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OBJECTIVES Chest wall blocks are an effective strategy for postoperative pain control in minimally invasive cardiac surgery, but, in the absence of clinical trials evaluating their safety in the presence of anticoagulant and antiplatelet drugs, it still is recommended to follow the same guidelines developed for the neuraxial procedures and for peripheral blocks. DESIGN Retrospective observational study. SETTING AOU Citta della Salute e della Scienza di Torino, University of Turin, Italy. PARTICIPANTS Between March 28, 2019 and October 19, 2020, 70 patients who underwent mitral valve surgery via right minithoracotomy were enrolled: 35 treated with continuous erector spinae plane block (ESPB) and 35 with continuous serratus anterior plane block (SAPB). INTERVENTIONS The primary objective was the evaluation of the number of blocks performed or catheters removed while coagulation was abnormal or antithrombotic and anticoagulant therapies were in progress. MEASUREMENTS AND MAIN RESULTS Eleven patients (15.7%) received fascial plane block with international normalized ratio (INR) > 1.40, four patients (5.71%) with a platelet count 1.40, in five patients (7.1%) with a platelet count

Patients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying of cardiovascular disease. Paradoxically, these patients also have a higher risk of hemorrhages, greatly complicating patient therapy. Platelets are central to hemostasis, and altered platelet function resulting in either platelet hyper- or hyporeactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. In this study, we summarize the knowledge on CKD-induced aberrations in hemostasis, with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation, and red blood cell count in CKD may contribute to altered hemostasis in these patients who are high risk. Furthermore, with patients with CKD commonly receiving antiplatelet therapy to prevent secondary atherothrombotic complications, we discuss antiplatelet treatment strategies and their risk versus benefit in terms of thrombosis prevention, bleeding, and clinical outcome depending on CKD stage. This reveals a careful consideration of benefits versus risks of antiplatelet therapy in patients with CKD, balancing thrombotic versus bleeding risk. Nonetheless, despite antiplatelet therapy, patients with CKD remain at high cardiovascular risk. Thus, deep insights into altered platelet activity in CKD and underlying mechanisms are important for the optimization and development of current and novel antiplatelet treatment strategies, specifically tailored to these patients who are high risk. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and antiplatelet therapy in patients with CKD.

Background Concomitant anticoagulant and antiplatelet therapy increases bleeding risk, but most data are derived from patients with atrial fibrillation. Patients with venous thromboembolism (VTE) may differ. Objective To study the management of patients diagnosed with acute VTE while receiving antiplatelet treatment. The primary outcome was the number of patients discharged with concomitant therapy. Secondary outcomes were clinically relevant bleeding, cardiovascular events, recurrent VTE and death during follow-up, according to discharge therapy. Methods We performed a post-hoc analysis of patients included in two prospective registries, sharing the same case report form, from 2007 to 2017. Results Among the 1694 identified patients, 254 (15.0%) were receiving antiplatelet treatment at VTE diagnosis, of whom 61 (24.0%) were discharged with concomitant anticoagulant and antiplatelet therapy. In multivariable analysis, age ≥ 80 years-old and the use of Direct Oral Anticoagulants for VTE therapy were associated with the decision to stop the antiplatelet, while having dual anti-platelet therapy at baseline, a history of coronaropathy or peripheral arterial disease were associated with concomitant anticoagulant and antiplatelet therapy. The decision to stop antiplatelet was associated with a non-significant 46% decrease in the risk of bleeding (OR 0.54 (0.16; 1.78)), and a non-significant 68% increase in the risk of cardiovascular events (OR 1.68 (0.44; 6.46)). Conclusion At acute VTE diagnosis, over 15% of patients were receiving antiplatelet agents, of whom 24% were discharged with concomitant anticoagulant and antiplatelet therapy. This therapeutic decision may be associated with a lower risk of cardiovascular events, but an increased risk of bleeding.

Early recanalization of the infarct-related artery to achieve myocardial reperfusion is the primary therapeutic goal in patients with ST-elevation myocardial infarction (STEMI). To decrease the duration of ischaemia, continuous efforts have been made to improve pre-hospital treatment and to target the early period after symptom onset. In this period the platelet content of the fresh coronary thrombus is maximal and the thrombi are dynamic, and thus more susceptible to powerful antiplatelet agents. There have been substantial advances in antiplatelet therapy in the last three decades with several classes of oral and intravenous antiplatelet agents with different therapeutic targets, pharmacokinetics, and pharmacodynamic properties. New parenteral drugs achieve immediate inhibition of platelet aggregation, and fast and easy methods of administration may create the opportunity to bridge the initial gap in platelet inhibition observed with oral P2Y12 inhibitors. Moreover, potential future management of STEMI could directly involve patients in the process of care with self-administered antiplatelet agents designed to achieve rapid reperfusion. However, the potential anti-ischaemic benefits of potent antiplatelet agents will need to be balanced against their risk of increased bleeding. This study presents a comprehensive and updated review of pre-hospital antiplatelet therapy among STEMI patients undergoing primary percutaneous intervention and explores new therapies under development.

Coronavirus disease 2019 (Covid-19) is associated with a high incidence of venous and arterial thromboembolic events. Currently, there are no clinical or laboratory markers that predict thrombotic risk. Circulating immature platelets are hyper-reactive platelets, which are associated with arterial thrombotic events. The aim of this study was to assess whether the proportion of circulating immature platelets is associated with disease severity in Covid-19 patients. Patients admitted with Covid-19 disease were prospectively assessed. Immature platelet count (IPC) and immature platelet fraction (IPF) were measured at admission and at additional time points during the hospital course using the Sysmex XN-3000 auto-analyzer. A total of 136 consecutive patients with Covid-19 were recruited [mean age 60 ± 19 years, 49% woman, 56 (41%) had mild-moderate disease and 80 (59%) had severe disease at presentation]. The median IPF% was higher in patients with severe compared to mild-moderate disease [5.8 (3.9–8.7) vs. 4.2 (2.73–6.45), respectively, p = 0.01]. The maximal IPC value was also higher in patients with severe disease [15 (10.03–21.56), vs 10.9 (IQR 6.79–15.62), respectively, p = 0.001]. Increased IPC was associated with increased length of hospital stay. Patients with severe Covid-19 have higher levels of IPF than patients with mild-moderate disease. IPF may serve as a prognostic marker for disease severity in Covid-19 patients.

There is limited data about the bleeding complication of antiplatelet therapy after coronary artery bypass graft (CABG) operations focused on diabetic patients. Herein, we aimed to evaluate the effects of aspirin and clopidogrel monotherapies on postoperative bleeding in these patients. A total of 165 diabetic patients who underwent isolated off-pump beating heart coronary artery bypass (OPCAB) operation were evaluated, 84 patients were included in this retrospective study. Patients were divided into groups according to the type of antiplatelet regime. Chest tube drainage amounts and the amount of blood product transfusions were evaluated. Acetylsalicylic acid (ASA) - group included 42 aspirin monotherapy and Clopidogrel - group included 42 clopidogrel monotherapy patients after propensity matching. The mean drainage amount in ASA - group was 670.24 ± 185.46 mL, in Clopidogrel - group was 921.43 ± 167.53 mL (p < 0.001). More packed red blood cell (PRBC) and fresh frozen plasma (FFP) units were needed in the Clopidogrel - group than in the ASA - group (2.05 ± 1.13 vs. 0.83 ± 0.93 units of PRBC, and 1.90 ± 0.58 vs. 1.05 ± 0.58 units of FFP, respectively, p < 0.001). In conclusion, clopidogrel had a stronger effect on bleeding in diabetic patients than aspirin after OPCAB surgery.

