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Background and purpose Mild traumatic brain injury (mTBI) in patients on antiplatelet (AP), anticoagulant (AC) or direct oral anticoagulant (DOAC) medication has become a systematic indication for head CT. However, the over-risk and impact of the intracranial hemorrhages (IH) detected with CT in this population remain unclear and need to be assessed. Materials and methods We prospectively assessed head CTs performed in adults taking AP/AC/DOAC referred after a mTBI to our Emergency Departments between September 2016 and January 2018. Frequency, type and severity of IH were described and frequency was analyzed as a function of treatment. Results 840 patients were prospectively included. 58.9% were treated with AP, 23.7% with AC, 11.7% with DOAC and 5.7% with a combination of antithrombotic agents. The rate of IH detected with head CT was 5.8% (n = 49), of which 81.6% (n = 40) and 18.4% (n = 9) with minor and intermediate severity respectively. No patient required surgical care and no death occurred. No statistically significant difference was found in treatment distribution between patients with or without IH (p = 0.98). Among the patients who discontinued their antithrombotic treatment after mTBI, three experienced thrombotic events during the hospitalization. Conclusions Our results showed a low frequency and severity of IH in mTBI patients indifferently treated with AP, AC or DOAC, without secondary neurological deterioration, death or need of surgical care. Our study suggests the limited benefit of systematic CT head scan as a standard practice for the management of mTBI patients under antithrombotic therapy.

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.

In Mexico, Cnidoscolus aconitifolius (chaya) has been used to treat cardiovascular diseases (CVD). Because CVD are the number one cause of mortality, chaya use has become a health strategy. The aim of this study was to evaluate the antithrombotic activity and identify the metabolites in the most active extract. Aqueous (Aq), ethanolic (EtOH), acetonic (An), ethyl acetate (AcOEt), diethyl ether (Et2O), and hexanic (Hx) extracts were obtained. Platelet aggregation, phospholipase A2, prothrombin time (PT), activated partial thromboplastin time (aPTT), and clot lysis were evaluated. Metabolites were identified by gas chromatography-mass spectrometry (GC-MS). EtOH showed the greatest inhibition of platelet aggregation and phospholipase A2. Ac had the greatest effect on PT and aPTT. AcOEt had the greatest effect on clot lysis. EtOH, with the highest potential, was analyzed by GC-MS; fatty acids and triterpenes were identified. Thus, EtOH showed greater antiplatelet activity and other extracts showed moderate activity. This is a preliminary antithrombotic study. Future research will allow the development of nutraceuticals or functional ingredients for the prevention and treatment of thrombosis.

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.

The risk of stroke recurrence is highest in the acute phase after transient ischemic attack (TIA) or ischemic stroke. Therefore, patients with TIA or ischemic stroke should be treated with antiplatelet medication for stroke prevention. The short-term use of dual antiplatelet therapy between 21 and 90 days may be considered in those with acute minor stroke or TIA and highrisk of recurrence. However, the long-term use of dual antiplatelet therapy is not recommended due to the risk of bleeding. The current stroke guideline does not specify the administration of an antiplatelet for the secondary prevention of ischemic stroke. However, as clinical studies progress, antiplatelet therapy may become a personalized treatment in the future.

Geriatric patients often have cardiovascular diseases that require differentiated perioperative management of hemostasis. The operation-related bleeding risk and the individual thromboembolism risk mutually influence each other, so that a differentiated preoperative assessment of the further prescription of coagulation-modulating medication is required. In many cases the active coagulation medication can be interrupted without replacement or continued unchanged. In cardiovascular diseases with antiplatelet medication, the preoperative risk-benefit assessment for most operations leads to the continuation of previous platelet aggregation inhibitor monotherapy; however, if there is a high risk of cardiovascular thromboembolism with dual platelet inhibition, the individual perioperative medication should be closely coordinated with a geriatrician or cardiologist.In most cases, the intake of vitamin K antagonists (VKA) can be preoperatively interrupted. In cases of high risk of thromboembolism, a temporary bridging with heparin must be carried out. The introduction of the four new direct oral antagonists (DOAC) has made the perioperative management of anticoagulation much easier. Bridging with heparin is not necessary. Perioperatively, only the dosage and timing of interruption of the DOACs have to be determined individually depending on the operative bleeding risk as well as the age, body weight and kidney function of the patient. If bleeding complications arise under the influence of the DOACs, antidotes are available for three of the four DOACs, which in acute cases can be used in addition to prothrombin complex concentrates and fresh frozen plasma to normalize coagulation.

