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Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size, and the content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor, respectively. The control group consisted of patients with risk factors for CHD, but with no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by the exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, and ADP 20, 5, 2.5 µM, and in the CHD/ACS groups, by TRAP 10 µM, and ADP 20 5 µM (±epinephrine 20 µM). Platelet size was assessed by the mean volume, % large forms, and forward scattering. RP were stained by thiazole orange. In the control group, activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease in platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in the CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and the reduced efficacy of antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) therapy holds promise for treating various clinical conditions. The activation process is crucial in releasing growth factors and cytokines from platelets, enhancing the therapeutic properties of PRP. Standard activation methods involve autologous thrombin or collagen, with variations in efficacy and growth factor release. This study explores the impact of acetylsalicylic acid (ASA), a commonly used antiplatelet drug, on PRP activation. The results indicate that non-activated PRP extracted from the whole blood of ASA-treated patients exhibits increased inflammatory cytokine concentrations, notably TNFa. After activation with autologous thrombin/CaCl2 or collagen IV, the measured fluorescence intensities suggest varying release patterns between treated and non-treated groups. Understanding the influence of ASA on platelet activation holds implications for personalized medicine and optimizing outcomes for individual patients undergoing PRP therapy. This research sheds light on the potential challenges associated with using antiplatelet drugs, emphasizing the need for careful consideration in tailoring PRP-based regenerative therapies. [ABSTRACT FROM AUTHOR]

The omega-3 polyunsaturated fatty acids (PUFAs) Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) exert multiple cardioprotective effects, influencing inflammation, platelet activation, endothelial function and lipid metabolism, besides their well-established triglyceride lowering properties. It is not uncommon for omega-3 PUFAs to be prescribed for hypertriglyceridemia, alongside antiplatelet therapy in cardiovascular disease (CVD) patients. In this regard, we studied the effect of EPA and DHA, in combination with antiplatelet drugs, in platelet aggregation and P-selectin and αIIbβ3 membrane expression. The antiplatelet drugs aspirin and triflusal, inhibitors of cyclooxygenase-1 (COX-1); ticagrelor, an inhibitor of the receptor P2Y12; vorapaxar, an inhibitor of the PAR-1 receptor, were combined with DHA or EPA and evaluated against in vitro platelet aggregation induced by agonists arachidonic acid (AA), adenosine diphosphate (ADP) and TRAP-6. We further investigated procaspase-activating compound 1 (PAC-1) binding and P-selectin membrane expression in platelets stimulated with ADP and TRAP-6. Both DHA and EPA displayed a dose-dependent inhibitory effect on platelet aggregation induced by AA, ADP and TRAP-6. In platelet aggregation induced by AA, DHA significantly improved acetylsalicylic acid (ASA) and triflusal's inhibitory activity, while EPA enhanced the inhibitory effect of ASA. In combination with EPA, ASA and ticagrelor expressed an increased inhibitory effect towards ADP-induced platelet activation. Both fatty acids could not improve the inhibitory effect of vorapaxar on AA- and ADP-induced platelet aggregation. In the presence of EPA, all antiplatelet drugs displayed a stronger inhibitory effect towards TRAP-6-induced platelet activation. Both omega-3 PUFAs inhibited the membrane expression of αIIbβ3, though they had no effect on P-selectin expression induced by ADP or TRAP-6. The antiplatelet drugs exhibited heterogeneity regarding their effect on P-selectin and αIIbβ3 membrane expression, while both omega-3 PUFAs inhibited the membrane expression of αIIbβ3, though had no effect on P-selectin expression induced by ADP or TRAP-6. The combinatory effect of DHA and EPA with the antiplatelet drugs did not result in enhanced inhibitory activity compared to the sum of the individual effects of each component. [ABSTRACT FROM AUTHOR]

Background: Incidence of infective endocarditis (IE) is progressively raising because of the increasing number of cardiovascular invasive procedures, support treatment and devices, awareness in the medical community, and improved diagnostic modalities. IE pathophysiology is a unique model of immunothrombosis, and the clinical course is often complicated by either embolic or hemorrhagic events. Managing antithrombotic treatment is challenging and the level of supporting evidence scant. The aim of this review was to discuss and present the embolic and bleeding complication associated with IE and review the available evidence on antithrombotic treatment in patients with IE with and without a previous indication to antithrombotic drugs. Summary: Embolic events occur in 20–40% of patients with IE and are associated with high morbidity and mortality. Acute ischemic stroke is the most common neurological complication. A beneficial effect of antithrombotic therapy in preventing ischemic stroke for patients with IE has never been formally tested in adequately powered randomized clinical trials. Atrial fibrillation is a common complication associated with severe infections, requiring anticoagulation. Furthermore, patients with IE have a high risk of unprovoked and anticoagulation treatment-related bleeding. In particular, intracerebral bleeding is the most severe complication in about 5% of patients with IE. Single antiplatelet therapy with low-dose aspirin after hospitalization for IE has been shown to reduce causes mortality within 90 days without an increase of hemorrhagic strokes. In the absence of bleeding complications, recent guidelines recommend to maintain low-dose aspirin. No data are available on the management of patients with IE while on dual antiplatelet therapy. Key Messages: Several gaps in knowledge remain about antithrombotic management in patients with IE and most of the evidence relies on observational studies. Individualized strategies based on clinical evaluation, comorbidities, patient engagement, and shared decisions strategies are encouraged. [ABSTRACT FROM AUTHOR]

In a double‐blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up‐dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D‐dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D‐dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D‐dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up‐dosing antihistamines may be more effective for CSU patients with high D‐dimer levels compared to up‐dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D‐dimer levels observed in the antiplatelet group. [ABSTRACT FROM AUTHOR]

Platelets play a significant role in hemostasis, forming plugs at sites of vascular injury to limit blood loss. However, if platelet activation is not controlled, it can lead to thrombotic events, such as myocardial infarction and stroke. To prevent this, antiplatelet agents are used in clinical settings to limit platelet activation in patients at risk of arterial thrombotic events. However, their use can be associated with a significant risk of bleeding. An enhanced comprehension of platelet signaling mechanisms should facilitate the identification of safer targets for antiplatelet therapy. Over the past decade, our comprehension of the breadth and intricacy of signaling pathways that orchestrate platelet activation has expanded exponentially. Several recent studies have provided further insight into the regulation of platelet signaling events and identified novel targets against which to develop novel antiplatelet agents. Antiplatelet drugs are essential in managing atherothrombotic vascular disease. The current antiplatelet therapy in clinical practice is limited in terms of safety and efficacy. Novel compounds have been developed in response to patient variability and resistance to aspirin and/or clopidogrel. Recent studies based on randomized controlled trials and systematic reviews have definitively demonstrated the role of antiplatelet therapy in reducing the risk of cardiovascular events. Antiplatelet therapy is the recommended course of action for patients with established atherosclerosis. These studies compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. However, in patients undergoing percutaneous coronary intervention, it is still unclear whether the efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy depends on the type of P2Y12 inhibitor. This paper focuses on the advanced-stage evaluation of several promising antiplatelet drugs. [ABSTRACT FROM AUTHOR]

