Lower Bleeding Research Articles

Discovery and Preclinical Characterization of Fulacimstat (BAY 1142524), a Potent and Selective Chymase Inhibitor As a New Profibrinolytic Approach for Safe Thrombus Resolution.

Chymase is a serine-protease produced by mast cells. In the past few decades, its role in fibrotic diseases triggered the search for orally available chymase inhibitors. Aiming at reducing adverse cardiac remodeling after myocardial infarction, our research efforts resulted in the discovery of fulacimstat (BAY 1142524). While clinical trials did not demonstrate efficacy in this indication, the recent discovery of a new unexpected biological role of chymase spurred a revival of interest in chymase inhibition: chymase was shown to inactivate plasmin within fibrin-rich clots. Chymase inhibitors are now considered as potential profibrinolytic drugs with low bleeding risk and therefore exceptional safety for the treatment of acute thrombosis settings such as stroke, pulmonary embolism, or venous thrombosis. This article describes the chemical optimization journey from a screening hit to the discovery of fulacimstat (BAY 1142524), a selective chymase inhibitor with a good safety profile, as well as its preclinical in vitro and in vivo characterization.

Applications of flexible ureteroscope lithotripsy with negative pressure suction and percutaneous nephrolithotomy in the treatment of 2-3cm diameter renal calculi.

Renal calculus, or kidney stone disease, presents a significant healthcare challenge globally, necessitating diverse therapeutic interventions. Percutaneous nephrolithotomy (PCNL) and flexible ureteroscope lithotripsy (FURL) are prominent among these interventions, with PCNL favored for stones > 2cm and FURL for smaller stones and applications of flexible ureteroscope lithotripsy with negative pressure suction for stones 1.5-2.5cm have some benefit. From June 2019 to January 2024, 310 patients undergoing FURL with negative pressure suction or PCNL for 2-3cm renal calculi were retrospectively analyzed. The demographic and clinical data were collected, and outcomes including stone-free rates (SFR), postoperative complications, and surgical parameters were compared. Comparable SFR were observed between FURL and PCNL groups at 1-month follow-up, although PCNL was superior to FURL after immediately post-surgery. FURL exhibited significantly fewer complications overall (5.7% vs. 19.3%, p = 0.044), shorter hospital stays, and lower postoperative pain levels. The surgical parameters favored FURL, showing lower bleeding volumes, shorter catheter removal times, and less hemoglobin decrease postoperatively. Despite similar stone clearance efficacy at 1-month follow-up, FURL demonstrated superior safety and postoperative outcomes compared to PCNL for 2-3cm renal calculi. These findings highlight the potential advantages of FURL in reducing complications, enhancing recovery, and optimizing patient care pathways.

Over-the-scope clips for Nonvariceal upper gastrointestinal bleeding: a systematic review and meta-analysis of randomized studies.

Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a common and potentially life-threatening condition. Over-the-scope clips (OTSCs) have emerged as a promising endoscopic treatment option for NVUGIB. We aimed to analyze the efficacy and safety of OTSCs compared to standard endoscopic treatments (ST) in patients with NVUGIB. We conducted a comprehensive search of PubMed, Embase, Scopus, and Cochrane Library databases from inception to June 2024 for randomized controlled trials (RCTs) comparing OTSCs with ST for NVUGIB. The primary outcomes were initial hemostasis and persistent bleeding. Secondary outcomes included rebleeding rates, mortality, hospital stays and others. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random/fixed-effects models. Six RCTs involving 621 patients were included in the meta-analysis. OTSCs demonstrated significantly higher initial hemostasis (OR 4.80, 95% CI 1.78-12.96; P = 0.002) and lower persistent bleeding rates (OR 0.17, 95% CI 0.05-0.56; P = 0.003) compared to ST group. The rebleeding rate was significantly lower in the OTSC group 7-days re-bleeding (OR 0.27, 95% CI 0.14-0.53; P = 0.001); 30-days rebleeding (OR 0.40, 95%CI 0.22, 0.70; P = 0.002). No significant differences were observed in mortality (OR 0.65, 95% CI 0.31-1.33; P = 0.38) and hospital stay (mean difference 0.79days 95%CI -0.57, 2.15) between the two groups. OTSCs are more effective than ST for achieving hemostasis and preventing rebleeding in patients with NVUGIB, without increasing mortality. Key message What is Already Known Previous studies have shown that nonvariceal upper gastrointestinal bleeding (NVUGIB) is a serious medical condition that needs effective endoscopic interventions. The success rates of standard treatments for achieving hemostasis and preventing rebleeding are not consistent. What This Study Adds According to this study, over-the-scope clips (OTSCs) have the same mortality rate as standard endoscopic treatments, but they significantly improve initial hemostasis and lower rebleeding rates. Impact on Research, Practice, or Policy The findings support the use of OTSCs as a preferred intervention for NVUGIB, which could affect clinical guidelines and encourage additional research focused on improving endoscopic techniques and patient outcomes in the management of gastrointestinal bleeding.

