Search

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

Anticoagulant therapy is a cornerstone treatment for coronavirus disease 2019 (COVID-19) due to the high rates of thromboembolic complications associated with this disease. We hypothesized that chronic antithrombotic therapy could play a protective role in patients hospitalized for COVID-19. Retrospective, observational study of all patients admitted to our hospital for >= 24 h from March 1 to May 31, 2020 with SARS-CoV-2. The objective was to evaluate clinical outcomes and mortality in COVID-19 patients receiving chronic anticoagulation (AC) or antiplatelet therapy (AP) prior to hospital admission. A total of 1612 patients were evaluated. The mean (standard deviation; SD) age was 66.5 (17.1) years. Patients were divided into three groups according to the use of antithrombotic therapy prior to admission (AP, AC, or no-antithrombotic treatment). At admission, 9.6% of the patients were taking anticoagulants and 19.1% antiplatelet therapy. The overall mortality rate was 19.3%. On the multivariate analysis there were no significant differences in mortality between the antithrombotic groups (AC or AP) and the no-antithrombotic group (control group). Patients on AC had lower ICU admission rates than the control group (OR: 0.41, 95% CI, 0.18-0.93). Anticoagulation therapy prior to hospitalization for COVID-19 was associated with lower ICU admission rates. However, there were no significant differences in mortality between the patients receiving chronic antithrombotic therapy and patients not taking antithrombotic medications. These findings suggest that chronic anticoagulation therapy at the time of COVID-19 infection may reduce disease severity and thus the need for ICU admission.

Graphical Abstract The year in coronary interventions. ACS, acute coronary syndrome; CCS, chronic coronary syndrome; COVID-19: coronavirus disease-19; DEB, drug-eluting balloon; DAPT, dual antiplatelet therapy; ISR, in-stent restenosis.

Stroke is a common and devastating condition caused by atherothrombosis, thromboembolism, or haemorrhage. Patients with chronic coronary syndromes (CCS) or peripheral artery disease (PAD) are at increased risk of stroke because of shared pathophysiological mechanisms and risk-factor profiles. A range of pharmacological and non-pharmacological strategies can help to reduce stroke risk in these groups. Antithrombotic therapy reduces the risk of major adverse cardiovascular events, including ischaemic stroke, but increases the incidence of haemorrhagic stroke. Nevertheless, the net clinical benefits mean antithrombotic therapy is recommended in those with CCS or symptomatic PAD. Whilst single antiplatelet therapy is recommended as chronic treatment, dual antiplatelet therapy should be considered for those with CCS with prior myocardial infarction at high ischaemic but low bleeding risk. Similarly, dual antithrombotic therapy with aspirin and very-low-dose rivaroxaban is an alternative in CCS, as well as in symptomatic PAD. Full-dose anticoagulation should always be considered in those with CCS/PAD and atrial fibrillation. Unless ischaemic risk is particularly high, antiplatelet therapy should not generally be added to full-dose anticoagulation. Optimization of blood pressure, low-density lipoprotein levels, glycaemic control, and lifestyle characteristics may also reduce stroke risk. Overall, a multifaceted approach is essential to best prevent stroke in patients with CCS/PAD.

International audience; Background Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel. Objectives We compared EV concentrations and EV procoagulant activity in plasma of patients after AMI treated with ticagrelor or clopidogrel. Methods After percutaneous coronary intervention, 60 patients with first AMI were randomized to ticagrelor or clopidogrel. Flow cytometry was used to determine concentrations of EVs from activated platelets (CD61(+), CD62p(+)), fibrinogen(+), phosphatidylserine (PS+), leukocytes (CD45(+)), endothelial cells (CD31(+), 146(+)), and erythrocytes (CD235a(+)) in plasma at randomization, after 72 hours and 6 months of treatment. A fibrin generation test was used to determine EV procoagulant activity. Results Concentrations of platelet, fibrinogen(+), PS+, leukocyte, and erythrocyte EVs increased 6 months after AMI compared to the acute phase of AMI (P = .17). Conclusions Ticagrelor attenuates the increase of EV concentrations in plasma after acute myocardial infarction compared to clopidogrel. The ongoing release of EVs despite antiplatelet therapy might explain recurrent thrombotic events after AMI and worse clinical outcomes on clopidogrel compared to ticagrelor.

Introduction The aim of the study was to evaluate selected parameters of the coagulation system during the perioperative period in patients undergoing endoscopic sinus surgery. Material and methods The study involved 121 patients: group I - 42 patients who did not receive anticoagulatory or antiplatelet medications, qualified for endoscopic sinus surgery under total intravenous anaesthesia (TIVA); group II - 40 patients who received in the perioperative period low-molecular-weight heparins, qualified for endoscopic sinus surgery under TIVA; group III - 39 patients diagnosed according to a schedule, due to vertigo or loss of hearing. All the patients received a full laryngological examination and detailed audiological and otoneurological diagnostics, and examination of selected haemostatic parameters before the surgery/diagnostics. Results The analysis of concentrations of coagulation parameters in groups I and II revealed a statistically significantly higher international normalized ratio value before surgery (I - 1.11; II - 1.08) and 48 h following surgery (I - 1.15; II - 1.10) in group I. The concentration of coagulation factor VII in the study patients was considerably higher in group I for all three measurements (481.93; 443.13; 486.02). The concentration of fibrinogen (coagulation factor I) was significantly lower in group I before surgery (3.2) and at 6 h after surgery (2.84). A significantly lower level of von Willebrand factor was found in group I before surgery (2.94). Comparing test results of groups I and III, who did not receive antiaggregants, statistically significant differences were observed in both tests for factors VII and VIII. Conclusions Concentrations of von Willebrand factor and prothrombin revealed statistically significant differences in between groups.

Background: Patients with proximal femur fracture on antiplatelet treatment benefit from early surgery. Our goal was to perform early surgery under neuraxial anaesthesia when indicated by the platelet function test. Methods: We conducted a multicentre randomised open-label parallel clinical trial. Patients were randomised to either early platelet function-guided surgery (experimental group) or delayed surgery (control group). Early surgery was programmed when the functional platelet count (as measured by Plateletworks) was &gt, 80 × 109/L. The primary outcome was the emergency admission-to-surgery interval. Secondary outcomes were platelet function, postoperative bleeding, medical and surgical complications, and mortality. Results: A total of 156 patients were randomised, with 78 in each group, with a mean (SD) age of 85.96 (7.9) years, and 67.8% being female. The median (IQR) time to surgery was 2.3 (1.5–3.7) days for the experimental group and 4.9 (4.4–5.6) days for the control group. One-third of patients did not achieve the threshold functional platelet count on the first day of admission, requiring more than one test. There was no difference in clinical outcomes between groups. Conclusions: A strategy individualised according to the platelet function test shortens the time to proximal femur fracture surgery under neuraxial anaesthesia in patients on chronic antiplatelet treatment. Better powered randomised clinical trials are needed to further evaluate the clinical impact and safety of this strategy.