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Summary: Background: Sneddon syndrome is an occlusive vasculopathy that presents clinically with generalized livedo racemosa on the skin and transient ischemic attacks, strokes, and cognitive or motor deficits in the central nervous system. Antiplatelet or anticoagulant therapy is recommended. Due to the limited therapeutic efficacy and the resulting serious complications, we propose combination therapy with additional infusion cycles of alprostadil and captopril and report initial long‐term results. Patients and methods: We performed a systematic retrospective analysis of all patients with primary Sneddon syndrome who received combination therapy in our clinic between 1995 and 2020. Therapeutic outcomes were evaluated using descriptive statistics compared to historical controls receiving monotherapy. We also analyzed the event rate of complications when combination therapy was discontinued. Results: During the 99.7 patient‐years of follow‐up, there were no transient ischemic attacks and the stroke rate dropped to 0.02 per patient‐year. In comparison, the rates of transient ischemic attacks and strokes in the historical controls ranged from 0.08 to 0.035 per patient‐year. After discontinuation of alprostadil therapy, eight events occurred in three patients. Conclusions: Combination therapy reduces the long‐term incidence of ischemic events in patients with primary Sneddon syndrome. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess bleeding risk after exodontia in patients with recent percutaneous coronary intervention during uninterrupted single or dual antiplatelet therapy. Study design: A total of 100 patients who had a history of percutaneous stent insertion during the past year candidate for extraction of teeth were included in the study. Fifty patients took aspirin 100mg (monotherapy group), and 50 patients took a combination of aspirin 100mg and clopidogrel 75mg (dual therapy group). After exodontia, the bleeding status was categorized as "complete hemostasis," "persistent bleeding," and "delayed bleeding." Personal data, underlying diseases, number of teeth and roots extracted, and type of procedure required for exodontia were statistically analyzed. Results: No significant difference was observed in the status of bleeding between the two groups regarding sex, age, underlying diseases, number of teeth and roots extracted, and type of procedure (p > 0.05). 39/50 (78%) of monotherapy patients and 32/50 (64%) of dual therapy patients achieved complete hemostasis. Persistent bleeding was noted in 11/50 (22%) of monotherapy participants, and 14/50 (28%) of dual therapy patients. Only 4/50 (8%) of dual therapy patients experienced delayed bleeding. However, these differences were not significant (p = 0.08). All persistent and delayed bleeding was easily controlled via local measures. Conclusion: Simple or complicated extraction of multiple teeth can be performed safely during the first year after percutaneous coronary intervention without interruption of antiplatelet therapy. [ABSTRACT FROM AUTHOR]

It is not uncommon for patients to suffer from both acute myocardial infarction and acute stroke during the hospitalization. According to some studies, about 12% of the elderly population initially hospitalized for acute ischemic stroke also develop type-1 acute myocardial infarction during the same hospitalization. On the other hand, about 0.9% of patients hospitalized for acute coronary syndrome develop acute stroke during the same hospitalization1. The therapeutic approach to such “overlapping” patients is challenging, especially if we also take into account a high risk of bleeding and/or active bleeding. Therefore, interdisciplinary collaboration between cardiology, neurology and interventional neuroradiology is of key importance. Timely intervention and adequate concomitant drug therapy (primarily antiplatelet and anticoagulant therapy) determine treatment outcomes and long-term results. In our recent clinical work, we treated a patient with a series of acute cardiac and cerebral incidents presenting multiple therapeutic dilemmas, who ultimately had an unfavourable neurological outcome.

Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size, and the content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor, respectively. The control group consisted of patients with risk factors for CHD, but with no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by the exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, and ADP 20, 5, 2.5 µM, and in the CHD/ACS groups, by TRAP 10 µM, and ADP 20 5 µM (±epinephrine 20 µM). Platelet size was assessed by the mean volume, % large forms, and forward scattering. RP were stained by thiazole orange. In the control group, activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease in platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in the CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and the reduced efficacy of antiplatelet therapy.

Introduction: The increased life expectancy of patients with haemophilia A (HA) has led to a growing prevalence of cardiovascular risk factors and events. There is still scarce evidence on the safety and appropriate duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) in HA patients. Aim: We describe our experience on the clinical management of Italian HA patients after ACS. Methods: Nine patients with congenital HA treated with DAPT after a revascularization procedure performed for ACS have been enrolled and followed at the Angelo Bianchi Bonomi Haemophilia and Thrombosis Center in Milan between 2005 and September 2022. The safety and efficacy of DAPT with or without FVIII prophylaxis were assessed. Results: Ten ACS events occurred in the nine HA patients (four mild and five severe). All events were treated with percutaneous transluminal coronary angioplasty with deployment of 1 to 3 drug‐eluting stents followed by DAPT for 1–12 months. All patients except one were treated with FVIII prophylaxis during DAPT aimed at achieving FVIII trough levels ≥20–30 IU/dL. DAPT was effective in all cases in preventing early ACS recurrence, with only a late recurrence. We observed two clinically relevant non‐major bleeds (one in a patient without FVIII prophylaxis) and three minor bleeds. No venous thrombosis occurred. Conclusion: The long‐term secondary antithrombotic prevention consisting of DAPT and FVIII prophylaxis achieving a trough level of 20–30 IU/dL can be effective and safe in HA patients. [ABSTRACT FROM AUTHOR]

Myocardial fibrosis is a feature found in most cardiac diseases and a key element contributing to heart failure and its progression. It has therefore become a subject of particular interest in cardiac research. Mechanisms leading to pathological cardiac remodeling and heart failure are diverse, including effects on cardiac fibroblasts, the main players in cardiac extracellular matrix synthesis, but also on cardiomyocytes, immune cells, endothelial cells, and more recently, platelets. Although transforming growth factor-β (TGF-β) is a primary regulator of fibrosis development, the cellular and molecular mechanisms that trigger its activation after cardiac injury remain poorly understood. Different types of anti-TGF-β drugs have been tested for the treatment of cardiac fibrosis and have been associated with side effects. Therefore, a better understanding of these mechanisms is of great clinical relevance and could allow us to identify new therapeutic targets. Interestingly, it has been shown that platelets infiltrate the myocardium at an early stage after cardiac injury, producing large amounts of cytokines and growth factors. These molecules can directly or indirectly regulate cells involved in the fibrotic response, including cardiac fibroblasts and immune cells. In particular, platelets are known to be a major source of TGF-β1. In this review, we have provided an overview of the classical cellular effectors involved in the pathogenesis of cardiac fibrosis, focusing on the emergent role of platelets, while discussing opportunities for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

AbstractThis retrospective study analyzed the efficacy of combined antiplatelet therapy with Argatroban in treating acute ischemic stroke (AIS) and its impact on patients’ coagulation and neurological functions. Clinical data of 113 AIS patients admitted between January 2021 and January 2023 were retrospectively analyzed. Patients were divided into control (n = 56) and observation (n = 57) groups based on treatment interventions. The control group patients were treated with antiplatelet drugs, while the observation group patients received combination therapy with apatinib on the basis of the control group treatment. Compared to the control group, the observation group demonstrated higher clinical efficacy, improved coagulation parameters, reduced stroke severity (measured by NIHSS), enhanced daily living abilities (BI scores), and lowered inflammatory and neural injury markers post-treatment. Adverse reaction incidence was similar between groups. Combining Argatroban with antiplatelet drugs in AIS management showed superior efficacy without increasing adverse effects, suggesting its potential for clinical application. [ABSTRACT FROM AUTHOR]