Clinical and economic benefits of patients undergoing lobectomy with the use of powered vascular staplers—based on China’s real-world data

Background Endoscopic surgery is widely performed with an increasing use of powered vascular staplers (PVS). However, few studies have examined PVS use in China, most of which have focused on clinical effects; fewer studies have examined the economic benefits of PVS. This study evaluated the clinical and economic benefits of the PVS compared to standard-of-care (SOC) staplers in lobectomy using results from a single-arm, multicenter clinical trial conducted in China and actual clinical use in a hospital collected in a real healthcare setting. Methods Patients with lung cancer undergoing thoracoscopic lobectomy were included in the study. The clinical and economic benefits of powered vascular stapler have been evaluated from a hospital’s perspective based on parameters such as bleeding occurrence, hospitalization time, secondary thoracotomy, and hospitalization costs. To compare the bleeding associated with use of PVS and SOC stapler in clinical use, PVS single-arm multi-center clinical trial data is used for the intervention group, and sampling data from hospitals is used for the control group. To ensure the outcome indicators between the two groups are comparable, we set the same inclusion criteria for the two groups of data and then used propensity score matching (PSM) to match two groups of patients according to the baseline characteristics. Results The results show that bleeding incidence in patients with SOC stapler group is 17.33% from hospital sampling data. In contrast, in the PVS group, it is 4.00%, and these rates are statistically different (P = 0.0167). Considering converted to open thoracic surgery, the rate of the SOC stapler group is 5.78% and that of the PVS group is 4.00%. These rates are not statistically different (P = 0.6166). Regarding hospitalization days, the length of the SOC stapler group is 18.97 days, while that in the PVS group is 12.38 days, and these data are statistically different (P = 0.0002). As patients in the PVS group have reduced bleeding, they will require less resource use from blood transfusion, drug services and surgical services. If PVS is used for transection of vessel, it can reduce the bleeding incidence by 13.33% and save 75.47 CNY in blood transfusion costs, 571.36 CNY in drug costs, and 183.38 CNY in surgical service costs per patient. From these three aspects, the hospital saves per patient 830.21 CNY. Conclusions Compared with the SOC stapler group, the PVS group has a lower bleeding incidence and shorter hospital days for lobectomy. In terms of blood transfusion costs, drug costs and surgical service costs, the hospital saves per patient 830.21 CNY.

The impact of OCEANIC-AF and the future of factor XIa inhibitors

The OCEANIC-AF trial was terminated early due to inferiority of asundexian compared with apixaban for the prevention of stroke and systemic embolism in patients with atrial fibrillation.1 However, the promisingly low bleeding rates support continued exploration of factor XIa inhibitors. Future efforts should focus on achieving greater factor XIa inhibition and identifying patient populations that may benefit most from these therapies.

Use of Direct Anticoagulants in Kidney Transplant Recipients: Review of the Current Evidence and Emerging Perspectives.

Thromboembolic events and atrial fibrillation are common among kidney transplant recipients (KTRs), and these conditions typically require anticoagulation. Traditionally, vitamin K antagonists were used for management, but the use of direct oral anticoagulants (DOACs) has increased in KTRs. In the general population, DOACs are recommended over warfarin, but the applicability of these recommendations to KTRs is unclear because of risk-benefit concerns. There is some hesitancy to use DOACs in KTRs because of their dependence on renal clearance for elimination, potential drug-drug interactions, and limited data. To date, studies of DOACs in KTRs have demonstrated that they are efficient in thromboembolic events, major bleeding is rare, and drug-drug interactions appear rare. However, no guidance yet exists about the use of DOACs, reversal of DOAC action, and the pre- and post-kidney transplant management of DOACs in KTRs, and the evidence base is scarce. Thus, decisions on DOAC use in KTRs are based on expert opinion and the resources and experiences of individual transplant centers. This review summarizes 10 published studies on the use of DOACs in 741 KTRs, evaluating the side effects, efficacy, drug-drug interactions, and perioperative management compared with those of 1320 KTRs using vitamin K antagonists. Although current data are limited, DOACs appear to be relatively safe and effective in KTRs, with some studies suggesting lower bleeding rates and better kidney function than with vitamin K antagonists. However, more research with larger patient groups is needed to draw definitive conclusions.