Sepsis is a complex syndrome with a high incidence, increasing by 8.7% annually over the last 20 years. Coagulopathy is a leading factor associated with mortality in patients with sepsis and range from slight thrombocytopenia to fatal disorders, such as disseminated intravascular coagulation (DIC). Platelet reactivity increases during sepsis but prospective trials of antiplatelet therapy during sepsis have been disappointing. Thrombocytopenia is a known predictor of worse prognosis during sepsis. The mechanisms underlying thrombocytopenia in sepsis have yet to be fully understood but likely involves decreased platelet production, platelet sequestration and increased consumption. DIC is an acquired thrombohemorrhagic syndrome, resulting in intravascular fibrin formation, microangiopathic thrombosis, and subsequent depletion of coagulation factors and platelets. DIC can be resolved with treatment of the underlying disorder, which is considered the cornerstone in the management of this syndrome. This review presents the current knowledge on the pathophysiology, diagnosis, and treatment of sepsis-associated coagulopathies.

Background No standard therapy is currently recommended for Corona-virus-19 disease (COVID-19). Autopsy studies showed high prevalence of platelet-fibrin rich micro-thrombi in several organs. Aim of the study was to evaluate safety and efficacy of antiplatelet therapy (APT) in COVID-19 hospitalized patients and its impact on survival. Methods 7824 consecutive patients with COVID-19 were enrolled in a multicenter-international prospective registry (HOPE-COVID19). Clinical data and in-hospital complications were recorded. AP regimen, including aspirin and other antiplatelet drugs, was obtained for each patient. Results During hospitalization 730 (9.3%) patients received AP drugs with single (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (73±12 vs 62±17 years, p Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64, Log Rank p=0.23), need of invasive ventilation (8.7% vs 8.5%, p=0.88) and bleeding (2.1% vs 2.4%, p=0.43); However, after excluding patients treated only with anticoagulation, APT was associated with lower mortality rates (Log Rank p At multivariable analysis including age, gender, diabetes, hypertension, respiratory failure, pre-hospital therapy with antiplatelet drugs, in-hospital APT, and anticoagulation therapy, in-hospital APT was associated with a lower mortality risk (relative risk 0.29, 95% CI 0.22–0.38, p Conclusions APT during hospitalization for COVID-19 could be associated with lower mortality risk without increased risk of bleeding. Randomized trials are needed to confirm these preliminary data. Funding Acknowledgement Type of funding sources: None. Figure 1

Background and objectives: Because few data are available, the aim of this study is to analyze the effects of antithrombotic agents (ATAs) on visual function and long-term risk of cardiovascular events and mortality in hypertensive patients with retinal vein occlusion (RVO). Materials and methods: Hypertensive patients with RVO were consecutively selected from 2008 to 2012 and followed for a median of 8.7 years. Ophthalmologists evaluated and treated RVO complications, and best-corrected visual acuity (BCVA) was checked at each visit during the first one year of follow-up. Survival analysis was conducted on the rate of the composite endpoint of all-cause deaths or non-fatal cardiovascular events. Results: Retrospectively, we collected data from 80 patients (age 68 ± 12 years, 39 males). Central and branch RVO was present in 41 and 39 patients, respectively, and 56 patients started ATAs (50 antiplatelet drugs, 6 warfarin, and 2 low-molecular weight heparin). Average BCVA of the cohort did not change significantly during one-year of follow-up. The only predictor of BCVA was the baseline BCVA value. There was a reduction in proportion and severity of macular edema and an increase in the cumulative proportion of retinal vein patency reestablishment during the follow-up, independent of treatment. ATAs had no effects on one-year BCVA, intraocular complications, or the composite endpoint rate. Conclusions: In this exploratory study, ATAs had no effect on BCVA during the first one year of follow-up and on the composite endpoint during the long-term follow-up. Further prospective studies need to be conducted with an accurate standardization of the intraocular and antithrombotic treatment to define the positive or negative role of ATAs in hypertensive patients with RVO.

Background Antiplatelet drugs may prevent recurrent ischemic events after ischemic stroke but their relative effectiveness and harms still need to be clarified. Within this network meta-analysis we aimed to summarize the current evidence for using antiplatelet drugs for secondary stroke prevention. Methods We searched MEDLINE, EMBASE and CENTRAL up to September 2020. Randomized controlled trials (RCTs) assessing antiplatelet drugs for secondary stroke prevention were included. We did pairwise meta-analyses and network meta-analyses using random-effects models. Primary outcomes were all strokes (ischemic or hemorrhagic) and all-cause mortality. Results The review included 57 RCTs, 50 (n = 165,533 participants) provided data for the meta-analyses. Compared to placebo/no treatment, moderate to high-confidence evidence indicated that cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day significantly reduced the risk of all strokes (odds ratios, ORs and absolute risk difference, ARD): cilostazol 0.51 (95 % confidence interval, CI, 0.37 to 0.71; 3.6 % fewer), clopidogrel 0.63 (95 % CI, 0.49 to 0.79; 2.7 % fewer), dipyridamole + aspirin 0.65 (95 % CI, 0.55 to 0.78; 2.5 % fewer), ticagrelor 0.68 (95 % CI, 0.50 to 0.93; 2.3 % fewer), ticlopidine 0.74 (95 % CI 0.59 to 0.93; 1.9 % fewer), aspirin ≤ 150 mg/day 0.79 (95 % CI, 0.66 to 0.95; 1.5 % fewer). Aspirin > 150 mg/day and the combinations clopidogrel/aspirin, ticagrelor/aspirin, also decrease all strokes but increase the risk of hemorrhagic events. Only aspirin > 150 mg/day significantly reduced all-cause mortality (OR 0.86, 95 % CI 0.76 to 0.97; ARD 0.9 %, 95 %CI 1.5–0.2 % fewer, moderate confidence). Compared to aspirin ≤ 150 mg/day, clopidogrel significantly reduced the risk of all strokes, cardiovascular events, and intracranial hemorrhage outcomes. Cilostazol also appeared to provide advantages but data are limited to the Asian population. Conclusions Considering the benefits and harms ratio, cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day appear to be the best choices as antiplatelet drugs for secondary prevention of patients with ischemic stroke or TIA. Systematic review registration PROSPERO CRD42020159896.

WOS: 000455438000004, PubMed ID: 30079702, Background: The use of warfarin and aspirin in combination is restricted to limited patients under relevant guidelines. Aims: To evaluate the prevalence of the inappropriate combination of aspirin and warfarin therapy in daily practice and its risks. Study Design: Cross-sectional study. Methods: The awareness, efficacy, safety, and time in the therapeutic range of warfarin in the Turkish population study is a multi-center observational study that includes 4987 patients using warfarin for any reason between January 1, 2014, and December 31, 2014. To determine the prevalence of inappropriate combination use in daily practice, all patients who had a history of atherosclerotic disease (ischemic heart disease, peripheral artery disease) or cerebrovascular disease (n=1498) were excluded. The data of 3489 patients were analyzed. We defined inappropriate combination as all patients who received aspirin and warfarin regardless of the indication for warfarin use, under the direction of the European Society of Cardiology guideline recommendation. Results: The mean age of patients was 59.2 +/- 13.8 years (41.8% male). The prevalence of the inappropriate use of warfarin and aspirin combination was 20.0%. The prevalence of combination therapy in patients with a primary indication for mechanical heart valve, non-valvular atrial fibrillation, and other reasons was 20.5%, 18.7%, and 21.0%, respectively. Multivariate logistic regression analysis revealed that age (odds ratio, 1.009; 95% confidence interval, 1.002-1.015; p=0.010), heart failure (odds ratio, 1.765; 95% confidence interval, 1.448-2.151; p