Critically ill patients are at high risk of hemostasis disorders, which can be associated with both an increased risk of bleeding and an increased risk of thromboembolic events. In the case of acute vascular events, specific therapy with drug anticoagulation or platelet aggregation inhibition is essential. In patients with pre-existing conditions, the appropriate continuation of anticoagulation during intensive care treatment is important. Furthermore, in everyday clinical practice, prophylaxis of thromboembolism as well as the question of potential therapeutic options in the treatment of sepsis and infection-triggered disorders of blood coagulation are important. Specific questions arise with the use of extracorporeal devices such as renal replacement and circulatory assist systems. A number of new anticoagulation and anti-platelet drugs have become available in recent years. Laboratory monitoring of anticoagulation is central. In this overview, current aspects of these topics are presented.Kritisch kranke Patienten sind in hohem Maße durch Störungen der Hämostase gefährdet, diese können sowohl mit einer verstärkten Blutungsneigung als auch mit einem erhöhten Risiko für thromboembolische Ereignisse einhergehen. Bei akuten vaskulären Ereignissen ist die spezifische Therapie mit medikamentöser Antikoagulation bzw. Plättchenaggregationshemmung essenziell, bei Patienten mit Vorerkrankungen ist die angepasste Fortführung einer vorbestehenden Antikoagulation während intensivmedizinischer Behandlung von Bedeutung, des Weiteren sind sowohl medikamentöse Thromboseprophylaxe als auch die Frage nach potenziell therapeutischen Optionen, wie Antikoagulanzien bei Sepsis und infektionsgetriggerten Störungen der Blutgerinnung, im klinischen Alltag wichtig. Spezifische Fragestellungen ergeben sich bei der Anwendung extrakorporaler Maßnahmen wie Nierenersatzverfahren sowie Kreislaufunterstützungs- und Ersatzverfahren. In den letzten Jahren sind eine Reihe neuer Präparate zur Antikoagulation und Plättchenhemmung verfügbar geworden. Die Therapiekontrolle über labordiagnostische Verfahren stellt einen zentralen Punkt dar. In dieser Übersichtsarbeit werden aktuelle Aspekte zu diesen Themen praxisnah aufgeführt.

Purpose Treatment schedules for antithrombotic therapy are complex, and there is a risk of inappropriate prescribing or continuation of antithrombotic therapy beyond the intended period of time. The primary aim of this study was to determine the frequency of unintentional guideline deviations in hospitalized patients. Secondary aims were to determine whether the frequency of unintentional guideline deviations decreased after intervention by a pharmacist, to determine the acceptance rate of the interventions and to determine the type of interventions. Methods We performed a non-controlled prospective intervention study in three teaching hospitals in the Netherlands. We examined whether hospitalized patients who used the combination of an anticoagulant plus at least one other antithrombotic agent had an unintentional guideline deviation. In these cases, the hospital pharmacist contacted the physician to assess whether this deviation was intentional. If the deviation was unintentional, a recommendation was provided how to adjust the antithrombotic regimen according to guideline recommendations. Results Of the 988 included patients, 407 patients had an unintentional guideline deviation (41.2%). After intervention, this was reduced to 22 patients (2.2%) (p Conclusion A significant number of hospitalized patients who used an anticoagulant plus one other antithrombotic agent had an unintentional guideline deviation. Intervention by a pharmacist decreased unintentional guideline deviations.

Background We aimed to analyse initiation of and persistence with P2Y12 inhibitors after first-time myocardial infarction (MI). Methods and results Using Danish nationwide registries, we identified patients ≥30 years with first-time MI during 1 January 2005–30 June 2016 and subsequent prescriptions of P2Y12 inhibitors. Independent factors related to initiation of and persistence with P2Y12 inhibitors were analysed by multivariable logistic regression and a Cox proportional hazards model. Patients were stratified by revascularization strategy: percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or medical therapy alone (MTA). Overall, 79 597 MI patients were included with 39 172 undergoing PCI, 2619 CABG, and 16 640 MTA, showing initiation of P2Y12 inhibitors of 93.4%, 49.0%, and 51.5%, respectively. Congestive heart failure, cerebrovascular disease, cardiac dysrhythmias, renal failure, previous bleeding, and oral anticoagulants were associated with less initiation of P2Y12 inhibitors. Female sex was associated with less initiation of P2Y12 inhibitors following MTA. MTA, coronary angiography, cerebrovascular disease, diabetes with complications, previous bleeding, antidiabetics, and ticagrelor as P2Y12 inhibitor were associated with non-persistence, whereas female sex, advanced age, and concomitant pharmacotherapy with angiotensin-converting enzyme inhibitors, beta-blockers, statins, oral anticoagulants, and aspirin were associated with high persistence. Conclusion Initiation of P2Y12 inhibitors in PCI-treated MI patients was high in contrast to those treated with CABG or MTA and patients with certain comorbidities. Further studies on the benefit–risk ratio of P2Y12 inhibitors in CABG-treated or MTA-treated patients and patients with comorbidities after first-time MI are warranted, as is focus on persistence among patients receiving MTA, patients with comorbidities, and users of ticagrelor.

Introdution COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls. Methods Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID‐19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add‐on therapy on the outcome of the patients hospitalized due to severe COVID‐19. In this cohort study, patients with a confirmed diagnosis of severe COVID‐19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety‐one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in‐hospital mortality (0.746 [0.560–0.994], p = 0.046). Aspirin use in hospitalized patients with COVID‐19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population., Highlights Aspirin administration decrease the rate of mortality in hospitalized patients with severe COVID‐19, independently.Although the crude analysis showed higher mortality rate in patients recieved aspirin, these patients have higher rate of underlying conditions.By performing stepwise COX regression analysis and adjusting the effect of comorbidities, aspirin administration was protective in hospitalized patients with severe COVID‐19.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread and have grave health and socioeconomic consequences worldwide. Researchers have raced to understand the pathophysiological mechanisms underpinning the disease caused by SARS-CoV-2 so that effective therapeutic targets can be discovered. This review summarises the key pharmacotherapies that are being investigated for treatment of COVID-19, including antiviral, immunomodulator and anticoagulation strategies.