Rivaroxaban or warfarin in atrial fibrillation and coronary stent implantation in real-world patients involving chronic kidney disease (REWRAPS): 5-year follow-up study

Abstract Background Recent guidelines recommended either non vitamin K antagonist oral anticoagulants (NOAC) or vitamin K oral anticoagulant (VKA) one year after coronary stenting in patients with atrial-fibrillation (AF). However, whether NOAC is still superior to VKA at 5-years in patients involving chronic kidney disease (CKD) with AF and coronary stenting >1-year remains unclear. Methods In a multicenter, prospective, non-randomized registry, 493 patients were treated with either rivaroxaban or warfarin, while the majority (66.3%) of them had CKD. The primary efficacy endpoint was major adverse cardiac and cerebral events (MACCE). The primary safety endpoint was major bleeding (Bleeding Academic Research Consortium [BARC] 3 and 5). Net adverse clinical events (NACE) were defined as the composite of all-cause mortality and major bleeding. Both crude and propensity score matched (PSM) analyses were performed. P <0.05 was considered as statistically significant. Results At a median follow-up of 4.8 years MACCE rates did not differ between rivaroxaban and warfarin in 486 patients with crude-analysis (23.0% versus 29.0%, hazard-ratio [HR], 0.79; 95% confidence interval [CI], 0.55 to 1.11; P=0.17), while in 316 patients with PSM-analysis rivaroxaban met non-inferiority criteria to warfarin (HR, 0.86; 95% CI, 0.56 to 1.33; p=0.020 for non-inferiority). Rivaroxaban was associated with lower major bleeding risk compared with warfarin (6.5% versus 12.6%; HR, 0.50; 95% CI, 0.27 to 0.91; P=0.025) at crude analyses, which was no longer significant at PSM analyses (5.7% versus 10.8%; HR, 0.53; 95% CI, 0.24 to 1.19; P=0.12). However, NACE rates were significantly lower in rivaroxaban compared to warfarin at both crude (19.0% versus 35.7%; HR, 0.50; 95% CI, 0.35 to 0.72; P=0.0002) and PSM-analyses (19.6% versus 31.0%; HR, 0.63; 95% CI, 0.40 to 0.98; P=0.043), respectively. Conclusions Rivaroxaban did not differ from warfarin for efficacy endpoints of MACCE but was associated with lower NACE rates (i.e. all-cause mortality and major bleeding) in AF and coronary stent in real-world patients having CKD at 5-year follow-up (NCT02024230).

Drug-coated balloon versus drug-eluting stent for de novo culprit lesion in acute coronary syndromes: a report from nationwide registry in japan

Abstract Background Randomized trials have demonstrated the non-inferiority of DCB strategy compared to DES strategy for ACS [1-3]. However, generalizability in clinical settings remains unclear. Purpose This study aims to compare the outcomes between drug-coated balloon (DCB) and drug-eluting stent (DES) strategies in percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) within a nationwide procedure-based registry. Methods This is a retrospective analysis of a cohort study from a prospective, nationwide registry from January 2017 to December 2020 in Japan, focusing on ACS patients who underwent DCB or DES strategy for a single de novo lesion. One-year incidence of all-cause death, cardiovascular death, non-cardiovascular death, non-fatal ACS, stroke, and major bleeding events were compared. Subgroup analysis included lesion-based and ST-elevation myocardial infarction/non-ST-elevation ACS stratification. Results Among 5,212 propensity-matched ACS patients, DCB and DES strategies showed no significant differences in one-year incidence of all-cause death (4.5% vs. 4.6%, hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.72-1.19), cardiovascular death (2.5% vs. 2.5%, HR: 0.90, 95% CI: 0.64-1.26), non-cardiovascular death (2.0% vs. 2.1%, HR: 0.96, 95% CI: 0.65-1.42), and non-fatal ACS (1.7% vs. 2.0%, HR: 1.04, 95% CI: 0.70-1.54). DCB showed higher stroke occurrence (0.8% vs. 0.3%, HR: 2.33, 95% CI: 1.06-5.08) but lower major bleeding events (1.4% vs. 2.3%, HR: 0.65, 95% CI: 0.43-0.99) (Figure 1). Subgroup analyses did not reproduce these findings (Figure 2). Conclusions ACS patients using the DCB strategy demonstrated clinical outcomes equivalent to those undergoing the DES strategy at one year. Further investigation with an extended follow-up is necessary to confirm these findings.

