Platelets, inflammation, and purinergic receptors in chronic kidney disease.

Platelets are anucleated cells that circulate in the bloodstream. Historically, platelets were thought to perform a singular function-stop bleeding via clotting. Although platelets do play a key role in hemostasis and thrombosis, recent studies indicate that platelets also modulate inflammation, and this platelet-induced inflammation contributes to the pathophysiology of various diseases such as atherosclerosis and diabetes mellitus. Thus, in recent years, our understanding of platelet function has broadened. In this review, we revisit the classic role of platelets in hemostasis and thrombosis and describe the newly recognized function of platelets in modulating inflammation. We cover the potential use of purinergic receptor antagonists to prevent platelet-modulated inflammation, particularly in patients with chronic kidney disease, and finally, we define key questions that must be addressed to understand how platelet-modulated inflammation contributes to the pathophysiology of chronic kidney disease.

Anticoagulant and non-anticoagulant therapy in thrombotic antiphospholipid syndrome: old drugs and new treatment targets.

In this review, we discuss the current evidence on classic and newer oral anticoagulant therapy, older drugs such as HCQ and statins, and new potential treatment targets in APS. Vitamin K antagonists (VKAs) remain the cornerstone treatment for thrombotic events in APS. In patients fulfilling criteria for definite APS presenting with a first venous thrombosis, treatment with VKAs with a target international normalized ratio (INR) 2.0-3.0 is recommended. In patients with arterial thrombosis, treatment with VKA with target INR 2.0-3.0 or 3.0-4.0 is recommended by recent guidelines, considering the individual's bleeding and thrombosis recurrence risk. A combination of VKAs and low-dose aspirin (75-100 mg/daily) may also be considered. According to available evidence direct oral anticoagulants should be avoided in patients with arterial thrombosis and/or those with triple aPL positivity. Adjunctive treatment with HCQ and/or statins can be considered, especially in anticoagulation treatment-refractory APS. Potential targeted treatments in APS include B-cell targeting, complement inhibition, mammalian target of rapamycin inhibition, IFN targeting, adenosine receptors agonists, CD38 targeting or chimeric antigen receptor T-cell therapy. The safety and efficacy of these treatment targets needs to be examined in well-designed randomized controlled trials.

Antithrombotic Therapy Following Structural Heart Disease Interventions: Current Status and Future Directions.

Interventions in structural heart disease cover many catheter-based procedures for congenital and acquired conditions including valvular diseases, septal defects, arterial or venous obstructions, and fistulas. Among the available procedures, the most common are aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure. Antithrombotic therapy for transcatheter structural heart disease interventions aims to prevent thromboembolic events and reduce the risk of short-term and long-term complications. The specific approach to antithrombotic therapy depends on the type of intervention and individual patient factors. In this review, we synopsize contemporary evidence on antithrombotic therapies for structural heart disease interventions and highlight the importance of a personalized approach. These recommendations may evolve over time as new evidence emerges and clinical guidelines are updated. Therefore, it's crucial for healthcare professionals to stay updated on the most recent guidelines and individualize therapy based on patient-specific factors and procedural considerations.

Trajectories of P2Y12 inhibitor adherence in patients with acute coronary syndromes.

PURPOSE: P2Y12 inhibitors (P2Y12i) reduce cardiac events after acute coronary syndromes (ACS). However, suboptimal P2Y12i adherence persists. We aimed to examine P2Y12i non-adherence using group-based trajectory methods and to identify adherence predictors. METHODS: We conducted a population-based, retrospective cohort study using administrative data in Ontario, Canada of patients ≥65 years admitted for ACS between April 2014 and March 2018 with a P2Y12i dispensed within 7 days of discharge. We used group-based trajectory models to characterize longitudinal 1-year adherence patterns. Predictors associated with each adherence trajectory were identified by multinomial logistic regression. RESULTS: We included 11 917 patients using clopidogrel and 9763 using ticagrelor, aged [mean ± SD]: 77.33 ± 8.31/73.59 ± 6.79 years; men: 56.2%/65.4%, respectively. We identified 3 longitudinal adherence trajectories, that differed by agent: 75% of clopidogrel and 68% of ticagrelor patients showed a consistently adherent trajectory, while 13%/17% were gradually, and 12%/15% were rapidly non-adherent, respectively (p < 0.001). Differing baseline characteristics in each cohort were associated with observed adherence trajectories. Concomitant atrial fibrillation and prior bleeding history were associated with non-adherence among clopidogrel users. Among ticagrelor users, women and older persons were more likely to be rapidly non-adherent, adherence declining steeply starting 1 month post-ACS. CONCLUSIONS: We identified distinct adherence trajectories for clopidogrel and ticagrelor post-ACS, with 3 out of 4 clopidogrel patients but only 2 out of 3 ticagrelor patients in the consistently adherent trajectory. Intensive interventions targeted to the period of steep adherence decline post-ACS, particularly for women and older persons initiating ticagrelor, and patients with atrial fibrillation on clopidogrel should be considered and investigated further.