Platelet glycoprotein IIb/IIIa inhibitors (GPIs) have been part of the adjuvant treatment of acute coronary syndrome for years. However, real-life data regarding the efficacy and safety of GPIs under the current indications are lacking in the setting of potent platelet inhibition. The objectives were to assess the efficacy and safety of abciximab versus tirofiban in patients with ST-elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and pretreated with ticagrelor, and to identify independent predictor factors of efficacy, bleeding and platelet drop. Three hundred sixty-two patients were divided by GPI administered. Clinical, laboratory, angiographic and outcome characteristics were compared. The primary objective was a composite efficacy endpoint (death from any cause, nonfatal myocardial infarction and nonfatal stroke) at 30 days. The secondary objectives were its individual components, safety (bleeding) and the impact on platelet count during hospital stay. The composite efficacy endpoint was similar in the abciximab and tirofiban groups (6.1% vs 7.3%

A growing number of patients undergoing percutaneous coronary intervention (PCI) with stent implantation also have atrial fibrillation. This poses challenges for their optimal antithrombotic management because patients with atrial fibrillation undergoing PCI require oral anticoagulation for the prevention of cardiac thromboembolism and dual antiplatelet therapy for the prevention of coronary thrombotic complications. The combination of oral anticoagulation and dual antiplatelet therapy substantially increases the risk of bleeding. Over the last decade, a series of North American Consensus Statements on the Management of Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention have been reported. Since the last update in 2018, several pivotal clinical trials in the field have been published. This document provides a focused updated of the 2018 recommendations. The group recommends that in patients with atrial fibrillation undergoing PCI, a non–vitamin K antagonist oral anticoagulant is the oral anticoagulation of choice. Dual antiplatelet therapy with aspirin and a P2Y12inhibitor should be given to all patients during the peri-PCI period (during inpatient stay, until time of discharge, up to 1 week after PCI, at the discretion of the treating physician), after which the default strategy is to stop aspirin and continue treatment with a P2Y12inhibitor, preferably clopidogrel, in combination with a non–vitamin K antagonist oral anticoagulant (ie, double therapy). In patients at increased thrombotic risk who have an acceptable risk of bleeding, it is reasonable to continue aspirin (ie, triple therapy) for up to 1 month. Double therapy should be given for 6 to 12 months with the actual duration depending on the ischemic and bleeding risk profile of the patient, after which patients should discontinue antiplatelet therapy and receive oral anticoagulation alone.

BACKGROUND: Reduced levels of hemoglobin (Hb) represent an established marker of impaired outcomes and increased cardiovascular risk in patients with coronary artery disease, challenging the management of dual antiplatelet therapy (DAPT). However, while anemia has emerged as an independent predictor of suboptimal platelet inhibition in patients receiving clopidogrel, no study has so far evaluated the impact of Hb levels on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were the aim of the present study. METHODS: Patients on DAPT with ASA + Ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by multiple electrode aggregometry. Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome [MI], target vessel revascularization) at longest available follow-up. RESULTS: We included 397 patients that were divided according to tertiles values of Hb (< 12.7, 12-7-14.09, ≥14.1 g/dl). Patients with lower Hb were older and displayed a more severe cardiovascular risk profile. Mean levels of platelet reactivity were enhanced in patients with lower Hb after stimulation with TRAP peptide (TRAP test, p = .03) and ADP (p = .02). Elevated platelet reactivity (HRPR) on Ticagrelor was more frequent among patients with reduced Hb (16.4% vs. 12% vs. 5.4%, p = .005, adjusted OR [95%CI] = 1.71[0.996;3.01], p = .056). At a mean follow-up of 820.9 ± 553.4 days, 21.4% of the patients experienced the primary composite endpoint, with a higher rate of events in patients with lower Hb (27.6% vs. 22.6% vs. 13.5%, p = .006, adjusted HR [95%CI] = 1.51[1.12; 2.03], p = .006), mainly driven by a higher rate of recurrent ACS. After correction for baseline differences lower Hb tertiles but not HRPR emerged as independent predictor of MACE (adjusted HR [95%CI] = 0.98[0.50; 1.92], p = .95). CONCLUSIONS: In the present study, we demonstrated that among patients on DAPT with ASA and ticagrelor after PCI for ACS, lower Hb levels are independently associated with a higher rate of HRPR and an increased rate of major ischemic events, and especially for recurrent ACS, although with no impact on survival. Neutral prognostic effect of HRPR was observed across Hb tertiles.

ObjectiveTo better define the clinical distinctions between the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related paediatric inflammatory multisystem syndrome (PIMS) and Kawasaki disease (KD).MethodsWe compared three groups of patients: group 1, cases from our national historic KD database (KD-HIS), before the SARS-CoV-2 pandemic; group 2, patients with KD admitted to an intensive care unit (KD-ICU) from both our original cohort and the literature, before the SARS-CoV-2 pandemic; and group 3, patients with PIMS from the literature.ResultsKD-HIS included 425 patients [male:female ratio 1.3, mean age 2.8 years (s.d. 2.4)], KD-ICU 176 patients [male:female ratio 1.3, mean age 3.5 years (s.d. 3.1)] and PIMS 404 patients [male:female ratio 1.4, mean age 8.8 years (s.d. 3.7)]. As compared with KD-HIS patients, KD-ICU and PIMS patients had a higher proportion of cardiac failure, digestive and neurological signs. KD-ICU and PIMS patients also had a lower frequency of typical KD-mucocutaneous signs, lower platelet count, higher CRP and lower sodium level. As compared with KD-HIS and KD-ICU patients, PIMS patients were older and more frequently had myocarditis; they also had fewer coronary abnormalities and lower sodium levels. Unresponsiveness to IVIG was more frequent in KD-ICU than KD-HIS and PIMS patients.ConclusionOn clinical grounds, KD-HIS, KD-ICU and PIMS might belong to a common spectrum of non-specific pathogen-triggered hyperinflammatory states. The causes of increasing inflammation severity within the three entities and the different effects on the heart remain to be determined.

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all‐cause mortality or nonfatal Q‐wave myocardial infarction at 2 years. At 2‐year follow‐up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per‐protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75–1.03; P =0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79–1.26; P =0.99). The per‐protocol and intention‐to‐treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.

Objectives This literature review was performed to assess the risk of bleeding in dental implantation procedures in patients taking antiplatelet drugs (APs), oral anticoagulants (OACs) and direct oral anticoagulants (DOACs). Study Design MEDLINE and SCOPUS databases were searched for English language publications through October 2019, using the keywords “dental implants,” “dental implantation,” “anticoagulants,” “platelet aggregation inhibitors,” and “hemorrhage.” Reference lists of relevant articles were also hand searched. Collected data regarding dental implantation procedures, type of medications (APs, OACs and DOAC), and postoperative bleeding episodes were analyzed. Results Nine studies were included in the review. Postoperative bleeding occurred in 10 (2.2%) of 456 of cases involving dental implant placements; in all of those cases, bleeding was controlled with the use of local hemostatic agents. The bleeding incidence in patients on antiplatelet medications was 0.4% (range 1 of 253 to 1 of 261). Among those taking oral anticoagulants, the bleeding incidence was 5.7% (range 6 of 105 to 6 of 113), and among those on direct oral anticoagulants, the bleeding incidence was 3.3% (3 of 90). The numbers of more extensive surgical procedures (i.e., sinus lift and bone augmentation procedures) were small, and additional information regarding the surgery, the specific antithrombotic used, or bleeding was often not provided, so further analysis was not possible. Conclusions Evidence supports continuing OACs, DOACs, or APs during dental implant surgery.

Since the initial description in 2019, the novel coronavirus SARS-Cov-2 infection (COVID-19) pandemic has swept the globe. The most severe form of the disease presents with fever and shortness of breath, which rapidly deteriorates to respiratory failure and acute lung injury (ALI). COVID-19 also presents with a severe coagulopathy with a high rate of venous thromboembiolism. In addition, autopsy studies have revealed co-localized thrombosis and inflammation, which is the signature of thromboinflammation, within the pulmonary capillary vasculature. While the majority of published data is on adult patients, there are parallels to pediatric patients. In our experience as a COVID-19 epicenter, children and young adults do develop both the coagulopathy and the ALI of COVID-19. This review will discuss COVID-19 ALI from a hematological perspective with discussion of the distinct aspects of coagulation that are apparent in COVID-19. Current and potential interventions targeting the multiple thromboinflammatory mechanisms will be discussed.