A study of intracoronary thrombolytic agents in high thrombotic burden lesions during primary PCI

Abstract Objectives High thrombus burden during Primary PCI begets worst possible outcomes, studies on adjunctive intracoronary thrombolytic agents show heterogeneous1,2 results & have limited long term follow-up. Although early studies support mechanical thrombectomy devices, larger randomized trial show that they are not able to reduce the MACE3, 4. There is no randomised clinical data for sustained mechanical thrombectomy devices till now. Purpose of the study The main purpose of this study is to analyse long term outcomes of low bleeding risk group patients undergoing Primary PCI with high thrombus burden, receiving intracoronary thrombolytic agents as an adjunctive therapy. Methods In this prospective observational single centre study, we analysed one year follow-up data of 108 consecutive primary PCI patients with high thrombus burden (G4, G5) and low bleeding risk, who were stratified into two groups basing on whether they receive intracoronary thrombolytic agent as an adjunctive agent before stent implantation. The primary outcome was NACE (Net Adverse Clinical Events, which include MACE, Death, ST/MI, major bleeding events), secondary outcomes include the individual components of the primary outcomes when analysed separately. Results The primary outcome events occurred in 21 patients (26%) in Primary stent group(PS, n=80), whereas it occurred in 2 patients(6%) in primary intra coronary thrombolysis group(PIT, n=28). Log-Rank (Mantel Cox) NACE curves show that PS group has high events when compared to PIT group(26% Vs 7%, p value – 0.042, Hazard ratio - 2.56; 95% CI - 0.76 – 8.57), there is no statistically significant difference in all other key secondary outcome event curves. Conclusion In patients presenting with STEMI, undergoing primary PCI, with high thrombus burden & low bleeding risk group, those receiving intracoronary thrombolytic agent as the adjunctive therapy before stent implantation, are able to reduce the NACE event rates during the one year of follow-up.Fig1:Log Rank (Mantel Cox) NACE curve

First-in-human study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of RBD4059, a GalNAc-siRNA drug targeting coagulation factor XI (FXI), in healthy subjects

Abstract Background Patients at risk of thrombosis/thromboembolism, require effective and safe anti-coagulation with high compliance. Inhibiting FXI has emerged as a promising strategy with potential for lower bleeding risk compared to currently approved anti-coagulants. Here we report on the safety, PK and PD effects of the GalNAc-conjugated siRNA RBD4059, specifically targeting and repressing FXI protein synthesis in the liver. Purpose Investigate safety, PK, and PD of first-in-human dosing of RBD4059 in healthy subjects. Methods A randomized, single-blind, placebo-controlled, single ascending dose (SAD) phase I study in healthy subjects (NCT05653037), in cohorts of eight randomized 3:1 to receive escalating doses of RBD4059 (50, 150, and 400 mg) or placebo administered subcutaneously. Results As of January 25, 2024, 24 subjects (with follow-up to week 24) with demographics and baseline clinical characteristics shown in Table 1 were enrolled. RBD4059 was well tolerated (Table 2), all related AEs were grade 1. There was no evidence of any clinically relevant bleeding events. Plasma exposure of RBD4059 tended to increase in proportion to the dose. Maximum concentration in plasma (Cmax) was reached in 2 to 4 h and then declined in line with one-compartment kinetics. The mean plasma half-life (t1/2) ranged from 3.2 to 7.0 h. RBD4059 treatment resulted in dose dependent and sustained reductions in FXI activity and FXI antigen (Figure 1A, B, D). Observed mean maximum percentage change from baseline in FXI activity from the 50 mg, 150 mg, and 400 mg SAD cohorts were 67.5%, 81.0%, and 85.8%, respectively, recovering with a maintained effect observed on D141 (50mg: 50.6% inhibition; 150mg: 68.2% inhibition). The reduction in FXI antigen showed a very similar pattern as the reduction in FXI activity, and reductions were accompanied by a concomitant increase in APTT. (Figure 1C, D). PKPD modelling supports that RBD4059 may be dosed every 3 months or less frequent with a >90% FXI reduction throughout the dosing interval, and will be tested in the upcoming phase 2 study. Conclusion(s) RBD4059 demonstrated favorable safety, predictable PK, and pronounced durable PD effect in the dose range of 50 mg - 400 mg. This first-in-human SAD study supports the further development of RBD4059 as an anticoagulant that can maintain a high level of PD effect with a once every 3 month or less frequent dosing regimen, with potential for enhanced compliance in chronic anti-coagulant therapy.Table 1 & Table 2Figure 1.Panels A-D

