The aim of this investigation was to characterize the hemostatic status of heart failure patients with implanted left ventricular assist devices (LVADs) to propose a mechanism associated with bleeding. Patients (n = 300) from 23 US hospitals were enrolled in the PREVENtion of HeartMate II Pump Thrombosis through Clinical Management (PREVENT) study. A biobank was established with serum and plasma samples prospectively collected from a cohort of 175 patients preimplant baseline (BL) and 3 months (3M) postimplant. Outcomes were collected for 6 months. Thrombin (prothrombin fragment 1.2 [F1.2], functional thrombin generation [TG]) and fibrinolytic activity (D-dimer, plasminogen activator inhibitor-1 [PAI-1]), but not contact activation (complement C5a), were elevated in heart failure patients at BL. F1.2, TG, and PAI-1 levels decreased 3M after LVAD implantation (p < 0.01) but did not revert to normal in all patients; conversely, D-dimer increased BL to 3M (p < 0.01). Compared with patients without events, thrombin activity (F1.2) was increased in patients with late bleeding (3-4 months postimplant) (p = 0.06) and in those with late gastrointestinal (GI) bleeding (p = 0.01). Patients with 3M F1.2 levels above the cohort mean had a higher incidence of bleeding (p < 0.001) and GI bleeding (p < 0.001) compared with those with below mean F1.2. Patients experiencing multiple bleeding events were more likely to have 3M F1.2 greater than the cohort mean. Despite anticoagulation with aspirin and warfarin, LVAD implanted patients exhibit hemostatic activation. Excess thrombin formation, particularly shown by increased F1.2, was demonstrated in association with bleeding in LVAD implanted patients.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a late systemic inflammatory response to a recent mild or asymptomatic coronavirus disease of 2019 infection. The pathophysiology is incompletely understood but it often features significant coagulopathy along with cardiac and endothelial dysfunction. Endothelial inflammation has been primarily described in acute coronavirus disease of 2019 infection, with less characterization in MIS-C. Here we describe novel findings of nearly universal severe and prolonged factor VIII (FVIII) and von Willebrand factor antigen elevations in an institutional cohort of patients with MIS-C ages younger than or 21 years old (N=31). All patients had elevated acute phase reactants and D-dimer at presentation and met published criteria for MIS-C. FVIII was high at presentation in 97% of patients but continued to rise during the ensuing weeks of treatment to a mean 429%, peaking on median day 17 of illness as an outpatient. FVIII levels were >600% in multiple patients. von Willebrand factor antigen was measured less frequently but showed similar trends. These escalations occurred amidst resolving cardiac dysfunction and acute phase reactant normalization and despite patients receiving multimodal anti-inflammatory treatments and aspirin and enoxaparin thromboprophylaxis. No thrombotic events occurred. Endothelial dysfunction represented by very elevated FVIII levels may persist longer than other acute phase reactants may reflect.

Atrial fibrillation is a common supraventricular tachyarrhythmia with uncoordinated atrial activation and ineffective atrial contraction. This leads to an increased risk of atrial thrombi, most commonly in the left atrial appendage, and increased risks of embolic strokes and/or peripheral thromboembolism. It is associated with significant morbidity and mortality. To meet the concerns of thrombi and stroke, anticoagulation has been the mainstay for prevention and treatment thereof. Historically, anticoagulation involved the use of aspirin or vitamin K antagonists, mainly warfarin. Since early 2010s, direct oral anticoagulants (DOACs) including dabigatran, rivaroxaban, apixaban, and edoxaban have been introduced and approved for anticoagulation of atrial fibrillation. DOACs demonstrated a dramatic reduction in the rate of intracranial hemorrhage as compared to warfarin, and offer the advantages of absolution of monitoring therefore avoid the risk of hemorrhages in the context of narrow therapeutic window and under-treatment characteristic of warfarin, particularly in high-risk patients. One major concern and disadvantage for DOACs was lack of reversal agents, which have largely been ameliorated by the approval of Idarucizumab for dabigatran and Andexanet alfa for both apixaban and rivaroxaban, with Ciraparantag as a universal reversal agent for all DOACs undergoing Fast-Track Review from FDA. In this article, we will be providing a broad review of anticoagulation for atrial fibrillation with a focus on risk stratification schemes and anticoagulation agents (warfarin, aspirin, DOACs) including special clinical considerations.