Background Dual antiplatelet therapy is commonly used for patients with acute coronary syndrome (ACS). This study aimed to evaluate the safety and efficacy of aspirin and prasugrel at standard dosages in Korean patients using clinical outcome data.Methods and Results:For this prospective multicenter phase IV post-marketing surveillance (PMS) study, ACS patients from 29 July 2012 to 28 July 2016 were recruited. Patients received aspirin at a dose of 75-150 mg daily and a standard dose of prasugrel. Bleeding events were recorded and summarized to evaluate safety. Data on adverse events (AEs) and composite events such as cardiovascular (CV) death, myocardial infarction (MI), and stroke were recorded and summarized to assess efficacy. Of the 3,283 patients recruited, data from 3,110 and 3,044 patients were included in the safety and efficacy analyses, respectively (median treatment duration, 172 days). The most frequently reported AE was ecchymosis (2.8%). The number of patients with major bleeding was 29/3,110 (0.93%). The discontinuation rate for any reason was 12.6%. The number of cases that ended in CV death, MI, stroke, stent thrombosis, or unplanned coronary revascularization was 26/3,044 (0.85%). Conclusions The present results are similar to those observed in clinical trials where administration of low-dose aspirin plus prasugrel was associated with a low rate of major bleeding and CV events.

Stagnant blood flow and organizing thrombus are intralesional components of patients with cerebral cavernous malformations (CCM). Stasis and inflammation are mechanisms of growth, lesional instability and acute hemorrhages with or w/o symptoms. We evaluate the association of pre-diagnostic aspirin and/or statin use with acute hemorrhages at diagnosis. Patients with a CCM diagnosis were identified and categorized according to their medications on admission into four groups (no therapy, statin, aspirin, combined). The primary outcome was an acute hemorrhage (with or w/o symptoms) at diagnosis reported in a standardized manner from the T2 weighted magnetic resonance image. A multivariate generalized linear mixed models (GLMM) was utilized to conduct per-lesion analysis. We identified 446 patients with 635 lesions. An acute hemorrhage at diagnosis was observed in 31% of the patients. There were 328 patients without statin or aspirin therapy, 34% of whom presented with acute hemorrhage. Of patients on aspirin therapy at diagnosis, 25% presented with hemorrhage. Of patients on statin therapy, 26% had a hemorrhage at diagnosis. Combined therapy in 44 patients demonstrated a lower proportion of patients with acute hemorrhages (7 patients, 16% incidence). A GLMM showed that patients in the combined therapy group to have significantly lower odds of having an acute hemorrhage at diagnosis compared to the reference group of no therapy (OR 0.24; 95% CI 0.09–0.59; P = 0.002). Patients with a CCM receiving therapy with both aspirin and statins were less likely to present at diagnosis with acute hemorrhage.

Lifelong anticoagulation with warfarin or alternative vitamin K antagonist is the standard anticoagulant treatment for thrombotic antiphospholipid syndrome. Anticoagulant-refractory thrombotic antiphospholipid syndrome can be broadly defined as breakthrough thrombosis while on standard oral anticoagulation treatment and its management is a major challenge given the serious nature of the thrombotic disease observed, which has become refractory to oral anticoagulation. The factors (genetic and cellular) that cause anticoagulant-refractory thrombotic antiphospholipid syndrome are now better understood. However, efforts to use this greater understanding have not yet transformed the capacity to treat it successfully in many patients. In this Viewpoint, we review the factors that are likely to be contributing to the cause of this syndrome and consider how they might be modified or inhibited. We also discuss management, including general strategies to minimise thrombotic risk, intensification of anticoagulation, addition of an antiplatelet agent, adjunctive treatment for thrombosis, immunomodulatory therapy, complement inhibition, vascular options, and future potential therapeutic targets.

Introduction: Approximately 2% of the population are anticoagulated and over 50% of over 65-year-olds are prescribed antiplatelet agents. Several systematic reviews have shown the safety of interrupting anticoagulation and antiplatelets for non-emergency surgery, although such reviews excluded upper limb procedures and represents the rationale for this review. Methods: The literature was systematically searched for studies concerning the outcomes of adult hand or wrist surgery on patients receiving anticoagulation or antiplatelet agents in direct comparison to controls (no anticoagulation or antiplatelet agents, or interruption of either). The primary outcome was reoperation for any complication related to postoperative bleeding, within 30 postoperative days. Results: Nine cohort studies (3628 individuals; 3863 operations) were included. Based on very low-quality evidence, anticoagulation did not affect the risk of reoperation for bleeding (RR 2.4 [95% CI 0.1, 57]; 3 studies, n=443) or bruising (RR 2.5 [95% CI 1.0, 6.3]; n=124; I2=0%). Based on low quality evidence, antiplatelet agents did not affect the risk of reoperation for bleeding (RR 0.8 [95% CI 0.3, 1.8]; 6 studies, n=1885; I2=0%) or bruising (RR 3.2 [95% CI 0.2, 44]; n=571; I2=66%). A sensitivity analysis showed that carpal tunnel decompression on patients receiving anticoagulants or antiplatelets appeared to be safe (RR 0.8 [95% CI 0.3, 1.8]; 6 studies, n=2077; I2=0%). Conclusions: Given the sparsity of events (bleeding and bruising) and low-quality of the literature, no firm conclusions can be drawn. The decision to interrupt antiplatelets or anticoagulants should be made jointly with expert physicians and the patient. Registration: PROSPERO ID CRD42018087755

Objectives To determine the effectiveness of nitric oxide agents in modifying the metabolic factors of pre-eclampsia and its effectiveness in preventing the onset of pre-eclampsia in high-risk pregnancies. Introduction Pre-eclampsia is a major cause of maternal death during the prenatal and neonatal periods. Nitric oxide is a vasodilator and platelet aggregation inhibitor responsible for the vascular adaptation of the placenta. Although various studies have established that nitric oxide is effective in preventing complications from pre-eclampsia, there is limited evidence to show that administering nitric oxide agents to high-risk women before 20 weeks' gestation will prevent the onset of pre-eclampsia. Inclusion criteria This review will consider randomized controlled trials that compare nitric oxide donors and precursors with a placebo or no intervention on pregnant women (18 to 44 years) with ≤ 20-week gestational age that are at high risk of pre-eclampsia. The primary outcome of interest will be the onset of pre-eclampsia. Secondary outcomes include increased systolic and diastolic blood pressure, elevated asymmetric dimethylarginine levels, decreased endothelial nitric oxide synthase activity, reduced maternal placental vasculature, and abnormal Doppler ultrasound waveforms. Methods Data sources will be drawn up from MEDLINE, CINAHL, ProQuest (Health and Medicine), and Web of Science from inception till current date. No language restrictions will be applied in the search strategy. Selected studies will be assessed against the JBI critical appraisal checklist, and the certainty of evidence and strength of recommendations from findings will also be ascertained. Systematic review registration number PROSPERO CRD42018099298.