Right anterior thoracotomy vs. upper hemisternotomy for aortic valve replacement with Perceval S: is there a difference?

Our study aimed to evaluate the early outcomes of aortic valve replacement with Perceval S sutureless valve through the right anterior thoracotomy and upper hemisternotomy approaches, and to determine if there are any differences between these two approaches. We carried out a study using data from 174 patients who underwent minimally invasive Perceval S valve implantation for aortic valve stenosis between January 2018 and August 2023. This was a retrospective, single-center observational study. The patients were divided into two groups: the hemisternotomy group (n = 100) and the right anterior thoracotomy group (n = 74). The overall in-hospital mortality was 1,7%. The cardiopulmonary bypass and cross-clamp times were longer in the right anterior thoracotomy group (p < .001). There were no statistically significant differences in terms of stroke, paravalvular leak, mechanical ventilation time, blood transfusion requirements, pacemaker implantation, reexploration for bleeding, conversion, wound infection, or in-hospital stay. Postoperative chest drainage was lower (p < .001) and postoperative atrial fibrillation occurred less frequently (p = .044) in the right anterior thoracotomy group. The median intensive care unit stay was shorter in the right anterior thoracotomy group (p = .018). Aortic valve replacement with the Perceval S valve through either an upper hemisternotomy or a right anterior thoracotomy is a procedure associated with low perioperative complication rates. Right anterior thoracotomy for an aortic valve replacement with the Perceval S valve was associated with lower postoperative bleeding, a lower postoperative atrial fibrillation incidence and a shorter intensive care unit stay compared to upper hemistornotomy.

Discovery of quinazoline-benzothiazole derivatives as novel potent protease-activated receptor 4 antagonists with improved pharmacokinetics and low bleeding liability

Protease-activated receptor 4 (PAR4) plays a critical role in the development of pathological thrombosis, and targeting PAR4 is considered a promising strategy for improving antiplatelet therapies. Here, we reported the design of a series of quinazoline-benzothiazole-based PAR4 antagonists using a scaffold-hopping strategy. Systematic structure-activity relationship exploration leads to the discovery of compounds 20f and 20g, which displayed optimal activity (h. PAR4-AP PRP IC50 = 6.39 nM and 3.45 nM, respectively) on human platelets and high selectivity for PAR4. Both of them also showed excellent metabolic stability in human liver microsomes (compound 20f, T1/2 = 249.83 min, compound 20g, T1/2 = 282.60 min) and favourable PK profiles in rats (compound 20f, T1/2 = 5.16 h, F = 50.5 %, compound 20g, T1/2 = 7.05 h, F = 27.3 %). More importantly, neither compound prolonged the bleeding time in the mouse tail-cutting model (10 mg/kg, p.o.). These results suggest that these compounds have great potential for use in antiplatelet therapies.

