Minimize Bleeding Risk Research Articles

Strategies for Perioperative Anticoagulant Reversal in Orthopedic Surgery: A Review.

The administration of anticoagulation therapy during major orthopedic surgeries is a clinical challenge due to the risk of thrombotic events and bleeding complications. This review aims to evaluate the current strategies and emerging developments in perioperative anticoagulation reversal. We conducted a literature review on the management of perioperative anticoagulant therapy, which included the current status of anticoagulant reversal agents, as well as personalized medicine, pharmacogenomics, artificial intelligence (AI), and novel drug delivery systems. The review indicates that reversal agents such as idarucizumab and andexanet alfa are crucial in managing bleeding associated with direct oral anticoagulants (DOACs). Personalized medicine, guided by pharmacogenomics, allows for tailored anticoagulation regimens. AI and machine learning (ML) algorithms can enhance the predictive capabilities for bleeding and thrombotic risks. Additionally, nanotechnology and biomarkers offer innovative approaches to drug delivery and personalized treatment. Integrating evidence-based guidelines with innovative reversal agents, personalized medicine, AI and nanotechnology opens a new era in perioperative anticoagulation management. These advancements can ensure patient safety, minimize bleeding risks, and improve surgical outcomes. Future research should focus on the clinical validation of these strategies to ensure their effectiveness across diverse patient populations.

PEGylation of New Thrombin Inhibitor Peptide Ultravariegin for Prolonged In Vivo Circulation and Enhanced Antithrombotic Effects.

Anticoagulant therapy is commonly used to prevent and treat arterial and venous blood clots in patients with cardiovascular disease, cerebrovascular disease, and cancer. Venous blood clots are the third leading cause of cardiovascular death following acute coronary artery disease and stroke. There is a significant need for effective anticoagulant therapy with minimal risk of bleeding. Variegin and its variants are a new type of antithrombin peptide that has shown promising results in preclinical studies. Variegin and its best variant, ultravariegin (UV), can more effectively inhibit blood clot formation while causing less bleeding than traditional medications such as heparin and bivalirudin. However, the short lifespan of UV remains a limitation for its use in clinical settings. PEGylation, a method of conjugating poly(ethylene glycol) (PEG) chains to peptides or drugs, may help improve the effectiveness of UV by extending its circulation time in the body. In this study, UV was PEGylated using maleimide-PEG5k and 10k. The impact of PEGylation on the antithrombin activity of UV was assessed in vitro and ex vivo in rat and rabbit plasma, showing minimal effects on the efficacy. In vivo studies in rats and rabbits revealed that PEGylated UV had a longer half-life and greater anticoagulant effects than unmodified UV did, especially when it was administered subcutaneously. PEGylation significantly extended the half-life of UV in rabbits, resulting in sustained anticoagulant effects for up to 4 days. This demonstrated that increasing the size of UV and shielding it with PEG could reduce clearance by the kidneys and prolong its circulation time. The improved half-life and antithrombin activity of PEGylated UV make it a more favorable choice for anticoagulant therapy.

Management of antithrombotic therapy in patients undergoing dental procedures

A growing number of patients receiving antithrombotic therapy require dental procedures. Dental interventions in these patients can be challenging, as the risk of bleeding from the continuation of antithrombotic therapy needs to be weighed against the thromboembolic risk associated with drug interruption or de-escalation. Most minor dental procedures, including simple dental cleaning and filling, pose minimal bleeding risk, and antiplatelet or anticoagulation therapy can be continued without interruption. Local hemostatic measures, such as tranexamic mouthwash, can be used, as needed, to reduce bleeding events following these interventions. Managing antithrombotic therapy during more invasive dental interventions and oral surgeries with a higher risk of perioperative bleeding necessitates the consideration of specific factors influencing the bleeding risk and thromboembolism. In patients receiving antithrombotic therapy for primary prevention, temporary interruption is reasonable. In others, the decisions may be more complex and more nuanced. In this article, we review the current evidence for managing patients receiving oral antiplatelet or anticoagulant drugs scheduled for various dental procedures and present a practical approach for the periprocedural management of antithrombotic treatments.

Efficacy and Safety of Low or Reduced Dose Direct Oral Anticoagulants Versus Dual Antiplatelet Therapy Following Left Atrial Appendage Closure: A Systematic Review and Meta-Analysis.