Venous thromboembolism (VTE) is a major issue in trauma patients. Without prophylaxis, the rate of deep venous thrombosis approaches 60%, and even with chemoprophylaxis may be nearly 30%. Advances in VTE reduction are imperative to reduce the burden of this issue in the trauma population. Novel approaches in VTE prevention may include new medications, dosing regimens, and extending prophylaxis to the post-discharge phase of care. Standard dosing regimens of low molecular weight heparin (LMWH) are insufficient in trauma, shifting our focus towards alternative dosing strategies to improve prophylaxis. Mixed data suggest that anti-Xa guided dosage, weight-based dosing, and thromboelastography are among these potential strategies. The concern for VTE in trauma does not end upon discharge, however. The risk for venous thromboembolism in this population extends well beyond hospitalization. Variable extended thromboprophylaxis regimens utilizing aspirin, LMWH, and direct oral anticoagulants have been suggested to mitigate this prolonged VTE risk, but the ideal approach for outpatient VTE prevention is still unclear. As part of The 2022 Consensus Conference to Implement Optimal Venous Thromboembolism Prophylaxis in Trauma, a multidisciplinary array of participants, including physicians from multiple specialties, pharmacists, nurses, advanced practice providers, and patients met to attack these issues. This paper aims to review the current literature on novel approaches for optimizing VTE prevention in injured patients and identify research gaps which should be investigated to improve VTE rates in trauma.

Single antiplatelet therapy represents the cornerstone of thrombosis prevention in atherosclerotic cardiovascular disease. Dual antiplatelet therapy (DAPT), consisting of aspirin plus a P2Y12 inhibitor, is the standard of care for patients with acute coronary syndrome or undergoing both coronary and peripheral percutaneous interventions. Recent data suggest the efficacy of DAPT also after minor stroke. In this setting, a large body of evidence has documented that genetic and acquired patients' characteristics may affect the magnitude of platelet inhibition induced by antiplatelet agents. The implementation of tools allowing the identification and prediction of platelet inhibition has recently been shown to improve outcomes, leading to an optimal balance between antithrombotic efficacy and bleeding risk. We are therefore clearly moving towards tailored antiplatelet therapy. The aim of this paper is to summarize the available evidence on the evaluation of platelet inhibition in patients with coronary, peripheral, or cerebrovascular atherosclerosis. We will here focus on antiplatelet therapy based on both aspirin and P2Y12 inhibitors. In addition, we provide practical insights into the clinical settings in which it appears reasonable to implement antiplatelet therapy monitoring.

The antiplatelet drug prasugrel inhibits platelet aggregation early after oral administration. This study examined whether prasugrel is effective in inhibiting infarct size and can reduce the incidence of major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). This study was a single-center, prospective, randomized pilot study. Among 80 ACS patients treated at our institution between August 2014 and September 2015, 76 ACS patients who underwent stenting and achieved thrombolysis in myocardial infarction flow grade 3 were assigned to receive aspirin plus prasugrel (prasugrel group; n = 37) or aspirin plus clopidogrel (clopidogrel group; n = 39). The primary endpoint was survival free of MACE. The secondary endpoint was the evaluation of infarct size defined as the area under the curve (AUC) of troponin I, calculated using the linear trapezoidal method. During follow-up (mean, 1262.4 ± 599.6 days), 14 patients showed MACE. No significant differences in CYP2C19 genotype were seen between groups. AUC of troponin I up to 72 hours after intervention tended to be smaller in the prasugrel group (1,927.1 ± 2,189.3 ng/mL) than in the clopidogrel group (3,186.0 ± 3,760.1 ng/mL, p = 0.08). Cumulative incidence of MACE was significantly higher in the clopidogrel group (log-rank test; p = 0.02). Compared with clopidogrel, prasugrel was associated with reduced infarct size and lower frequency of long-term outcomes among ACS patients undergoing stenting.