Serologic investigation and management of an antibody screen negative para-Bombay phenotype during pregnancy

Abstract Introduction/Objective Individuals with the Bombay and para-Bombay red blood cell (RBC) phenotypes express anti- H antibodies associated with acute hemolytic transfusion reactions. The rarity of compatible donor units creates unique logistical challenges. However, para-Bombay individuals have been shown to tolerate transfusion of non- Bombay RBCs without acute hemolysis. Therefore, accurate serologic identification and judicious management of blood products are crucial when planning to transfuse patients with anti-H. This is especially true during pregnancy, as early onset of labor and fetal distress can occur without warning. Methods/Case Report A 24-year-old gravida 2 para 1 (G2P1) at approximately 38 weeks gestation with the fetus in breech position was transferred to our hospital after anti-H antibodies were detected. Although our in-house antibody screen was negative on automated solid-phase red cell adherence (SPRCA) testing, manual tube testing revealed the presence of anti-H antibodies, and forward typing with Ulex europaeus lectin confirmed the absence of H-antigen. Further, Lewis B phenotyping and saliva neutralization demonstrated the presence of H-antigen in secretions, consistent with the O-para-Bombay phenotype. Finally, differential adsorption ruled out other clinically significant allo- antibodies. An external cephalic version (ECV) was initially planned since vaginal delivery carries lower bleeding risk than cesarean section (CS). Three frozen Bombay RBC units were obtained, with one possibly compromised before arrival. Four pre-warmed, cross-match compatible units of O-positive RBCs (non-Bombay) were also prepared. Acknowledging the unpredictability of ECV, the challenge of timing thawed frozen units, and the possibilities of massive hemorrhage versus wasting rare donor blood, our transfusion service ultimately recommended an elective CS with only one Bombay unit deglycerolized. The patient underwent an uneventful procedure without transfusion. Results (if a Case Study enter NA) NA Conclusion Overall, this case highlights key diagnostic and management considerations for patients with Bombay and para-Bombay phenotypes. First, automated SPRCA testing may provide false negative results for anti-H antibodies. Second, backup transfusion strategies for para-Bombay patients may include non-Bombay RBCs. Finally, the procurement, preparation, and use of rare donor blood products requires multidisciplinary clinical decision-making to optimize patient outcomes, especially for high-risk labor when unexpected acute bleeding events can occur.

Factor Replacement Treatment for Hemophilia A: Achievements and Perspectives.

The mainstay of treatment for persons with hemophilia A (PwHA) with severe bleeding phenotype is prophylaxis. The pharmacokinetic (PK) profile of native factor VIII (FVIII) imposes the need for rather frequent intravenous injections to ensure effective prophylaxis, but this represents a relevant treatment burden and is associated with suboptimal adherence to treatment. In this light, the advent of extended half-life (EHL) FVIII molecules has improved prophylaxis feasibility and outcomes by favoring treatment individualization and tailoring protection according to specific clinical and nonclinical needs. Different technologies have been used to enhance FVIII PK properties including Fc-fusion and conjugation with polyethylene glycol. Data from clinical development programs for such molecules, together with growing real-world experience, have shown numerous benefits related to the use of EHL FVIII in PwHA. Recently a new class of ultra-long-acting EHL FVIII has been developed to further improve protection against bleeding episodes and achieve the ambitious goal of providing PwHA with hemostatic protection in the nonhemophilia range over longer time periods, hence ensuring very low bleeding rates and improving joint health and quality of life. In this review, the achievements and perspectives of replacement therapies for PwHA are summarized and discussed.

General anesthesia is associated with lower perioperative bleeding and better functional outcomes than spinal anesthesia for endoscopic enucleation of the prostate: a single-center experience.

Holmium laser enucleation of the prostate (HoLEP) and bipolar transurethral enucleation of the prostate (B-TUEP) are safe and effective treatment options for benign prostatic hyperplasia (BPH). Spinal anesthesia (SA) is widely used for endoscopic enucleation of the prostate (EEP) in place of general anesthesia (GA). We aimed to assess the impact of GA vs. SA on blood loss, postoperative course and functional outcomes after HoLEP and B-TUEP. After propensity score matching, we analyzed data from 148 patients treated with EEP in our centre for symptomatic BPH. We recorded patient's characteristics, procedural data, type of anesthesia (SA vs. GA). Postoperatively we evaluated hemoglobin drop, catheterization time (CT), and length of hospital stay (LOS). Functional outcomes were evaluated with the International Prostate Symptoms Score (IPSS) at baseline and 3 months after surgery. Descriptive statistics and linear regression models tested the association between anesthesia type and EEP outcomes. After matching groups were comparable in terms of pre- and intra-operative variables. Of all, 111 (75%) patients were treated under SA. Haemoglobin drop was lower in GA compared to SA group (1 vs. 1.4g/dL, p < 0.01). CT was shorter in the GA group (1 vs. 2 days, p = 0.01). Postoperative IPSS score was lower in GA group (4 vs. 8, p = 0.04). Multivariable linear regression models revealed that prostate volume (p = 0.01) and SA vs. GA (p = 0.01) were associated with higher haemoglobin drop, after accounting for age and use of anticoagulants/antiplatelets. Similarly, SA vs. GA (p = 0.02) and postoperative complications occurrence (p < 0.001) were associated with a longer LOS, after accounting for age, prostate volume and use of anticoagulants/antiplatelets. EEP can be safely performed under both GA and SA. GA offers better outcomes in terms of perioperative bleeding and 3-month functional outcomes.