The effect of current antithrombotic therapy on mortality in nursing home residents with COVID-19: a multicentre retrospective cohort study.

BACKGROUND: The first wave of COVID led to an alarmingly high mortality rate among nursing home residents (NHRs). In hospitalised patients, the use of anticoagulants may be associated with a favourable prognosis. However, it is unknown whether the use of antithrombotic medication also protected NHRs from COVID-19-related mortality. OBJECTIVES: To investigate the effect of current antithrombotic therapy in NHRs with COVID-19 on 30-day all-cause mortality during the first COVID-19 wave. METHODS: We performed a retrospective cohort study linking electronic health records and pharmacy data in NHRs with COVID-19. A propensity score was used to match NHRs with current use of therapeutic dose anticoagulants to NHRs not using anticoagulant medication. The primary outcome was 30-day all-cause mortality, which was evaluated using a logistic regression model. In a secondary analysis, multivariable logistic regression was performed in the complete study group to compare NHRs with current use of therapeutic dose anticoagulants and those with current use of antiplatelet therapy to those without such medication. RESULTS: We included 3521 NHRs with COVID-19 based on a positive RT-PCR for SARS-CoV-2 or with a well-defined clinical suspicion of COVID-19. In the matched propensity score analysis, NHRs with current use of therapeutic dose anticoagulants had a significantly lower all-cause mortality (OR = 0.73; 95% CI: 0.58-0.92) compared to NHRs who did not use therapeutic anticoagulants. In the secondary analysis, current use of therapeutic dose anticoagulants (OR: 0.62; 95% CI: 0.48-0.82) and current use of antiplatelet therapy (OR 0.80; 95% CI: 0.64-0.99) were both associated with decreased mortality. CONCLUSIONS: During the first COVID-19 wave, therapeutic anticoagulation and antiplatelet use were associated with a reduced risk of all-cause mortality in NHRs. Whether these potentially protective effects are maintained in vaccinated patients or patients with other COVID-19 variants, remains unknown.

ANMCO/SIMEU consensus document on the use of reversal agents for antithrombotic therapies in patients with ongoing bleeding or at high risk of haemorrhagic events.

In recent decades, an incredible evolution in antithrombotic therapies used for treating patients with atherosclerosis, atrial fibrillation, and venous thromboembolism has been observed, leading to the availability of increasingly safe drugs. Nonetheless, bleeding complications remain a significant concern, with considerable health, social, and economic implications. To improve the acute management of patients experiencing or at risk for major bleeding events, specific reversal agents for antithrombotic drugs have been recently developed. While these agents demonstrate effectiveness in small-scale pharmacodynamic studies and clinical trials, it is imperative to balance the benefits of reversing antiplatelet or anticoagulant therapy against the risk of prothrombotic effects. These risks include the potential loss of antithrombotic protection and the prothrombotic tendencies associated with bleeding, major surgery, or trauma. This joint document of the Italian Association of Hospital Cardiologists (Associazione Nazionale Medici Cardiologi Ospedalieri) and the Italian Society of Emergency Medicine (Società Italiana di Medicina d'Emergenza-Urgenza) delineates the key features and efficacy of available reversal agents. It also provides practical flowcharts to guide their use in patients with active bleeding or those at elevated risk of major bleeding events.