BackgroundThis study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization.MethodsThis cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire.ResultsThis study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0–26) and 43.68 ± 6.01 (range: 21–50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P = 0.035), high school or technical school education (OR = 2.356, P = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P = 0.002), BMI ≥ 24.0 kg/m2 (OR = 0.372, P = 0.011), junior high school (OR = 3.699, P = 0.002), high school or technical school (OR = 2.903, P = 0.028), high associate degree or above education (OR = 6.068, P = 0.014), monthly average income 3,000–5,000 RMB (OR = 0.296, P = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P = 0.021), with hypertension (OR = 0.333, P = 0.003), blood tests every 2–3 weeks (OR = 10.811, P = 0.011), blood tests every month (OR = 4.221, P = 0.024), and blood tests every 2–3 months (OR = 3.342, P = 0.033) were independently associated with attitude.ConclusionCAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes.

Abstract Background For ischaemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs or reducing the dose of antiplatelet drugs was a conventional clinical therapy method. But not a study to prove which way was better. And the machinery learning methods could help to obtain which way more suit for some patients. Methods Data from consecutive ischaemic stroke patients with gastrointestinal haemorrhage were prospectively collected. The outcome was a recurrent stroke rate, haemorrhage events, mortality and favourable functional outcome (FFO). We analysed the data using conventional logistic regression methods and a supervised machine learning model. We used unsupervised machine learning to group and analyse data characters. Results The patients of stopping antiplatelet drugs had a lower rate of bleeding events (p = 0.125), mortality (p = 0.008), rate of recurrence of stroke (p = 0.161) and distribution of severe patients (mRS 3–6) (p = 0.056). For Logistic regression, stopping antiplatelet drugs (OR = 2.826, p = 0.030) was related to lower mortality. The stopping antiplatelet drugs in the supervised machine learning model related to mortality (AUC = 0.95) and FFO (AUC = 0.82). For group by unsupervised machine learning, the patients of better prognosis had more male (p

Introduction: The number of patients on antithrombotic drugs for coronary heart disease or cerebrovascular disease has been increasing with the aging of society. We occasionally need to decide whether to continue or discontinue antithrombotic drugs before spine surgery. The purpose of this study is to understand the current perioperative management of antithrombotic drugs before elective spine surgery in Japan. Methods: In 2021, members of the Japanese Society for Spine Surgery and Related Research (JSSR) were asked to complete a web-based questionnaire survey that included items concerning the respondents' surgical experience, their policy regarding discontinuation or continuation of antithrombotic drugs, their reasons for decisions concerning the management of antithrombotic drugs, and their experience of perioperative complications related to the continuation or discontinuation of these drugs. Results: A total of 1,181 spine surgeons returned completed questionnaires, giving a response rate of 32.0%. JSSR board-certified spine surgeons comprised 75.1% of the respondents. Depending on the management policy regarding antithrombotic drugs for each comorbidity, approximately 73% of respondents discontinued these drugs before elective spine surgery, and about 80% also discontinued anticoagulants. Only 4%-5% of respondents reported continuing antiplatelet drugs, and 2.5% reported continuing anticoagulants. Among the respondents who discontinued antiplatelet drugs, 20.4% reported having encountered cerebral infarction and 3.7% reported encountering myocardial infarction; among those who discontinued anticoagulants, 13.6% reported encountering cerebral embolism and 5.4% reported encountering pulmonary embolism. However, among the respondents who continued antiplatelet drugs and those who continued anticoagulants, 26.3% and 27.2%, respectively, encountered an unexpected increase in intraoperative bleeding, and 10.3% and 8.7%, respectively, encountered postoperative spinal epidural hematoma requiring emergency surgery. Conclusions: Our findings indicate that, in principle, >70% of JSSR members discontinue antithrombotic drugs before elective spine surgery. However, those with a discontinuation policy have encountered thrombotic complications, while those with a continuation policy have encountered hemorrhagic complications.

The article deals with antithrombotic therapy and the evaluation of bleeding diathesis in elective gastrointestinal endoscopies. It discusses whether discontinuation of antithrombotic medication before the procedure is necessary and whether coagulation testing can reduce the risk of post-interventional bleeding. It is recommended to assess bleeding diathesis using a questionnaire and to perform coagulation testing in case of increased bleeding risk. The use of antithrombotic drugs and the challenges in managing these medications before and after endoscopic procedures are also discussed. The recommendations for therapy during endoscopic procedures were published in 2016 by American and European/British authorities. It is stated that clopidogrel does not significantly increase the risk of bleeding after colon polypectomy compared to acetylsalicylic acid. The current international guidelines support the recommendation to no longer interrupt antithrombotic drugs before polypectomy, unless it is a procedure with a high bleeding risk. The recommendations were developed in collaboration with an experienced hematologist and are based on current guidelines and recommendations from America, Europe, and the United Kingdom. [Extracted from the article]

Advances in the treatment of hemophilia have increased the life expectancy of this population and we are currently facing diseases associated with aging, including cardiovascular ones. Coronary atherosclerosis, with acute myocardial infarction as the most severe form of manifestation, has been recognized as part of the comorbidities of hemophiliacs. However, little is known about peripheral artery disease. Available data show that hemophiliacs have cardiovascular risk factors and atherosclerosis similar to the general population. Impaired thrombus formation and phenotype of atheroma plaque rather than the burden of atherosclerosis explains their lower cardiovascular mortality. Since the effect of traditional cardiovascular risk factors overpowers that of decreased coagulability and promotes the onset and progression of atherosclerotic lesions, screening for traditional cardiovascular risk factors and peripheral artery disease should be integrated into standard hemophilia care. There is evidence that invasive treatments and long-term antithrombotic therapy are generally safe, provided that coagulation factor levels are taken into account and replacement therapy is given when necessary. [ABSTRACT FROM AUTHOR]

The blood platelet plays an important role but often remains under‐recognized in several vascular complications and associated diseases. Surprisingly, platelet hyperactivity and hyperaggregability have often been considered the critical risk factors for developing vascular dysfunctions in several neurodegenerative diseases (NDDs) like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, platelet structural and functional impairments promote prothrombotic and proinflammatory environment that can aggravate the progression of several NDDs. These findings provide the rationale for using antiplatelet agents not only to prevent morbidity but also to reduce mortality caused by NDDs. Therefore, we thoroughly review the evidence supporting the potential pleiotropic effects of several novel classes of synthetic antiplatelet drugs, that is, cyclooxygenase inhibitors, adenosine diphosphate receptor antagonists, protease‐activated receptor blockers, and glycoprotein IIb/IIIa receptor inhibitors in NDDs. Apart from this, the review also emphasizes the recent developments of selected natural antiplatelet phytochemicals belonging to key classes of plant‐based bioactive compounds, including polyphenols, alkaloids, terpenoids, and flavonoids as potential therapeutic candidates in NDDs. We believe that the broad analysis of contemporary strategies and specific approaches for plausible therapeutic treatment for NDDs presented in this review could be helpful for further successful research in this area. [ABSTRACT FROM AUTHOR]