6511 Provider Opinions on Holding Antiplatelet and Anticoagulant Drugs Prior to Thyroid Nodules FNA Biopsy: A Survey Study

Abstract Disclosure: M.D. Lundholm: None. P.P. Rao: None. Objective: It is thought that anticoagulant (AC) or antiplatelet (AP) therapy at the time of thyroid nodule fine needle aspiration biopsy (TNFNAB) may increase the risk of non-diagnostic results and post-procedure hematomas. However, interrupting a patient’s AC or AP can lead to procedural delays or have thrombotic consequences. Since there is currently no consensus on whether or not to hold these medications, this study aims to survey the expertise of our providers across multiple specialties. Methods: A survey was sent out to Cleveland Clinic providers who have performed TNFNABs for patients with an active prescription for AC or AP since 2010. Providers were asked if they routinely held a number of blood thinner medication classes and included a free response section for open-ended comments. Results: The survey responses represented 60 providers (of 68 invited, 88% response rate). Respondents were 51.7% medical endocrinologists, 30% interventional radiologists, 13% surgical endocrinologists, and 5% ENTs. Of respondents, 13.3% held aspirin 81 mg, 15.0% held aspirin 325 mg, 41.7% held other antiplatelet agents, 73.3% held warfarin, 43.3% held direct oral anticoagulants (DOACs), and 43.3% held heparin. No department was uniform in practice, with the least agreement (responses closest to 50%) amongst medical endocrinologists. In a subset of 15 providers who have performed ≥100 TNFNABs on patients with AC/AP, a consensus emerged not to hold aspirin at any dose, but there was no agreement in any other AC/AP categories (hold rates ranging 53.5-66.6%). Free response themes reiterated that the main concerns for continuing blood thinners are hematomas and non-diagnostic results. Other comments included consideration of the nodule features such as location as well as strategies used to lower risk for hematomas (i.e., small-gauge needles, ice, holding pressure). A couple responses referred to the Society of Interventional Radiology (SIR) and the International Society on Thrombosis and Haemostasis (ISTH) guidelines which offer INR and platelet goal recommendations prior to any procedure with a low bleeding risk. Discussion: A survey of Cleveland Clinic providers demonstrated that ≥85% continue aspirin therapies prior to TNFNAB. However, there is no such agreement in any other category of AC/AP medication, even amongst the most experienced providers. The closest guidelines available come from SIR and ISTH and rely on recent platelet and/or INR information, which may not be available in routine endocrinology practice. The caveat is that these recommendations are not specific to TNFNAB and do not take into account the nuances of this procedure. Conclusion: There is wide variation in provider opinions and practice patterns regarding AC and AP medications prior to TNFNAB. This highlights the need for further study into the safety and adequacy of TNFNAB performed on uninterrupted AC or AP therapy. Presentation: 6/3/2024

Atypical venous drainage system and distinct vascular characteristics in pediatric intracerebral hemorrhage caused by multiple micro arteriovenous malformations.