Perioperative management of antithrombotics in elective intracranial procedures: systematic review, critical appraisal.

PURPOSE: Perioperative management of patients medicated with antithrombotics requiring elective intracranial procedures is challenging. We ought to (1) identify the clinical practice guidelines (CPGs) and recommendations (CPRs) on perioperative management of antithrombotic agents in elective intracranial surgery and (2) assess their methodological quality and reporting clarity. METHODS: The study was conducted following the 2020 PRISMA guidelines for a systematic review and has been registered (PROSPERO, CRD42023415710). An electronic search was conducted using PubMed, Scopus, and Google Scholar. The search terms used were "adults," "antiplatelets," "anticoagulants," "guidelines," "recommendations," "english language," "cranial surgery," "brain surgery," "risk of bleeding," "risk of coagulation," and "perioperative management" in all possible combinations. The search period extended from 1964 to April 2023 and was limited to literature published in the English language. The eligible studies were evaluated by three blinded raters, by employing the Appraisal of Guidelines for Research & Evaluation II (AGREE-II) analysis tool. RESULTS: A total of 14 sets of guidelines were evaluated. Two guidelines from the European Society of Anaesthesiology and one from the American College of Chest Physicians found to have the highest methodological quality and reporting clarity according to the AGREE-II tool. The interrater agreement was good with a mean Cohens Kappa of 0.70 (range, 46.5-94.4%) in the current analysis. CONCLUSION: The perioperative management of antithrombotics in intracranial procedures may be challenging, complex, and demanding. Due to the lack of high quality data, uncertainty remains regarding the optimal practices to balance the risk of thromboembolism against that of bleeding.

Impact of antithrombotic agents on outcomes in patients requiring surgery for chronic subdural haematoma: a systematic review and meta-analysis.

A chronic subdural haematoma (CSDH) is a collection of aged blood between the dura and the brain, typically treated with surgical evacuation. Many patients with CSDH have comorbidities requiring the use of antithrombotic medications. The optimal management of these medications in the context of CSDH remains unknown, as the risk of recurrence must be carefully weighed against the risk of vaso-occlusive events. To better understand these risks and inform the development of clinical practice guidelines, we conducted a systematic review and meta-analysis. A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline and Embase databases. The study was registered with PROSPERO (CRD42023397061). A total of 44 studies were included, encompassing 1 prospective cohort study and 43 retrospective cohort studies. Pooled odds ratios (ORs) were calculated for CSDH recurrence and vaso-occlusive events in patients taking anticoagulant or antiplatelet medications compared to patients not receiving antithrombotic therapy. GRADE was used to assess the quality of evidence. In patients on anticoagulant therapy at CSDH diagnosis, the pooled OR for CSDH recurrence was 1.41 (95% CI 1.11 to 1.79; I2 = 28%). For patients on antiplatelet therapy, the pooled OR was 1.31 (95% CI 1.08 to 1.58; I2 = 32%). Patients taking antithrombotic medications had a significantly higher risk of vaso-occlusive events, with a pooled OR of 3.74 (95% CI 2.12 to 6.60; I2 = 0%). There was insufficient evidence to assess the impact of time to recommence antithrombotic medication on CSDH outcomes. We found that baseline antithrombotic use is associated with the risk of CSDH recurrence and vaso-occlusive events following surgical evacuation. The evidence base is of low quality, and decisions regarding antithrombotic therapy should be individualised for each patient. Further high-quality, prospective studies or registry-based designs are needed to better inform clinical decision-making and establish evidence-based guidelines.

Adherence to secondary stroke prevention medications in Singapore: a single center study.