Background: For ischaemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs or reducing the dose of antiplatelet drugs was a conventional clinical therapy method. But not a study to prove which way was better. And the machinery learning methods could help to obtain which way more suit for some patients. Methods: Data from consecutive ischaemic stroke patients with gastrointestinal haemorrhage were prospectively collected. The outcome was a recurrent stroke rate, haemorrhage events, mortality and favourable functional outcome (FFO). We analysed the data using conventional logistic regression methods and a supervised machine learning model. We used unsupervised machine learning to group and analyse data characters. Results: The patients of stopping antiplatelet drugs had a lower rate of bleeding events (p = 0.125), mortality (p = 0.008), rate of recurrence of stroke (p = 0.161) and distribution of severe patients (mRS 3–6) (p = 0.056). For Logistic regression, stopping antiplatelet drugs (OR = 2.826, p = 0.030) was related to lower mortality. The stopping antiplatelet drugs in the supervised machine learning model related to mortality (AUC = 0.95) and FFO (AUC = 0.82). For group by unsupervised machine learning, the patients of better prognosis had more male (p < 0.001), younger (p < 0.001), had lower NIHSS score (p < 0.001); and had a higher value of serum lipid level (p < 0.001). Conclusions: For ischemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs had a better prognosis. Patients who were younger, male, with lesser NIHSS scores at admission, with the fewest history of a medical, higher value of diastolic blood pressure, platelet, blood lipid and lower INR could have a better prognosis. [ABSTRACT FROM AUTHOR]

目的 明确真实世界内蒙古包头地区40岁及以上人群抗血小板聚集类药物的使用情况，以及不同人群服药率的影响因素。 方法 采用以居委会、村委会为单位的多级、整群、随机抽样方法，在2021年6月—2022年9月抽取包头地区40岁及以上常住居民。采用调查问卷形式收集研究对象的一般资料、既往病史及抗血小板聚集类药物使用情况。按照是否有心脑血管疾病（cardio cerebrovascular diseases，CVD）以及是否存在CVD危险因素将研究对象分为3组：CVD组（既往患CVD人群）、CVD危险因素组（无CVD病史，有以下1个或多个CVD危险因素：高血压、糖尿病、高血脂、吸烟史、饮酒史、肥胖）、健康对照组（无CVD病史，无CVD危险因素）。比较3组间一般资料的差异。根据是否服用抗血小板聚集类药物，将CVD组和CVD危险因素组的研究对象分别分为服药组和未服药组，采用单因素和多因素分析调查两组中影响服药的相关因素。 结果 ①研究共纳入2100例有效调查对象，其中CVD组298例（14.2%）、CVD危险因素组1040例（49.5%）、健康对照组762例（36.3%）。3组人群中抗血小板聚集类药物应用率分别为51.68%（154例）、33.46%（348例）和6.69%（51例），组间差异有统计学意义（P＜0.001）。②多因素分析显示，CVD组中较高学历（以小学及以下学历为基线，高中OR 2.429，95%CI 1.277～4.619，P=0.007、本科及以上学历OR 8.500，95%CI 1.015～12.165，P=0.048）以及合并糖尿病（OR 2.820，95%CI 1.377～5.777，P=0.005）的患者更倾向于应用抗血小板聚集类药物；CVD危险因素组中抗血小板聚集类药物应用率受个人经济收入（以＜1.0万/年为基线，＞5.0万/年 OR 18.547，95%CI 8.948～38.444，P＜0.001）、学历（以小学及以下学历为基线，本科及以上学历OR 5.512，95%CI 1.736～17.495，P=0.004）、吸烟史（OR 0.712，95%CI 0.541～0.936，P=0.015）、BMI（与低BMI患者相比，BMI正常OR 5.640，95%CI 1.172～27.144，P=0.031）；肥胖 （OR 8.440，95%CI 1.684～42.293，P=0.009）、患高血压（OR 246.029，95%CI 112.44～538.337， P＜0.001）、患糖尿病（OR 117.689，95%CI 51.041～271.367，P＜0.001）等因素的独立影响。③CVD组和CVD危险因素组的服药原因中医师处方占比最高，分别为83.12%和79.60%；健康对照组服药原因从高到低依次为自觉应该服用（47.06%）、亲友介绍（29.41%）、广告媒体宣传（13.73%）和医师处方（9.80%）。 结论 内蒙古包头地区40岁及以上人群中使用抗血小板聚集类药物进行CVD一级、二级预防的情况不理想，不同人群服药影响因素各不相同，且存在健康人群不规范和错误用药情况。 Abstract: Objective To clarify the use of antiplatelet aggregating drugs in people aged 40 years and above in Baotou area of Inner Mongolia in the real world, and the factors influencing the rate of taking drugs in different populations. Methods A multilevel, whole-group, random sampling method with neighborhood and village committees was used to draw permanent residents aged 40 years and above in Baotou area from June 2021 to September 2022. A questionnaire was used to collect general information, past medical history and the use of anti-platelet aggregating drugs from the study population. The subjects were divided into three groups according to the presence or absence of cardio cerebrovascular diseases (CVD) and the presence of CVD risk factors: CVD group (with previous CVD), CVD risk factor group (no history of CVD, with one or more of the following CVD risk factors: hypertension, diabetes mellitus, hyperlipidemia, history of smoking, history of alcohol consumption, obesity), the healthy control group (no history of CVD, no risk factors for CVD). The differences in general information between the 3 groups were compared. The subjects in the CVD group and the CVD risk factor group were divided into the medication group and the non-medication group according to whether they were taking antiplatelet aggregation drugs or not, and the relevant factors affecting medication taking in the two groups were investigated using univariate and multifactorial analyses. Results ①A total of 2100 validated subjects were included in the study, including 298 cases (14.2%) in the CVD group, 1040 cases (49.5%) in the CVD risk factor group, and 762 cases (36.3%) in the healthy control group.The rates of taking antiplatelet aggregation drugs in the three groups were 51.68% (154 cases), 33.46% (348 cases), and 6.69% (51 cases), respectively, with statistically significant differences between groups (P50 000/year, OR 18.547, 95%CI 8.948-38.444, P