Hemorrhagic brain micro-arteriovenous malformations (micro-AVMs) are considered to constitute a relatively significant portion of pediatric AVMs, though they are often associated with a low bleeding rate, as seen in hereditary hemorrhagic telangiectasia, which frequently involves multiple micro-AVMs. We present a rare case of a 10-year-old girl with multiple hemorrhagic micro-AVMs. Intraoperative findings during the emergency operation for hematoma evacuation and post-operative superselective angiography highlighted the unique angioarchitecture of three micro-AVMs (two lesions in the superficial areas and one lesion in the deep-seated area) and the atypical bleeding source due to the complex congestive venous drainage system. One micro-AVM was successfully occluded by a transarterial emboliozation, and remaining two micro-AVMs underwent gamma knife irradiation as a salvage therapy. Superselective angiography is crucial for detecting micro-AVMs, offering detailed insights into small, localized abnormal vascular drainage systems, and guiding therapeutic strategy. Additionally, micro-AVM-associated unique vascular hypersensitivity, such as vasospasm, requires careful consideration, as invasive procedures may significantly alter the visibility of the entire micro-AVM network.

Direct Oral Anticoagulants for RheumaticHeart Disease-Associated Atrial Fibrillation Post-Bioprosthetic Mitral Valve Replacement.

The efficacy of direct oral anticoagulants (DOACs) in preventing ischemic and thromboembolic events may be suboptimal in atrial fibrillation (AF) patients with rheumatic mitral stenosis. However, their safety and effectiveness after mitral valve replacement (MVR) using bioprosthetic valves is unclear. This study sought to evaluate the safety and effectiveness of DOACs vs warfarin among patients with rheumatic heart disease (RHD)-associated AF after bioprosthetic MVR. We performed an observational analysis identifying patients with RHD and AF who underwent bioprosthetic MVR. Primary effectiveness and safety outcomes were ischemic events and major bleeding, respectively. Secondary outcomes included all-cause mortality, cardiac thrombosis, myocardial infarction, and all-cause hospitalization. Propensity score matching was performed to account for the differences in baseline characteristics and comorbidities. A total of 3,950 patients were identified; 76% were on warfarin and 24% on DOAC post-MVR. The DOAC group had a higher burden of baseline comorbidities and prior cardiovascular procedures compared with the warfarin group. The propensity score matching balanced baseline characteristics in 1,832 patients (916 in each group), with a mean age of 69 years. At the 5-year follow-up, DOACs were associated with a lower incidence of major bleeding compared with warfarin (HR: 0.76; 95%CI: 0.62-0.94), with no significant difference in ischemic events, mortality, cardiac thrombosis, myocardial infarction, or hospitalization. Among patients with RHD-associated AF patients post-bioprosthetic MVR, DOACs are associated with lower major bleeding and comparable effectiveness, indicating a potential alternative to warfarin. Further randomized controlled trials are warranted to validate these findings in this population.

Unusual presentations in systemic lupus erythematosus with concurrent IgA nephropathy lesion: a rare case report from Eastern Nepal

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs. While lupus nephritis (LN) is seen in SLE, concurrent IgA nephropathy lesion is rare. Uncommon manifestations like cutaneous ulcers and orbital involvement present diagnostic challenges, and this case from Nepal emphasizes careful diagnostic approach in such cases. Case presentation: A 42-year-old female presented with bilateral lower limb swelling, gum bleeding, and epistaxis. Initial evaluation revealed pancytopenia and suspected renal involvement. Renal biopsy showed IgA nephropathy lesions, but clinical and laboratory findings favored lupus nephritis. Treatment with immunosuppressive agents was initiated. Despite therapy, the patient developed cutaneous ulcers and orbital cellulitis. Decreasing anti-ds DNA levels were noted during the course of treatment. Discussion: The diagnosis of lupus nephritis in the presence of IgA nephropathy lesions emphasizes the complexity of SLE diagnosis. Treatment with immunosuppressive agents targeting the underlying autoimmune process, yet the development of cutaneous ulcers and orbital cellulitis highlights the importance of timely intervention in managing SLE complications. In resource-limited settings, clinicians should initiate interventions based on clinical and lab findings while awaiting detailed biopsy results. Conclusion: This case highlights diagnostic challenges in SLE and emphasizes the necessity for careful monitoring and timely intervention in managing complications. The interplay between SLE and IgA Nephropathy (IgAN) suggests that SLE may trigger or exacerbate it, complicating disease management. Further exploration is needed to enhance the understanding and management of complex autoimmune disorders like SLE.

Incidence and clinical impact of inappropriate periprocedural and perioperative management of antiplatelet therapy

Background and aimsThere is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in “real life” in Spain. MethodsA prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy. ResultsWe included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents. ConclusionsDespite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the “real world” remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic.