Minor Bleeding Research Articles

Analysis of early results of edoxaban and warfarin in the treatment of deep vein thrombosis

Aim: Deep Vein Thrombosis (DVT) is an acute onset disease. Warfarin and new oral anticoagulants (NOAC) can be used for treatment. Edoxaban is one of the NOACs that acts directly as a ‘Factor Xa inhibitor’. The aim of our study was to investigate early treatment complications and efficacy in patients treated with warfarin and edoxaban. Material and Methods: The results of a total of 100 patients who started drug treatment for DVT between September 2018 and March 2020 were retrospectively analysed. The patients included in the study were divided into two groups according to the type of anticoagulant used [Warfarin (n=50), Edoxaban (n=50)]. Patients' routine examinations and colour Doppler ultrasound (CDUSG) results at baseline and 1-month follow-up were compared with their bleeding status. Results: Clinical status and CDUSG revealed acute DVT in 57 patients, subacute DVT in 32 patients, and chronic DVT in 11 patients. The recanalisation rate at 1 month was higher with edoxaban (80%) and lower with warfarin (62%) and this difference was statistically significant (p=0.008). The most common complication during follow-up was minor bleeding, which occurred in 24% and 18% of patients using Warfarin and Edoxaban, respectively. There was no mortality due to minor, major or cerebrovascular events in any of the patients. Conclusion: In our study, we evaluated the early results of anticoagulant therapy in patients with DVT and found faster recanalization and fewer complications in the NOAC group in agreement with the literature. Further randomised, advanced and large-scale studies are needed to evaluate the efficacy of the drugs.

Comparison of Therapeutic Effects Between Pulsed Field Ablation and Cryoballoon Ablation in the Treatment of Atrial Fibrillation: A Systematic Review and Meta-analysis

Pulsed field ablation (PFA) is a novel nonthermal ablation technique for the treatment of atrial fibrillation (AF) patients, with safety comparable to traditional catheter ablation surgery. The present study aims to evaluate and compare the procedural efficiency and safety profiles of PFA and cryoballoon ablation (CBA) in the management of AF. We performed a systematic search across PubMed, the Cochrane Library, and Embase databases, encompassing the literature up to February 2024, to inform our systematic review and meta-analysis. When assessing outcome indicators, the risk ratio and its corresponding 95% confidence interval (CI) were calculated for dichotomous variables. For continuous variables, the mean difference (MD) and the associated 95% CI were determined. In this scenario, a relative risk (RR) value of less than 1 and an MD value of less than 0 are deemed favorable for the PFA group. This could translate to a reduced likelihood of procedural complications or enhanced procedural performance within the PFA group. In this analysis, 9 observational studies encompassing 2875 patients with AF were included. Among these, 38% (n = 1105) were treated with PFA, while 62% (n = 1770) received CBA. The results indicated that PFA was associated with a significantly shorter procedural duration compared with CBA, with an MD of −10.49 minutes (95% CI, −15.50 to −5.49; P < 0.0001). Nevertheless, no statistically significant differences were observed when comparing the 2 treatment cohorts concerning fluoroscopy time (MD, 0.71; 95% CI, −0.45 to 1.86; P = 0.23) and the recurrence of atrial arrhythmias during follow-up (RR, 0.95; 95% CI, 0.78–1.14; P = 0.57). In terms of perioperative complications, the PFA group showed a significantly decreased risk of phrenic nerve palsy (RR, 0.15; 95% CI, 0.06–0.39; P < 0.0001) and an increased risk of cardiac tamponade (RR, 3.48; 95% CI, 1.26–9.66; P = 0.02) compared with the CBA group. No significant differences were noted between the PFA and CBA groups regarding the incidence of stroke/transient ischemic attack (RR, 0.99; 95% CI, 0.30–3.22; P = 0.99), vascular access complication (RR, 0.87; 95% CI, 0.36–2.10; P = 0.76), atrial esophageal fistula (RR, 0.33; 95% CI, 0.01–8.13; P = 0.50), and major or minor bleeding events (RR, 0.39; 95% CI, 0.09–1.74; P = 0.22). Our research results indicate that compared with CBA, PFA not only shortens the procedure time but also demonstrates noninferiority in terms of fluoroscopy duration and the recurrence rate of atrial arrhythmias. PFA and CBA have both demonstrated their respective advantages in perioperative complications.

Davydov-Moore vaginoplasty in Mayer-Rokitansky-Küster-Hauser syndrome: sexual and surgical outcomes.