OBJECTIVE: To explore the clinical characteristics and risk factors of patients with hemorrhage of digestive tract caused by antiplatelet drugs. METHODS: Retrospective study method was used, a total of 180 patients with cardiovascular and cerebrovascular diseases who were treated with antiplatelet drugs [ aspirin and ( or ) clopidogrel] for hemorrhage of digestive tract from 2021 to 2022 in the gastroenterology department of the hospital were extracted as the observation group, and 180 patients with cardiovascular and cerebrovascular diseases who were treated with antiplatelet drugs [ aspirin and ( or) clopidogrel] during the same period without hemorrhage of digestive tract were extracted as the control group. The clinical characteristics of hemorrhage of digestive tract in the observation group were analyzed. General demographic data, biochemical indexes and the use of antiplatelet drugs were collected. Logistic regression analysis was used to explore the influencing factors of hemorrhage of digestive tract caused by antiplatelet drugs, and the receiver operator characteristic curve was established to evaluate the accuracy of the influencing factors in predicting hemorrhage of digestive tract. RESULTS: Of the 180 patients with hemorrhage of digestive tract, the highest proportion of the first clinical symptoms was black stool ( 72 cases, 40. 0%), and the lowest proportion was only stool occult blood test positive (17 cases, 9. 4%). The proportion of patients with mild bleeding was the highest (87 cases, 48. 3%), followed by moderate bleeding (74 cases, 41. 1%). The proportion of patients with moderate anemia took the lead (97 cases, 53. 9%), while patients with severe anemia were the lowest (35 cases, 19. 4%). The main endoscopic lesions were erosive gastritis (110 cases, 61. 1%), followed by peptic ulcer (38 cases, 21. 1%). Logistic regression analysis showed that age, history of hypertension, history of digestive tract diseases, Helicobacter pylori ( Hp ) infection, Hp infection complicated with mucosal atrophy, abnormal hemoglobin (Hb), abnormal serum creatinine (Cr), type of drug use, course of treatment, and combination of PPI were the influencing factors for hemorrhage of digestive tract caused by antiplatelet drugs (P<0. 05). The obtained dependent variables were combined to predict the probability of hemorrhage of digestive tract caused by antiplatelet drugs, with a predictive sensitivity of 0. 606, a specificity of 0. 900, a Yoden index of 0. 506, a threshold of 0. 616, and an area under the curve of 0. 809. CONCLUSIONS: The first symptom of hemorrhage of digestive tract caused by antiplatelet drugs is mostly black stool. Mild to moderate bleeding and moderate anemia can be observed. Age, history of hypertension, history of digestive tract diseases, Hp infection, Hp infection complicated with mucosal atrophy, abnormal Hb, abnormal Cr, type of drug use, course of treatment, and combination of PPI are related factors that affect hemorrhage of digestive tract caused by antiplatelet drugs. Clinical intervention should be actively targeted at bleeding factors, and joint evaluation of factors affecting hemorrhage of digestive tract caused by antiplatelet drugs has certain predictive value. [ABSTRACT FROM AUTHOR]

Copyright of Evaluation & Analysis of Drug-Use in Hospitals of China is the property of Evaluation & Analysis of Drug-Use in Hospitals of China Editorial Board and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Patients with severe infections and a pre-existing indication for antithrombotic therapy, i.e. antiplatelet agents, anticoagulant drugs, or their combinations, require integrated clinical counselling among coagulation, infectious disease, and cardiology specialists, due to sepsis-induced coagulopathy that frequently occurs. Bacterial and viral pathogens constitute an increasing threat to global public health, especially for patients with ongoing antithrombotic treatment who have a high risk of thrombotic recurrences and high susceptibility to severe infections with increased morbidity and mortality. Similarly, sepsis survivors are at increased risk for major vascular events. Coagulopathy, which often complicates severe infections, is associated with a high mortality and obligates clinicians to adjust antithrombotic drug type and dosing to avoid bleeding while preventing thrombotic complications. This clinical consensus statement reviews the best available evidence to provide expert opinion and statements on the management of patients hospitalized for severe bacterial or viral infections with a pre-existing indication for antithrombotic therapy (single or combined), in whom sepsis-induced coagulopathy is often observed. Balancing the risk of thrombosis and bleeding in these patients and preventing infections with vaccines, if available, are crucial to prevent events or improve outcomes and prognosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the clinical characteristics and risk factors of patients with hemorrhage of digestive tract caused by antiplatelet drugs. METHODS: Retrospective study method was used, a total of 180 patients with cardiovascular and cerebrovascular diseases who were treated with antiplatelet drugs [ aspirin and ( or ) clopidogrel] for hemorrhage of digestive tract from 2021 to 2022 in the gastroenterology department of the hospital were extracted as the observation group, and 180 patients with cardiovascular and cerebrovascular diseases who were treated with antiplatelet drugs [ aspirin and ( or) clopidogrel] during the same period without hemorrhage of digestive tract were extracted as the control group. The clinical characteristics of hemorrhage of digestive tract in the observation group were analyzed. General demographic data, biochemical indexes and the use of antiplatelet drugs were collected. Logistic regression analysis was used to explore the influencing factors of hemorrhage of digestive tract caused by antiplatelet drugs, and the receiver operator characteristic curve was established to evaluate the accuracy of the influencing factors in predicting hemorrhage of digestive tract. RESULTS: Of the 180 patients with hemorrhage of digestive tract, the highest proportion of the first clinical symptoms was black stool ( 72 cases, 40. 0%), and the lowest proportion was only stool occult blood test positive (17 cases, 9. 4%). The proportion of patients with mild bleeding was the highest (87 cases, 48. 3%), followed by moderate bleeding (74 cases, 41. 1%). The proportion of patients with moderate anemia took the lead (97 cases, 53. 9%), while patients with severe anemia were the lowest (35 cases, 19. 4%). The main endoscopic lesions were erosive gastritis (110 cases, 61. 1%), followed by peptic ulcer (38 cases, 21. 1%). Logistic regression analysis showed that age, history of hypertension, history of digestive tract diseases, Helicobacter pylori ( Hp ) infection, Hp infection complicated with mucosal atrophy, abnormal hemoglobin (Hb), abnormal serum creatinine (Cr), type of drug use, course of treatment, and combination of PPI were the influencing factors for hemorrhage of digestive tract caused by antiplatelet drugs (P<0. 05). The obtained dependent variables were combined to predict the probability of hemorrhage of digestive tract caused by antiplatelet drugs, with a predictive sensitivity of 0. 606, a specificity of 0. 900, a Yoden index of 0. 506, a threshold of 0. 616, and an area under the curve of 0. 809. CONCLUSIONS: The first symptom of hemorrhage of digestive tract caused by antiplatelet drugs is mostly black stool. Mild to moderate bleeding and moderate anemia can be observed. Age, history of hypertension, history of digestive tract diseases, Hp infection, Hp infection complicated with mucosal atrophy, abnormal Hb, abnormal Cr, type of drug use, course of treatment, and combination of PPI are related factors that affect hemorrhage of digestive tract caused by antiplatelet drugs. Clinical intervention should be actively targeted at bleeding factors, and joint evaluation of factors affecting hemorrhage of digestive tract caused by antiplatelet drugs has certain predictive value. [ABSTRACT FROM AUTHOR]

Keywords: adverse drug events; antiplatelet drugs; ischemic heart disease; pharmacogenetics; polymorphism; precision medicine EN adverse drug events antiplatelet drugs ischemic heart disease pharmacogenetics polymorphism precision medicine 202 207 6 07/07/23 20230801 NES 230801 INTRODUCTION AND BACKGROUND The conventional treatment for acute coronary syndromes (ACS) includes percutaneous coronary intervention with stent placement requiring dual antiplatelet therapy with acetylsalicylic acid (ASA) and an antiplatelet drug (clopidogrel, prasugrel or ticagrelor). Adverse drug events, antiplatelet drugs, ischemic heart disease, pharmacogenetics, polymorphism, precision medicine Use of ASA was extracted from patient records because ASA, as an over-the-counter drug, is not recorded in the drug purchase registry. Neither I CYP3A5*3 i nor I CYP4F2 i rs3093135 carrier status was associated with the occurrence of bleeding events. [Extracted from the article]