Bone fractures are a global public health concern, yet no thorough investigation of low-dose aspirin usage to prevent fractures in the elderly has been conducted. Many interventional human and animal studies have tried to detect the correct role of low-dose aspirin on fractures in elderly persons. The literature doesn't consist of a retrospective observational study that includes a large number of older individuals and evaluates the accurate effect of aspirin on the fractures post falling from low heights. This cross-sectional includes 7132 elderly persons and aimed to detect if there was a link between taking low-dose aspirin to prevent fractures in the elderly. Data was extracted from the National Health and Nutrition Examination Survey (NHANES) database for 2017-2020 and 2013-2014. Demographic and examination data were collected during in-home interviews and study visits to a mobile examination center. Standardized questionnaires were used to collect information such as age, gender, race, educational level, and family income-to-poverty ratio. Body mass index (BMI), weight, standing height, upper leg length, upper arm length, arm circumference, and wrist circumference were all measured during the examination. The study examined 8127 patients, with 7132 elderly patients suitable for data analysis. The odds ratio of fractures due to a fall from standing height or less was 0.963 (95 percent confidence interval 0.08-1.149) in low-dose aspirin users, while having parents with osteoporosis had a related risk of 1.23. (95 percent confidence interval 0.81-1.8). The total number of fractures was 1295; with hip fractures constituting up to 13.82%, wrist fractures of 66.56%, and spine fractures of 19.61%. There was no significant difference in femur and spine bone mineral density (BMD) in the two groups (use low dose aspirin and don't use). Females had a 5.6 times greater fracture risk related to a fall from standing height or less (1 time or more) than males (P-value < 0.001). Furthermore, taking aspirin had no effect on the occurrence of fractures from standing height or less in older people (P-value = 0.468). In addition, the logistic regression after performing the propensity matching score confirmed that there was no impact of taking aspirin on the occurrence of fractures (P-value > 0.05). This cross-sectional study reveals that taking low-dose aspirin to prevent fractures in the elderly is statistically insignificant. However, fractures are more common in older persons, especially in older women; thus, more widespread injury prevention initiatives and access to osteoporosis prevention and diagnosis for older people should improve to minimize the overall burden.

Objectives. To assess whether the use of cardioprotective therapies for type 2 diabetes varies by gender and whether the risk of cardiovascular events is higher in women versus men in the REWIND trial, including an international type 2 diabetes patient population with a wide range of baseline risk. Design. Gender differences in baseline characteristics, cardioprotective therapy, and the achieved clinical targets at baseline and two years were analyzed. Hazards for cardiovascular outcomes (fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, cardiovascular death, all-cause mortality, and heart failure hospitalization), in women versus men were analyzed using two Cox proportional hazard models, adjusted for randomized treatment and key baseline characteristics respectively. Time-to-event analyses were performed in subgroups with or without history of cardiovascular disease using Cox proportional hazards models that included gender, subgroup, randomized treatment, and gender-by-subgroup interactions. Results. Of 9901 participants, 46.3% were women. Significantly fewer women than men had a cardiovascular disease history. Although most women met treatment targets for blood pressure (96.7%) and lipids (72.8%), fewer women than men met the target for cardioprotective therapies at baseline and after two years, particularly those with prior cardiovascular disease, who used less renin-angiotensin-aldosterone system inhibitors, statins, and aspirin than men. Despite these differences, women had lower hazards than men for all outcomes except stroke. No significant gender and cardiovascular disease history interactions were identified for cardiovascular outcomes. Conclusions. In REWIND, most women met clinically relevant treatment targets, but in lower proportions than men. Women had a lower risk for all cardiovascular outcomes except stroke. Clinical trials.gov registration number: NCT01394952.

Purpose: A hemocompatible substrate can offer a wonderful facility for nitric oxide (NO) production by vascular endothelial cells in reaction to the inflammation following injuries. NO inhibits platelet aggregation this is especially critical in small-diameter vessels. Methods: The substrate films were made of polyurethane (PU) in a casting process and after plasma treatments, their surface was chemically decorated with polyethylene glycol (PEG) 2000, gelatin, gelatin-aspirin, gelatin-heparin and gelatin-aspirin-heparin. The concentrations of these ingredients were optimized in order to achieve the biocompatible values and the resulting modifications were characterized by water contact angle and Fourier transform infra-red (FTIR) assays. The values of NO production and platelet adhesion were then examined. Results: The water contact angle of the modified surface was reduced to 26±4∘ and the newly developed hydrophilic chemical groups were confirmed by FTIR. The respective concentrations of 0.05 mg/ml and 100 mg/mL were found to be the IC50 values for aspirin and heparin. However, after the surface modification with aspirin, the bioactivity of the substrate increased in compared to the other experimental groups. In addition, there was a synergistic effect between these reagents for NO synthesis. While, heparin inhibited platelet adhesion more than aspirin. Conclusion: Because of the highly hydrophilic nature of heparin, this reagent was hydrolyzed faster than aspirin and therefore its influence on platelet aggregation and cell growth was greater. Taken together, the results give the biocompatible concentrations of both biomolecules that are required for endothelial cell proliferation, NO synthesis and platelet adhesion.

Bilateral adrenal hemorrhage is a rare cause of adrenal insufficiency which has been rarely associated with myeloproliferative neoplasms. Here, we report two cases of bilateral adrenal hemorrhage revealed by abdominal pain, malaise, and fatigue in two octogenarian males previously diagnosed with JAK2 V617F-positive essential thrombocythemia. Both patients were on long-term direct oral anticoagulant treatment for atrial fibrillation. Evolution was favorable under steroid replacement therapy, associated with cytoreduction, aspirin, and switch of direct oral anticoagulants for vitamin K antagonists.

Background: Aspirin exacerbated respiratory disease (AERD) is an inflammatory condition that consists of eosinophilic asthma, chronic rhinosinusitis with nasal polyps, and respiratory reactions to cyclooxygenase-1 inhibitors. Aspirin therapy after aspirin desensitization (ATAD) is the most extensively studied treatment paradigm for AERD. Objective: The objective was to identify which time point of ATAD was most predictive of long-term outcomes as measured by the 22-item Sino-Nasal Outcome Test (SNOT-22). Methods: A retrospective chart review was conducted of patients at a single institution who underwent endoscopic sinus surgery, followed by ATAD, and had remained on ATAD for 2 consecutive years. SNOT-22 scores were recorded at predesensitization as well as at the 3-, 6-, 12-, and 24-month postdesensitization time points. The patients were separated into two cohorts at each of the data collection time points based on whether their SNOT-22 scores were < 20 (responders) or ≥ 20 (nonresponders). Responder status was compared between each time point and at 24-month postdesensitization. The odds ratios (OR) were then calculated between the two groups at each of the following time points: postsurgery/predesensitization, and 3-, 6-, and 12-month postdesensitization. Results: There were 70 patients who met the inclusion criteria of having 24-month postdesensitization SNOT-22 scores available. Responder status at 6 months after surgery had the most predictive OR 16.5 (95% confidence interval, 3.71-73.44) for long-term outcomes at 24 months. Conclusion: The SNOT-22 scores after 6 months of ATAD showed the greatest predictive value for long-term quality-of-life outcomes and, therefore, poor 6-month SNOT-22 scores could serve as a basis for consideration of alternative therapies.

Drug repurposing is a strategy used to develop new treatments based on approved or investigational drugs outside the scope of their original clinical indication. Since this approach benefits from the original toxicity data of the repurposed drugs, the drug-repurposing strategy is time-saving, and inexpensive. It has a higher success rate compared to traditional drug discovery. Several repurposing candidates have been identified in silico screening and in vitro methodologies. One of the best examples is non-steroidal anti-inflammatory drugs [NSAIDs]. Tumor-promoting inflammation is one of the hallmarks of cancer, revealing a connection between inflammatory processes and tumor progression and development. This explains why using NSAIDs in the context of neoplasia has become a topic of interest. Indeed, identifying NSAIDs with antitumor activity has become a promising strategy for finding novel cancer treatment opportunities. Indeed, several commercial anti-inflammatory drugs, including aspirin, ibuprofen, diclofenac, celecoxib, tepoxalin and cyclovalone, naproxen, and indomethacin have presented antitumor activity, and some of them are already in clinical trials for cancer treatment. However, the benefits and complications of using NSAIDs for cancer treatment must be carefully evaluated, particularly for cancer patients with no further therapeutic options available. This review article provides insight into the drug repurposing strategy and describes some of the well-known NSAIDs that have been investigated as repurposed drugs with potential anticancer activity.