Increased Risk Of Bleeding Research Articles

A Thorough Literature Review of the Potential Benefits and Drawbacks of Long-Term Aspirin Use for the Primary Prevention of Cardiovascular Disease.

This article examines the role of aspirin in the primary prevention of cardiovascular disease. It highlights findings from major studies such as ASPREE (ASPirin in Reducing Events in the Elderly), ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events), and ASPREE-XT (ASPirin in Reducing Events in the Elderly - eXTension) , among others. The review focuses on aspirin's role in primary prevention for specific populations including older adults, diabetics, hypertension patients, rheumatoid arthritis patients, kidney transplant recipients, and those with specific lipoprotein(a) genotypes, among other groups. We review these studies, noting aspirin's role in reducing events such as myocardial infarctions and its potential for increasing bleeding risks. The review also considers the implications for patients with kidney disease, referencing the Chronic Renal Insufficiency Cohort (CRIC) study and the International Polycap Study-3 (TIPS-3) trial. Additionally, it addresses the shifting paradigms in guidelines from the US Preventive Services Task Force and other entities, underscoring the importance of individualized aspirin use by balancing benefits against bleeding risks. The article further explores the concept of platelet reactivity, discusses strategies for improving adherence to aspirin therapy, and identifies existing research gaps, such as the phenomenon of aspirin resistance. It concludes by suggesting potential areas for future investigation to enhance understanding and application of aspirin in cardiovascular disease prevention.

Heparins May Not Be the Optimal Anticoagulants for Sepsis and Sepsis-Associated Disseminated Intravascular Coagulation.

Historically, heparin has had the longest historical use as an anticoagulant and continues this day to be the primary therapeutic option for preventing thrombosis and thromboembolism in critically ill hospitalized patients. Heparin is also used to treat sepsis and sepsis-associated disseminated intravascular coagulation (DIC) in various countries. However, the efficacy and safety of heparin for this indication remains controversial, as adequately powered randomized clinical studies have not demonstrated as yet a survival benefit in sepsis and sepsis-associated DIC, despite meta-analyses and propensity analyses reporting improved outcomes without increasing bleeding risk. Further, activated protein C and recombinant thrombomodulin showed greater improvements in outcomes compared with heparin, although these effects were inconclusive. In summary, further research is warranted, despite the ongoing clinical use of heparin for sepsis and sepsis-associated DIC. Based on Japanese guidelines, antithrombin or recombinant thrombomodulin may be a preferable choice if they are accessible.

A lower fibrinogen threshold does not lead to increased bleeding risk in patients receiving therapeutic plasma exchange: A prospective single-center analysis.

Plasma exchange (PLEX) therapy is indicated for several disorders. The 5% albumin is often used as a sole replacement fluid during most PLEX. However, each 1.0 plasma volume exchange depletes coagulation factors by ~65%. Although most coagulation factors recover to hemostatic levels within 24 h post-PLEX, fibrinogen requires 48-72 h to recover. Fibrinogen is the key coagulation protein for hemostasis. Therefore, fibrinogen is often monitored during the acute course of PLEX, and plasma is supplemented to prevent bleeding if fibrinogen is <100 mg/dL. We conducted a prospective, single-center, observational study to evaluate bleeding risk in adults who received an acute course of PLEX with a fibrinogen level of 80-100 mg/dL without plasma supplementation during the procedure or before central venous catheter removal. The study group was compared to patients with plasma fibrinogen >100 mg/dL. Among the 275 patients who received 1406 PLEXes, 62 patients (23%) who underwent 323 PLEXes met the inclusion criteria, and only 2 (3%) patients had bleeding while on oral anticoagulants. In contrast, out of 275 patients, 143 (52%) with fibrinogen levels >100 mg/dL received 751 PLEX treatments, and bleeding occurred in 2 (1%) while on low-molecular-weight heparin. Our findings suggest that a pre-procedure fibrinogen threshold of 80-100 mg/dL without plasma supplementation does not increase bleeding risk unless patients were on anticoagulation.

Genetic assessment of efficacy and safety profiles of coagulation cascade proteins identifies Factors II and XI as actionable anticoagulant targets.

Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed. To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38-0.51, P = 2.6e-28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39-0.76, P = 4.2e-04) but not with bleeding (OR = 1.13, 95% CI = 0.93-1.36, P = 2.2e-01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58-0.64, P = 4.1e-85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69-0.86, P = 4.1e-06) but not with bleeding (OR = 1.01, 95% CI = 0.95-1.08, P = 7.5e-01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses. These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.

Bleeding risk from anticoagulant thromboprophylaxis in patients with multiple myeloma: a MarketScan analysis

BackgroundMultiple myeloma (MM) is associated with high risk of venous thromboembolism (VTE). Anticoagulant prophylaxis is frequently recommended but underutilized partly due to the absence of studies assessing bleeding risk. ObjectivesTo determine the rate of severe (hospitalized) bleeding from thromboprophylaxis in patients treated for MM and identify clinical risk factors for bleeding in this population. MethodsUsing the MarketScan database, we analyzed 6656 patients treated for MM between 2013 and 2021. Concomitant thromboprophylaxis was defined using prescription claims. Hospitalized bleeding was identified through the Cunningham algorithm. Bleeding rates were compared by thromboprophylaxis status, and Cox regression identified risk factors for bleeding. ResultsAnticoagulant thromboprophylaxis was used in 6.6% (436) patients treated for MM. Patients on thromboprophylaxis had a higher rate of immunomodulatory-based therapy (63.8% vs 46.7%; P < .01) and lower rate of antiplatelet use (2.1% vs 4.7%; P < .01). Bleeding occurred in 1.4% of them during median follow-up of 1.3 years. Rate of severe bleeding was not different between those on prophylaxis (7.8 per 1000 person-years) and those not on prophylaxis (10.1 per 1000 person-years). No association was identified between thromboprophylaxis and bleeding. Factors associated with increased bleeding included age (hazard ratio [HR], 1.38 per 10 years increase in age), comorbidity index (HR, 1.18 per SD increase), history of bleeding (HR, 1.54), hypertension (HR, 1.87), and renal disease (HR, 1.56). ConclusionRisk of serious bleeding from thromboprophylaxis in patients treated for MM was low, and concomitant anticoagulant therapy did not result in increased bleeding risk. Clinical risk factors for bleeding included age, comorbidity index, bleeding history, hypertension, and renal disease.

Risk factors for postoperative bleeding following endoscopic submucosal dissection in early gastric cancer: A systematic review and meta-analysis.

Early gastric cancer (EGC) presents a significant challenge in surgical management, particularly concerning postoperative bleeding following endoscopic submucosal dissection. Understanding the risk factors associated with postoperative bleeding is crucial for improving patient outcomes. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review and meta-analysis were conducted across PubMed, Embase, Web of Science, and the Cochrane Library without publication date restrictions. The inclusion criteria encompassed observational studies and randomized controlled trials focusing on EGC patients undergoing endoscopic submucosal dissection and their risk factors for postoperative bleeding. The Newcastle-Ottawa Scale was utilized for quality assessment. The effect size was calculated using random or fixed-effects models based on the observed heterogeneity. We assessed the heterogeneity between studies and conducted a sensitivity analysis. In our meta-analysis, 6 studies involving 4868 EGC cases were analyzed. The risk of postoperative bleeding was notably increased with intraoperative ulcer detection (odds ratio: 1.97, 95% confidence interval [CI]: 1.03-3.76, I2 = 61.0%, P = .025) and antithrombotic medication use (odds ratio: 2.02, 95% CI: 1.16-3.51, I2 = 57.2%, P = .039). Lesion resection size showed a significant mean difference (5.16, 95% CI: 2.97-7.98, P < .01), and longer intraoperative procedure time was associated with increased bleeding risk (mean difference: 11.69 minutes, 95% CI: 1.82-26.20, P < .05). Sensitivity analysis affirmed the robustness of these findings, and publication bias assessment indicated no significant bias. In EGC treatment, the risk of post-endoscopic submucosal dissection bleeding is intricately linked to factors like intraoperative ulcer detection, antithrombotic medication use, the extent of lesion resection, and the length of the surgical procedure. These interwoven risk factors necessitate careful consideration and integrated management strategies to enhance patient outcomes and safety in EGC surgeries.

Unraveling the Paradox: Can Anticoagulation Improve Outcomes in Patients With Heart Failure and Increased Bleeding Risk?