Objective. To investigate the incidence and influencing factors affecting the non- adherence behavior of patients with coronary heart disease (CHD) to antiplatelet therapy after discharge and to construct a personalized predictive tool. Methods. In this retrospective cohort study, 289 patients with CHD who were admitted to the Department of Cardiology of The First Affiliated Hospital of the University of Science and Technology of China between June 2021 and September 2021 were enrolled. The clinical data of all patients were retrospectively collected from the hospital information system, and patients were followed up for 1 year after discharge to evaluate their adherence level to antiplatelet therapy, analyze their present situation and influencing factors for post-discharge adherence to antiplatelet therapy, and construct a nomogram model to predict the risk of non-adherence. Results. Based on the adherence level to antiplatelet therapy within 1 year after discharge, the patients were divided into the adherence (nD216) and non-adherence (nD73) groups. Univariate analysis revealed statistically significant differences between the two groups in terms of variable distribution, including age, education level, medical payment method, number of combined risk factors, percutaneous coronary intervention, duration of antiplatelet medication, types of drugs taken at discharge, and CHD type (P <0:05). Furthermore, multivariate logistic regression analysis revealed that, except for the medical payment method, all the seven abovementioned variables were independent risk factors for non-adherence to antiplatelet therapy (P < 0:05). The areas under the receiver operating characteristic curve before and after the internal validation of the predictive tool based on the seven independent risk factors and the nomogram were 0.899 (95% confidence interval [CI]: 0.858-0.941) and 0.89 (95% CI: 0.847-0.933), respectively; this indicates that the tool has good discrimination ability. The calibration curve and Hosmer-Lemeshow goodness of fit test revealed that the tool exhibited good calibration and prediction consistency (2 D5:17, P D0:739). Conclusion. In this retrospective cohort study, we investigated the incidence and influencing factors affecting the non-adherence behavior of patients with CHD after discharge to antiplatelet therapy. For this, we constructed a personalized predictive tool based on seven independent risk factors affecting non-adherence behavior. The predictive tool exhibited good discrimination ability, calibration, and clinical applicability. Overall, our constructed tool is useful for predicting the risk of non- adherence behavior to antiplatelet therapy in discharged patients with CHD and can be used in personalized intervention strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist), or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen and sedimented in multiwell plates, and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, prolonged the lag phase and decreased the maximum rate of plasma clotting and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients. [ABSTRACT FROM AUTHOR]

Antiplatelet drugs such as aspirin and clopidogrel are the cornerstones of the secondary prevention of coronary heart disease ( CHD), which can significantly improve treatment outcomes; however, long-term use increases the risk of bleeding and drug resistance. Recent clinical studies have shown that the combination of Chinese medicinals for promoting blood circulation and removing blood stasis with antiplatelet drugs has further reduced the disability rate and mortality of patients with CHD without increasing the risk of bleeding, but the evidence needs to be further strengthened for clinical application. Therefore, to achieve the secondary prevention of CHD, it is important to expand the clinical and mechanistic studies on the prevention and treatment of CHD with Chinese medicinals for promoting blood circulation and removing blood stasis combined with antiplatelet drugs according to the requirements of evidence-based medicine,objectively evaluating its efficacy and safety advantages, and exploring its biological mechanism. [ABSTRACT FROM AUTHOR]

Purpose Antithrombotic agents have a role in coronavirus disease 2019 (COVID-19) treatment, but the pandemic disrupted medication supply. This study examined changes in the volume of oral and parenteral anticoagulant and antiplatelet medications at US hospitals during the pandemic. Methods IQVIA National Sales Perspective (NSP) data was used to determine the monthly volume of anticoagulants and antiplatelets purchased at US hospitals between January 2018 and February 2021. Mean monthly medication volumes, reported as extended units (EUs), and year-over-year changes in medication volume were determined. A single-group interrupted time series analysis was used to evaluate changes in the rate of growth of monthly medication volumes before (January 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic. Results Overall, there was a 43.4% decline in the total volume of anticoagulants and antiplatelets at US hospitals in March 2020, driven by a decrease in heparin volume. Mean monthly volumes decreased significantly (P < 0.05) for parenteral anticoagulants (–106,691,340 EU [95% CI, –200,033,910 to –13,348,780]), oral anticoagulants (–354,800 EU [95% CI, –612,180 to –97,420]), and parenteral antiplatelets (–391,880 EU [95% CI, –535,420 to –248,330]). During the pandemic, the monthly volume of oral anticoagulants, parenteral anticoagulants, and parenteral antiplatelets grew significantly more than in the prepandemic period. This growth was primarily seen in volumes of apixaban, argatroban, enoxaparin, heparin, eptifibatide, and tirofiban. Apixaban and heparin volumes continued a prepandemic uptrend, while argatroban and eptifibatide volumes reversed trend. Conclusion Rapid changes in anticoagulant and antiplatelet volume at US hospitals during the COVID-19 pandemic highlight the need for institutional protocols to manage fluctuating medication volume demands. [ABSTRACT FROM AUTHOR]

Objective: Antiplatelet medications are increasingly being used for primary and secondary prevention of ischemic attacks owing to the increasing prevalence of ischemic stroke occurrences. Currently, many patients receive antiplatelet therapy (APT) to prevent thromboembolic events. However, long‐term use of APT might also lead to an increased occurrence of intracerebral hemorrhage (ICH) and affect the prognosis of patients with ICH. Furthermore, some research suggest that restarting APT for patients who have previously experienced ICH may result in rebleeding events. The precise relationship between APT and ICH remains unknown. Methods: We searched PubMed for the most recent related literature and summarized the findings from various studies. The search terms included "antiplatelet," "intracerebral hemorrhage," "cerebral microbleeds," "hematoma expansion," "recurrent," and "reinitiate." Clinical studies involving human subjects were ultimately included and interpreted in this review, and animal studies were not discussed. Results: When individuals are administered APT, the risk of thrombotic events should be weighted against the risk of bleeding. In general, for some patients' concomitant with risk factors of thrombotic events, the advantages of antiplatelet medication may outweigh the inherent risk of rebleeding. However, the use of antiplatelet medications for other patients with a higher risk of bleeding should be carefully evaluated and closely monitored. In the future, a quantifiable system for assessing thrombotic risk and bleeding risk will be necessary. After evaluation, the appropriate time to restart APT for ICH patients should be determined to prevent underlying ischemic stroke events. According to the present study results and expert experience, most patients now restart APT at around 1 week following the onset of ICH. Nevertheless, the precise time to restart APT should be chosen on a case‐by‐case basis as per the patient's risk of embolic events and recurrent bleeding. More compelling evidence‐based medicine evidence is needed in the future. Conclusion: This review thoroughly discusses the relationship between APT and the development of ICH, the impact of APT on the course and prognosis of ICH patients, and the factors influencing the decision to restart APT after ICH. However, different studies' conclusions are inconsistent due to the differences in quality control. To support future clinical decisions, more large‐scale randomized controlled trials are required. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Stroke is the property of Chinese Journal of Stroke Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Antiplatelet and anticoagulant therapy are required in the treatment of peripheral arterial disease (PAD) to prevent thrombosis and maintain vascular patency, and the selection of an appropriate antiplatelet and anticoagulant therapy strategy is essential to ensure efficacy and clinical prognosis. This paper summarizes and analyzes the antiplatelet and anticoagulant therapy regimens and clinical research results of PAD at home and abroad. New regimen of antiplatelet drugs combined with anticoagulant drugs in patients with PAD is significantly better than traditional antiplatelet or anticoagulant therapy alone, without increasing the risk of bleeding. The emerging antiplatelet combined with anticoagulant therapy (aspirin + rivaroxaban) is currently the safest and most effective treatment strategy, and patients can benefit the most, marking a new era of PAD treatment mode. [ABSTRACT FROM AUTHOR]