Klinisch wird COVID-19 („corona virus disease“ 2019) zunehmend als systemische Erkrankung gesehen, in deren Zentrum eine Multiorganbeteiligung durch einen hyperkoagulatorischen Zustand im Sinne einer Vaskulopathie steht. Eine Behandlung mit Thrombozytenfunktionshemmern oder Heparinen erscheint die logische Konsequenz. Die aktuelle Studienlage, zumindest fur ASS, ergibt allerdings keine Hinweise auf eine Wirksamkeit. Entsprechend der zu nennenswerten Anteilen primar mikrostrukturellen Gefasveranderungen sollte die radiologische Diagnostik nicht nur Makrogefaspathologien, sondern auch Hinweise auf diffuse Perfusionsstorungen darstellen. In der Lunge sind beispielsweise Perfusionsausfalle nachweisbar, die nur teilweise durch pulmonalarterielle Fullungsdefekte zu erklaren sind. Ahnliche Befunde zeigen sich in fast allen Organsystemen. Eine therapeutische Intervention mittels niedermolekularer Heparine bei hospitalisierten Patienten in situationsadaptierter Dosierung ist indiziert und wird ausfuhrlich besprochen. Bei Nachweis von Mikro- und Makrogefasthrombosierung im Rahmen von COVID-19 spielt die erweiterte radiologische Diagnostik eine zentrale Rolle und ist die Basis der Therapie und Sekundarpravention.

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.

Closure of a patent foramen ovale (PFO) in patients after cryptogenic/cardioembolic stroke is recommended by current guidelines for patients who are 16–60 years of age with a high-risk PFO (class of recommendation A, level of evidence I). The use of double-disk occlusion devices followed by antiplatelet therapy is recommended. The procedure of interventional PFO closure compared with other interventions in cardiology is rather easy to learn. However, it should be performed carefully to avoid postinterventional complications. The number needed to treat (NNT) to avoid one stroke in 5 years in the RESPECT trial was 42, in the CLOSE trial even lower with 20. In the REDUCE trial, the NNT was 28 at 2 years. This can be reduced by longer follow-up, e.g., at 10 years the NNT is 18. While other conditions such as migraine are currently under investigation with respect to the impact of PFO closure, sufficiently powered trials are lacking so that closure in diseases other than stroke should always be individualized.

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.

Investigations have shown that infection from the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is responsible also for initiating severe inflammatory responses that can lead macrovascular and microvascular thrombosis. Several studies have already described acute limb ischemia and peripheral arterial disease in critically ill patients with Coronavirus disease 2019 (Covid-19), as well as coronary artery disease and ischemic stroke as a manifestation usually associated with respiratory distress. However, what still remains unclear is how long inflammation and thrombotic derangements can last after recovery from the symptoms of Covid-19. Hence, in this article we report 3 cases of arterial thrombotic sequalae after this viral infection. To the best of our knowledge, this is the first cases' series that had described different delayed vascular arterial complications, which occurred after the index infection, with a negative nasopharyngeal swab and Covid-19 systemic symptoms resumption. A better understanding of the coagulopathy in Covid-19 could have an essential role to guide prevention and treatment of arterial thromboembolic events, both during and after the viral infection. Further investigations are required to confirm these data and to estabilish the type, dose and duration of anticoagulant/antiplatelet therapy not just during but also after Covid-19 infection.

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.

Background and objectives Neuraxial hematoma is a rare complication of the epidural technique which is commonly used for high quality postoperative pain relief. In case of urgent initiation of multiple antithrombotic therapy, the optimal timing of epidural catheter removal and need for treatment modification may be quite challenging. There are no specific guidelines and published reports are scarce. Case report We present the uneventful removal of an indwelling epidural catheter in a patient who was put on emergency triple antithrombotic treatment with Low Molecular Weight Heparin (LMWH), aspirin and clopidogrel in the immediate postoperative period, due to acute coronary syndrome. In order to define the optimal conditions and timing for catheter removal, so as to reduce the risk of complications, various laboratory tests were conducted 3 hours after aspirin/clopidogrel intake. Standard coagulation tests revealed normal platelet count, normal prothrombin time and normal activated partial thromboplastin time, while Platelet Function Analysis (PFA-200) revealed abnormal values (increased COL/EPI and COL/ADP values, both indicating inhibition of platelet function). The anti-Xa level, estimated 4 hours after LMWH administration, was within therapeutic range. At the same time, Rotational Thromboelastometry (ROTEM) showed a relatively satisfactory coagulation status overall. The epidural catheter was removed 26 hours after the last dual antiplatelet dose and the next dose was given 2 hours after removal. Enoxaparin was withheld for 24 hours and was resumed after 6 hours. Neurologic checks were performed regularly for alarming signs and symptoms suggesting development of an epidural hematoma. No complications occurred. Conclusion Point-of-care coagulation and platelet function monitoring may provide a helpful guidance in order to define the optimal timing for catheter removal, so as to reduce the risk of complications. A case-specific management plan based on a multidisciplinary approach is also important.

Introduction Prehospital therapy of ST-elevation myocardial infarction (STEMI) with αIIbβ3 antagonists improves clinical outcomes, but they are difficult to use in prehospital settings. RUC-4 is a novel αIIbβ3 antagonist being developed for prehospital therapy of STEMI that rapidly achieves high-grade platelet inhibition after subcutaneous administration. Standard light transmission aggregometry (LTA) is difficult to perform during STEMI, so we applied VerifyNow (VN) assays to assess the pharmacodynamics of RUC-4 relative to aspirin and ticagrelor. Methods Blood from healthy volunteers was anticoagulated with phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) or sodium citrate, treated in vitro with RUC-4, aspirin, and/or ticagrelor, and tested with the VN ADP + PGE1, iso-TRAP, and base channel (high concentration iso-TRAP + PAR-4 agonist) assays. The results were correlated with both ADP (20 µM)-induced LTA and flow cytometry measurement of receptor occupancy and data from individuals treated in vivo with RUC-4. Results RUC-4 inhibited all three VN assays, aspirin did not affect the assays, and ticagrelor markedly inhibited the ADP + PGE1 assay, slightly inhibited the iso-TRAP assay, and did not inhibit the base channel assay. RUC-4's antiplatelet effects were potentiated in citrate compared with PPACK. Cut-off values were determined to correlate the results of the VN iso-TRAP and base channel assays with 80% inhibition of LTA. Conclusion The VN assays can differentiate the early potent anti-αIIbβ3 effects of RUC-4 from delayed effects of P2Y12 antagonists in the presence of aspirin. These pharmacodynamic assays can help guide the clinical development of RUC-4 and potentially be used to monitor RUC-4's effects in clinical practice.

Introduction: Gnetum macrostachyum is a known Thai medicinal plant as a source of bioactive oligostilbenes, which possess platelet inhibitory activities. The study aimed to evaluate the in vitro human platelet aggregation inhibitory activities of macrostachyols A-D (compounds 1-4) isolated from the roots of G. macrostachyum. Methods: The in vitro human platelet aggregation assay was assayed with a 96-well microtiter plate format. The well-known aggregating agents were used to investigate the possible mechanism of inhibition, including adenosine diphosphate (ADP), arachidonic acid (AA), thromboxane A2 analog (U-46619), collagen, thrombin, and thrombin receptor-activating peptide-6 (TRAP-6). Results: Compound 1 was more potent than ibuprofen (positive control) on the adenosine diphosphate- induced platelet aggregation assay (P < 0.05). Compound 3 was more potent than 1, 2, and 4 (P < 0.05), but all active oligostilbenes were less potent than the positive control (P < 0.05) on the arachidonic acid-induced platelet aggregation assay. The oligostilbenes 1, 2, 3, and 4 also displayed the inhibitory effects on the U-46619-induced platelet aggregation. The tetrameric stilbenes 1 was the only compound that exhibited inhibitory effects on thrombin-induced platelet aggregation without TRAP-6 mediated platelet aggregation. Conclusion: The findings revealed the inhibitory effects of oligostilbenes on human platelet aggregation through a target-specific experimental design. It suggests that oligostilbenes from this plant might be applied as antiplatelet aggregation agents in platelet hyperreactivity- related diseases.