Background: Patients with established coronary artery disease or peripheral artery disease often have diabetes mellitus. These patients are at high risk of future vascular events. Methods: In a prespecified analysis of the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies), we compared the effects of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg daily) versus placebo plus aspirin in patients with diabetes mellitus versus without diabetes mellitus in preventing major vascular events. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included all-cause mortality and all major vascular events (cardiovascular death, myocardial infarction, stroke, or major adverse limb events, including amputation). The primary safety end point was a modification of the International Society on Thrombosis and Haemostasis criteria for major bleeding. Results: There were 10 341 patients with diabetes mellitus and 17 054 without diabetes mellitus in the overall trial. A consistent and similar relative risk reduction was seen for benefit of rivaroxaban plus aspirin (n=9152) versus placebo plus aspirin (n=9126) in patients both with (n=6922) and without (n=11 356) diabetes mellitus for the primary efficacy end point (hazard ratio, 0.74, P =0.002; and hazard ratio, 0.77, P =0.005, respectively, P interaction =0.77) and all-cause mortality (hazard ratio, 0.81, P =0.05; and hazard ratio, 0.84, P =0.09, respectively; P interaction =0.82). However, although the absolute risk reductions appeared numerically larger in patients with versus without diabetes mellitus, both subgroups derived similar benefit (2.3% versus 1.4% for the primary efficacy end point at 3 years, Gail-Simon qualitative P interaction P interaction =0.02; 2.7% versus 1.7% for major vascular events, P interaction P interaction =0.001). Conclusions: In stable atherosclerosis, the combination of aspirin plus rivaroxaban 2.5 mg twice daily provided a similar relative degree of benefit on coronary, cerebrovascular, and peripheral end points in patients with and without diabetes mellitus. Given their higher baseline risk, the absolute benefits appeared larger in those with diabetes mellitus, including a 3-fold greater reduction in all-cause mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01776424.

Supplemental Digital Content is available in the text., Background: Patients with established coronary artery disease or peripheral artery disease often have diabetes mellitus. These patients are at high risk of future vascular events. Methods: In a prespecified analysis of the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies), we compared the effects of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg daily) versus placebo plus aspirin in patients with diabetes mellitus versus without diabetes mellitus in preventing major vascular events. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included all-cause mortality and all major vascular events (cardiovascular death, myocardial infarction, stroke, or major adverse limb events, including amputation). The primary safety end point was a modification of the International Society on Thrombosis and Haemostasis criteria for major bleeding. Results: There were 10 341 patients with diabetes mellitus and 17 054 without diabetes mellitus in the overall trial. A consistent and similar relative risk reduction was seen for benefit of rivaroxaban plus aspirin (n=9152) versus placebo plus aspirin (n=9126) in patients both with (n=6922) and without (n=11 356) diabetes mellitus for the primary efficacy end point (hazard ratio, 0.74, P=0.002; and hazard ratio, 0.77, P=0.005, respectively, Pinteraction=0.77) and all-cause mortality (hazard ratio, 0.81, P=0.05; and hazard ratio, 0.84, P=0.09, respectively; Pinteraction=0.82). However, although the absolute risk reductions appeared numerically larger in patients with versus without diabetes mellitus, both subgroups derived similar benefit (2.3% versus 1.4% for the primary efficacy end point at 3 years, Gail-Simon qualitative Pinteraction

Purpose We evaluated efficacy and safety profile of patients with anticoagulation therapy (AT) undergoing holmium laser enucleation of the prostate (HoLEP). Methods Within our prospective institutional database (11/2017 to 11/2019), we analyzed functional outcomes and 30-day complication rates of HoLEP patients according to Clavien–Dindo classification (CLD), stratified according to specific AT vs. no AT. Further analyses consisted of uni- and multivariate logistic regression models (LRM) predicting complications. Results Of 268 patients undergoing HoLEP, 104 (38.8%) received AT: 25.7% were treated with platelet aggregation inhibitors (PAI), 8.2% with new oral anticoagulants (NOAC) and 4.9% with AT-combinations or coumarins bridged with low molecular weight heparins (LMWH/combination). Patients receiving AT were significantly more comorbid (p p p = 0.04), age (OR 1.04, p = 0.02) and bioptical or incidental prostate cancer (OR 2.5, p = 0.01) represented independent risk factors. Conclusion Despite higher overall complication rates in AT patients, major complications were not more frequent in AT patients. HoLEP is safe and effective in anticoagulated patients.

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has forced a redesign of healthcare services. Resource reallocation will have consequences on the routine management of chronic diseases, including cardiovascular disease (CVD). We consider how to mitigate potential adverse effects. RECENT FINDINGS: Combination therapy is well established in hypertension. Many guidelines recommend dual antihypertensive therapy as the initial treatment step as this results in faster blood pressure control, albeit with limited evidence of improved outcomes. Control of CVD risk factors through multiclass combination therapy (the polypill) was proposed many years ago. This approach has not been adopted by Western healthcare systems despite improving surrogate outcomes. Recently, the PolyIran trials have demonstrated improved CVD outcomes without increased adverse events, in both primary and secondary prevention. SUMMARY: The COVID-19 pandemic allows models of chronic healthcare to be rethought. Current practices are resource-intensive and there is a need to simplify titration and monitoring protocols in CVD. Moving toward the use of polypill combinations allied with telehealth consultations may be one solution.

Drug resistance in Clostridioides difficile becomes a public health concern worldwide, especially as the hypervirulent strains show decreased susceptibility to the first-line antibiotics for C. difficile treatment. Therefore, the simultaneous discovery and development of new compounds to fight this pathogen are urgently needed. In order to determinate new drugs active against C. difficile, we identified ticagrelor, utilized for the prevention of thrombotic events, as exhibiting potent growth-inhibitory activity against C. difficile. Whole-cell growth inhibition assays were performed and compared to vancomycin and metronidazole, followed by determining time-kill kinetics against C. difficile. Activities against biofilm formation and spore germination were also evaluated. Leakage analyses and electron microscopy were applied to confirm the disruption of membrane structure. Finally, ticagrelor’s ability to synergize with vancomycin and metronidazole was determined using checkerboard assays. Our data showed that ticagrelor exerted activity with a MIC range of 20–40 µg/mL against C. difficile. This compound also exhibited an inhibitory effect on biofilm formation and spore germination. Additionally, ticagrelor did not interact with vancomycin nor metronidazole. Our findings revealed for the first time that ticagrelor could be further developed as a new antimicrobial agent for fighting against C. difficile.

In patients with stable ischemic heart disease (IHD) and/or peripheral artery disease (PAD), current secondary prevention, including the antiplatelet monotherapy, is associated with a significant residual risk of recurrent cardiovascular complications (CVC). Practical application of results from many modern studies evaluating the effect of secondary prevention of atherothrombosis is complicated. An additional influence on coagulation may play a key role in prevention of atherothrombosis. In the COMPASS study, adding rivaroxaban 2.5 mg, b.i.d., to the acetylsalicylic acid (ASA) monotherapy significantly reduced the risk of death from cardiovascular complications, myocardial infarction or stroke, or all-cause death compared to the ASA monotherapy, in patients with IHD or PAD. The combination antithrombotic therapy was associated with an increased risk of major, but not fatal, or intracranial bleeding. In addition, PAD patients had a reduced risk of severe ischemic lower limb complications, including amputations. According to the subgroup analysis in the COMPASS study, supplementing ASA with rivaroxaban 2.5 mg, b.i.d., may appear most beneficial for patients with stable atherosclerotic disease and with a high risk of severe CVC without causing an increased risk of bleeding.

Purpose Evidence on the use of antithrombotic pharmacotherapy in patients undergoing revascularization of lower extremities for symptomatic peripheral arterial disease (PAD) is reviewed. Summary Individuals with PAD can experience leg pain, intermittent claudication, critical limb ischemia, and acute limb ischemia. In such patients, revascularization may be indicated to improve the quality of life and to prevent amputations. Antithrombotic therapy is often intensified in the postrevascularization period to prevent restenosis of the index artery and to counteract the prothrombotic state induced by the intervention. Therapeutic modalities include dual antiplatelet therapy (DAPT), anticoagulation, a combination of antiplatelet and anticoagulation therapy, and addition of cilostazol to single antiplatelet therapy. Subgroup analyses of data from randomized clinical trials provided low-quality evidence for the use of DAPT in patients with a below-knee prosthetic bypass graft and anticoagulation for those with a venous bypass graft. Cilostazol, when added to aspirin therapy, has been shown to prevent index vessel reocclusion after an endovascular intervention in patients at low risk for thrombosis in several small randomized trials. Conclusion There is a considerable paucity of high-quality evidence on the optimal antithrombotic regimen for patients undergoing lower extremity revascularization, with no particular therapy shown to consistently improve patient outcomes. The decision to initiate intensified antithrombotic therapy should include a close examination of its risk–benefit profile. The demonstrated benefit of such treatment is restricted to the prevention of index artery reocclusion, while an increased risk of bleeding may lead to significant morbidity and mortality.

Almost all of global maternal mortality caused by HDP occurs in low to middle-income countries (LMIC). However, limited guidance is available to local primary care practitioners who are usually the main health care providers. This review examined existing international practice guidelines to identify potential practices to improve HDP management in Indonesian primary care settings. We performed structured literature search strategies and snowballing searches in six databases (MEDLINE, Web of Science, EMBASE, CINAHL, Cochrane reviews and Google Scholar) for guidelines that were published between 2007 and 2018 using relevant keywords and phrases of 'guidelines', 'hypertensive disorders of pregnancy' or 'preeclampsia' and 'primary care'. The AGREE II instrument was used to assess quality and reporting of the eligible guidelines. Thematic analysis was performed on all of the guidelines and the results were discussed among the project investigators. Sixteen international practice guidelines or similar management recommendations were reviewed. Almost all of them were partially applicable, with some managements potentially able to be adopted to Indonesian primary care settings. Three main themes for improving HDP management were identified, namely clinical management, care planning, and professional communication. These potential improvements in managing women with HDP in Indonesia may also be relevant in other LMIC. Further contextualisation is required to facilitate their adoption in practice settings.

Background and aims: The optimal duration of dual antiplatelet therapy (DAPT) after myocardial infarction (MI) in patients treated with second-generation drug-eluting stent (DES) is unclear, therefore, we aim to evaluate the ischemic and bleeding risk according to DAPT duration using a pooled-analysis of two randomized trials. Methods: MI patients treated with durable-polymer second-generation DES from two randomized trials, SMART-DATE and DAPT-STEMI, were pooled. The primary endpoint was a composite of net adverse clinical events (NACEs) defined by all-cause mortality, any MI, stroke and BARC 3-5 bleeding, between 6 and 18 months after index percutaneous coronary intervention. Results: A total of 2016 patients were analyzed, 1014 were treated with 6-month DAPT versus 1002 patients with ≥12-month DAPT duration. The primary endpoint occurred in 2.7% vs 2.5% (HR 1.07; 95%CI 0.62–1.85, p = 0.80) of cases, in 6 vs ≥ 12-month DAPT, respectively. The composite of cardiac death, MI and stroke was similar (2% vs 1.6%, HR 1.24, 95%CI 0.65–2.4, p = 0.52). BARC 3-5 bleeding occurred more frequently in the ≥12-month DAPT (0.2% vs 0.9%, HR 0.22, 95%CI 0.05–1.02 p = 0.05, log rank p = 0.03). MI occurred more frequently in the 6-month DAPT (1.6% vs 0.6%, HR 2.66, 95%CI 1.04–6.79, p = 0.04). Stent thrombosis was similar in both arms (0.7% vs 0.5%, p = 0.26). Conclusions: Six vs ≥ 12-month DAPT, followed by aspirin alone, resulted in comparable NACEs in patients with event-free MI at six months after durable-polymer DES implantation. However, single therapy with aspirin beyond the 6 months reduced bleeding rates but was associated with a higher rate of MI compared to ≥12-month DAPT.

Background Optimal management of patients with extracranial blunt cerebrovascular injury (BCVI) remains controversial, with both anticoagulation and antiplatelet therapy being recommended. The purpose of this study was to evaluate the efficacy and safety of using acetylsalicylic acid (ASA) in the management of BCVI. Methods Patients with BCVI were identified from the registry of a Level 1 trauma center between 2010 and 2017. Digital imaging and electronic medical records were reviewed for patient information including demographic characteristics, injury type, therapy, outcomes, and follow-up. Results Over the study period, 13,578 patients were admitted following blunt trauma, with 94 (0.7%) having confirmed BCVI (mean age, 42 years; 72% male). Mean Injury Severity Score and Glasgow Coma Score were 27 and 10, respectively. BCVI was identified in 130 vessels with Biffl grade I (38%) and grade II injury (29%) being most common. Twelve (13%) patients experienced an ischemic event, but only 3 events occurred after diagnosis. ASA was primary treatment for 56 (60%) patients. Thirty patients (32%) received no treatment; 21 patients died within 24 hours of primary injury. Only 4 patients had ASA contraindications. Four patients (7%) had ASA-related complications; there were 2 cases of intracranial hemorrhage progression and 2 cases of gastrointestinal bleeding. Follow-up vascular imaging at a mean of 36 days demonstrated stable or improved levels of BCVI in 94% of patients. Conclusions An ASA-based management strategy for BCVI was efficacious and relatively safe in this study. This approach may be the preferred treatment for BCVI, but confirmation is needed.

Background It is unknown whether contemporary drug‐eluting stents have a similar safety profile in high bleeding risk patients treated with 1‐month dual antiplatelet therapy following percutaneous coronary interventions. Methods and Results We performed an interventional, prospective, multicenter, single‐arm trial, powered for noninferiority with respect to an objective performance criterion to evaluate the safety of percutaneous coronary interventions with Synergy bioresorbable‐polymer everolimus‐eluting stent followed by 1‐month dual antiplatelet therapy in patients with high bleeding risk. In case of need for an oral anticoagulant, patients received an oral anticoagulant in addition to a P2Y 12 inhibitor for 1 month, followed by an oral anticoagulant only. The primary end point was the composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis at 1‐year follow‐up. The study was prematurely interrupted because of slow recruitment. From April 2017 to October 2019, 443 patients (age, 74.8±9.2 years; women, 29.1%) at 10 Italian centers were included. The 1‐year primary outcome occurred in 4.82% (95% CI, 3.17%–7.31%) of patients, meeting the noninferiority compared with the predefined objective performance criterion of 9.4% and the noninferiority margin of 3.85% ( P noninferiority Conclusions Among high bleeding risk patients undergoing percutaneous coronary interventions with the Synergy bioresorbable‐polymer everolimus‐eluting stent, a 1‐month dual antiplatelet therapy regimen is safe, with low rates of ischemic and bleeding events. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03112707 .

[Figure: see text].

We aimed to investigate association between mean platelet volume (MVP), platelet distribution width (PDW) and red cell distribution width (RDW) and mortality in patients with COVID-19 and find out in which patients the use of acetylsalicylic acid (ASA) affects the prognosis due to the effect of MPV on thromboxan A2. A total of 5142 patients were divided into those followed in the intensive care unit (ICU) and those followed in the ward. Patient medical records were examined retrospectively. ROC analysis showed that the area under curve (AUC) values were 0.714, 0.750, 0.843 for MPV, RDW and D-Dimer, the cutoff value was 10.45fl, 43.65fl, 500.2 ng/mL respectively. (all P 10.45 f/l and D-Dimer >500.2 ng/mL, treatment with ASA had lower in-hospital and 180-day mortality than patients without ASA in ICU patients (HR = 0.773; 95% CI = 0.595-0.992; P = .048, HR = 0.763; 95% CI = 0.590-0.987; P = .036). Administration of low-dose ASA in addition to anti-coagulant according to MPV and D-dimer levels reduces mortality.

Funder: ZNS - Hannelore Kohl Stiftung; funder-id: http://dx.doi.org/10.13039/501100007731, Funder: OneMind (USA), Funder: Integra LifeSciences; funder-id: http://dx.doi.org/10.13039/100009006, Background: Traumatic brain injury (TBI) is an important global public health burden, where those injured by high-energy transfer (e.g., road traffic collisions) are assumed to have more severe injury and are prioritised by emergency medical service trauma triage tools. However recent studies suggest an increasing TBI disease burden in older people injured through low-energy falls. We aimed to assess the prevalence of low-energy falls among patients presenting to hospital with TBI, and to compare their characteristics, care pathways, and outcomes to TBI caused by high-energy trauma. Methods and findings: We conducted a comparative cohort study utilising the CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) Registry, which recorded patient demographics, injury, care pathway, and acute care outcome data in 56 acute trauma receiving hospitals across 18 countries (17 countries in Europe and Israel). Patients presenting with TBI and indications for computed tomography (CT) brain scan between 2014 to 2018 were purposively sampled. The main study outcomes were (i) the prevalence of low-energy falls causing TBI within the overall cohort and (ii) comparisons of TBI patients injured by low-energy falls to TBI patients injured by high-energy transfer—in terms of demographic and injury characteristics, care pathways, and hospital mortality. In total, 22,782 eligible patients were enrolled, and study outcomes were analysed for 21,681 TBI patients with known injury mechanism; 40% (95% CI 39% to 41%) (8,622/21,681) of patients with TBI were injured by low-energy falls. Compared to 13,059 patients injured by high-energy transfer (HE cohort), the those injured through low-energy falls (LE cohort) were older (LE cohort, median 74 [IQR 56 to 84] years, versus HE cohort, median 42 [IQR 25 to 60] years; p < 0.001), more often female (LE cohort, 50% [95% CI 48% to 51%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001), more frequently taking pre-injury anticoagulants or/and platelet aggregation inhibitors (LE cohort, 44% [95% CI 42% to 45%], versus HE cohort, 13% [95% CI 11% to 14%]; p < 0.001), and less often presenting with moderately or severely impaired conscious level (LE cohort, 7.8% [95% CI 5.6% to 9.8%], versus HE cohort, 10% [95% CI 8.7% to 12%]; p < 0.001), but had similar in-hospital mortality (LE cohort, 6.3% [95% CI 4.2% to 8.3%], versus HE cohort, 7.0% [95% CI 5.3% to 8.6%]; p = 0.83). The CT brain scan traumatic abnormality rate was 3% lower in the LE cohort (LE cohort, 29% [95% CI 27% to 31%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001); individuals in the LE cohort were 50% less likely to receive critical care (LE cohort, 12% [95% CI 9.5% to 13%], versus HE cohort, 24% [95% CI 23% to 26%]; p < 0.001) or emergency interventions (LE cohort, 7.5% [95% CI 5.4% to 9.5%], versus HE cohort, 13% [95% CI 12% to 15%]; p < 0.001) than patients injured by high-energy transfer. The purposive sampling strategy and censorship of patient outcomes beyond hospital discharge are the main study limitations. Conclusions: We observed that patients sustaining TBI from low-energy falls are an important component of the TBI disease burden and a distinct demographic cohort; further, our findings suggest that energy transfer may not predict intracranial injury or acute care mortality in patients with TBI presenting to hospital. This suggests that factors beyond energy transfer level may be more relevant to prehospital and emergency department TBI triage in older people. A specific focus to improve prevention and care for patients sustaining TBI from low-energy falls is required.

BACKGROUND Patients undergoing kidney transplantation are often placed on anticoagulation or antiplatelet therapy, and their perioperative management is often challenging. This study aimed to determine the safety of continuing anticoagulation or antiplatelet therapy prior to kidney transplantation. The primary outcome was bleeding after transplantation. MATERIAL AND METHODS Patients who underwent kidney transplantation between January 2017 and July 2019 were included and divided into 3 groups: pretransplant anticoagulation with warfarin (WARF; n=23); pretransplant antiplatelet therapy with clopidogrel/aspirin (ASA/CLOP; n=32); and control (CTL; n=197). Patients received kidneys from live or deceased donors. Preoperative INRs and platelet counts were compared to ensure therapeutic anticoagulation in the warfarin group and no significant platelet count variation among groups. The primary outcome was graft exploration for bleeding at 3 and 6 months after transplantation. Secondary outcomes included perioperative transfusion requirements, prolonged length of stay (>7 days), and outcomes at 3 and 6 months after transplantation, including hemodialysis and rejection rates and creatinine levels. RESULTS Pretransplant INR was significantly greater in the warfarin group (CTL 1.1, WARF 2.2, ASA/CLOP 1.2; P

Gastrointestinal bleeding (GIB) is the most common serious bleeding complication of antiplatelet therapy. The bleeding risk score (BRS) of GIB may help to determine the risk of bleeding, and provides a reference for the formulation of antiplatelet therapy regimen in clinical practice, but we found that no specific risk scores are available in East Asian patients. This study analyzed patients who were administered antiplatelet therapy from May 2015 to December 2018 in two medical centers. Patient's baseline data were obtained. We assessed four BRSs (New Score, RIETE Score, Cuschieri Score, de Groot Score) and compared them using the area under the receiver operating characteristic curve (AUC). The 4,052 patients enrolled in this study had an average age of 69.6 ± 10.8 years, and 65.9% of them were male. Among the 4,052 patients included, 171 patients experienced GIB within 6 months of follow-up. In the study population, the AUCs for the New, RIETE, Cuschieri, and de Groot scores were 0.673 (95% confidence interval (CI) 0.616-0.729, P < .001), 0.742 (95% CI 0.690-0.794, P < .001), 0.598 (95% CI 0.537-0.659, P = .002), and 0.875 (95% CI 0.839-0.912, P < .001), respectively. After validation, the de Groot Score has better performance. Among the four scores, the de Groot Score might be more suitable for helping Chinese clinicians to predict the risk of GIB in patients taking antiplatelet drugs, and reduce GIB events.