BACKGROUND AND OBJECTIVES: Antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) has changed in recent years with new data from large randomized trials and updates to clinical guidelines. This study aimed to investigate the trends in periprocedural antithrombotic regimens in Korean patients with AF undergoing PCI with non-vitamin K antagonist oral anticoagulants (NOACs).METHODS: Using the claims database of the Health Insurance Review and Assessment during 2013-2018, 27,594 patients with AF undergoing PCI were identified. The annual prevalence of PCI and prescriptions of each antithrombotic agent, including antiplatelet agents and oral anticoagulants, within 30 days after PCI were investigated.RESULTS: During 2013-2018, the number of patients with AF undergoing PCI increased up to 1.3-fold (from 3,913 to 5,075 patients per year). After the introduction of NOACs, the proportion of dual antiplatelet therapy (DAPT) decreased from 71.9% to 49.8% but still occupied the largest proportion among antithrombotic regimens. Triple antithrombotic therapy (TAT) use increased from 25.4% to 46.0%, and NOAC has rapidly replaced warfarin as the oral anticoagulant of choice. TAT was preferred to DAPT for patients with CHA₂DS₂-VASc score ≥2. Among various factors, prior intracranial hemorrhage was the most powerful predictor of favoring DAPT use over TAT.CONCLUSION: Since the introduction of NOACs, the patterns of periprocedural antithrombotic regimens have changed rapidly toward more use of TAT, specifically with NOAC-based regimen. Appropriate stroke prevention with oral anticoagulants is still underutilized in patients with AF undergoing PCI in Korea.

We conducted this retrospective analysis to assess whether oral antiplatelet drugs (APDs) during radiotherapy increase bleeding risk. Patients who underwent radiotherapy for esophageal cancer (EC) in the Third Affiliated Hospital of Soochow University from January 2015 to December 2019 were screened. After the differences in clinical parameters were eliminated by a propensity-score matched (PSM) analysis at a 1:1 ratio, the thrombocytopenia, consumption of platelet-increasing drugs, suspension of radiotherapy, and bleeding in patients taking APDs were compared with those in the control group. A total of 986 patients were included in the original dataset. Of these, 34 patients took APDs during radiotherapy. After matching, the APD and control groups each retained 31 patients. There was no significant difference in platelet concentrations between the two groups before radiotherapy (P = .524). The lowest platelet concentration during radiotherapy in the APD group was significantly lower (P = .033). The consumption of platelet-increasing drugs in the APD group was higher than that in the control group (P

Background Patients using antiplatelet drugs following infarctions, acute coronary syndrome or stroke pose a significant clinical problem if it is necessary to perform surgery, including dental surgery, since they are at risk of prolonged or secondary post-extraction bleeding. Discontinuation of this therapy is associated with a high risk of serious thromboembolic complications. The purpose of this study was to assess the effectiveness of TachoSil fibrin-collagen patches in stopping and preventing of secondary post-extraction bleeding in patients undergoing chronic antiplatelet therapy. Methods The study was conducted through retrospective examination of the medical records of 153 patients using chronic antiplatelet therapy and those qualified for tooth extraction. The largest group comprised 74 patients using aspirin and clopidogrel as dual platelet antiaggregation therapy; in this group 75 tooth extractions were carried out. In all of the patients TachoSil fibrin-collagen patches and stiches were applied to the wounds resulting from tooth removal. Results Following tooth extraction, primary bleeding was stopped in all the patients and their wounds closed via coagulation within 20–30 min. In eight cases, accounting for 4.9% of the patients, secondary bleeding occurred and was successfully stopped only by applying a pressure dressing soaked in tranexamic acid. Secondary bleeding occurred in three patients on the second day and in five patients on the third day following tooth removal. Conclusion Topical application of TachoSil patches following tooth removal in patients using single or dual antiplatelet therapy effectively stopped bleeding and prevented secondary bleeding after tooth extraction.

Our aim was to assess whether long-term adherence to a Mediterranean diet (MedDiet) and leisure-time physical activity (LTPA) were associated with a lower initiation of cardiovascular drug use. We studied the association between cumulative average of MedDiet adherence and LTPA and the risk of cardiovascular drug initiation in older adults at high cardiovascular risk (PREvención con DIeta MEDiterránea trial participants) non-medicated at baseline: glucose-lowering drugs (n = 4437), antihypertensives (n = 2145), statins (n = 3977), fibrates (n = 6391), antiplatelets (n = 5760), vitamin K antagonists (n = 6877), antianginal drugs (n = 6837), and cardiac glycosides (n = 6954). One-point increases in MedDiet adherence were linearly associated with a decreased initiation of glucose-lowering (HR: 0.76 [0.71–0.80]), antihypertensive (HR: 0.79 [0.75–0.82]), statin (HR: 0.82 [0.78–0.85]), fibrate (HR: 0.78 [0.68–0.89]), antiplatelet (HR: 0.79 [0.75–0.83]), vitamin K antagonist (HR: 0.83 [0.74, 0.93]), antianginal (HR: 0.84 [0.74–0.96]), and cardiac glycoside therapy (HR: 0.69 [0.56–0.84]). LTPA was non-linearly related to a delayed initiation of glucose-lowering, antihypertensive, statin, fibrate, antiplatelet, antianginal, and cardiac glycoside therapy (minimum risk: 180–360 metabolic equivalents of task-min/day). Both combined were synergistically associated with a decreased onset of glucose-lowering drugs (p-interaction = 0.04), antihypertensive drugs (p-interaction &lt, 0.001), vitamin K antagonists (p-interaction = 0.04), and cardiac glycosides (p-interaction = 0.01). Summarizing, sustained adherence to a MedDiet and LTPA were associated with lower risk of initiating cardiovascular-related medications.

Intracerebral hemorrhage (ICH) represents a major, global, unmet health need with few treatments. A significant minority of ICH patients present taking an anticoagulant; both vitamin-K antagonists and increasingly direct oral anticoagulants. Anticoagulants are associated with an increased risk of hematoma expansion, and rapid reversal reduces this risk and may improve outcome. Vitamin-K antagonists are reversed with prothrombin complex concentrate, dabigatran with idarucizumab, and anti-Xa agents with PCC or andexanet alfa, where available. Blood pressure lowering may reduce hematoma growth and improve clinical outcomes and careful (avoiding reductions ≥60 mm Hg within 1 h), targeted (as low as 120–130 mm Hg), and sustained (minimizing variability) treatment during the first 24 h may be optimal for achieving better functional outcomes in mild-to-moderate severity acute ICH. Surgery for ICH may include hematoma evacuation and external ventricular drainage to treat hydrocephalus. No large, well-conducted phase III trial of surgery in ICH has so far shown overall benefit, but meta-analyses report an increased likelihood of good functional outcome and lower risk of death with surgery, compared to medical treatment only. Expert supportive care on a stroke unit or critical care unit improves outcomes. Early prognostication is difficult, and early do-not-resuscitate orders or withdrawal of active care should be used judiciously in the first 24–48 h of care. Implementation of acute ICH care can be challenging, and using a care bundle approach, with regular monitoring of data and improvement of care processes can ensure consistent and optimal care for all patients.