OBJECTIVES: Recurrent strokes are associated with greater disability and mortality than first-time strokes. However, adherence to secondary stroke prevention medications has been reported to be suboptimal. We assessed medication adherence to antihypertensives, antiplatelets, and statins after acute ischemic stroke and identified factors associated with non-adherence behavior to each drug class. METHODS: This single center study is an extension of a larger prospective cohort study of ischemic stroke patients assessed at an outpatient post stroke clinic. Medication adherence behavior and medication knowledge was determined by direct questioning, and perceptions towards medications via the Beliefs about Medicines Questionnaire. Factors associated with non-adherence in each drug class were determined using logistic regression. RESULTS: Rates of adherence differed between antihypertensives (77.9%), antiplatelets (80.3%), and statins (64.7%) (p < 0.001) amongst the 193 patients surveyed. Non-adherence to antihypertensives was associated with living alone, taking < 5 medications, and stronger beliefs that medications are harmful. For antiplatelets, non-diabetic patients and patients with stronger beliefs that medications are harmful were more likely to be non-adherent. Patients non-adherent to statins were more likely to have a longer time since ischemic event and have a transient ischemic attack as the index event. CONCLUSIONS: Overall, medication adherence behavior to secondary stroke prevention medications was poor, with statins the least adhered to. Factors associated with non-adherence to each drug class could guide the development of tailored interventions to improve adherence to secondary stroke prevention medications.

Antithrombotics alter intracerebral hemorrhage presentation without affecting minimally invasive endoscopic evacuation.

OBJECTIVES: Intracerebral hemorrhages are associated with significant morbidity and mortality. While the ENRICH trial supports the efficacy of surgical evacuation for lobar hemorrhages, the impact of antithrombotic therapies on minimally invasive surgery outcomes remains unexplored. This study evaluates the effects of chronic anticoagulants and antiplatelets on the technical and longterm outcomes of minimally invasive intracerebral hemorrhage evacuation. MATERIALS AND METHODS: A prospectively collected registry of patients undergoing minimally invasive surgery for intracerebral hemorrhage from a single institution was analyzed (December 2015-September 2022). Data included key demographics, comorbidities, antithrombotic/reversal status, presenting clinical/radiographic characteristics, procedural metrics, and clinical outcomes. Patients were divided into control (neither therapy), antiplatelet-only, and anticoagulant-only groups, with antiplatelet/anticoagulant reversals conducted per current American Heart Association/American Stroke Association guidelines. Variables significant in univariate analyses (p<0.05) were advanced to multivariable regression models. RESULTS: Among 226 intracerebral hemorrhage patients treated with minimally invasive surgery, 41% (N=93) had antithrombotic medication history; 28% (N=64) received antiplatelets, and 9% (N=21) received anticoagulants. Patients on both therapies (N=6) were excluded. The antiplatelet group presented more frequently with lobar hemorrhages (56% vs. 37%; p=0.022), while patients on anticoagulants showed increased rates of intraventricular hemorrhage co-presentation (62% vs. 46%; p=0.011) compared to controls. Despite univariate analyses showing a higher postoperative hematoma volume (3.9 vs. 2.9 milliliters; p=0.020) and lower evacuation percentage (88% vs. 92%; p=0.019) for the antiplatelet group, and longer procedures for patients on anticoagulants (2.3 vs. 1.7 hours; p=0.042) compared to control, multivariable analyses indicated that antiplatelets and anticoagulants had no significant impact on these technical outcomes. Longitudinally, antithrombotics were not associated with increased rebleeding, less frequent discharge to home, lower 30-day mortality, or worse, 6-month Modified Rankin Scale scores. CONCLUSIONS: Patients on chronic antiplatelets and anticoagulants exhibited characteristic intracerebral hemorrhage phenotypes without worse technical or long-term outcomes after minimally invasive intracerebral hemorrhage evacuation, suggesting the procedure's safety for these patients.

Cervical epidural hematoma masquerading as thrombosis of intracranial flow diverter in situ: A diagnostic and therapeutic conundrum.

Cervical epidural hematoma (EDH) is a rare but very serious cause of acute neurologic compression that needs early diagnosis and rapid intervention. Acute hemiparesis is an infrequent presentation of cervical EDH and often mimics cerebrovascular accident. In this case, we describe the management of a case of cervical EDH presenting as acute hemiparesis in an elderly female patient which mimicked as thrombosis of intracranial flow diverter in situ. The report emphasizes that cervical EDH should be considered as differential diagnosis in patients who present with acute hemiparesis especially, who are on antiplatelets or anticoagulants. Also, in a patient considered high-risk for surgery, conservative management can be considered under close supervision and intensive monitoring, especially, in non-expanding hematoma and non-progressive neurological deterioration.