Experiments were undertaken to identify the nature of a previously identified inhibitor of PAF-induced platelet aggregation (PA) in human saliva. Human saliva fractionated by preparative thin layer chromatography (TLC) yielded a fraction that co-migrated with fatty acids (FAs) and inhibited PAF-induced aggregation of platelets. Synthetic FAs tested for their capacities to inhibit 0.1 nM PAF-induced PA showed that only the cis-unsaturated compounds were inhibitory with activities of some of the polyunsaturated FAs (PUFA) reaching almost 100% at 20 μM. Eicosapentanoic acid (EPA) and 8,11,14-eicosatrienoic acid also deaggregated the PAF-induced aggregates. With the exception of oleic acid (OLA), cis-monounsaturated FAs, and elaidic acid, the trans isomer of OLA, were poor inhibitors. In a direct comparison with other platelet agonists, ADP, thrombin, and ionophore A23187, the active saliva fraction and selected individual FAs inhibited, to greater or lesser extent, PA induced by each of the agonists. EPA, OLA, linoleic acid (LNA), and the active saliva fraction were potent inhibitors of ADP-induced PA, EPA completely inhibited thrombin-induced PA and the saliva fraction showed only weak - moderate inhibitory activity to both thrombin- and ionophore A23187-induced PA. Other reports of endogenous PAF inhibitors in mammalian tissues are compared to the present results. PAF can trigger and amplify inflammatory cascades suggesting a possible modulation role for cis-unsaturated FAs in some diseases.

Background Antithrombotics are frequently prescribed for patients with a limited life expectancy. In the last phase of life, when treatment is primarily focused on optimizing patients’ quality of life, the use of antithrombotics should be reconsidered. Methods We performed a secondary analysis of a retrospective review of 180 medical records of patients who had died of a malignant or non-malignant disease, at home, in a hospice or in a hospital, in the Netherlands. All medication prescriptions and clinical notes of patients using antithrombotics in the last three months of life were reviewed manually. We subsequently developed case vignettes based on a purposive sample, with variation in setting, age, gender, type of medication, and underlying disease. Results In total 60% (n=108) of patients had used antithrombotics in the last three months of life. Of all patients using antithrombotics 33.3 % died at home, 21.3 % in a hospice and 45.4 % in a hospital. In total, 157 antithrombotic prescriptions were registered; 30 prescriptions of vitamin K antagonists, 60 of heparins, and 66 of platelet aggregation inhibitors. Of 51 patients using heparins, 32 only received a prophylactic dose. In 75.9 % of patients antithrombotics were continued until the last week before death. Case vignettes suggest that inability to swallow, bleeding complications or the dying phase were important factors in making decisions about the use of antithrombotics. Conclusions Antithrombotics in patients with a life limiting disease are often continued until shortly before death. Clinical guidance may support physicians to reconsider (dis)continuation of antithrombotics and discuss this with the patient.

Treatment fragmentation between hospitals and the community can result in catastrophic outcomes; uninterrupted treatment with anti-coagulant and platelet-aggregation inhibitors is particularly important. We assessed the proportion and characteristics of patients who did not visit their primary community-based physician within one week of discharge from our department of cardiovascular medicine, and the proportion that failed to procure essential drugs at the community pharmacy.We prospectively studied 423 patients who were discharged from our department. They were provided detailed explanations, tablets for seven days, prescriptions, and a printed drug plan. We traced the time from discharge until a visit with a primary community-based physician, and the time until the procurement of medications, using our computerized community-hospital-integrated system. Complete data were available for 313 patients, of whom 220 were treated with anticoagulants or platelet aggregation inhibitors. For 175 patients, these drugs were initiated during index hospitalizations. Only one patient did not receive platelet aggregation inhibitors despite recommendations. Seventy-nine patients (25%) first visited their primary care physicians more than one week after discharge. Predictors for delayed visits were living alone (hazard ratio 1.91) and having an in-house caregiver (hazard ratio 2.01).In conclusion, all but one patient continued drug therapy after discharge from the hospital. The simple pre-discharge steps included patient education, and provision of a one-week supply of tablets and prescriptions. Treatment continuation was independent of visits to the community-based primary physician. Patients living alone or with an in-house caregiver more often delayed visits to primary physicians yet continued relevant drug therapy.

Background Patients with coronavirus disease 2019 (COVID-19) exhibit high thrombotic risk. The evidence on a potential independent prognostic role of antiplatelet treatment in those patients is limited. The aim of the study was to evaluate the prognostic impact of pre-admission low-dose acetylsalicylic acid (ASA) in a wide series of hospitalized patients with COVID-19. Methods This cohort study included 984 COVID-19 patients stratified according to ASA intake before hospitalization: ASA+ (n = 253) and ASA− (n = 731). Patients were included in ASA+ group if they received it daily in the 7 days before admission. 213 (83%) were on ASA 100 mg daily. Primary endpoint was a composite of in-hospital death and/or need for respiratory support upgrade, secondary endpoints were in-hospital death and need for respiratory support upgrade. Results Mean age was 72 [62; 81] with 69% of male patients. ASA+ patients were significantly older, with higher prevalence of comorbidities. No significant differences regarding the degree of respiratory dysfunction were observed. At 30-day Kaplan-Meier analysis, ASA+ patients had higher survival free from the primary endpoint and need for respiratory support upgrade, conversely in-hospital death did not significantly differ between groups. At multivariate analysis ASA intake was independently associated with a lower probability of reaching primary endpoint (HR 0.697, 95% C.I. 0.525–0.924; p = 0.012). Conclusions In COVID-19 patients undergoing hospitalization, pre-admission treatment with ASA is associated with better in-hospital outcome, mainly driven by less respiratory support upgrade.

International audience; at least moderate ischaemia on a stress test, is there a benefit to adding cardiac catheterization and, if feasible, revascularization to optimal medical therapy? The study team randomized 5179 patients into an invasive or conservative strategy. What is noteworthy from the baseline characteristics is the high proportion of diabetes, a preserved ejection fraction in the majority of patients, well-managed LDL, and history of angina in 90% of patients. Only 10% had silent ischaemia. While the ISCHEMIA study-the largest trial of invasive vs. conservative strategy in patients with stable ischaemic heart disease-demonstrated that an initial invasive strategy of cardiac catheterization and revascularization in patients with stable coronary artery disease and moderate-to-severe ischaemia had no overall outcomes' advantage compared with medical therapy alone, the results also showed that patients with angina nevertheless derived a quality of life benefit. Procedural MIs were increased and spontaneous MIs were decreased with the invasive strategy. There was no heterogeneity of treatment effect on the primary endpoint, including by severity of ischaemia or extent of coronary disease. 'The implications', said Prof. Hochman, 'are that a validated measure of patient-reported quality of life should be collected before deciding about an invasive strategy.

Without urgent treatment, the risk of major stroke in the week after a transient ischemic attack (TIA) or minor stroke can be as high as 10%.1 Some studies have shown that immediate medical treatme...