The aim of this study was to compare surgical and sexual outcomes after Davidov-Moore vaginoplasty in women with Mayer-Rokitansky-Küster-Hauser syndrome (MRKH). In the case-series study, we described seven women, at a median age of 22.6 ± and BMI 22.8 ± 2.3kg/m2. We measured peri- and postsurgical parameters, including surgery-related neovaginal length and sexual initiation time. Sexual outcomes were measured using the Female Sexual Function Index (FSFI) before and 6months after vaginoplasty. All surgical procedures were performed successfully, with one minor perioperative bleeding. The mean time of vaginoplasty was 82.1min and the mean duration of hospitalization was six days. After a 6-month follow-up, vaginal length was 8.1-times longer than before surgery (10 vs. 81mm). The time from the surgery to the initiation of vaginal intercourse was between 17 to 22weeks. The mean FSFI score indicated good results, with no women below 23 score, and was 4.3- times higher when compared with the pre-surgical one (6.7 vs 29.1). Contrary to the FSFI score before surgery, the post-surgical FSFI revealed higher scores in all six different domains: desire (2.5-times), arousal (4.1-times), lubrication (3.8-times), orgasm (3.4-times), satisfaction (3.3-times) and comfort (11-times). Laparoscopic Davydov-Moore vaginoplasty might be considered as a safe procedure with satisfactory anatomic and sexual outcomes. It should be considered as a treatment option for the creation of neovagina in women with MRKH.

Abstract 4137274: Optimal Timing of Pharmacoinvasive Strategy and its Impact on Clinical in Patients with ST-Elevation Myocardial Infarction: a Real-World Perspective

Background: Pharmacoinvasive strategy remains the cornerstone therapy for ST-elevation myocardial infarction (STEMI) where primary percutaneous coronary intervention (PCI) is unfeasible. Guidelines recommend PCI within 2 to 24 hours post-fibrinolysis. However, meta-analysis suggests that a shorter interval (<4h) between fibrinolysis and PCI (lysis-PCI time) significantly reduces the 30-day risk of death and reinfarction. Real-world applicability is limited due to trial exclusions of elderly patients and those with chronic kidney disease. This study aims to evaluate the impact of lysis-PCI timing on in-hospital mortality and major adverse cardiovascular events (MACE). Hypothesis: We hypothesize that shorter lysis-PCI times (<9h) increase in-hospital mortality and MACE, especially in patients over 80 years. Goals: To determine the impact of lysis-PCI timing on in-hospital mortality and MACE in STEMI patients. Methods: This retrospective cohort study of 1,043 STEMI patients in Brasília, Brazil, used multivariable categorical logistic regression models to assess the association of three lysis-PCI intervals (<9h; 9-18h; >18h) with in-hospital mortality and 4p-MACE (death, acute myocardial infarction, stroke, heart failure). Propensity score matching (1:1) was used to adjust for cardiovascular risk factors. Statistical significance was set at p<0.05. Results: The lysis-PCI timing groups showed no significant differences in admission Killip class, GRACE score, or age. However, the <9h group had higher incidences of in-hospital mortality (p=0.004), heart failure (p=0.002), cardiogenic shock (p=0.001), cardiac arrest within 24 hours (p=0.003), minor bleeding (p=0.006), and MACE (p=0.002). Multivariable categorical logistic regression revealed that each 4-h delay in lysis-PCI time reduced the risk of death (HR 0.560, 95% CI 0.381-0.771; p=0.001) and MACE (HR 0.877, 95% CI 0.811-0.948; p=0.001). These findings remained consistent after propensity score analysis (death: HR 0.721, 95% CI 0.516-0.956; p=0.034). Among patients older than 80, shorter lysis-PCI times were associated with increased mortality and MACE, even after propensity adjustment (Figure 1). Conclusion(s): Shorter lysis-PCI times (<9h) are associated with higher in-hospital mortality and MACE across all age groups, with a pronounced effect in patients over 80 years. These findings underscore the need for careful consideration of lysis-PCI timing, especially in elderly populations.

Laboratory and Molecular Diagnosis of Factor XI Deficiency.

The prevalence of factor XI (FXI) deficiency is 1 per 10 to 20,000 in the general population, much higher than that reported in most texts. The prevalence is higher in Ashkenazi Jews where it is about 1:20. Clinically, FXI deficiency presents as a mild bleeding disorder mostly associated with posttraumatic or postsurgical hemorrhages or unexplained minor bleeding. It is often discovered due to incidental finding of a prolonged activated partial thromboplastin time (aPTT) on routine laboratory screening. FXI deficiency is an autosomal recessive bleeding disorder with many causative F11 gene defects. Diagnosis is based on FXI activity, antigen levels, and molecular diagnostics. As FXI levels do not correlate with bleeding symptoms, identification of pathogenic genetic variants may be a more accurate predictor of bleeding risk and therefore aid in the clinical management of the patient. Two variants in the F11 gene account for most cases found in the Jewish and Arab populations. Patients with FXI deficiency can develop inhibitors to FXI although spontaneously acquired inhibitors are extremely rare. We will discuss laboratory and molecular assays used to diagnose FXI deficiency as well as interferences that can complicate diagnosis including new anticoagulants and acquired FXI inhibitors.

Safety and Efficacy of Lumen-Apposing Metal Stents for Management of Late Refractory Gastro-jejunal Structures in Patients with Roux-en-Y Gastric Bypass (with Video).

Roux-en-Y gastric bypass (RYGB) related late gastro-jejunal (GJ) strictures are often resistant to endoscopic balloon dilations. Lumen-apposing metal stents (LAMSs) have been used to treat benign strictures with favorable results. However, the data remains limited to justify LAMS use for management of post-RYGB late GJ strictures. We aim to evaluate the safety and efficacy of LAMS placement for the management of late GJ strictures that are refractory to balloon dilations in post-RYGB patients. This was a single center retrospective study that included all post-RYGB patients who underwent LAMS placement for management of late GJ strictures that had previously failed balloon dilations. Primary outcomes were technical and clinical success, and secondary outcomes were LAMS-related adverse events. A total of 28 patients underwent LAMS placement for management of GJ strictures. Median age was 60.5 (IQR 50.5, 67.0) years and majority were females (27, 96.4%). Median interval between surgery and first diagnosis of GJ stricture was 13 years (IQR 7, 17.5). 20 × 10 mm LAMS was the most used stent (n = 24, 85.7%). The median procedure time was 23.5 (IQR 14.5, 32.0) minutes. Technical and short-term clinical success of LAMS placement was 100% (95% CI 87.9-100.0). Long-term success was achieved in 19 out of 25 patients (76.0%, 95% CI 56.6-88.5) that had over 3 months follow-up after LAMS removal. Stent migration was noted in 2 (7.1%) patients, and 1 (3.6%) patient each experienced pain and minor bleeding without the need for additional interventions. No patient in our cohort required surgical revision of GJ anastomosis. Placement of LAMS is safe, technically feasible, and associated with a high clinical success rate in patients with late GJ strictures after RYGB who have failed prior balloon dilations. Placement of LAMS can be considered early in patients requiring multiple balloon dilations.

Concurrent diagnosis of severe haemophilia A and acute lymphoblastic leukemia in a child: First report in Greece

Haemophilia A is a congenital bleeding disorder resulting by deficiency of coagulation factor VIII and Acute Lymphoblastic Leukemia (ALL) Is the most common cancer type in children. The concurrence of hemophilia and ALL in pediatric patients is quite rare. We report a case of a 2.5 year old boy, with an uneventful past history, which presented with pallor, petechiae, ecchymoses and lethargy to the emergency department. A full blood count on admission revealed severe leukocytosis, anemia and thrombocytopenia. Diagnosis of ALL was confirmed and the patient was put on chemotherapy. Excessive bleeding from the site of entry of the central venous catheter led to complementary testing, which revealed very low levels of Factor VIII and severe Haemophilia A was also diagnosed. The patient suffered from minor gastrointestinal bleeds and a severe intrabdominal hemorrhage due to an abcess eruption during his treatment for ALL. To date, very few cases of ALL and Haemophilia have been reported in children, and due to this rarity there are no guidelines concerning the adjustments in treatment in this small population of patients.

Tracheostomy Cuff Herniation following Cardiac and Pulmonary Arrest

Tracheostomy is a common procedure performed on patients who require long-term airway maintenance and ventilation support. It is preferred over endotracheal intubation due to its reduced airway resistance, lower risk of displacement compared with the endotracheal tube, increased patient comfort, improved weaning from mechanical ventilation, and enhanced suction capabilities. According to the literature, patients needing airway support for fewer than 12 days can undergo translaryngeal intubation, while tracheostomy is indicated for patients requiring ventilatory support for more than 20 days. Although tracheostomy is frequently performed in ICUs and operating rooms, several complications can arise following the procedure. These complications include leakage, obstruction of the tracheal tube, minor or major bleeding or oozing, barotrauma, infections, tracheoesophageal fistula, stenosis, and injury to surrounding peripheral tissues such as arteries, veins, and nerves.1 While herniation of the endotracheal cuff is a more common cause of airway obstruction and hypoxia, tracheostomy tube cuff herniation is a rare complication of this procedure.1-7 In this report, we present a rare case of cardiopulmonary arrest following the implantation of a tracheostomy tube cuff in a female patient and its management.

Current evidence on the effectiveness and safety of oral anticoagulants in superficial venous thrombosis: a systematic review and meta-analysis.

Previous studies suggest fondaparinux as an effective regimen for superficial venous thrombosis (SVT), but the inconvenience of prolonged parenteral injections has prompted investigations into oral anticoagulants (OACs). This study aims to evaluate the current evidence on the effectiveness and safety of OACs in the treatment of SVT. Following the PRISMA 2020 guidelines, we conducted a systematic review and meta-analysis registered in PROSPERO (CRD42024535625). A comprehensive literature search was performed across multiple databases up to April 2024. Studies were included if they involved adult patients diagnosed with SVT, treated with OACs, and reported relevant efficacy and safety outcomes. Both randomized controlled trials (RCTs) and observational studies were considered. Data extraction and risk of bias assessments were independently performed by two authors. The search identified 1531 studies, with six studies (three RCTs and three prospective cohort studies) meeting inclusion criteria. Meta-analysis for Rivaroxaban-treated group showed DVT occurrence was 1.30% (95% CI 0.17-3.07%), SVT extension was 0.32% (95% CI: 0.00-1.58%), SVT recurrence was 0.75% (95% CI: 0.00-3.30%), clinically relevant non-major bleeding was 1.95% (95% CI: 0.46-4.11%), minor bleeding was 5.68% (95% CI: 3.02-9.01%). These estimates were for patients treated with rivaroxaban 10-20 mg once daily over 42 days to 37 months. No major bleeding was reported with rivaroxaban 10 mg once daily. This systematic review and meta-analysis demonstrate that OACs, especially rivaroxaban, are effective and safe for the treatment of SVT. They offer a convenient alternative to parenteral anticoagulants, potentially improving patient compliance and outcomes. However, further large-scale studies are warranted to confirm these findings.

Oral invasive procedures in Glanzmann Thrombasthenia: a retrospective observational study

BackgroundGlanzmann Thrombasthenia (GT) is a very rare inherited autosomal bleeding disease affecting megakaryocyte lineage with impacts on oral health such as gingival bleeding and requiring specific management protocols. Only very few clinical cases have been published in the dental and hematological literature. ObjectivesThis study focuses on a series of 21 patients affected specifically by GT and their hemorrhagic prophylaxis management with the use of recombinant factor VIIa (rFVIIa) for dental extractions and full-mouth debridement. Results41 full-mouth debridement and 176 dental extractions were performed along 102 sessions of dental care in outpatient setting. A total of 226 injections of rFVIIa was delivered. The mean of injection was 2.2 (range 1 to 4) per dental procedure. The overall rate of bleeding complication was 5.9% (n = 6). All of these six hemorrhagic complications were classified as minor bleeding. No thromboembolic event was observed nor allergic reaction. ConclusionThe data presented in this retrospective observational study support the efficacy and safety of rFVIIa for the prevention of bleeding for invasive dental procedures in patients affected by GT. rFVIIa protocol presented here seems to be a safe and efficient protocol for the prevention of bleeding for invasive oral procedures.

Consequences of the Poor Anticoagulation Control of Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonists.

Background: The prevention of thromboembolisms through anticoagulation and heart rate control is crucial in managing non-valvular atrial fibrillation (NVAF). This study aimed to analyze the consequences of poor anticoagulation control with vitamin K antagonists (VKAs) in Spanish patients with NVAF, focusing on thrombotic events, bleeding, mortality, healthcare resources (HRU), and costs. Methods: This observational, retrospective study used electronic medical records (BIG-PAC® database) of NVAF patients who started VKA treatment between 1 January 2016 and 31 December 2018. Patients were followed up for two years and classified by poor or adequate anticoagulation control. Demographic and clinical characteristics, treatments, incidence of cardiovascular events, mortality rates, HRU, and costs were analyzed. Results: Patients with poor control (n = 2136) had a 75% greater probability of suffering a cardiovascular event compared to patients with adequate control (n = 2351) (HR, 1.75 [95%CI: 1.43-2.14; p < 0.001]). Cardiovascular events, major bleeding, minor bleeding, systemic thromboembolism, and ischemic strokes were reduced by 32.1%, 46.2%, 29.6%, 22.2%, and 16.1%, respectively. It was estimated that adequate anticoagulant control saved EUR 455/patient with NAVF due to reduced hospitalization for cardiovascular events. Conclusions: For VKA-treated NVAF patients, poor anticoagulation control was associated with a higher number of cardiovascular events, greater consumption of HRU, and higher management costs than for patients with adequate control.

Cardiac amyloidosis and left atrial appendage closure: a multicenter retrospective study

Abstract Background Thromboembolic stroke risk remains a clinical challenge in cardiac amyloidosis (CA) patients with atrial fibrillation because of the increased prevalence of left atrial appendage thrombi irrespective of CHA2DS2-VASc score and a higher prevalence of factors that increase the risk of bleeding with anticoagulation. Left atrial appendage closure (LAAC) is an effective option in patients with atrial fibrillation and high bleeding risk; however, data describing a LAAC strategy for stroke prevention in patients with CA is limited. Among non-CA patients, procedural success and serious complication rates are around 98% and 3% respectively. Purpose In this multicenter retrospective study, we aimed to investigate whether left atrial appendage closure (LAAC) could reduce the risk of bleeding complications and ischemic cerebrovascular events in patients with CA. Methods In an international multi-center retrospective study, patients with CA that underwent LAAC were included. The diagnosis of CA was established on the basis of histologic confirmation or advanced multimodality cardiac imaging as per current consensus statements. Results A total of 28 patients (93% male; 87% ATTR-CA; 13% AL-CA; mean age 80 years) met inclusion criteria. At baseline, mean CHA2DS2-VASc and HAS-BLED scores were 4 and 3 respectively, mean left ventricular ejection fraction was 50%, and mean indexed left atrial volume was 58 mL/m2. 21% of patients had a prior history of ischemic stroke, 14% prior history of hemorrhagic stroke, 7% prior transient ischemic attack, and 54% had a prior history of major or minor bleeding. Procedural success was achieved in 26 patients (93%) with procedural complications occurring in 2 patients (vascular access site bleeding and cardiac tamponade). Regarding in-hospital and follow-up complications, 0% ischemic stroke, 0% hemorrhagic stroke, and major or minor bleeding in 4% of patients. During follow up, device thrombosis occurred in only 1 patient. Conclusion LAAC is a feasible and effective alternative to anticoagulation in patients with CA and excessive bleeding risk, with procedural success and complication rates similar to reported studies of non-CA patients.

Comparison of 600 mg VS 300 mg clopidogrel loading dose for patients with ischemic heart disease: a meta-analysis of randomized controlled trials

Abstract Background While a 600-mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300-mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether a higher clopidogrel LD regimen in primary percutaneous coronary intervention outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease. Purpose The objective of this meta-analysis is to validate current randomized trials that investigate the efficacy and safety of two clopidogrel loading regimens (600 mg vs 300 mg) in patients with ischemic heart disease treated with primary percutaneous coronary intervention. Method A systematic literature search for randomized controlled trials was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov. and Herdin PH. Studies included those between 2010 - 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects. Result Nine randomized control studies involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only 8 studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced incidence of overall MACE (OR:0.82, 95% CI:0.74-0.91, p=0.0002), nonfatal myocardial infarction (OR:0.56; 95% CI:0.32-0.99, p = 0.15) and target vessel revascularization (OR 0.63; 95% CI 0.41 to 0.95, p = 0.03 ), without significant difference in terms of cardiac death (OR:0.89; 95% CI:0.76-1.04, p=0.15) and stroke (OR 0.92; 95% CI 0.67 to 1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR:1.27; 95% CI:1.08-1.49, p=0.005] without significant difference in minor bleeding (OR:1.05; 95% CI:0.94-1.17, p=0.35). Conclusion The administration of 600 mg of clopidogrel LD reduces the overall risk of MACE with an associated increased risk of major bleeding in patients with ischemic heart disease undergoing primary percutaneous coronary intervention.MACE OUTCOMES

Impact of procedural and patient-related risks on 1-year outcomes for patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent implantation

Abstract Background While early de-escalation of dual antiplatelet therapy (DAPT) and P2Y12 inhibitor monotherapy following short DAPT are becoming standard treatments for patients after percutaneous coronary intervention (PCI), the impact of procedural and patient-related risks on clinical outcomes of PCI for patients receiving the above DAPT regimen has never been established. Purpose To evaluate the impact of procedural and patient-related risk factors on 1-year cardiovascular and bleeding outcomes in patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent (BP-DES) implantation. Methods Using data from the multi-centre regional-wide REIWA registry, we assessed clinical outcomes according to each risk factor and compared between patients with and without either procedural or patient-related risk factors. The primary end point was net adverse clinical events (NACE), defined as a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke) and bleeding outcomes (TIMI major or minor bleeding), which was same with that for STOPDAPT-2 trial. Procedural risk was defined as a factor of complex PCI which was previously published and included the follows: treatment of three vessels, three or more lesions, three or more stents, bifurcation with two stents, long stenting (total stent length &amp;gt;60 mm) and target of chronic total occlusion. Additionally, patient-related risk factors were defined as chronic kidney disease, anaemia, peripheral vascular disease, heart failure and advanced age (≧75 years). Results Among 1,202 patients treated BP-DES with 1-month DAPT, 276 patients (23.0%) had at least one procedural factors and 510 patients (42.4%) had one or more patient-related risks. Compared with each risk factor, patients with patient-related risk factor were more likely to have higher NACE rates, whereas low NACE rates were observed in patients with each procedural risk factor (Figure 1). In addition, during 1-year follow-up, patients with patient-related risk factors had a significantly higher incidence of NACE compared with patients without such risks (4.90 % vs. 1.73 %, p = 0.002) (Figure 2). However, no significant differences in NACE rates was observed between patients with and without procedural risk factors (2.54% vs. 3.24%, p = 0.555). Conclusion In patients undergoing BP-DES implantation and 1 month DAPT followed by P2Y12 inhibitor monotherapy, patient-related risk factors had an impact on 1-year clinical outcomes, while procedural risk factors no longer had small impact on those outcomes.

Efficacy and safety of reduced-dose and slow-infusion intravenous alteplase regimen in patients with acute pulmonary embolism at intermediate-high-risk

Abstract Background In patients with intermediate-high-risk (IHR) pulmonary embolism (PE), full-dose systemic thrombolytic treatment (STT) has been documented to lower the risk of hemodynamic decompensation and mortality, at the expense of an elevated risk of life-threatening bleeding. In this study, we aimed to evaluate the safety of reduced-dose STT regimen while maintaining effective reperfusion. Methods This single-center study comprised 124 retrospectively evaluated patients (female 58.9 % and mean age 55.4+15.8 years) diagnosed with acute PE at IHR status in accordance with European Society of Cardiology (ESC) 2019 acute PE guidelines in whom intravenous (i.v.) alteplase treatments were utilized. Patients fulfilling at least one of the following criteria have been included in the study: systolic blood pressure ≤ 110 mm Hg, heart rate &amp;gt; 100 bpm, SaO2 &amp;lt; 90 % on room air, respiratory rate &amp;gt; 20 breaths per minute, or serum lactate &amp;gt; 2 mmol/L. Exclusion criteria were any contraindication for STT and symptom onset &amp;gt; 14 days. Standard protocol for initial STT was i.v. infusion of alteplase of 25 mg over 4-6 hours. After completion of the infusion, a second STT in the same manner if one of the following criteria were present; heart rate &amp;gt; 100 bpm, SaO2 &amp;lt; 90 % or signs of organ hypoperfusion. Results Syncope and concomitant deep vein thrombosis were documented in 27.4 % and 49.2 % of patients, respectively. Baseline vital measures were as follows; heart rate: 112 +16.6 bpm, systolic blood pressure: 123+14.9 mm Hg, SaO2: 89 % (85-93), serum lactate 2.35 (1.6-2.9) mmol/L. Median alteplase dose and infusion duration were 50 (25-50) mg and 6 (4-10) hours, respectively. There were significant improvements in clinical parameters, pulmonary thrombus burden, pressure strain and right ventricular size and function as assessed by computed tomography and echocardiography (p&amp;lt; 0.001 for all). Minor and major bleeding events occurred in 3.2 % and 4.8 % of patients, respectively. One major bleed was due to cerebellar hemorrhage, but did not require surgery and patient was discharged without sequela. There were 6 (4.8 %) in-hospital deaths in which 2 were attributed to major hemorrhages and 4 due to hemodynamic decompensation. Conclusion In patients with acute IHR PE, reduced-dose and slow-infusion i.v. alteplase regimen seems to be a clinically relevant and safe reperfusion alternative to full-dose STT protocols associated with well-known major bleeding risks.

Staggered botulinum toxin-a injections into parotid and submandibular glands prior to four-duct ligation for pediatric sialorrhea.

This study aimed to assess the effectiveness of four-duct ligation following Botulinum toxin-A injections into the parotid and submandibular glands in pediatric patients with sialorrhea resistant to nonsurgical treatments. Prior research has individually explored either surgical or Botulinum toxin interventions; however, the safety and efficacy of the combined approach to these treatments have yet to be documented. Patients were assessed before surgery and 6, 12, and 24months post-operatively. Evaluations involved interviews with parents and caregivers, conducted face-to-face or by telephone, using the Drooling Severity and Frequency Scales. Additionally, metrics such as the daily count of bib changes and the hourly frequency of saliva wiping were recorded. Quality-of-life assessments were performed before and after the surgical procedures. All complications associated with the interventions were carefully recorded. The study group consisted of 25 participants, with a median age of 6years (range 2-17years). Each participant was diagnosed with a neurological, metabolic, or genetic disorder. Evaluations were conducted periodically, culminating in a final follow-up at 24months. The treatment demonstrated a 100% success rate at six months post-operation (25/25 patients), which slightly decreased to 96% at the 12-month mark (24/25 patients) and further to 84% by the 24-month follow-up (21/25 patients). Major complications were not observed. However, minor complications were reported in six patients (24%): three exhibited temporary facial swelling (12%), two encountered minor bleeding (8%), and one experienced excessive dryness (4%). The combination of Botulinum toxin-A injection 3 weeks prior to the four-duct ligation procedure demonstrated high success rates and substantially reduced the incidence of infectious and cosmetic complications. Consequently, this staggered approach to combination treatment is recommended for managing pediatric sialorrhea cases that are resistant to non-surgical interventions.

Complication comparison in intermediate-to-high risk venous thromboembolism patients, treated with high vs standard dose apixaban and rivaroxaban after low molecular weight heparin

Abstract Background In patients with intermediate-to-high risk venous thromboembolism (VTE), current guidelines recommend initial treatment with low molecular weight heparin (LMWH), followed by an oral anticoagulant. However, the studies supporting these guidelines have only focused on the use of Edoxaban and Dabigatran after 5 days of LMWH treatment. To date there are no studies supporting similarly implemented guidelines for Apixaban and Rivaroxaban. Purpose To investigate the incidence of bleeding complications and thrombosis in intermediate-to-high risk VTE patients, when treated with either lead-in high or standard dose Rivaroxaban or Apixaban, following initial LMWH treatment. Methods Through a real-life retrospective study of 844 intermediate-to-high risk VTE patients, 584 were initially treated with LMWH and subsequently Apixaban or Rivaroxaban and divided into two groups. The first group of 514 patients, received high dose Apixaban or Rivaroxaban (10mg x 2 for 7 days and 15mg x 2 for 21 days respectively) before being reduced to their standard doses. The remaining 70 patients, instead transitioned directly to the standard doses (5mg x 2 and 20mg x 1 respectively) from LMWH. All patients started treatment between 2018 and 2023, and all complications were recorded until one year following initiation of treatment. Treatment complications include recurrent VTE, separated into deep vein thrombosis and pulmonary embolism, and bleeding complications in the form of fatal, non-fatal, minor and a drop in haemoglobin. The recurrence of VTE and incidence of bleeding complications were evaluated as the primary efficacy outcome and safety outcome respectively. Results Overall, 4.7% of patients treated with initial high dose Apixaban or Rivaroxaban suffered major bleeding complications as opposed to 2.9% treated with the standard dose (p=&amp;lt;0.05). Out of all complications, 5 were fatal, all of which were part of the high dose group and included 3 cerebral and 2 gastrointestinal bleeds. However, minor bleeding complications were more frequent in the standard dose group, presenting in 26.1% of patients, while, paradoxically, the high dose group had similar complications in only 15.8% of patients (p=&amp;lt;0.05). Although treated with a higher dose, 6/478 (1,26%) incurred a recurrent thrombus within a year of treatment, while the standard dose group had no cases of recurrence, though this was not a statistically significant result. Conclusion Directly transitioning from LMWH to standard dose Apixaban/Rivaroxaban in intermediate-to-high risk VTE, leads to a statistically significant reduced incidence of major bleeding complications, without an increased risk of recurrent thrombosis.

Clinical and peri procedural outcomes using reduced dose prasugrel vs standard dose ticagrelor in elderly patients of acute coronary syndrome undergoing PCI

Abstract Introduction The novel antiplatelet agent prasugrel is generally not indicated in elderly(&amp;gt;75-years) patients in standard dose(60 mg loading and 10 mg maintenance) however, there is a scarce data on safety and efficacy of reduced dose prasugrel(30 mg loading and 5 mg maintenance dose) among elderly patients undergoing elective PCI. Some previous studies have raised concerns regarding the differences in pharmacodynamic and pharmacokinetic responses to prasugrel in asian ethnicities. The efficacy and safety of reduced dose prasugrel in elderly patients has not been investigated. Therefore, in this study we have compared the efficacy and safety of a reduced dose prasugrel with standard dose ticagrelor in elderly Indian patients undergoing elective PCI for acute coronary syndrome (ACS). Purpose To study the periprocedural and intermediate term clinical outcomes using reduced dose prasugrel versus standard dose ticagrelor in elderly Indian patients of acute coronary syndrome undergoing PCI. Methods This was a single centre, randomised, prospective cohort study. Based on the previous reference studies, at 95% level of significance and 80% of power, the sample size was calculated as 73 in each group. Study was conducted from May 2021 to October 2022 (18 months). Patients &amp;gt;75 years of age with ST-segment–elevation (STE) or Non ST elevation (NSTE) ACS treated with PCI were included. The study was approved by the institutional ethics review board. Participants were assigned to receive a standard dose of ticagrelor (180 mg loading followed by 90 mg twice daily, n=73) or a reduced dose prasugrel (30 mg loading followed by 5 mg once daily, n=73). The primary efficacy end point of the study was a composite of major adverse cardiac events (MACE) including cardiovascular mortality , non fatal MI and stroke. The secondary safety end points were major and minor bleeding events. Patients were followed up at 15 days, 3 months and 6 months. Results The baseline clinical and demographic characteristics were comparable in the both groups. The composite of primary efficacy end points at 6 months occurred significantly more in ticagrelor group vs reduced dose prasugrel group(13.7% vs 4.1% P value=0.05) and composite of secondary safety end point were comparable in both the groups(21.9% vs 16.4% respectively, p=0.44). Dyspnoea was seen more frequently in standard dose ticagrelor group as compared to reduced dose prasugrel group (15.1% vs. 6.8% respectively, p value=0.133). Conclusion The results of our study indicate that the reduced dose prasugrel is safe in elderly patients, has similar bleeding events as compared to standard dose ticagrelor group and is better tolerated. The reduced dose prasugrel is significantly more efficacious as compared to standard dose ticagrelor in elderly patients in terms of reduced MACE events. Although large scale randomized studies may be warranted in such populations to draw a broader conclusion.Baseline characteristicsEnd results

Baseline characteristics, management patterns and outcome in patients with pulmonary embolism and malignancy: Insights from a single-centre study

