SU por FA. Se recogieron datos clínicos y ACO. La variable principal estuvo compuesta por muerte, tromboembolia o sangrado mayor en 1 año. RESULTADOS: Se incluyeron 690 pacientes, 386 mujeres (55,9%). Al alta, 575 pacientes (83,3%) estaban con ACO. En 96 de ellos se inició en el SU. Tras 1 año, la variable principal sucedió en 158 pacientes (22,9%): 118 (17,1%) fallecieron, 22 (2,7%) tuvieron una complicación tromboembólica y 34 (4,9%) una hemorragia mayor. Tras ajustar por las principales características clínicas, la ACO se asoció a una reducción en la variable principal (HR: 0,372, IC 95%: 0,236-0,587, p 0,001), pero no se asoció con la hemorragia mayor. En las mujeres, la ACO se asoció con una reducción en la variable principal (HR: 0,372, IC 95%: 0,236-0,587, p 0,001) y una menor mortalidad (HR: 0,281, IC 95%: 0,168-0,469, p 0,001), incluidos pacientes con nueva prescripción y en aquellos dados de alta. Esta asociación no alcanzó significación en los hombres. CONCLUSIONES: La prescripción de ACO en los SU a pacientes mayores con FA es segura y contribuye a reducir la mortalidad. En este grupo etario, las mujeres se benefician más que los hombres de iniciar la ACO en la fase aguda.