Long-term outcome of cervical artery dissection.

OBJECTIVE: The aim of the study is to evaluate the natural history of extracranial cervical artery dissection (CAD) including comorbidities, symptoms at presentation, recurrence of symptoms, and long-term outcome following different treatment approaches. METHODS: A retrospective review of patients treated for acute CAD was performed over a 5-year period from January 2017 to April 2022. RESULTS: Thirty-nine patients were included in the study, 25 (64.1%) with acute internal carotid artery dissection and 14 (35.9%) with acute vertebral artery dissection. Thirty-four patients (87.1%) had spontaneous CAD, and five patients (12.8%) had traumatic CAD. The mean age of the cohort was 54.2 years. The mean time from symptom onset to presentation was 4.34 days. The most common symptoms in internal carotid artery dissection were unilateral weakness (44%), headache (44%), slurred speech (36%), facial droop (28%), unilateral paraesthesia (24%), neck pain (12%), visual disturbance (8%), and Horner's syndrome (8%). The most common symptoms in vertebral artery dissection were headache (35.7%), neck pain (35.7%), vertigo (28.57%), ataxia (14.28%), and slurred speech (14.28%). The imaging modalities used for diagnosis included computed tomography angiography (48.7%), magnetic resonance angiography (41%), and duplex ultrasound (10.2%). In patients with carotid artery dissection, 57% had severe stenosis, 24% had moderate stenosis, and 20% had mild stenosis. All patients treated were managed conservatively with either anticoagulation or antiplatelets. Long-term clinical follow-up was available for 33 patients (84.6%). Thirty patients (90.9%) reported complete resolution of symptoms, and three patients (9%) reported persistent symptoms. Anatomic follow-up with imaging was available for 17 patients (43.58%). Thirteen patients (76.47%) had complete resolution of dissection, two patients (11.76%) had partial resolution of dissection, and two patients (11.76%) had persistent dissection. There was one death unrelated to CAD in a multi-trauma patient. There were four early recurrent symptoms in the first 3 to 8 weeks post discharge. The mean follow-up time was 308.27 days. CONCLUSIONS: The majority of CADs can be managed conservatively with good clinical and anatomical outcome and low rates of recurrence.

Population-Attributable Risk Fractions for Antiplatelets and Anticoagulants in Spontaneous Intracranial Hemorrhages.

INTRODUCTION: Concerns about spontaneous intracranial hemorrhages (sICHs) have increased over time with the increasing use of antithrombotic agents. Hence, we aimed to analyze the risk and risk fractions for antithrombotics in sICHs in South Korea. METHODS: From the National Health Insurance Service-National Sample Cohort including 1,108,369 citizens, 4,385 cases, aged 20 years or more and newly diagnosed as sICHs between 2003 and 2015, were included in this study. A total of 65,775 sICH-free controls were randomly selected at a ratio of 1:15 from individuals with the same birth year and sex according to a nested case-control study design. RESULTS: Although the incidence rate of sICHs started to decrease from 2007 onward, the use of antiplatelets, anticoagulants, and statins continued to increase. Antiplatelets (adjusted odds ratio [OR] 3.59, 95% confidence interval [CI] 3.18-4.05), anticoagulants (adjusted OR 7.46, 95% CI 4.92-11.32), and statins (adjusted OR 1.98, 95% CI 1.79-2.18) were significant risk factors for sICHs even after adjusting for hypertension, alcohol intake, and cigarette smoking. From 2003-2008 to 2009-2015, the population-attributable fractions changed from 28.0% to 31.3% for hypertension, from 2.0% to 3.2% for antiplatelets, and from 0.5% to 0.9% for anticoagulants. CONCLUSION: Antithrombotic agents are significant risk factors for sICHs, and their contribution is increasing over time in Korea. These findings are expected to draw the attention of clinicians to precautions to be taken when prescribing antithrombotic agents.

Perioperative Antiplatelet Bridging With Cangrelor: A Cohort Study and Narrative Review.

BACKGROUND: In patients who received a cardiac stent, practice guidelines recommend dual antiplatelet therapy (DAPT). However, an urgent procedure may be required necessitating interruption of DAPT. Intravenous cangrelor was previously shown to be an alternative due its short-half life and quick onset/offset. OBJECTIVE: To determine the safety and effectiveness of cangrelor bridging for patients undergoing invasive procedures in a veteran population. METHODS: Retrospective cohort of patients from Michael E. DeBakey VA Medical Center and the VA North Texas Health Care Systems who underwent perioperative cangrelor bridging. The primary outcome was the incidence of bleeding using the Bleeding Academic Research Consortium (BARC) criteria. The secondary outcome was a composite of nonfatal stroke, myocardial infarction (MI), mortality, and unplanned revascularization within 30 days. A narrative review was also performed to summarize cangrelor bridging for noncardiac invasive procedure. RESULTS: There were 41 patients that met the eligibility criteria. Patients were predominantly Caucasian (57.5%) men with a median age of 70 years. The median duration on cangrelor bridging was 2.6 days with 11 and 30 patients undergoing cardiac and noncardiac invasive procedures, respectively. Nine patients (22%) had a bleeding event of which 8 were minor. One was severe due to significant iliopsoas hematoma following drain placement. All bleeding events occurred postoperatively except for 2 perioperative events that occurred during orthopedic procedures. Ischemic events up to 30 days occurred in 3 patients (7.3%) which consisted of 1 (2.4%) nonfatal MI requiring revascularization and 2 (4.9%) deaths, 1 of which was sudden cardiac. CONCLUSION AND RELEVANCE: This study suggests that cangrelor bridging may be a reasonable alternative to holding oral P2Y12 inhibitors in patients requiring interruption of antiplatelet therapy for an urgent surgery/invasive procedure.

Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines.

PURPOSE OF REVIEW: Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature. RECENT FINDINGS: Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90 days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions. The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

Risk of Bleeding with Endoscopic Ultrasound-Guided Tissue Acquisition in Patients on Antithrombotic Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: The present guidelines stratify endoscopic ultrasound-guided tissue acquisition (EUS-TA) as a high-bleeding risk procedure in patients on antithrombotics. However, the data regarding the same are conflicting. Therefore, this meta-analysis aimed to analyze the bleeding event rates associated with EUS-TA in patients receiving antithrombotic therapy. METHODS: A literature search from January 2000 to August 2022 was done for studies on EUS-guided TA in patients receiving antithrombotics. The primary outcome was incidence of overall and major bleeding. Pooled event rates across studies were expressed with summative statistics. RESULTS: A total of 12 studies were included in the meta-analysis. The pooled risk of overall bleeding and major bleeding in patients on antithrombotics was 2.0% (0.6-3.4) and 0.8% (0.0-1.6), respectively. In patients taking thienopyridine or anticoagulants, the pooled risk of overall bleeding and major bleeding was 2.4% (0.9-3.9) and 1.7% (0.4-3.1), respectively. Patients on antithrombotics had a higher odd of overall bleeding (OR 2.12, 1.20-3.83) and major bleeding (OR 3.58, 1.11-11.52) compared to controls. The odds of overall bleeding (OR 0.95, 95%CI 0.38-2.42) and major bleeding (OR 1.57, 95%CI 0.45-5.54) were comparable between patients on antithrombotics who continued and those who discontinued it preprocedural. CONCLUSION: Despite an increase risk of bleeding with EUS-TA in patients on antithrombotics, the pooled incidence remains low. Compared to the previous guidelines stating thienopyridine use as high risk for bleeding, the present analysis showed a bleeding rate of less than 1%. Discontinuing antithrombotics prior to EUS-TA does not reduce the bleeding risk significantly, requiring strict monitoring.

Occurrence of intraocular hemorrhages under monotherapy or combination therapy of antiplatelets and anticoagulants using the Japanese Adverse Drug Event Report database.

Purpose: An intraocular hemorrhage is an adverse event that can lead to visual acuity impairment. Antithrombotic therapy with antiplatelet agents and anticoagulants may increase intraocular hemorrhage. However, since their frequency is low, studies on the risk of intraocular hemorrhage with these drugs, especially under combination therapy, are limited. This study aimed to investigate the occurrence of intraocular hemorrhages under monotherapy and combination therapy with antiplatelets and anticoagulants by analyzing a large pharmacovigilance database. Methods: Intraocular hemorrhage signals with oral antiplatelets and anticoagulants were evaluated by calculating reporting odds ratios and information components using the Japan Adverse Drug Reactions Report database from April 2004 to March 2022. In addition, differences in signals between younger and elderly patients, affecting factors, and time-to-onset from initial antiplatelet and anticoagulant treatments were analyzed. Results: Aspirin, clopidogrel, warfarin, apixaban, and rivaroxaban, but not ticagrelor, ticlopidine, prasugrel, dabigatran, and edoxaban showed intraocular hemorrhage signals under monotherapy. In combination therapy, dual therapy (aspirin + P2Y12 inhibitors, warfarin, direct oral anticoagulants, and P2Y12 inhibitors + warfarin) and triple therapy (aspirin + P2Y12 inhibitors + warfarin) resulted in intraocular hemorrhage signals. Intraocular hemorrhage signals were observed in younger patients receiving monotherapy with aspirin and in elderly patients receiving monotherapy and combination therapy with warfarin. Affecting factors were diabetes mellitus in patients with prasugrel, use of medications for intravitreal injections, and posterior sub-Tenon injections with some antiplatelets and anticoagulants. The median period of intraocular hemorrhage occurrence after starting monotherapy with aspirin, clopidogrel, warfarin, or rivaroxaban was within 90 days. Conclusion: In addition to monotherapy with several antiplatelets and anticoagulants, combination therapy using aspirin, P2Y12 inhibitors, and warfarin has the potential risk of intraocular hemorrhage. Particular attention should be paid to the occurrence of intraocular hemorrhages in younger patients taking aspirin, in elderly patients taking warfarin, and within the first 90 days of antiplatelet and anticoagulant use.

Bleeding risk in female patients undergoing intravesical injection of onabotulinumtoxinA for overactive bladder: a Danish retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: We aimed to examine the risk of bleeding in female patients undergoing intravesical onabotulinumtoxinA (BTX-A) treatments and provide clinical recommendations for the perioperative management of patients on antithrombotic therapy prior to BTX-A treatments. METHODS: This was a retrospective cohort of Danish female patients, who had their first BTX-A treatment because of an overactive bladder at the Department of Gynecology and Obstetrics, Herlev and Gentofte University Hospital, between January 2015 and December 2020. Data extraction was from an electronic medical journal system. BTX-A, Botox® Allergan was injected in the detrusor at 10-20 sites. Significant bleeding during or after a BTX-A treatment was defined as persistent macroscopic hematuria. Bleeding reporting was based on information obtained from journal notes. RESULTS: We included 400 female patients, who had a total of 1,059 BTX-A treatments. Median age at first BTX-A treatment was 70 years (IQR 21), and median number of BTX-A treatments was 2 (range 1-11). In total, 27.8% (n=111) received antithrombotic therapy. Within this group, 30.6% and 69.4% were on anticoagulant and antiplatelet therapy. No cases of hematuria were reported in our cohort. We found that no patients stopped their antithrombotic therapy, were bridged, or monitored by International Normalized Ration (INR) levels. CONCLUSIONS: We suggest that BTX-A treatments might be classified as low-risk procedures. Discontinuation of antithrombotic therapy is not required in the perioperative management of this patient group.

Safety of dual antiplatelet therapy in the acute phase of aneurysmal subarachnoid hemorrhage: a propensity score-matched study.

OBJECTIVE: With the evolution of neuroendovascular treatments, there is a great trend to treat acutely ruptured wide-necked aneurysms with stent-assisted coiling (SAC) and flow diverters (FDs), which inevitably requires dual antiplatelet therapy (DAPT). This therapy can increase the rate of hemorrhagic complications following other neurosurgical maneuvers, such as external ventricular drain (EVD) placement or removal. In this study, the authors aimed to evaluate the safety of DAPT in patients with aneurysmal subarachnoid hemorrhage (SAH) treated with SAC or FDs and the therapy's potential benefit in reducing cerebral ischemia and cerebral vasospasm. METHODS: In this retrospective study, the authors reviewed the records of patients who had been admitted to their hospital with acute aneurysmal SAH and treated with SAC, FDs, and/or coiling between 2012 and 2022. Patients were classified into two groups: a DAPT group, including patients who had received DAPT for SAC or FDs, and a non-DAPT group, including patients who had not received any antiplatelet regimen and had been treated with coiling. Perioperative hemorrhagic and ischemic complications and clinical outcomes were compared between the two groups. RESULTS: From among 938 cases of acute ruptured aneurysms treated during 10 years of study, 192 patients were included in this analysis, with 96 patients in each treatment group, after propensity score matching. All basic clinical and imaging characteristics were equivalent between the two groups except for the neck size of aneurysms (p < 0.001). EVD-related hemorrhage was significantly higher in the DAPT group than in the non-DAPT group (p = 0.035). In most patients, however, the EVD-related hemorrhage was insignificant. Parent artery or stent-induced thrombosis was higher in the DAPT group than in the non-DAPT group (p = 0.003). The rate of cerebral ischemia was slightly lower in the DAPT group than in the non-DAPT group (11.5% vs 15.6%, p = 0.399). In the multivariate analysis, cerebral ischemia, rebleeding before securing the aneurysm, extracranial hemorrhage, and cerebral vasospasm were the predictive factors of a poor clinical outcome (p < 0.001, p < 0.001, p = 0.038, and p = 0.038, respectively). CONCLUSIONS: The DAPT regimen may be safe in the setting of acute aneurysmal SAH. Although EVD-related hemorrhage is more common in the DAPT group than the non-DAPT group, it is usually insignificant without any neurological deficit.

The implications of antithrombotic agents on subdural hematoma evacuation: what does "reversal" truly entail?

OBJECTIVE: The optimal perioperative management of antithrombotic therapy (ATT) in patients requiring urgent neurosurgical intervention for subdural hematoma (SDH) is poorly understood. The delicate equilibrium of effective hemostasis while preventing thrombosis is complex and relies on numerous factors such as indication for and type of ATT, medical comorbidities, and extent of neurological injury. This study aimed to analyze the impact of ATT and reversal strategies on surgical outcomes to highlight current challenges in the management of these high-risk patients. METHODS: The authors performed a retrospective surgical cohort analysis of 100 patients undergoing urgent SDH evacuation at a level I trauma center between March 2020 and May 2021. The patients were first stratified into two cohorts based on preoperative ATT use and then further segregated by receipt of reversal agents. Statistical analysis included the chi-square test, Welch two-sample t-test, and multivariate logistic regression. The primary outcome was mortality. Secondary endpoints included radiographic SDH reexpansion, revision surgery, improvement in preoperative neurological deficits, and incidence of thromboembolism. A crossover cohort was secondarily analyzed in patients for whom ATT was interrupted for a minimum duration equal to effective drug metabolism. Finally, ATT reinitiation patterns were examined. RESULTS: Of 100 patients, 48% received ATT, 54.2% of whom were given reversal agents. ATT use was significantly associated with decreased rates of postoperative neurological improvement (p = 0.023) with trends toward increased mortality (p = 0.078), SDH reexpansion (p = 0.12), and need for revision surgery (p = 0.10). Patient crossover revealed a 4 times greater likelihood of death in patients without ATT interruption prior to surgery (p = 0.040) without an observable impact on secondary outcomes. ATT reversal contributed no improvement in outcomes other than a decreased intensive care unit length of stay when adjusted for in-hospital mortality (p = 0.014). The rate of postoperative thromboembolism following ATT reversal was 11.5%. ATT reinitiation was highly variable, occurring in 59.5% of patients, with median times of 17 and 15 days for antiplatelets and anticoagulants, respectively. CONCLUSIONS: Use of preoperative ATT portends poor clinical outcomes following nonelective SDH evacuation regardless of attempts to reverse these medications with replacement blood products. This study further reinforces the critical need for judicious use of ATT and optimization of reversal strategies in high-risk patient populations as best guided by multidisciplinary teams and evolving clinical practice guidelines.