The ticagrelor represents a cornerstone of antiplatelet therapy and its use has been supported, over the years, by several clinical trials that have enrolled thousands of patients; while the PLATO study initially demonstrated its effectiveness in the immediate treatment of acute coronary syndromes, the PEGASUS study documented the benefit of prolonging this treatment beyond 12 months from the heart attack. Over the past few months, two new randomized clinical trials have been published that have seen the use of ticagrelor in different clinical settings. The TWILIGHT study showed that in high-risk patients who completed 3 months of double antiplatelet drugs after coronary angioplasty, ticagrelor monotherapy is associated with a 44% reduction in the risk of clinically relevant bleeding in the absence of an increase in the ischaemic risk. The THEMIS study instead concluded that in the population of diabetics with stable coronary artery disease, but without a history of heart attack or stroke, a strategy that involves the addition of ticagrelor to the acetylsalicylic acid is not advisable as in the face of a benefit in the prevention of events ischaemic an increased risk of bleeding has been observed. Only in the subgroup of diabetic patients with a history of previous angioplasty would a more powerful antithrombotic therapy seem to be advantageous.

Background Spontaneous retroperitoneal haemorrhage (SRH) is a rare cause of retroperitoneal haemorrhage in patients who are on anticoagulants or antiplatelet agents or both. Case summary We report here a rare and catastrophic complication of use of anticoagulants and antiplatelet drugs in a case undergoing coronary angioplasty. The patient had multiple coronary risk factors and developed acute myocardial infarction with pulmonary oedema and hypotension during hospitalization for treatment of lower respiratory tract infection and diabetic ketoacidosis. He underwent successful angioplasty of the culprit vessel but later developed hypotension attributable to retroperitoneal haemorrhage. No bleeding site was identified despite extensive evaluation of the aorta and iliac vessels. Discussion A diagnosis of SRH is considered when a patient on anticoagulants or antiplatelet drugs develops retroperitoneal haemorrhage without any specific identifiable site of bleeding in the retroperitoneum. Diffuse vasculopathy and atherosclerosis or vasculitis of the small vessels in the retroperitoneum may result in rupture of the most friable vessels and result in bleeding. Intense cough, forceful vomiting or sneezing may also be responsible for traumatizing the vessels and resulting in bleeding. Most cases recover with conservative management but some may benefit from interventional occlusion of the leak or surgical decompression in cases of abdominal compartment syndrome.

Platelets are a heterogeneous small anucleate blood cell population with a central role both in physiological haemostasis and in pathological states, spanning from thrombosis to inflammation, and cancer. Recent advances in proteomic studies provided additional important information concerning the platelet biology and the response of platelets to several pathophysiological pathways. Platelets circulate systemically and can be easily isolated from human samples, making proteomic application very interesting for characterizing the complexity of platelet functions in health and disease as well as for identifying and quantifying potential platelet proteins as biomarkers and novel antiplatelet therapeutic targets. To date, the highly dynamic protein content of platelets has been studied in resting and activated platelets, and several subproteomes have been characterized including platelet-derived microparticles, platelet granules, platelet releasates, platelet membrane proteins, and specific platelet post-translational modifications. In this review, a critical overview is provided on principal platelet proteomic studies focused on platelet biology from signaling to granules content, platelet proteome changes in several diseases, and the impact of drugs on platelet functions. Moreover, recent advances in quantitative platelet proteomics are discussed, emphasizing the importance of targeted quantification methods for more precise, robust and accurate quantification of selected proteins, which might be used as biomarkers for disease diagnosis, prognosis and therapy, and their strong clinical impact in the near future.

El ticagrelor es un medicamento antiagregante plaquetario utilizado como prevención secundaria en pacientes con síndrome coronario agudo. Dentro de las reacciones adversas reportadas secundarias a su administración se encuentran hemorragias, cefalea, disnea, epistaxis, pausas ventriculares o bradicardia, hiperuricemia y elevación de la creatinina. No obstante, las reacciones de hipersensibilidad han sido raras. Presentamos un paciente masculino de 63 años con infarto agudo del miocardio, elevación de ST y documentándose en cateterismo cardíaco ectasia y enfermedad de flujos lentos. Requirió terapia de antiagregación dual con ácido acetilsalicílico (ASA) y ticagrelor, con posterior urticaria de origen medicamentoso según concepto de dermatología. Se manejó con esteroide tópico, antihistamínico oral y retiro de ticagrelor. Se considera un caso raro de reacción al antiagregante plaquetario descrito.

Background: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. Methods: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. Results: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78–1.30; P =0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13–1.00; P =0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85–3.16; P =0.18). Conclusions: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01777503.

Background: The relationship between obstructive sleep apnea (OSA) and platelet reactivity in patients undergoing percutaneous coronary intervention (PCI) has not been defined. The present prospective, single-center study explored the relationship between platelet reactivity and OSA in patients with PCI. Methods: A total of 242 patients were finally included in the study. OSA was screened overnight by polysomnography. Platelet reactivity was assessed with a sequential platelet counting method, and the platelet maximum aggregation ratio (MAR) and average aggregation ratio were calculated. All patients were assigned per apnea-hypopnea index (AHI) to non-OSA (n = 128) and OSA (n = 114) groups. The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity (HPR) on aspirin and clopidogrel, and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel. Results: Median AHI was significantly higher in the OSA group than in the non-OSA group (34.5 events/h vs. 8.1 events/h, Z= −13.422, P < 0.001). Likewise, median arachidonic acid- and adenosine diphosphate-induced maximum aggregation rate (MAR) in the OSA group was significantly higher than those in the non-OSA group (21.1% vs. 17.7%, Z= −3.525, P < 0.001 and 45.8% vs. 32.2%, Z= −5.708, P < 0.001, respectively). Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin (odds ratio [OR]: 1.055, 95% confidence interval [CI]: 1.033–1.077, P < 0.001) and clopidogrel (OR: 1.036, 95% CI: 1.017–1.056, P < 0.001). The cutoff value of AHI for HPR on aspirin was 45.2 events/h (sensitivity 47.1% and specificity 91.3%), whereas cutoff value of AHI for HPR on clopidogrel was 21.3 events/h (sensitivity 68.3% and specificity 67.7%). Conclusion: Platelet reactivity appeared to be higher in OSA patients with PCI despite having received a loading dose of aspirin and clopidogrel, and OSA might be an independent predictor of HPR on aspirin and clopidogrel. Key words: Antiplatelet Drugs; Maximum Aggregation Rate; Obstructive Sleep Apnea; Percutaneous Coronary Intervention; Platelet Reactivity

Novel antiplatelet drugs, including ticagrelor, are being successively introduced into the therapy of atherothrombotic conditions due to their superiority over a standard combination of clopidogrel with acetylsalicylic acid in patients with acute coronary syndromes (ACS). A P2Y12 receptor antagonist, ticagrelor, is unique among antiplatelet drugs, because ticagrelor inhibits the platelet P2Y12 receptor in a reversible manner, and because it demonstrates a wide palette of advantageous pleiotropic effects associated with the increased concentration of adenosine. The pleiotropic effects of ticagrelor comprise cardioprotection, restoration of the myocardium after an ischemic event, promotion of the release of anticoagulative factors and, eventually, anti-inflammatory effects. Beyond the advantageous effects, the increased concentration of adenosine is responsible for some of ticagrelor's adverse effects, including dyspnea and bradycardia. Large-scale clinical trials demonstrated that both standard 12-month therapy and long-term use of ticagrelor reduce the risk of cardiovascular events in patients with ACS, but at the expense of a higher risk of major bleeding. Further trials focused on the use of ticagrelor in conditions other than ACS, including ischemic stroke, peripheral artery disease and status after coronary artery bypass grafting. The results of these trials suggest comparable efficacy and safety of ticagrelor and clopidogrel in extra-coronary indications, but firm conclusions are anticipated from currently ongoing studies. Here, we summarize current evidence on the superiority of ticagrelor over other P2Y12 antagonists in ACS, discuss the mechanism underlying the drug-drug interactions and pleiotropic effects of ticagrelor, and present future perspectives of non-coronary indications for ticagrelor.

MicroRNAs are short non - coding RNAs that correlate with the levels of platelet activation which can be utilized as a biomarker when guiding P2Y12 inhibitors therapy. In this literature review, the perspectives of microRNA as a novel biomarker are discussed when guiding P2Y12 inhibitors therapy among the patients with coronary artery disease.Микро-РНК - короткие некодирующие цепочки РНК, в отношении которых обнаружено, что уровни специфических семейств микро-РНК коррелируют с уровнем активации тромбоцитов, что может быть использовано в качестве биомаркера при оценке терапии ингибиторами P2Y12-рецепторов. В обзоре обсуждены перспективы использования микро-РНК как нового транскриптомного биомаркера прогнозирования индивидуального фармакологического ответа на ингибиторы P2Y12 у пациентов с ишемической болезнью сердца.

Background Heavy menstrual bleeding (HMB) is common among reproductive‐aged women receiving oral antithrombotics and frequently results in a negative impact on quality of life. Methods We translated the Menstrual Bleeding Questionnaire (MBQ) into Thai by forward translation, back‐translation, pretesting, and cognitive interviewing. The translated questionnaire was content validated by a gynecologist. A validation study was conducted for the translated MBQ and defined the optimal score for the diagnosis of HMB. We then performed a cross‐sectional study to determine the prevalence of HMB using the translated MBQ. Reproductive‐aged Thai women who visited outpatient clinics receiving oral antithrombotics were asked to assess menstrual characteristics after receiving antithrombotics. The impact of menstruation on quality of life was assessed by using the MBQ. Results The translated MBQ had excellent reliability (intraclass correlation coefficient = 0.93) and discriminated between women with and without HMB (area under the receiver operating characteristic curve = 0.93). A score of 21.5 had 82.9% sensitivity and 83.1% specificity in the diagnosis of HMB. The mean (standard deviation) of the score was significantly higher in the HMB group than in the normal menstrual bleeding group (30.4 [9.4] vs 15.4 [5.6]; P

Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general population, the role of VWF in acute and chronic liver injury has not been examined in depth in experimental settings. We tested the hypothesis that VWF deficiency inhibits experimental liver injury and fibrosis. Wild-type (WT) and VWF-deficient mice were challenged with carbon tetrachloride (CCl4) and the impact of VWF deficiency on acute liver injury and chronic liver fibrosis was determined. VWF deficiency did not significantly affect acute CCl4-induced hepatocellular necrosis in mice. Chronic CCl4 challenge, twice weekly for 6 weeks, significantly increased hepatic stellate cell activation and collagen deposition in livers of WT mice. Interestingly, hepatic induction of several profibrogenic and stellate cell activation genes was attenuated in VWF-deficient mice. Moreover, birefringent sirius red staining (indicating type I and III collagens) and type I collagen immunofluorescence indicated a reduction in hepatic collagen deposition in CCl4-exposed VWF-deficient mice compared to CCl4-exposed WT mice. The results indicate that VWF deficiency attenuates chronic CCl4-induced liver fibrosis without affecting acute hepatocellular necrosis. The results are the first to demonstrate that VWF deficiency reduces the progression of liver fibrosis, suggesting a mechanistic role of elevated plasma VWF levels in cirrhosis. (C) 2017 Elsevier Inc. All rights reserved.

Type 2 diabetes mellitus (T2DM) is associated with several cardiovascular (CV) risk factors such as insulin resistance, obesity, hypertension, dyslipidaemia, non-alcoholic fatty liver disease as well as platelet and haemostatic abnormalities increasing the risk of thrombosis. Therefore, T2DM patients are at an increased risk for CV disease (CVD). Areas covered: This narrative review discusses the treatment of T2DM. This includes lifestyle measures (diet, exercise and smoking cessation) as well as hypolipidaemic, antihypertensive, weight reducing, antiplatelet and glucose lowering drugs. The focus is on the effects of these therapeutic strategies on CVD risk. Randomized controlled clinical trials (RCTs) reporting CVD outcomes with such drugs in T2DM patients are also reviewed. Expert opinion: Apart from current guidelines, the findings of RCTs on CVD outcomes in T2DM patients should be taken into consideration in daily clinical practice. Multiple risk factors should be targeted simultaneously in such high-risk patients in order to efficiently reduce the risk of CV events.

Essentials: Vessel stenosis due to large thrombus formation increases local shear 1-2 orders of magnitude. High shear at stenotic sites was exploited to trigger eptifibatide release from nanocapsules. Local delivery of eptifibatide prevented vessel occlusion without increased tail bleeding times. Local nanocapsule delivery of eptifibatide may be safer than systemic antiplatelet therapies. Summary: Background: Myocardial infarction and stroke remain the leading causes of mortality and morbidity. The major limitation of current antiplatelet therapy is that the effective concentrations are limited because of bleeding complications. Targeted delivery of antiplatelet drug to sites of thrombosis would overcome these limitations. Objectives: Here, we have exploited a key biomechanical feature specific to thrombosis, i.e. significantly increased blood shear stress resulting from a reduction in the lumen of the vessel, to achieve site-directed delivery of the clinically used antiplatelet agent eptifibatide by using shear-sensitive phosphatidylcholine (PC)-based nanocapsules. Methods: PC-based nanocapsules (2.8 × 1012) with high-dose encapsulated eptifibatide were introduced into microfluidic blood perfusion assays and into in vivo models of thrombosis and tail bleeding. Results: Shear-triggered nanocapsule delivery of eptifibatide inhibited in vitro thrombus formation selectively under stenotic and high shear flow conditions above a shear rate of 1000 s-1 while leaving thrombus formation under physiologic shear rates unaffected. Thrombosis was effectively prevented in in vivo models of vessel wall damage. Importantly, mice infused with shear-sensitive antiplatelet nanocapsules did not show prolonged bleeding times. Conclusions: Targeted delivery of eptifibatide by shear-sensitive nanocapsules offers site-specific antiplatelet potential, and may form a basis for developing more potent and safer antiplatelet drugs.

Current guidelines for the management of atrial fibrillation (AF) recommend using anticoagulants as first-line drugs for stroke prevention, but in real medical practice antiplatelet drugs are often prescribed to elderly patients. Review of clinical and pharmacoepidemiological studies allows us to conclude that risk associated with acetylsalicylic acid (ASA) use in patients ≥75 years can overweigh its potential benefit. Other antiplatelet drugs are poorly studied in patients with AF. Dual antiplatelet therapy (ASA + clopidogrel) can be prescribed to elderly patients with cardiovascular comorbidity who are deemed unsuitable candidates for anticoagulant therapy for reasons other than bleeding risk or those who refuse to take oral anticoagulants. Combined therapy of antiplatelet drugs with warfarin or new oral anticoagulants results in no reduction in stroke rate compared with anticoagulant monotherapy but is associated with increased risk of bleeding and can’t be recommended.

Introduction: Type 2 diabetes mellitus (T2DM) is an important and common cardiovascular risk factor. The purpose of the study was to evaluate the frequency of use of oral antiplatelet drugs (OAPs) and oral anticoagulant drugs (OACs) among the elderly with T2DM in Poland. Material and methods: The study was based on the data collected in the Polish national PolSenior study. Results: Among 4979 PolSenior participants aged 65 and over, 883 (17.8%) had previously diagnosed T2DM. Among them, 441 (49.9%) used at least one drug in pharmacological cardiovascular prevention, i.e. OAPs (mostly ASA) in 405 (45.9%) cases and OACs in 38 (4.3%). The use of these drugs significantly depended on the sex (p = 0.02) and personal income (p = 0.05). Age, place of residence and level of education did not affect the prevalence of pharmacological prevention. Previous stroke and myocardial infarction were mostly associated with OAPs, whereas a history of atrial fibrillation (AF) was related to OAC treatment. Among participants treated with OAPs, therapy was applied as secondary cardiovascular prevention in 211 (52.1%) subjects, and as primary prevention in 194 (47.9%) subjects. Among participants treated with OACs, 24 (64.9%) persons had a history of AF. Secondary cardiovascular pharmacological prevention should be considered in 45 untreated participants (12.5%), and primary cardiovascular pharmacological prevention (SCORE ≥ 10 and/or AF) in 154 participants (42.7%). Conclusions : Cardiovascular pharmacological prevention in the elderly with T2DM in Poland seems to be unsatisfactory. Educational programmes concerning current recommendations for pharmacological cardiovascular prevention should be developed among general practitioners.

Antiplatelet drugs are often used on a regular basis as a part of primary or secondary prevention of cardiovascular diseases. Patients on antiplatelet therapy often require Noncardiac Surgery and in this situation the current issue becomes antiplatelet drug suspension timing whether it is safe, and how to overcome the lack of their implementation in the perioperative period. Venous thromboembolism is a major public health issue and one of the leading causes of mortality in general. It is also the cause of significant mor­bidity inducing short- and long-term complications. It has been demonstrated that anticoagulant therapy is effective in the prevention of Venous thromboembolism although it may be a potential cause of bleeding. However, benefit-risk ratio of widespread used postoperative prophylactic antico­agulation therapy is highly positive inpatients with moderate or high risk of deep vein thrombosis.

Use of antiplatelet therapy in the world indicates real difference in individual drug effect between patients, including the effect on prognosis. Problems of personification of individual approach, concerning antiplatelet therapy, are discussed.

Currently the problem of preventing cerebrovascular disorders, in which antiplatelet therapy takes one of the leading places, remains relevant. The efficiency of the therapy depends on a large number of modifiable and non-modifiable factors. There are many methods to assess the severity of the response to antiplatelet therapy, but there is no common approach to the assessment of the results and their prognostic significance. Further studies of this issue are essential with the aim of individualization of antiplatelet therapy thereby increasing its efficiency and safety.

Background Diabetes mellitus, largely type 2, affects nearly 10% of the global adult population according to the World Health Organization. Diabetes is an independent risk factor for atherosclerotic cardiovascular diseases, including coronary artery disease. Diabetes patients experience a two to three-fold increased incidence of coronary artery disease, despite improved metabolic control and management of other cardiovascular risk factors. Discussion Platelet abnormalities and activation as well as reduced antiplatelet drug responsiveness characterise diabetes mellitus. Mechanisms linking diabetes to platelet and vascular abnormalities, atherogenesis and atherosclerotic cardiovascular disease are still only partially known, highlighting the unique complexity of the pro-atherogenic clinical scenario and its treatment. Consistently, a higher residual cardiovascular risk characterises patients with diabetes compared with those without, in spite of improved antiplatelet and antithrombotic treatment combinations. Randomised clinical trials aimed at optimising antiplatelet treatment specifically in patients with diabetes are lacking, both in acute and chronic coronary artery disease settings. Thus, patients with diabetes are treated with regimens validated in studies including only variable proportions of diabetes patients. Myocardial revascularisation appears to confer a comparable relative benefit between diabetes patients and patients without diabetes, and generally coronary artery bypass grafting has a better outcome in diabetes mellitus versus peripheral coronary intervention. New glucose-lowering drugs have been shown to reduce the incidence of major cardiovascular events in secondary prevention. Type 1 diabetes mellitus remains less explored than type 2 in this context. Conclusion Diabetes-tailored antithrombotic strategies in acute and chronic coronary artery disease remain an unmet clinical need, requiring ad-hoc trials and precision pharmacological strategies.

International audience; Over the past two decades, aspirin has emerged as a promising chemoprotective agent to prevent colorectal cancer (CRC). In 2016, the mounting evidence supporting its chemoprotective effect, from both basic science and clinical research, led the US Preventive Services Task Force to recommend regular use of low-dose aspirin in some subgroups of patients for whom the benefits are deemed to outweigh the risks. In contrast, data on the chemoprotective effect of aspirin against other cancers are less clear and remain controversial. Most data come from secondary analyses of cardiovascular prevention trials, with only a limited number reporting cancer outcomes as a prespecified endpoint, and overall unclear findings. Moreover, the potential chemoprotective effect of aspirin against other cancers has been recently questioned with the publication of 3 long-awaited trials of aspirin in the primary prevention of cardiovascular diseases reporting no benefit of aspirin on overall cancer incidence and cancer-related mortality. Data on the chemoprotective effects of other antiplatelet agents remain scarce and inconclusive, and further research to examine their benefit are warranted. In this narrative review, we summarize current clinical evidence and continuing controversies on the potential chemoprotective properties of antiplatelet agents against cancer.

Background: Nowadays, patients involved in antiplatelet therapy required special attention during oral surgery procedures, due to the antiplatelet drugs assumption. The motivations of the assumption may be different and related to the patient&rsquo, s different systemic condition. For this reason, accordingly to the current international guidelines, different protocols can be followed. The aim of this work is to analyze how the dentist&rsquo, s approach to these patients has changed from the past to the present, evaluating the risk exposure for the patients. Methods: This review paper considered different published papers in literature through quoted scientific channels, going in search of &ldquo, ancient&rdquo, works in such a way as to highlight the differences in the protocols undertaken. The analyzed manuscripts are in the English language, taking into consideration reviews, case reports, and case series in such a way as to extrapolate a sufficient amount of data and for evaluating the past therapeutic approaches compared to those of today. Results: Colleagues in the past preferred to subject patients to substitution therapy with low molecular weight anticoagulants, by suspending antiplatelet agents to treatment patients, often for an arbitrary number of days. The new guidelines clarify everything, without highlighting an increased risk of bleeding during simple oral surgery in patients undergoing antiplatelet therapy. Conclusion: Either patients take these medications for different reasons, because of cardiovascular pathologies, recent cardiovascular events, or even for simple prevention, although the latest research shows that there is no decrease of cardiovascular accidents in patients who carry out preventive therapy. Surely, it will be at the expense of the doctor to assess the patient&rsquo, s situation and risk according to the guidelines. For simple oral surgery, it is not necessary to stop therapy with antiplatelet agents because the risk of bleeding has not increased, and is localized to a post-extraction alveolus or to an implant preparation, compared to patients who do not carry out this therapy. From an analysis of the results it emerges that the substitutive therapy should no longer be performed and that it is possible to perform oral surgery safely in patients who take antiplatelet drugs, after a thorough medical history. Furthermore, by suspending therapy, we expose our patients to more serious risks, concerning their main pathology, where present.

Background: Dental treatment in patients on antiplatelet drug therapy is a long standing debate. Discontinuation of medication increases the risk of thrombotic complications, whereas continuation leads to increased postoperative bleeding. Aim: We conducted this prospective cross-sectional study to assess risk of bleeding in patients continuing antiplatelet medication while performing minor oral surgical procedures such as single or multiple teeth extraction, transalveolar extraction of third molar, biopsy, and alveoloplasty. Materials and Methods: We calibrated the steps taken to achieve hemostasis, time taken to arrest bleeding, and correlated time taken to achieve hemostasis in patients under antiplatelet drug therapy (Group A [n = 64] - aspirin, Group B [n = 36] - aspirin and clopidogrel) and in patients without any drug therapy (Group C [n = 100] healthy patients). Results: Out of 200 patients, Level 1 hemostatic measures were required for 129 (64.5%) patients, Level 2 hemostatic measures were taken for 68 (34.0%) patients, and Level 3 hemostatic measures were taken for 3 (1.5%) patients. Chi-square test conducted to compare the local hemostatic measures taken for minor oral surgical procedure for all groups was statistically significant (P ≤ 0.001). Conclusion: Overall, there was no postoperative bleeding within 24 h of extraction in any patient group. In conclusion, surgical procedures can be safely accomplished in patients receiving single or dual antiplatelet therapy when appropriate local hemostatic measures are taken.

The article describes the basic principles of correction and prevention of subclinical forms of placental insufficiency in patients with anamnestic risk factors for the development of this pathology. Pathogenetic substantiation of administration of antiplatelet and angioprotective therapy during pregnancy in risk group patients is provided. It is given to discuss the possibilities of early detection of risk factors and prevention of clinical manifestations.

Antiplatelet agents have a predominant role in the therapeutic treatment of acute coronary syndrome (ACS) and myocardial infarction. Recently, ticagrelor has been incorporated in the European Society of Cardiology guidelines for the management of ACS with ST elevation and non-ST elevation.1 The AHA/ACC guidelines further advocate the choice of ticagrelor over clopidogrel in patients with ACS with non-ST elevation treated with an early invasive strategy.2 In fact, major studies have proven the benefits of ticagrelor on cardiovascular death, myocardial infarction, and stroke without an increase in major bleeding risk

The evidence suggests that antiplatelet agents (APA) slightly increase the risk of death and disease progression in patients with traumatic brain injury or spontaneous intracranial hemorrhage (ICH). There is little evidence that APA reversal with platelet (PLT) transfusion may improve the outcome. In this systematic review and meta-analysis, our goal was to evaluate the differences in mortality, severe disability, and hematoma expansion related to PLT transfusion. We retrieved randomized or cohort studies comparing adult patients on APA with traumatic brain injury or ICH who were treated with PLT or not. We calculated the standardized risk difference and 95% confidence interval. A random-effects model was applied to analyze the data. The heterogeneity of the retrieved trials was evaluated through the I2 statistic. Our review included 16 clinical trials. We observed a significant difference between the 2 groups only for hematoma expansion: risk difference was –0.10 (10%; 95% confidence interval, –0.14 to –0.05; P

Present study was to evaluate whether switching ticagrelor to clopidogrel would impact platelet reactivity and cardiovascular outcomes in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). A total of 202 ACS patients after PCI were enrolled and prescribed ticagrelor. Before discharge, 138 (68%) patients were switched to clopidogrel. Peripheral blood was obtained before switching and at 48 hours after switching to measure platelet reactivity. Patients were followed for 30 days to evaluate cardiovascular events. Compared to ticagrelor group, patients in clopidogrel group were more likely to be male (69.6% vs 65.6%), smokers (34.1% vs 31.3%) and had higher prevalence of hypertension (75.4% vs 71.9%). The frequency of right coronary artery lesion was significantly higher in ticagrelor group (34.4% vs 30.4%). There were no significant differences in baseline platelet reactivity (37.6 ± 5.2% vs 38.4 ± 4.9%). Forty-eight hours after switching to clopidogrel, platelet reactivity in clopidogrel group was significantly higher (46.3 ± 5.6% vs 38.1 ± 5.0%, P

Platelet activation is the first response to tissue damage and, if unrestrained, may promote chronic inflammation-related cancer, mainly through the release of soluble factors and vesicles that are rich in genetic materials and proteins. Platelets also sustain cancer cell invasion and metastasis formation by fostering the development of the epithelial-mesenchymal transition phenotype, cancer cell survival in the bloodstream and arrest/extravasation at the endothelium. Furthermore, platelets contribute to tumor escape from immune elimination. These findings provide the rationale for the use of antithrombotic agents in the prevention of cancer development and the reduction of metastatic spread and mortality. Among them, low-dose aspirin has been extensively evaluated in both preclinical and clinical studies. The lines of evidence have been considered appropriate to recommend the use of low-dose aspirin for primary prevention of cardiovascular disease and colorectal cancer by the USA. Preventive Services Task Force. However, two questions are still open: (i) the efficacy of aspirin as an anticancer agent shared by other antiplatelet agents, such as clopidogrel; (ii) the beneficial effect of aspirin improved at higher doses or by the co-administration of clopidogrel. This review discusses the latest updates regarding the mechanisms by which platelets promote cancer and the efficacy of antiplatelet agents.