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.

Coronary intraluminal white clot formation, apparently in response to acetylcholine testing, may explain a woman’s long-term history of daily chest pain and multiple myocardial infarctions. Acetylcholine testing reproduced chest pain and revealed luminal filling defects in multiple vessels; imaging showed fresh white platelet clots. Antiplatelet prasugrel has substantially suppressed her symptoms. (Level of Difficulty: Advanced.), Central Illustration

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.

AIMS We aimed to evaluate the validity of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria for East Asian patients undergoing contemporary percutaneous coronary intervention (PCI) from the PENDULUM registry. METHODS AND RESULTS This post hoc analysis included 6,267 Japanese patients undergoing PCI between December 2015 and June 2017 enrolled in PENDULUM. The primary endpoint was the incidence of major bleeding at 12 months post index PCI. In total, 3,185 (50.8%) and 3,082 (49.2%) patients were stratified to the ARC-HBR and non-ARC-HBR groups, respectively, and almost all patients had overlapping criteria. Incidence of major bleeding was 4.2% versus 1.4% in the ARC-HBR group versus the non-ARC-HBR group (hazard ratio 3.00 [95% confidence interval: 2.11-4.27]; p

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: Guidelines recommend the discontinuation of clopidogrel prior to gastrostomy tube placement. The aim of this study was to examine the safety and feasibility of performing radiologically inserted gastrostomy (RIG) tube placement in patients taking clopidogrel and/or aspirin. Methods: We performed an institutional review board–approved retrospective analysis of the medical records for 237 consecutive patients following RIG tube placement secondary to dysphagia from August 2017 to January 2019. Antiplatelet medications and RIG type placement techniques (push vs pull) were compared with bleeding complications. Complications were categorized based on the Society of Interventional Radiology clinical practice guidelines. Of the 237 patients with RIG tubes placed, 77 patients were on antiplatelet therapy: 55 on single antiplatelet therapy and 22 on dual antiplatelet therapy. Of the 55 patients on single antiplatelet therapy, 26 were taking clopidogrel and 29 were taking aspirin. Results: A total of 9 bleeding complications were observed. The most common complication was minimal bleeding or hematoma around the incision site (n=7). No statistically significant increase was seen in bleeding rates when comparing patients on any antiplatelet therapy regimen vs none (P=0.15), single antiplatelet therapy vs none (P=0.13), clopidogrel vs none (P=0.71), or dual antiplatelet therapy vs none (P=0.61). No significant increase in the bleeding complication rate was noted when comparing the aspirin-only regimen vs clopidogrel alone (P=0.34). Conclusion: These findings suggest that the risk of bleeding complications is not increased in patients taking clopidogrel and/or aspirin prior to RIG tube placement.

This letter demonstrates, for the first time, a novel, rapid automated whole blood clot retraction assay utilizing quartz crystal microbalance resonant frequency monitoring. Tissue factor is selected to initiate coagulation. The test turnaround time is 10–20 min, during which a real-time coagulation trace is recorded in parallel with a reference coagulation trace. The reference sample is the same blood sample that is treated by platelet aggregation inhibitor, and the difference between the two traces indicates the quantitative platelet effect on clotting. This differential approach enables determination of a hematocrit-independent parameter characterizing the intensity of clot retraction. In the case of samples with normal hemostatic characteristics, the intensity of retraction is a linear function of platelet count, whereas the retraction is reduced in the case of platelet hypofunction. Moreover, in combination with a clotting time parameter derived from the same coagulation trace, the method allows primary differentiation between three groups of bleeding disorders of various etiology, including platelet disorders, defects in plasma factors, and hypofibrinogenaemia.

Background: Ticks puncture the skin of their hosts and secrete saliva, containing antiplatelet proteins, into the blood. Here, we studied disagregin, a potent platelet-inhibiting protein derived from the salivary glands of Ornithodoros moubata, an African soft tick. Whereas conventional alpha IIb beta 3 antagonists contain an Arg-Gly-Asp (RGD) sequence for platelet integrin binding, disagregin contains an Arg-Glu-Asp (RED) sequence, hypothesizing a different mode of inhibitory action.Objectives: We aimed to compare the inhibitory effects of disagregin and its RGD variant (RGD-disagregin) on platelet activation and to unravel the molecular basis of disagregin-alpha IIb beta 3 integrin interactions.Methods: Disagregin and RGD-disagregin were synthesized by tert-butyloxycarbonyl -based solid-phase peptide synthesis. Effects of both disagregins on platelet aggregation were assessed by light transmission aggregometry in human platelet-rich plasma. Whole-blood thrombus formation was investigated by perfusing blood over collagen I with and without tissue factor at a high wall-shear rate (1000 s(-1)) in the presence of disagregin, RGD-disagregin, or eptifibatide.Results: Disagregin showed inhibition of collagen- and ADP-induced platelet aggregation with half maximal inhibitory concentration values of 64 and 99 nM, respectively. This resembled the complete antiaggregatory effect of eptifibatide. Multiparameter assessment of thrombus formation showed highly suppressed platelet adhesion and aggregate formation with both disagregins, in contrast to eptifibatide treatment, which incompletely blocked aggregation under flow. Fibrin formation under flow was delayed by both disagregin and RGD-disagregin (P Conclusions: Both alpha IIb beta 3-blocking disagregins have a strong potential to suppress collagen-tissue factor-mediated platelet adhesion, thrombus formation, and fibrin formation. Both disagregins can be seen as potential new alpha IIb beta 3 inhibitors.

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.

Introduction Recent trials report positive results for preventing vascular events with dual antiplatelet therapy (DAPT) in patients with high-risk TIA or minor ischemic stroke. We aimed to investigate this population regarding influence of age on vascular risk factors, hospital stay and mortality. Patients and methods Data on patients aged 40–100 years with TIA or ischemic stroke in the Swedish Stroke Register during 2012–13 were linked with national registers. To identify patients with high-risk TIA (ABCD2 ≥6) or minor ischemic stroke (NIHSS ≤5) eligible for DAPT, we excluded patients with atrial fibrillation, anticoagulant use, prior major bleeding, or unknown stroke severity. Findings We identified 10,053 potential DAPT-candidates (mean age 72.6 years, 45.2% female, 16.4% with TIA). With advancing age, most vascular risk factors increased. Antiplatelet treatment increased from 31.9% before the event to 95.5% after discharge. Within 1 year following index event, the proportion of patients with ≥1 re-admission increased with age (29.2% in 40–64 year-olds; 47.2% in 85–100 year-olds). All-cause death per 100 person-years was 6.9 (95% CI 6.4–7.4) within 1 year, and highest in the first 30 days (15.2; 95% CI 12.8–18.2). For each year of increased age, the risk of death increased with 3.5% (p = 0.128) in patients 40–64 years and with 11.8% (p Conclusions While in theory representing a subset of patients with mild injury, our observational study highlights substantial use of health-care resources and high mortality rates among patients with high-risk TIA or minor ischemic stroke assumed eligible for DAPT.

Oral health care providers must be aware of the impact of bleeding disorders on their patients during any dental procedure and management of such mishaps. Adequate knowledge of the mechanisms underlying hemostasis, and the optimised management of such patients, are therefore very important for these issues. Initial recognition of a bleeding disorder, in such patients with a systemic pathologic process, may occur in dental practice. The dental treatment of these patients might get complicated during the course of the treatment due to the use of anticoagulant and/or antiplatelet drugs raises a challenge in the daily practice of dental professionals. Adequate hemostasis is critical for the success of any invasive dental procedure, because bleeding problems can give rise to complications associated with important morbidity-mortality. Besides, prophylactic, restorative and surgical dental care of patients with any bleeding disorders is handled skilfully by practitioners who are well educated regarding the pathology, complications which could arise and treatment options associated with these conditions. The purpose of this paper is to review common bleeding disorders and their effects on the dental aspect. Many authors consider that patient medication indicated for the treatment of background disease should not be altered or suspended unless so indicated by the prescribing physician. Local hemostatic measures have been shown to suffice for controlling possible bleeding problems resulting from dental treatment.

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.