Heart failure (HF) patients frequently present with comorbidities such as atrial fibrillation (AF) or other cardiovascular conditions, elevating their risk of thromboembolic events. Consequently, anticoagulation therapy is often considered for thromboprophylaxis, although its initiation in HF patients is complicated by concomitant bleeding risk factors. This review explores the paradoxical relationship between HF, increased bleeding risk, and the potential benefits of anticoagulation. Through an examination of existing evidence from clinical trials, observational studies, and meta-analyses, we aim to elucidate the role of anticoagulation in HF patients with increased bleeding risk. Despite guidelines recommending anticoagulation for certain HF patients with AF or other thromboembolic risk factors, uncertainty persists regarding the optimal management strategy for those at heightened risk of bleeding. The review discusses the pathophysiological mechanisms linking HF and thrombosis, challenges in bleeding risk assessment, and strategies to minimize bleeding risk while optimizing thromboprophylaxis.Shared decision-making between clinicians and patients is emphasized as essential for individualized treatment plans that balance the potential benefits of anticoagulation against the risk of bleeding complications. Furthermore, it examines emerging anticoagulant agents and their potential role in HF management, highlighting the need for further research to delineate optimal management strategies and inform evidence-based practice. In conclusion, while anticoagulation holds promise for improving outcomes in HF patients, careful consideration of patient-specific factors and ongoing research efforts are essential to optimize therapeutic strategies in this population.

Antithrombotic therapy in acute coronary syndrome

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. In patients with acute coronary syndromes, balancing the reduction in cardiovascular events and increase in major bleeding during treatment with more potent P2Y12 inhibitors such as prasugrel and ticagrelor is still an issue. A special focus is on patients already treated with oral anticoagulants for stroke prevention in atrial fibrillation who require additional platelet inhibition following coronary stenting. This article summarizes the major recommendations given in the most recent Guideline for "Acute Coronary Syndromes" published by the European Society of Cardiology (ESC). The recommendations finally address strategies to reduce an increased bleeding risk based on clinical predictors.

What Do We Really Know About the Effect of Prolonged Heart Rhythm Monitoring After Stroke?

The bulk of the current knowledge on atrial fibrillation (AF)-associated stroke risk and benefit of oral anticoagulation derives from studies on patients with clinically diagnosed AF. Subclinical AF (SCAF), defined as AF discovered during the interrogation of prolonged heart monitoring, is often asymptomatic and short-lasting, is associated with increased stroke risk compared with sinus rhythm, and may progress to clinical AF. Despite the extensive screening for and treatment of SCAF, especially in secondary stroke prevention, the net benefit of this practice is not established. Recent studies of SCAF have provided new insights: (1) SCAF is extremely common and may sometimes indicate physiological findings, (2) the stroke risk associated with SCAF is lower than that of clinically detected AF, and (3) any benefit on stroke risk may be countered by increased bleeding risk (no net benefit). How should we interpret the latest knowledge in the setting of poststroke AF screening and prevention?

Risk factors for intracerebral hemorrhage in small-vessel disease and non-small-vessel disease etiologies-an observational proof-of-concept study.

Sporadic cerebral small-vessel disease (CSVD), i.e., hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA), is the main cause of spontaneous intracerebral hemorrhage (ICH). Nevertheless, a substantial portion of ICH cases arises from non-CSVD etiologies, such as trauma, vascular malformations, and brain tumors. While studies compared HA- and CAA-related ICH, non-CSVD etiologies were excluded from these comparisons and are consequently underexamined with regard to additional factors contributing to increased bleeding risk beyond their main pathology. As a proof of concept, we conducted a retrospective observational study in 922 patients to compare HA, CAA, and non-CSVD-related ICH with regard to factors that are known to contribute to spontaneous ICH onset. Medical records (available for n = 861) were screened for demographics, antithrombotic medication, and vascular risk profile, and CSVD pathology was rated on magnetic resonance imaging (MRI) in a subgroup of 185 patients. The severity of CSVD was assessed with a sum score ranging from 0 to 6, where a score of ≥2 was defined as advanced pathology. In 922 patients with ICH (median age of 71 years), HA and CAA caused the majority of cases (n = 670, 73%); non-CSVD etiologies made up the remaining quarter (n = 252, 27%). Individuals with HA- and CAA-related ICH exhibited a higher prevalence of predisposing factors than those with non-CSVD etiologies. This includes advanced age (median age: 71 vs. 75 vs. 63 years, p < 0.001), antithrombotic medication usage (33 vs. 37 vs. 19%, p < 0.001), prevalence of vascular risk factors (70 vs. 67 vs. 50%, p < 0.001), and advanced CSVD pathology on MRI (80 vs. 89 vs. 51%, p > 0.001). However, in particular, half of non-CSVD ICH patients were either aged over 60 years, presented with vascular risk factors, or had advanced CSVD on MRI. Risk factors for spontaneous ICH are less common in non-CSVD ICH etiologies than in HA- and CAA-related ICH, but are still frequent. Future studies should incorporate these factors, in addition to the main pathology, to stratify an individual's risk of bleeding.