Abstract Background and aim The presence of malignancy is an important factor that increases the risk of venous thromboembolism. On the other hand, acute pulmonary embolism (PE) is one of the main causes of death in this setting. In this study, we evaluated the impact of active malignancy on the treatment choices, and short and long term clinical outcomes in patients with acute PE. Methods In this study conducted in a tertiary center, 872 acute PE patients (age 61.6±16.8 years, female 57.5 %) from different risk categories were treated with thrombolytic, anticoagulant and catheter-based therapies in accordance with currently available acute PE guidelines. The population was retrospectively analyzed and divided into two groups according to the presence of active malignancy. Results Active malignancy was documented in 129 (14.8 %) patients. In the groups with and without malignancy, the proportions of low-, intermediate-low-, intermediate-high-, and high-risk PE patients were 3.1 % vs. 15.6 %, 17.8 % vs. 16.7 %, 60.5 % vs. 60 %, and 18.6 % vs. 7.7 %, respectively (p&amp;lt;0.001). While the two groups did not differ in terms of echocardiographic and computed tomographic pulmonary angiography (CTPA) characteristics, the presence of contraindications for thrombolytic were more frequent in the malignancy group (22.5% vs. 10.9%, p&amp;lt;0.001). Ultrasound-assisted thrombolysis (USAT), rheolytic thrombectomy (RT), systemic thrombolysis (ST) and anticoagulation-alone (AC) therapies were noted in 27.3 %, 6.4 %, 6.4 % and 49.7 % of overall PE patients. The RT and AC therapies were more frequent in PE patients with malignancy whereas ST and USAT were more frequently used in the absence of malignancy. Notably, lytic dosages and treatment durations in USAT and ST protocols were comparable between malignant and non-malignant PE cohorts. Regardless of the presence of malignancy and the treatment modality chosen, significant improvements were achieved in the clinical, echocardiographic and CTPA measures of the PE severity (p&amp;lt;0.001 for all). Major and minor bleeding rates were also similar in both groups, while in-hospital and, as expected, long-term mortality were higher in the malignancy cohort. Active malignancy and PESI score were found to be independent predictors for composite end-point of 60-day mortality and PE-related rehospitalization (adjusted odds ratio (OR): 2.43; 95 % CI: 1.32 - 4.47, p=0.04) and (OR: 1.02; 95 % CI: 1.01-1.01, p&amp;lt;0.001), respectively. Malignancy (OR: 3.5, 95 % CI: 2.15-5.75, p&amp;lt; 0.001) and chronic obstructive pulmonary disease (OR: 2.51, 95 % CI: 1.35-4.68, p&amp;lt; 0.003) were independent predictors of long-term mortality. Conclusion Concomitant malignancy adversely affects both short- and long-term outcomes in patients with acute PE. Although these patients are more vulnerable, it is possible to achieve satisfactory treatment success with acceptable bleeding rates with the inclusion of catheter-based methods as treatment option.Survival plot

Effects of rivaroxaban on vascular endothelial function and circulating endothelial progenitor cells: a randomized controlled trial

Abstract Background Combination of low dose rivaroxaban with aspirin was shown to reduce major adverse cardiovascular events when compared to aspirin monotherapy in COMPASS trial. The beneficial effect of rivaroxaban beyond factor Xa inhibition remains unknown. Purpose This randomized controlled trial explored the effects of rivaroxaban on vascular endothelial function and circulating endothelial progenitor cells in patients with stable atherosclerotic disease. Methods An investigator-initiated, investigator-blinded, single-center randomized clinical trial was conducted from May 2021 to August 2023. 142 patients were randomized in 1:1 ratio to receive rivaroxaban 2.5mg twice daily plus aspirin 100mg once daily (Treatment Group) or aspirin 100mg once daily (Control Group) and had follow-up for 3 months. The primary outcome was change of flow mediated dilation (FMD) from baseline to 3-month follow-up. Key secondary outcomes included change of circulating endothelial progenitor cells (CD45+/34+/133+, CD45+/34+/KDR+), platelet activation marker (CD41+/62p+), inflammatory marker (CD14+/11b+) and thrombo-inflammatory maker (CD14+/42b+) measured by flow cytometry, as well as platelet function (aspirin reaction unit, ARU) measured by blood biochemistry. Intention-to-treat analysis was performed with analysis of covariance (ANCOVA) and P &amp;lt; 0.05 was considered statistically significant. Results Overall, 142 patients were enrolled in the study. One patient was excluded from analysis due to protocol deviation. Among the remaining 141 patients (78.8% male and mean age 69±9 years), there were 71 in Treatment Group and 70 in Control Group. The recruited patients had a high prevalence of cardiovascular comorbidities including 76.6% with hypertension, 50.4% with hyperlipidemia, 45.4% with diabetes, and 92.2% with percutaneous coronary intervention. At 3 months, Treatment Group had greater FMD improvements (+2.18±5.66% vs +1.57±5.07%, P=0.03), and more reduction in platelet activation marker (-0.33±13.55% vs +5.78±21.60%, P=0.01). There was no significant change in circulating endothelial progenitor cells, inflammatory marker, thrombo-inflammatory maker, and platelet function. Minor bleeding occurred in 2 patients (2.82%) in Treatment Group and none in Control Group (P&amp;gt;0.05). Conclusion In patients with stable atherosclerotic disease, addition of rivaroxaban to aspirin was well tolerated, and it improved vascular endothelial function and reduced platelet activation.