• Significant platelet activation is a hallmark of severe COVID-19. • Platelet activation biomarkers are associated with COVID-19 in-hospital mortality. • After adjustment for confounding factors, only coagulopathy was linked to mortality. • Antiplatelet agents were not a protective factor against COVID-19 mortality. Coronavirus disease 2019 (COVID-19) is associated with an inflammatory cytokine burst and a prothrombotic coagulopathy. Platelets may contribute to microthrombosis, and constitute a therapeutic target in COVID-19 therapy. To assess if platelet activation influences mortality in COVID-19. We explored two cohorts of patients with COVID-19. Cohort A included 208 ambulatory and hospitalized patients with varying clinical severities and non-COVID patients as controls, in whom plasma concentrations of the soluble platelet activation biomarkers CD40 ligand (sCD40L) and P-selectin (sP-sel) were quantified within the first 48 hours following hospitalization. Cohort B was a multicentre cohort of 2878 patients initially admitted to a medical ward. In both cohorts, the primary outcome was in-hospital mortality. In cohort A, median circulating concentrations of sCD40L and sP-sel were only increased in the 89 critical patients compared with non-COVID controls: sP-sel 40,059 (interquartile range 26,876–54,678) pg/mL; sCD40L 1914 (interquartile range 1410–2367) pg/mL (P < 0.001 for both). A strong association existed between sP-sel concentration and in-hospital mortality (Kaplan-Meier log-rank P = 0.004). However, in a Cox model considering biomarkers of immunothrombosis, sP-sel was no longer associated with mortality, in contrast to coagulopathy evaluated with D-dimer concentration (hazard ratio 4.86, 95% confidence interval 1.64–12.50). Moreover, in cohort B, a Cox model adjusted for co-morbidities suggested that prehospitalization antiplatelet agents had no significant impact on in-hospital mortality (hazard ratio 1.05, 95% CI 0.80–1.37; P = 0.73). Although we observed an association between excessive biomarkers of platelet activation and in-hospital mortality, our findings rather suggest that coagulopathy is more central in driving disease progression, which may explain why prehospitalization antiplatelet drugs were not a protective factor against mortality in our multicentre cohort. [ABSTRACT FROM AUTHOR]

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Low‐dose aspirin has been hypothesized to prevent cancer risk by inhibiting platelet aggregation. However, the anti‐cancer effect of low‐dose aspirin has recently been questioned and its effect on breast cancer development remains unclear. The impact of other antiplatelet drugs on breast cancer risk has rarely been evaluated. Thus, this study aimed to investigate the associations between breast cancer risk and antiplatelet drug use in a nationwide nested case‐control study. From the Danish healthcare registries, we identified as cases all women with invasive breast cancer diagnosis between 2001 and 2018 (n = 68 852). The date of diagnosis corresponded to the index date. We matched cases to 10 population controls on age and calendar time, using risk set sampling. Controls were assigned the same index date as their matched case. We used the prescription registry to identify exposure to low‐dose aspirin, clopidogrel and dipyridamole. We defined ever use of antiplatelet drugs as at least two prescriptions filled up to 1 year before the index date. We applied conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for breast cancer associated with the use of antiplatelet drugs, overall, by breast cancer subtype and by cumulative dose. Twelve percent of women had ever been exposed to low‐dose aspirin, 2% to clopidogrel and 2% to dipyridamole. In multivariable models, breast cancer risk was not associated with ever use of low‐dose aspirin (OR = 1.00 [0.97‐1.03]), clopidogrel (OR = 0.93 [0.87‐1.00]), and dipyridamole (OR = 1.02 [0.94‐1.10]), compared with never use, and there was no evidence of a dose‐response relation. However, we found an inverse association between dipyridamole use and breast cancer risk among women aged <55 years old, with suggestion of a dose‐response relationship (OR per 1000 Defined Daily Doses = 0.72 [0.54‐0.95]). Associations did not differ by breast cancer histological type, estrogen receptor status or clinical stage at diagnosis. Overall, the findings from this study do not support the use of antiplatelet drugs for breast cancer prevention. [ABSTRACT FROM AUTHOR]

BackgroundAspirin use in COPD has been associated with reduced all-cause mortality in meta-regression analysis with few equivocal studies. However, the effect of aspirin on COPD morbidity is unknown.MethodsSelf-reported daily aspirin use was obtained at baseline from SPIROMICS participants with COPD (FEV1/FVC < 70%). Acute exacerbations of COPD (AECOPD) were prospectively ascertained through quarterly structured telephone questionnaires up to 3 years and categorized as moderate (symptoms treated with antibiotics or oral corticosteroids) or severe (requiring ED visit or hospitalization). Aspirin users were matched one-to-one with nonusers, based on propensity score. The association of aspirin use with total, moderate, and severe AECOPD was investigated using zero-inflated negative binomial models. Linear or logistic regression was used to investigate the association with baseline respiratory symptoms, quality of life, and exercise tolerance.ResultsAmong 1,698 participants, 45% reported daily aspirin use at baseline. Propensity score matching resulted in 503 participant pairs. Aspirin users had a lower incidence rate of total AECOPD (adjusted incidence rate ratio [IRR], 0.78; 95% CI, 0.65-0.94), with similar effect for moderate but not severe AECOPD (IRR, 0.86; 95% CI, 0.63-1.18). Aspirin use was associated with lower total St. George's Respiratory Questionnaire score (β, -2.2; 95% CI, -4.1 to -0.4), reduced odds of moderate-severe dyspnea (modified Medical Research Council questionnaire score ≥ 2; adjusted odds ratio, 0.69; 95% CI, 0.51-0.93), and COPD Assessment Test score (β, -1.1; 95% CI, -1.9 to -0.2) but not 6-min walk distance (β, 0.7 m; 95% CI, -14.3 to 15.6).ConclusionsDaily aspirin use is associated with reduced rate of COPD exacerbations, less dyspnea, and better quality of life. Randomized clinical trials of aspirin use in COPD are warranted to account for unmeasured and residual confounding.Trial registryClinicalTrials.gov; No.: NCT01969344; URL: www.clinicaltrials.gov.