Chronic disseminated candidiasis in a patient with acute leukemia - an illustrative case and brief review for clinicians

Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.

LDL-C Levels and Bleeding Risk in Patients Taking DAPT After Minor Ischemic Stroke or TIA

Evidence on the bleeding risk associated with low-density lipoprotein cholesterol (LDL-C) levels in patients receiving dual antiplatelet therapy (DAPT) remains sparse. To investigate the association of LDL-C levels with bleeding risk in patients with minor ischemic stroke (MIS) or high-risk transient ischemic attack (HRTIA) receiving DAPT. This cohort study was an analysis of pooled data from 2 randomized, double-blind, placebo-controlled clinical trials in China of patients with MIS or HRTIA who were receiving DAPT: the CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) trial enrolled patients at 114 sites from October 2009 to July 2012, and the CHANCE-2 enrolled patients at 202 centers from September 2019 to March 2021. Both sets of patients were followed up for 90 days. Data analysis was performed from August 2022 to May 2023. Baseline LDL-C levels and receipt of ticagrelor-aspirin and clopidogrel-aspirin DAPT. The primary outcome was any bleeding, and the secondary outcome was severe or moderate bleeding within 3 months after randomization. The association of LDL-C levels and all outcomes was assessed by using the Cox proportional hazard model. Hazard ratios (HRs) with 95% CIs were calculated on univariable (unadjusted) Cox regression models. Adjusted HRs (aHRs) and their 95% CIs were calculated on multivariable Cox regression models. In total, 8996 patients with acute MIS or HRTIA who were receiving DAPT were included in the 2 trials, of whom 1066 without serum specimens and 490 patients with missing baseline LDL-C value were excluded. Finally, 7440 patients with DAPT (4486 in the clopidogrel-aspirin group and 2954 in the ticagrelor-aspirin group) were included in this study. The median (IQR) age was 64.32 (56.56-71.30) years, and 2479 patients (33.32%) were women. A total of 270 (3.63%) bleeding events were reported at 3 months, and LDL-C less than 70 mg/dL was associated with an increased risk of both any bleeding (aHR, 1.48; 95% CI, 1.03-2.12), and severe or moderate bleeding (aHR, 2.78; 95% CI, 1.18-6.53). The risk of any bleeding was increased at lower LDL-C levels in the ticagrelor-aspirin group (aHR, 1.71; 95% CI, 1.08-2.72). However, an increased risk of any bleeding was not observed in the clopidogrel-aspirin group (aHR, 1.30; 95% CI, 0.73-2.30). There was no significant association between LDL-C levels and the risk of severe or moderate bleeding in either the ticagrelor-aspirin or clopidogrel-aspirin group. These findings suggest that low LDL-C levels are associated with an increased bleeding risk within 3 months among patients with MIS or HRTIA receiving DAPT, especially those taking ticagrelor-aspirin. Weighing the risks and benefits is crucial when simultaneously considering the selection of LDL-C target strategies and DAPT regimens among these patients.

Dose-dependent increase in risk of bleeding and bleeding complications in relation to SSRI use at delivery

IntroductionDepression during pregnancy is a severe state that increases the risk of suicide, as well as adverse newborn outcomes. Selective serotonin re-uptake inhibitors (SSRIs) are effective for the treatment of depression, but increase the risk of bleeding complications at delivery. Knowledge on the dose dependency of this association is lacking. MethodsA hospital-based cohort study of all women who gave birth at Karolinska University Hospital in Stockholm over the 5-year period from 2007 to 2011, with or without SSRI use, was undertaken. In total, 334 women who delivered vaginally and were exposed to SSRIs at delivery were identified. All other women who delivered vaginally formed the control group (n = 31,929). The electronic maternal health records of the 334 SSRI users were scrutinized, and the women were categorized into two groups: moderate (n = 246) or high (n = 88) SSRI dose at delivery. The main outcome was bleeding complications at delivery in relation to SSRI dose. ResultsA dose-dependent increase in the rate of postpartum haemorrhage (≥1000 ml) was found, affecting 8.4 %, 14.6 % and 23.9 % (p ≤ 0.001) of women in the control group, the moderate-dose group and the high-dose group, respectively. In addition, a dose-dependent increase in the rate of postpartum anaemia was found, affecting 7.0 %, 9.3 % and 15.9 % (p = 0.001) of women in the control group, the moderate-dose group and the high-dose group, respectively. Mean blood loss of 406 ml, 483 ml and 482 ml (p ≤ 0.001) was found in the control group, the moderate-dose group and the high-dose group, respectively. Women exposed to SSRIs delivered earlier, but did not have higher prevalence of pre-eclampsia compared with the control group. ConclusionsThe dose-dependent relationship between SSRIs and bleeding complications may be clinically useful in the management of this vulnerable group of women.

Chronic liver disease-associated severe thrombocytopenia in Spain: Results from a retrospective study using machine learning and natural language processing

BackgroundPatients with chronic liver disease (CLD) often develop thrombocytopenia (TCP) as a complication. Severe TCP (platelet count<50×109/L) can increase morbidity and complicate CLD management, increasing bleeding risk during invasive procedures. ObjectivesTo describe the real-world scenario of CLD-associated severe TCP patients’ clinical characteristics. To evaluate the association between invasive procedures, prophylactic treatments, and bleeding events in this group of patients. To describe their need of medical resource use in Spain. MethodsThis is a retrospective, multicenter study including patients who had confirmed diagnosis of CLD and severe TCP in four hospitals within the Spanish National Healthcare Network from January 2014 to December 2018. We analyzed the free-text information from Electronic Health Records (EHRs) of patients using Natural Language Processing (NLP), machine learning techniques, and SNOMED-CT terminology. Demographics, comorbidities, analytical parameters and characteristics of CLD were extracted at baseline and need for invasive procedures, prophylactic treatments, bleeding events and medical resources used in the follow up period. Frequency tables were generated for categorical variables, whereas continuous variables were described in summary tables as mean (SD) and median (Q1–Q3). ResultsOut of 1,765,675 patients, 1787 had CLD and severe TCP; 65.2% were male with a mean age of 54.7 years old. Cirrhosis was detected in 46% (n=820) of patients and 9.1% (n=163) had hepatocellular carcinoma. Invasive procedures were needed in 85.6% of patients during the follow up period. Patients undergoing procedures compared to those patients without invasive procedures presented higher rates of bleeding events (33% vs 8%, p<0.0001) and higher number of bleedings. While prophylactic platelet transfusions were given to 25.6% of patients undergoing procedures, TPO receptor agonist use was only detected in 3.1% of them. Most patients (60.9%) required at least one hospital admission during the follow up and 14.4% of admissions were due to bleeding events with a hospital length of stay of 6 (3, 9) days. ConclusionsNLP and machine learning are useful tools to describe real-world data in patients with CLD and severe TCP in Spain. Bleeding events are frequent in those patients who need invasive procedures, even receiving platelet transfusions as a prophylactic treatment, increasing the further use of medical resources. Because that, new prophylactic treatments that are not yet generalized, are needed.

Case Report: Life-Threatening Fluoxetine-Linked Postoperative Bleeding Informed by Pharmacogenetic Evaluation.

Selective serotonin reuptake inhibitors (SSRI) are commonly used for the treatment of depression and anxiety. Inhibition of serotonin reuptake in platelets increases bleeding risk in patients taking SSRIs. Here, we present the case of a 52-year-old patient who developed severe postsurgical bleeding requiring blood transfusion following panniculectomy. SSRI-induced bleeding is dose-related and strongly influenced by individual variations in drug metabolizing enzymes and transporters. Supplementary file1 (MP4 8441 KB).

Anticoagulant therapy likely increases risk of bleeding in Gynura segetum-induced hepatic sinus obstruction syndrome.

This study aimed to analyze the clinical characteristics of Gynura segetum (Tusanqi)-induced hepatic sinusoidal obstruction syndrome (HSOS) and the benefits and risks of anticoagulant therapy for Tusanqi-induced HSOS. This was a retrospective analysis of 49 patients with Tusanqi-induced HSOS who were treated with anticoagulation or standard therapy between July 2006 and December 2022. Clinical manifestations included abdominal pain (n = 47) and peritoneal or pleural effusion (n = 46); 2 patients died. Nineteen patients requested standard medical treatment, while 30 were treated with anticoagulants. HSOS resolved within 6 months in 22 patients but did not resolve in 27 patients. The resolution rate was higher in the anticoagulant than standard treatment group (P = .037). Logistic regression analysis revealed that a history of chronic liver disease or treatment increased the risk of poor outcomes. Bleeding complications occurred in 6 patients in the anticoagulant treatment group. Early diagnosis and anticoagulant treatment are beneficial for rapid recovery after Tusanqi-induced HSOS. However, anticoagulant treatment is associated with the risk of multisite bleeding.

Milvexian: A Focus on a New Oral Anticoagulant that Targets Factor XIa for Thromboembolism Prophylaxis.

Drugs that target factor XI and/or XIa have been evaluated as alternatives to existing anticoagulants, in light of studies that indicate that a decrease in Factor XI/XIa levels or activity may result in a lower risk of thrombosis without a significant increase in bleeding risk. Milvexian is an investigational small-molecule factor XIa inhibitor that has recently completed phase 2 clinical trials. Preclinical studies were suggestive of its potential to prevent arterial and venous thrombosis. It was well-tolerated in healthy participants, as well as in participants with mild or moderate hepatic impairment and moderate or severe renal impairment. Notably, patients who received milvexian after knee arthroplasty had a dose-proportional lower incidence of venous thromboembolism compared to patients who received postoperative enoxaparin, and they had a lower incidence of clinically relevant bleeding. A separate phase 2 trial was conducted that assessed the use of milvexian for secondary stroke prevention in patients who had ischemic stroke or transient ischemic attack. It failed its primary objective of establishing a dose-response relationship between milvexian and a composite endpoint of symptomatic ischemic stroke or covert brain infarction. The trial did, however, show a reduction in the relative risk of symptomatic ischemic stroke across most of the treatment groups receiving various dosages of milvexian compared to placebo. The efficacy of milvexian in secondary stroke prevention will be further assessed in an upcoming phase 3 trial. Additional upcoming phase 3 trials will also assess its efficacy in stroke prevention in patients with atrial fibrillation as well as in event reduction in patients with acute coronary syndrome.

Retrospective Analysis of Potential Adverse Drug Interactions in the Drugs Prescribed to the Elderly at a Tertiary Health Care Center in Raipur, Chhattisgarh, Central India.

Background The elderly population differs from adults in having various physiological changes and multiple diseases, which demand the use of multiple medications. The practice of polypharmacy in the elderly leads to numerous harmful effects like adverse drug reactions, adverse drug-drug interactions (DDIs), poor compliance, etc. Methodology This study collected 295 case files of elderly patients retrospectively in the Departments of General Medicine, Cardiology and Nephrology after obtaining Institute Ethics Committee approval to look for the potential adverse DDIs with their severity according to the clinical significance. Results and interpretation The total numberof adverse DDIs identified was 156, the maximum in Category 'C.' Salbutamol plus carvedilol/propranolol, ramipril plus telmisartan and ivabradine plus diltiazem were the adverse DDIs categorized under severity 'X'. The identified DDIs were categorised according to the mechanism such as increased bleeding risk, hypokalemia, hyperkalaemia, reduced effect of drugs and increased effect of drugs. Conclusion Polypharmacy can lead to several adverse consequences in the elderly, of whichadverse DDIs play a crucial role in harmful health outcomes. This study brings out the significance of predicting drug interactions beforehand which can reduce the risk of bleeding and other risks of hyper/hypokalaemia, hyponatremia and hypoglycaemia.

Abstract 25: Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Recent Direct Oral Anticoagulant Use: A Systematic Review and Meta-Analysis

Introduction: Intravenous thrombolysis (IVT) is efficacious treatment of acute ischemic stroke (AIS). However, certain circumstances associated with increased bleeding risk, such as recent direct oral anticoagulation (DOAC) intake limits its use. Nonetheless, emerging evidence has shown promising results in this patient group. We investigated the safety and efficacy of IVT in patients with AIS and recent DOAC use. Methods: We conducted systematic review and meta-analysis of proportions evaluating IVT with recent DOAC use. Outcomes of interest were symptomatic intracranial hemorrhage (sICH), any ICH, serious systemic bleeding (SSB), and 90-day functional independence (mRS 0-2). Moreover, we calculated pooled odds ratios (OR) for each outcome using a random effect meta-analysis to compare the rates between the patients with DOAC and non-DOAC upon IVT. Ultimately, we completed a sensitivity analysis for idarucizumab, NIHSS, and the timing of DOAC administration. Results: Our meta-analysis included 14 studies with 247079 patients (3610 in DOAC and 243469 in non-DOAC). In the DOAC group, the rate of sICH was 3% (95%CI 3 - 4%), any ICH was 12% (95%CI 7 - 19%), SSB 0.7% (95%CI 0 - 1%), and 90-day mRS 0-2 was 57% (95%CI 43 - 70%). No difference in the rates of sICH (3.4vs.3.5%; OR=0.95; 95%CI 0.67 - 1.36), any ICH (17.7vs.17.3%; OR=1.23; 95%CI 0.61 - 2.48), SSB (0.7vs.0.6%; OR=1.27; 95%CI 0.79 - 2.02), and 90-day mRS 0-2 (46.4vs.56.8%; OR=1.21; 95%CI 0.400 - 3.67) was found between DOAC and non-DOAC groups. Subgroup analysis revealed no significant difference in the sICH rate between idaricuzumab and no idaricizumab administration prior to IVT [Figure 1]. Conclusions: Our analysis demonstrated no significant difference in functional independence and hemorrhagic complication rates in AIS patients treated with IVT with recent DOAC compared to the no-DOAC group. Further prospective randomized clinical trials are needed to shed more light on this topic.

Abstract WP166: Bleeding Risks Among Hemorrhagic Stroke Patients Started on Serotonergic Antidepressants During Subacute Recovery

Background: Early initiation of antidepressants (ADs) are associated with improved functional recovery, but are associated with an increased risk of major bleeds among hemorrhagic stroke (HS) patients. Our objectives were to determine if increased bleeding risk remained if ADs were initiated during subacute recovery and if bleed risks were comparable between AD classes. Methods: A cohort of AD naive first time HS patients (ICD-10 codes 160-162) were identified from Electronic Medical Records of 70 large healthcare organizations (2003-2023). Patients without AD use were considered “No AD” whereas patients started on ADs during subacute recovery (i.e., at least 3 months after the indexed HS) were grouped as Selective Serotonin/Serotonin &amp; Norepinephrine Reuptake Inhibitors (SSRI/SNRI) or “Other AD” (i.e., Mirtazapine, bupropion, trazodone, or tricyclic ADs). Baseline differences were adjusted for using 1:1 matched propensity score (PS). Outcomes included the 1-year risk of a major bleeding event (e.g., gastrointestinal/intracranial bleed or shock), recurrent HS, fall, ischemic stroke (IS) and death Results: The cohort consisted of n=257,595 patients split into 3 groups: No AD (n=250,103), SSRI/SNRI (n=4,180) or Other AD (n=3,312). Matching resulted in good covariate balance for both the SSRI/SNRI vs. No AD (n=8,250 patients) and Other AD vs. SSRI/SNRI (n=6,380 patients) comparisons. SSRI/SNRIs (vs. No AD) were associated with a 33% increase in the risk of a major bleed (RR: 1.33, 95%CI: 1.22-1.45) and significantly higher risks of recurrent HS, fall, IS and death. There were no significant differences in adverse outcomes between AD classes. Discussion: Increased risk of major bleeds and recurrent HS remains if ADs are started during subacute recovery, a time period which aligns with community-based recovery. Our findings may inform care practices of primary care providers and rehabilitation professionals to decrease preventable adverse outcomes.