This meta-analysis aimed to compare the efficacy and safety of low-dose direct oral anticoagulants (DOACs) versus dual antiplatelet therapy (DAPT) in patients undergoing left atrial appendage closure (LAAC). A comprehensive literature search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, and Scopus, up to August 12, 2024. Studies comparing low-dose DOACs with DAPT in post-LAAC patients were included. The primary outcomes of interest were thromboembolic events, major bleeding, and all-cause mortality. Four studies, including two randomized controlled trials and two observational studies, met the inclusion criteria, with a total of 828 patients (319 in the DOAC group and 509 in the DAPT group). The meta-analysis revealed that patients treated with DOACs had a significantly lower risk of thromboembolic events compared to those receiving DAPT. DOACs were also associated with a significantly reduced risk of device-related thrombosis. Although the risk of stroke was lower in the DOAC group, the difference was not statistically significant. The risk of death did not differ significantly between the two groups. Regarding safety outcomes, patients receiving DOACs experienced fewer bleeding events compared to those on DAPT, with the difference being statistically significant. However, high heterogeneity was reported among the study results for bleeding events. These findings suggest that low-dose DOACs may be a more effective and safer alternative to DAPT for post-LAAC antithrombotic management, particularly in patients at high risk for both thromboembolic and bleeding events. DOACs demonstrated superior efficacy in reducing the risk of stroke, systemic embolism, and other thrombotic complications, while also minimizing bleeding risks.

COMPARATIVE STUDY OF CLOPIDOGREL VS PRASUGREL IN PATIENTS UNDERGOING ELECTIVE PERCUTANEOUS CORONARY INTERVENTION (PCI)

Antiplatelet therapy is a cornerstone in managing patients undergoing percutaneous coronary intervention (PCI) to prevent thrombotic complications. Prasugrel and clopidogrel are two commonly used agents, but their comparative efficacy and safety remain a subject of ongoing research, particularly in elective PCI cases. Objective: This study aimed to compare the safety and efficacy of prasugrel and clopidogrel in patients undergoing elective PCI, focusing on clinical outcomes such as minor and major bleeding, stent thrombosis, and mortality. Methods: This retrospective cohort study was conducted at a tertiary care hospital in Pakistan between January and July 2024. A total of 200 patients undergoing elective PCI were included in the study. Patients received either clopidogrel (300 mg or 600 mg) or prasugrel (60 mg) as part of their antiplatelet therapy. Clinical outcomes were assessed, including minor and major bleeding, thrombosis, and death. Statistical analyses were performed using Pearson correlations, chi-square tests, and regression analysis. SPSS software (version 25.0) was used for data analysis, with statistical significance set at p < 0.05. Results: Of the 200 patients, 48.5% were male, and 51.5% were female, with the majority aged between 61 and 70. Prasugrel (60 mg) was the most commonly used loading dose (35.5%). Minor bleeding events were significantly higher in the prasugrel group compared to the clopidogrel group (p = 0.05). However, no significant differences were observed in major bleeding, stent thrombosis, or mortality between the two groups. A positive correlation between minor bleeding and stent thrombosis was noted (p = 0.048), while regression analysis confirmed that prasugrel did not significantly increase the risk of major bleeding or death. Conclusion: Prasugrel was associated with a higher incidence of minor bleeding compared to clopidogrel, but both agents exhibited comparable safety profiles in terms of major bleeding, thrombosis, and mortality in patients undergoing elective PCI. The findings suggest that prasugrel can be considered a safe and effective alternative to clopidogrel in elective PCI, with careful patient selection to minimize bleeding risks.

Coronary artery bypass grafting in acute coronary syndromes: modern indications and approaches.

Acute coronary syndromes (ACS) are a leading cause of morbidity and mortality worldwide, with approximately 1.2 million hospitalizations annually in the U.S. This review aims to explore the contemporary evidence regarding revascularization strategies, including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), in ACS patients. It also addresses the unresolved questions concerning the optimal procedural aspects of surgery and antithrombotic therapy for secondary prevention postsurgery. Recent studies highlight that while PCI is generally preferred for its timeliness in high-risk non-ST-elevation ACS (NSTE-ACS) patients, CABG offers a benefit in terms of cardiovascular events in those with multivessel disease, particularly in the presence of diabetes and higher coronary disease complexity. For ST-elevation myocardial infarction (STEMI), CABG is less frequently utilized due to the preference for primary PCI, but it remains crucial for patients with complex anatomy or failed PCI. Furthermore, the optimal timing and type of antiplatelet therapy post-CABG remain controversial, with current evidence supporting the use of dual antiplatelet therapy (DAPT) to reduce ischemic events but necessitating careful management to balance bleeding risks. In patients with ACS, the choice between PCI and CABG depends on the complexity of coronary disease and patient comorbidities. CABG is particularly beneficial for multivessel disease in NSTE-ACS and specific STEMI cases where PCI is not feasible. The management of antiplatelet therapy postsurgery requires a nuanced approach to minimize bleeding risks while preventing thrombotic complications. Further randomized clinical trials are needed to solidify these findings and guide clinical practice.

The impact of anti-thrombotic therapy on bleeding outcomes and thrombosis following laparoscopic cholecystectomy: a meta-analysis.

Acute cholecyctitis is a common condition which requires immediate or elective surgical interventions and this condition is one among the common causes for emergency hospitalization among the elderly population. However, controversies have been observed with the use of anti-thrombotic agents in patients undergoing laparoscopic cholecyctectomy. Few studies have reported increased risk of bleeding in patients with anticoagulants whereas other studies have reported no significant bleeding outcomes. Nevertheless, the lack of evidence-based guidelines further complicates decision-making. In this analysis we aimed to systematically assess the impact of anti-thrombotic therapy on bleeding outcomes and thrombosis following laparoscopic cholecystectomy. MEDLINE, EMBASE, Cochrane database, Google scholar, Web of Science and http://www.ClinicalTrials.gov were searched for relevant publications based on anti-thrombotic therapy among patients who underwent laparoscopic cholecystectomy. The endpoints in this analysis included: intra-operative bleeding, post-operative bleeding, blood loss, patients requiring blood transfusion and thrombotic complications. The Revman 5.4 software was used to analyze data in this analysis. Risk ratio (RR) with 95% confidence intervals (CIs) were used to represent the data following analysis. A total number of 4008 participants (enrollment period 2002-2019) were included in this analysis whereby 756 participants were assigned to an anti-thrombotic therapy and 3592 participants were in the control group. Our results showed that antithrombotic therapy was associated with significantly higher risk of intra-operative bleeding (RR: 2.23, 95% CI: 1.77-2.79; P = 0.00001), post-operative bleeding (RR: 4.77, 95% CI: 1.13-20.10; P = 0.03), and blood loss (RR: 3.01, 95% CI: 1.13-8.06; P = 0.03). Patients requiring blood transfusion (RR: 4.80, 95% CI: 1.90-12.13; P = 0.0009) were also significantly higher in the anti-thrombotic group. However, thrombotic complications (RR: 2.17, 95% CI: 0.50-9.42; P = 0.30) were not significantly higher. Through this analysis, we concluded that anti-thrombotic therapy was associated with significantly increased risks of intra-operative and post-operative bleeding events following laparoscopic cholecystectomy. Patients requiring blood transfusion were also significantly higher. Therefore, stopping anti-thrombotic agents prior to laparoscopic cholecystectomy could significantly minimize bleeding risks.

The first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the factor XI monoclonal antibody SHR-2004 in healthy subjects

ABSTRACT Background Inhibiting the coagulation factor XI (FXI) is a novel strategy for prevention and treatment of thromboembolism without affecting extrinsic coagulation pathways. SHR-2004 is a humanized monoclonal antibody that selectively binds to FXI and factor XIa (FXIa). Research design & methods This randomized, double-blind, dose-escalation, placebo-controlled study evaluated SHR-2004 administered either intravenously (i.v.; Part A) or subcutaneously (s.c.; Part B). In Part A, 24 subjects received a single i.v. dose of SHR-2004 (0.1, 0.3, or 1.0 mg/kg) or placebo. In Part B, 40 subjects received a single s.c. dose of SHR-2004 (0.5, 1.0, 3.0, or 4.5 mg/kg) or placebo. Results SHR-2004 was well tolerated. Plasma exposure to SHR-2004 increased in a dose-dependent manner. The geometric mean half-time ranged from 11.6 to 13.0 days. FXI activity decreased, and the activated partial thromboplastin time (APTT) was prolonged after i.v. and s.c. administration in a dose- and time-dependent manner. FXI activity was nearly completely abolished immediately after administering the highest i.v. dose, with the average APTT prolonged to nearly three times of baseline. Conclusion SHR-2004 is a promising candidate for further development as an anticoagulant drug that exerts effective anticoagulation with minimal risk of bleeding. Clinical trial registration www.clinicaltrials.gov identifier is NCT05369767.

Debates Surrounding the Use of Antithrombotic Therapy in Hemophilic Patients with Cardiovascular Disease: Best Strategies to Minimize Severe Bleeding Risk.

Navigating through antithrombotic therapy in patients with both hemophilia and cardiovascular pathology presents a complex scenario with inherent challenges and opportunities. The presence of hemophilia, characterized by impaired blood clotting, adds a layer of complexity to the management of cardiovascular conditions requiring antiplatelet therapy and anticoagulation. Striking a delicate balance between the necessity for antithrombotic treatment to prevent cardiovascular events and the heightened risk of severe bleeding in individuals with hemophilia demands a nuanced and carefully considered approach. The challenges revolve around identifying an optimal therapeutic strategy that effectively mitigates cardiovascular risks without exacerbating bleeding tendencies. In hemophilic patients with cardiovascular disease, the decision to use antiplatelet therapy requires careful consideration of the individual's bleeding risk profile, considering factors such as the severity of hemophilia, history of bleeding episodes, and concurrent medications. The goal is to provide effective antithrombotic treatment while minimizing the potential for excessive bleeding complications. Conventional anticoagulants like warfarin pose difficulties due to their potential to increase the risk of bleeding. On the other hand, emerging options like novel direct oral anticoagulants (DOACs) present an opportunity, offering predictable pharmacokinetics and user-friendly administration. However, a comprehensive exploration of their safety and efficacy in hemophilic patients is imperative. Achieving the right equilibrium between preventing cardiovascular events and minimizing bleeding risk is pivotal in selecting the most effective therapeutic option for individuals with hemophilia and cardiovascular pathology. A multidisciplinary approach, integrating the expertise of hematologists and cardiologists, becomes essential to customize treatments and address the intricacies of this medical challenge.

Progress towards permanent respiratory support.

Although lung transplantation stands as the gold standard curative therapy option for end-stage lung disease, the scarcity of available organs poses a significant challenge in meeting the escalating demand. This review provides an overview of recent advancements in ambulatory respiratory assist systems, selective anticoagulation therapies that target the intrinsic pathway, and innovative surface coatings to enable permanent respiratory support as a viable alternative to lung transplantation. Several emerging ambulatory respiratory assist systems have shown promise in both preclinical and clinical trials. These systems aim to create more biocompatible, compact, and portable forms of extracorporeal membrane oxygenation that can provide long-term respiratory support. Additionally, innovative selective anticoagulation strategies, currently in various stages of preclinical or clinical development, present a promising alternative to currently utilized nonselective anticoagulants. Moreover, novel surface coatings hold the potential to locally prevent artificial surface-induced thrombosis and minimize bleeding risks. This review of recent advancements toward permanent respiratory support summarizes the development of ambulatory respiratory assist systems, selective anticoagulation therapies, and novel surface coatings. The integration of these evolving device technologies with targeted anticoagulation strategies may allow a safe and effective mode of permanent respiratory support for patients with chronic lung disease.

IC Regimen: Delaying Resistance to Lorlatinib in ALK Driven Cancers by Adding Repurposed Itraconazole and Cilostazol.

Lorlatinib is a pharmaceutical ALK kinase inhibitor used to treat ALK driven non-small cell lung cancers. This paper analyses the intersection of past published data on the physiological consequences of two unrelated drugs from general medical practice-itraconazole and cilostazol-with the pathophysiology of ALK positive non-small cell lung cancer. A conclusion from that data analysis is that adding itraconazole and cilostazol may make lorlatinib more effective. Itraconazole, although marketed worldwide as a generic antifungal drug, also inhibits Hedgehog signaling, Wnt signaling, hepatic CYP3A4, and the p-gp efflux pump. Cilostazol, marketed worldwide as a generic thrombosis preventative drug, acts by inhibiting phosphodiesterase 3, and, by so doing, lowers platelets' adhesion, thereby partially depriving malignant cells of the many tumor trophic growth factors supplied by platelets. Itraconazole may enhance lorlatinib effectiveness by (i) reducing or stopping a Hedgehog-ALK amplifying feedback loop, by (ii) increasing lorlatinib's brain levels by p-gp inhibition, and by (iii) inhibiting growth drive from Wnt signaling. Cilostazol, surprisingly, carries minimal bleeding risk, lower than that of aspirin. Risk/benefit assessment of the combination of metastatic ALK positive lung cancer being a low-survival disease with the predicted safety of itraconazole-cilostazol augmentation of lorlatinib favors a trial of this drug trio in ALK positive lung cancer.

Optimization of Dual Antiplatelet Therapy in Pakistani Patients Undergoing PCI: A Strategy to Minimize Bleeding Risks and Improve Outcomes

Background: Percutaneous Coronary Intervention (PCI) is essential for treating coronary artery disease. The use of Dual Antiplatelet Therapy (DAPT) is crucial to prevent thrombotic complications but presents bleeding risks. This challenge is accentuated by the variability in genetic, demographic, and regional factors, particularly in Pakistan, where there is a high prevalence of cardiovascular diseases. Objective: To optimize DAPT strategies for Pakistani patients undergoing PCI by minimizing bleeding risks while ensuring therapeutic efficacy, aiming to pioneer personalized cardiovascular care. Methods: A retrospective cohort analysis was conducted at Lady Reading Hospital, Peshawar, involving 500 patients who underwent PCI and received DAPT from January 1, 2023, to January 1, 2024. Comprehensive data collection included patient demographics, clinical histories, specifics of PCI procedures, and outcomes of bleeding and thrombotic events, through a detailed review of medical records. Results: The cohort predominantly consisted of males (70%), with an average age of 58 years. Most patients (96%, n=480) were prescribed aspirin and clopidogrel, while a smaller fraction (4%, n=20) received aspirin and ticagrelor. Compliance was high, with 90% adherence. Bleeding occurred in 10% of the cohort (n=50), with major bleeds necessitating hospitalization in 4% (n=20). Thrombotic events were noted in 3% of patients (n=15). Conclusion: The study underscores the importance of personalized DAPT regimens that address individual risks and regional healthcare challenges in Pakistan. Tailored approaches are essential for optimizing treatment efficacy and safety, advocating for advanced, nuanced cardiovascular care practices.

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.

The Platelet Aggregation Inhibition Activity of Polyphenols can be mediated by 67kda Laminin Receptor: A New Therapeutic Strategy For the Treatment of Venous Thromboembolism.

Thrombotic disease is still a major killer. Aspirin, Ticagrelor, Clopidogrel, etc. are the most widely used conventional antiplatelet drugs. The significant number of patients who are resistant to this drug shows a poor outcome. Developing a new antiplatelet agent with a stable antiplatelet effect and minimal bleeding risk is required for a patient who is resistant to antiplatelet drugs. Protein-ligand docking was performed using Autodock Vina 1.1.2 to study the interaction of 67LR with different Polyphenols. Among the 18 polyphenols, thearubigin has the highest binding affinity towards 67LR and gallic acid shows the lowest binding affinity. Among the 18 molecules, the top 10 molecules from the highest to lowest binding affinity range from-10.6 (thearubigin) to -6.5 (Epigallocatechin). Polyphenols may inhibit platelet aggregation through 67 LR and can be an alternative treatment for Thrombotic Disease. Moreover, it will be interesting to know whether polyphenols interfere with the same pathways as aspirin and clopidogrel. Effective polyphenols could help prototype the compound development of novel antiplatelet agents.

Anticoagulants for atrial fibrillation: from warfarin and DOACs to the promise of factor XI inhibitors.

Anticoagulation is the mainstay of stroke prevention in appropriate patients with atrial fibrillation. Due to advances in pharmacotherapy the anticoagulants used for this purpose have evolved significantly over the past decades with the aim of optimizing effectiveness while minimizing bleeding risks. Though significant improvements have been made toward this goal, bleeding risk remains the major concern with these therapies. An investigational class of agents which inhibit Factor XI have shown promise in pre-clinical and early clinical trials to significantly minimize bleeding while maintaining efficacy against stroke and systemic embolism. This mini-review will discuss anticoagulants currently used for stroke prevention in patients with atrial fibrillation including warfarin and direct oral anticoagulants. We will also review the mechanism of action and data from early clinical trials for Factor XI inhibitors and discuss their potential advantages and shortcomings.

Insertion Multi-Parachute Suturing and Knotting (IMS-K) Technique for Aortic Surgery.

Successful surgical interventions for aortic surgery, such as hemiarch repair and total arch replacement, pivot on the foundation of optimal anastomosis. We propose an alternative approach to anastomosis. The "insertion multi-parachute suturing and knotting" (IMS-K) technique entails the deployment of two parachute sutures, which can be effectively employed for both proximal and distal anastomoses. The first suture is applied loosely to the posterior half of the anastomosis and subsequently parachuted down, tightening the suture with a nerve hook. The second suture replicates the procedure in the anterior half of the anastomosis, loosely securing it in a similar manner and tightening it with a nerve hook at the end. As a result, the artificial graft is completely inserted into the aorta with a substantial grip. This technique simplifies the aortic anastomosis by ensuring procedural simplicity while minimizing bleeding risk, thus potentially advancing surgical outcomes.

Assessing the efficacy of VerifyNow platelet-function testing in predicting postoperative hemorrhagic complications of neuroendovascular surgery: A systematic review and meta-analysis (part 2).

Dual antiplatelet therapy is used to reduce the risk of thromboembolic complications in neuroendovascular surgery. However, the predictive utility of preoperative platelet-sensitivity testing for decreasing bleed risk in patients undergoing endovascular neurointervention remains unclear. We conducted a systematic review and meta-analysis to illustrate the association between platelet response and risk of hemorrhagic complications from neuroendovascular surgery, examine the efficacy of the VerifyNow platelet reactivity unit (PRU) assay in predicting hemorrhagic outcomes, and assess whether a clinically useful threshold for platelet response can be defined to standardize guidelines. PubMed, Embase, and Scopus were searched. Articles were screened for relevance by title and abstract, followed by full text. Of 735 resultant articles, 17 studies of 2084 patients undergoing neuroendovascular intervention were included. Diagnoses included both intracranial and extracranial pathologies, of which 37.8% were treated with flow diversion, 22.4% with stent-assisted coil embolization, 14.3% with intracranial stenting, 12.8% with simple coil embolization, 5.8% with balloon-assisted coil embolization, 2.0% with extracranial stenting, and 4.8% with an alternate method. Precisely, 52.9% (9 out of 17) of studies determined platelet hyperresponse to be an independent predictor of postoperative hemorrhagic complications, with 11.8% (2 out of 17) of studies reporting a similar but non-statistically significant trend. 35.3% (6 out of 17) of studies found no relationship between platelet response and postoperative hemorrhagic complications. The estimated clinical threshold for PRU to prevent hemorrhagic complications varied considerably across studies (range: <46-118 PRU). Meta-analysis found platelet hyperresponse to have more than a 3-fold increased risk of hemorrhagic complications compared to normoresponders (relative risk = 3.2, p = 0.001). Although this meta-analysis shows the predictive utility of the P2Y12 assay for postoperative hemorrhagic complications in neuroendovascular surgery, the optimal therapeutic threshold for minimizing bleeding risk is still uncertain. To better understand the utility of the P2Y12 assay in the perioperative period, further prospective research is needed.

Management strategies in persons with inherited haemophilia requiring antithrombotic therapy: A scoping review

AbstractBackgroundThromboembolic events are increasingly reported in the aging haemophilia population. The purpose of this study was to understand current practices and identify knowledge and research gaps in the management of persons with haemophilia requiring antithrombotic therapy for cardiovascular disorders (CVD) or venous thromboembolism (VTE).MethodsWe searched MEDLINE, EMBASE and Scopus for studies reporting on more than two patients with inherited haemophilia A or B, without inhibitors, requiring antithrombotic therapy for CVD or VTE. Data were extracted by two independent reviewers and analysed using descriptive statistics and narrative synthesis.ResultsWe included 32 studies reporting on 432 persons with haemophilia. Three themes described the observed practice variation: (1) Difficulty weighing competing bleeding and thrombotic risks; (2) Tensions in providing standards of care and minimizing bleeding risk; (3) Advocacy for individualized strategies and multidisciplinary care. Different management strategies were used to treat persons with haemophilia in the setting of thromboembolic events, such as avoiding or choosing lower intensity antithrombotic therapy, or procedural alternatives to antithrombotic therapy. Initiation or alteration in haemostatic therapies along with antithrombotic therapy were common strategies and reported in 30 studies. However, data on target factor levels and bleeding and thrombotic events were largely missing.DiscussionOur scoping review highlights unmet needs in the management of an aging population of persons with haemophilia with increasing prevalence of CVD and VTE. Management is inconsistent and divergent from those of non‐haemophilic patients. Prospective data are needed to inform optimal and evidence‐based management strategies of CVD and VTE in persons with haemophilia.

Dual-Antiplatelet Therapy After Coronary Artery Bypass Grafting: A Survey of UK Cardiac Surgeons

Antiplatelet therapy after coronary artery bypass grafting (CABG) is important in postoperative medical management. Although cardiac surgeons are well-versed in the guidelines regarding discontinuation of dual-antiplatelet therapy (DAPT; aspirin and a P2Y12 antagonist) before CABG to minimize bleeding risk, there is considerable variability in DAPT dosing after CABG. The objective of this study was to explore the current trends in DAPT after CABG in the UK to improve understanding of the existing practice. This study used an online survey with 9 questions about the use of DAPT after CABG. An invitation to participate was sent to all adult cardiac surgeons currently in practice in the UK and the Republic of Ireland. The study was conducted in the UK and the Republic of Ireland. Participants in this study were adult cardiac surgeons currently in practice in the UK and the Republic of Ireland. There were no interventions in this study. Responses were received from across the UK (85.4% UK; 4% each from Scotland and Northern Ireland, 1.3% from Wales) and 5.3% from the Republic of Ireland. Fifty-seven percent of the respondents performed between 50 and 100 CABGs per year. Ninety-one percent of the respondents prescribe DAPT postoperatively, but the choice of which patients receive it varied. Most responding surgeons used DAPT for selective patient cohorts, such as those with acute coronary syndrome (51%), diffuse coronary artery disease (42%), perioperative myocardial infarction (36%), coronary endarterectomy (31%), or when bypassing a stented coronary artery (23%). Thirty-eight percent of the respondents began all their patients with CABGs on DAPT. The most preferred P2Y12 antagonist was clopidogrel, used by 75% of respondents and introduced on day 1 after surgical revascularization (71%). The routine duration for DAPT is 12 months, which 78% of the respondents preferred. The main reason for not starting DAPT in those surveyed was the bleeding risk associated with DAPT (72%). The survey uncovered variation in the use of DAPT after CABG. However, DAPT remains the preferred strategy after CABG in the UK. The study highlighted the need to develop standardized protocols for DAPT after CABG.

The association between duration of and indications for proton pump inhibitor use and risk of gastric polyps.

The development of fundic gland polyps (FGPs) is the most common side effect of long-term proton pump inhibitor (PPI) use; however, the effect of drug use characteristics and their impact on the risk of other gastric polyp development remain unclear. We aimed to identify the influence of PPI administration, as well as its duration and dose, in the development of gastric polyps. A prospective cohort study was conducted on consecutive patients who underwent gastroscopy between September 2017 and August 2019. Detailed characteristics of gastric polyps, Helicobacter pylori infection, and PPI use were analyzed. Among the 2723 patients included, gastric polyps (75% FGPs, 22% hyperplastic) were detected in 16.4%, and 60% were prescribed PPI. The risk of FGPs and hyperplastic polyps according to the duration of PPI use were as follows: 2-5 years [odds ratio (95% confidence interval); 2.86 (2.00-4.11) and 2.82 (1.69-4.78)]; 6-9 years [7.42 (5.03-11.01) and 2.32 (1.05-4.78)]; ≥10 years [14.94 (10.36-21.80) and 3.52 (1.67-7.03)]. Multivariate analysis confirmed that the risk of FGPs was 17.16 (11.35-26.23) for ≥10 years of PPI use. Portal hypertension-related conditions were associated with hyperplastic polyps [4.99 (2.71-9.20)]. Duration of and indications for PPI use are the most predictive factors for the development of gastric polyps. Prolonged PPI use increases the risk of polyp development and the number of patients with polyps, which may burden endoscopic practice. Highly selected patients may require particular care despite minimal risk of dysplasia and bleeding generally.