Objective: Patients using anticoagulant and/or antiplatelet (AC/AP) medications are at an increased risk of intracranial hemorrhage (ICH) subsequent to head trauma and current guidelines recommend a head computed tomography (CT) scan for these patients. There is a lack of consensus about management recommendations for mild head trauma patients on AC/AP treatment who had an initially normal head CT. The aim of this study was to determine the rate of delayed ICH after a 24-hour observation in patients with mild head trauma using AC/AP who had an initially normal head CT. Method: Patients aged 18 and older, using AC/AP drugs with mild head trauma were included prospectively. Patients underwent head CT for suspected bleeding. A repeat CT scan was performed after a 24-hours observation period for the patients who had an initially normal head CT for detecting delayed intracranial hemorrhage. Results: A total of 101 patients were included and, 57.4% (n=58) of the patients were female. Delayed ICH was detected in 2.9% (n=3) of the patients after a 24-hour observation. None of the patients with delayed ICH needed surgical treatment or further intervention. Delayed ICH was found in patients who used acetylsalicylic acid (n=1), dabigatran (n=1), and apixaban (n=1). Conclusion: In patients with mild head trauma using AC/AP, delayed intracranial hemorrhage is rare and may be clinically insignificant. A repeat CT scanning after 24-hour observation may not be necessary for patients with mild head trauma using AC/AP therapy who had initially normal head CT. [ABSTRACT FROM AUTHOR]

Metal complexes displaying antiplatelet properties is a promising research area. In our methodology, Platelet-Activating Factor (PAF), the most potent lipid pro-inflammatory mediator, serves as a biological probe. The antiplatelet activity is exerted by the inhibition of the PAF-induced aggregation in washed rabbit platelets (WRPs) and in rabbit plasma rich in platelets (rPRPs). Herein, the synthesis and biological investigation of a series of organometallic tin(II) and tin(IV) complexes, featuring the oxygen tripodal Kläui ligands [(η5-C5R5)Co{P(OEt)2O}3]−, {R = H, (LOEt−); Me (L*OEt−)}, are reported. Reaction of NaLOEt (1a) and NaL*OEt (1b) with SnCl2, yielded the rare four-coordinate LOEtSnCl (2a) and L*OEtSnCl (2b) complexes. Accordingly, LOEtSnPh3 (3a) and L*OEtSnPh3 (3b) were prepared, starting from Ph3SnCl. Characterization includes spectroscopy and X-ray diffraction studies for 2a, 2b and 3b. The antiplatelet activity of the lead complexes 2b and 3a (IC50 = 0.5 μΜ) is superior compared to that of 1a and 1b, while both complexes display a pronounced inhibitory activity against thrombin (IC50 = 1.8 μM and 0.6 μM). The in vitro cytotoxic activities of 3a and 2b on human Jurkat T lymphoblastic tumor cell line is higher than that of cisplatin. [ABSTRACT FROM AUTHOR]

Background: We evaluated a strategy to shorten the time from admission to surgery in patients with proximal femur fractures on chronic antiplatelet therapy. We reported a 12-month follow-up on complications and quality of life (QoL). Methods: Multicentre, open-label, randomized, parallel clinical trial. Patients were randomized to either early platelet function-guided surgery (experimental group) or delayed surgery (control group). Medical and surgical complications and QoL (EQ-5D-5L questionnaire) were assessed during the hospital stay, and after hospital discharge at 30 days, and 6 and 12 months. Results: From 156 randomized patients, 143 patients underwent surgery. The mean age was 85.5 (7.8) years and 68.0% were female. After hospital discharge, 5.7% of patients had surgical wound complications and 55.9% had medical complications, with 42.7% having serious adverse events. QoL improved significantly after surgery, with the best scores at the six-month follow-up. The overall mortality was 32.2%. There were no differences between early and delayed surgery groups in any assessed outcomes. Conclusion: It seems safe to reduce the time of surgery under neuraxial anaesthesia in patients with hip fractures on chronic antiplatelet therapy by platelet function testing. QoL in particular improves in the first six months after surgery. [ABSTRACT FROM AUTHOR]

Advances in the treatment of hemophilia have increased the life expectancy of this population and we are currently facing diseases associated with aging, including cardiovascular ones. Coronary atherosclerosis, with acute myocardial infarction as the most severe form of manifestation, has been recognized as part of the comorbidities of hemophiliacs. However, little is known about peripheral artery disease. Available data show that hemophiliacs have cardiovascular risk factors and atherosclerosis similar to the general population. Impaired thrombus formation and phenotype of atheroma plaque rather than the burden of atherosclerosis explains their lower cardiovascular mortality. Since the effect of traditional cardiovascular risk factors overpowers that of decreased coagulability and promotes the onset and progression of atherosclerotic lesions, screening for traditional cardiovascular risk factors and peripheral artery disease should be integrated into standard hemophilia care. There is evidence that invasive treatments and long-term antithrombotic therapy are generally safe, provided that coagulation factor levels are taken into account and replacement therapy is given when necessary.

Coronavirus disease 2019 (COVID-19) is a pandemic syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection induces a process of inflammation and thrombosis supported by an altered platelet activation state. This platelet activation is peculiar being characterized by the formation of platelet-leukocytes rather than platelet–platelet aggregates and by an increased procoagulant potential supported by elevated levels of TF positive platelets and microvesicles. Therapeutic strategies targeting, beyond systemic inflammation (i.e. with tocilizumab, an anti interleukin-6 receptor), this state of platelet activation might therefore be beneficial. Among the antithrombotic drugs proposed as candidates to treat patients with SARS-CoV-2 infection, antiplatelet drugs, such as aspirin are showing promising results.

BackgroundWith the aging of the population, the characterization of frailty and comorbidity burden is increasingly taking on particular importance. The aims of the present study are to analyze such conditions in a population affected by Atrial Fibrillation (AF), matching it with a population without AF, and to recognize potential independent factors associated with such common cardiovascular disease.MethodsThis study included subjects consecutively evaluated over 5 years at the Geriatric Outpatient Service, University Hospital of Monserrato, Cagliari, Italy. A sum of 1981 subjects met the inclusion criteria. The AF-group was made up of 330 people, and another 330 people were randomly selected to made up the non-AF-group. The sample was subjected to Comprehensive Geriatric Assessment (CGA).ResultsIn our sample, severe comorbidity burden (p = 0.01) and frailty status (p = 0.04) were significantly more common in patients with AF than without AF, independently on gender and age. Furthermore, the 5-years follow-up demonstrated that survival probability was significantly higher in AF-group (p = 0.03). The multivariate analysis (AUC: 0.808) showed that the presence of AF was independently positively associated with a history of coronary heart disease (OR: 2.12) and cerebrovascular disease (OR: 1.64), with the assumption of Beta Blockers (OR: 3.39), and with the number of drugs taken (OR: 1.12), and negatively associated with the assumption of antiplatelets (OR: 0.09).ConclusionsElderly people with AF are frailer, have more severe comorbidities, and take more drugs, in particular beta blockers, than people without AF, who conversely have a higher survival probability. Furthermore, it is necessary to pay attention to antiplatelets, especially in AF-group, in order to avoid dangerous under- or over-prescriptions.