Background Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality that imposes a serious medical burden. Antiplatelet therapy is a potential strategy for preventing ARDS in patients with a high risk of developing this condition. A meta-analysis was performed to investigate whether antiplatelet therapy could reduce the incidence of newly developed ARDS and its associated mortality in high-risk patients. Methods The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Medline, and the Web of Science were searched for published studies from inception to 26 October 2017. We included randomized clinical trials, cohort studies and case-control studies investigating antiplatelet therapy in adult patients presenting to the hospital or ICU with a high risk for ARDS. Baseline patient characteristics, interventions, controls and outcomes were extracted. Our primary outcome was the incidence of newly developed ARDS in high-risk patients. Secondary outcomes were hospital and ICU mortality. A random-effects or fixed-effects model was used for quantitative synthesis. Results We identified nine eligible studies including 7660 high-risk patients who received antiplatelet therapy. Based on seven observational studies, antiplatelet therapy was associated with a decreased incidence of ARDS (odds ratio (OR) 0.68, 95% confidence interval (CI) 0.52–0.88; I2 = 68.4%, p = 0.004). In two randomized studies, no significant difference was found in newly developed ARDS between the antiplatelet groups and placebo groups (OR 1.32, 95% CI 0.72–2.42; I2 = 0.0%, p = 0.329). Antiplatelet therapy did not reduce hospital mortality in randomized studies (OR 1.15, 95% CI 0.58–2.27; I2 = 0.0%; p = 0.440) or observational studies (OR 0.80, 95% CI 0.62–1.03; I2 = 31.9%, p = 0.221). Conclusions Antiplatelet therapy did not significantly decrease hospital mortality in high-risk patients. However, whether antiplatelet therapy is associated with a decreased incidence of ARDS in patients at a high risk of developing the condition remains unclear. Electronic supplementary material The online version of this article (10.1186/s13054-018-1988-y) contains supplementary material, which is available to authorized users.

Insufficient platelet inhibition has been reported in up to 40% of aspirin-treated patients, including patients with essential thrombocytosis. To maintain sufficient platelet inhibition, a shorter dosing interval with aspirin has been suggested. We aimed to investigate the antiplatelet effect of low-dose aspirin given twice-daily compared to standard once-daily dosing in patients with essential thrombocytosis. We included 22 patients, who were treated for 7 days with standard once-daily aspirin (75 mg once-daily) followed by 7 days treatment of twice-daily aspirin (37.5 mg twice-daily). The two regimens were separated by 14 days aspirin washout. Blood samples were obtained 1h and 24h/12h after the last pill intake in each regimen. The effect of aspirin was evaluated by: (1) platelet aggregation measured by whole blood impedance aggregometry (Multiplate® Analyser) using arachidonic acid (ASPItest 0.5 mM) as agonist and (2) serum thromboxane B2levels determined using an enzyme-linked immunosorbent assay. The difference in platelet aggregation from 1h to the end of the dosing interval (24h/12h) was used to compare the two regimens. We demonstrated a significantly smaller difference in platelet aggregation in the twice-daily regimen compared to the once-daily: mean of difference = 228 AU*min (95% confidence interval (CI): 92-363, p < 0.01). In addition, a significantly smaller difference in thromboxane B2was demonstrated in the twice-daily regimen compared to the once-daily regimen: mean of difference = 16.3 ng/mL (95% CI: 9.9-22.7, p < 0.01). In conclusion, twice-daily dosing with low-dose aspirin provides a more consistent platelet inhibition compared with standard once-daily dosing in patients with essential thrombocytosis.

The clinical, cell and genetic factors are distinguished among reasons for resistance to antiplatelet drugs. There are many methods to detect sensitivity to antiplatelet drugs, but they all have disadvantages. Moreover, there is no unified approach for interpretation of received results, and no recommendations for their practical use. It is necessary to work out unified procedure to assess platelet function, to define indications for its usage and to work out unified criteria of resistance. Individualized approach and each patient’s peculiarities consideration are essential when prescribing antiplatelet therapy.

Supplemental Digital Content is available in the text., Objective— Despite successful translation of bioresorbable vascular grafts for the repair of congenital heart disease, stenosis remains the primary cause of graft failure. In this study, we investigated the efficacy of long-term treatment with the antiplatelet drugs, aspirin and cilostazol, in preventing stenosis and evaluated the effect of these drugs on the acute phase of inflammation and tissue remodeling. Approach and Results— C57BL/6 mice were fed a drug-mixed diet of aspirin, cilostazol, or normal chow during the course of follow-up. Bioresorbable vascular grafts, composed of poly(glycolic acid) mesh sealed with poly(l-lactide-co-ε-caprolactone), were implanted as inferior vena cava interposition conduits and followed up for 2 weeks (n=10 per group) or 24 weeks (n=15 per group). Both aspirin and cilostazol suppressed platelet activation and attachment onto the grafts. On explant at 24 weeks, well-organized neotissue had developed, and cilostazol treatment resulted in 100% graft patency followed by the aspirin (67%) and no-treatment (60%) groups (P

Background & Aims Patients who develop lower gastrointestinal bleeding (LGIB) while receiving anti-coagulants or anti-platelets have increased severity of bleeding and risk of re-bleeding. We compared outcomes of patients receiving anti-platelets, anti-coagulants, or direct oral anti-coagulants (DOACs) who develop LGIB, as well as the effects of withholding these drugs on their course of bleeding. Methods We performed a retrospective study of 2528 consecutive adult patients with LGIB at 143 hospitals in the United Kingdom, from September through December 2015; 917 were taking anti-coagulant or anti-platelet drugs and 1218 were taking neither (unexposed). We collected data on demographic features of patients, interventions or medications, outcomes, laboratory test results, and patient readmission until patient death, discharge, or 28 days after admission (whichever came first). Re-bleeding was defined as additional transfusion requirements and/or a decrease in hematocrit ≥20% after 24 hrs of clinical stability. Multivariate regression was used to examine the relationship between drug class on presentation with LGIB and re-bleeding, mortality, and cardiovascular events. Rates of re-bleeding and cardiovascular complications in patients who had these drugs withheld were also analyzed. Results Patients receiving anti-platelets, but not those receiving warfarin (n = 232) or DOACs (n = 102), had a higher risk of in-hospital re-bleeding (monotherapy hazard ratio [HR], 3.57; 95% CI, 1.13–11.28; n = 504 and dual anti-platelet therapy hazard ratio, 5.3; 95% CI, 1.56–18.54; n = 79) compared with the unexposed group. This risk was not lower in patients who received anti-platelets and had the drug withheld for fewer than 5 days, compared to those who continued the drug throughout admission (HR, 0.98; 95% CI, 0.45–2.17) No differences were observed in risk-adjusted mortality or re-admission with further bleeding for patients receiving anti-platelets, DOACs, or warfarin. Cardiovascular events were too few to allow meaningful comparison. Conclusions In patients with LGIB, antiplatelet drugs, but not warfarin or DOACs, are associated with an increased risk of re-bleeding. Withholding anti-platelets during admission does not lead to reduction in re-bleeding.

BACKGROUND: Platelet aggregation inhibitors (PAI) are among the most frequently prescribed drugs in older people, though evidence about risks and benefits of their use in older adults is scarce. The objectives of this systematic review are firstly to identify the risks and benefits of their use in the prevention and treatment of vascular events in older adults, and secondly to develop recommendations on discontinuing PAI in this population if risks outweigh benefits. METHODS: Staged systematic review consisting of three searches. Searches 1 and 2 identified systematic reviews and meta-analyses. Search 3 included controlled intervention and observational studies from review-articles not included in searches 1 and 2. All articles were assessed by two independent reviewers regarding the type of study, age of participants, type of intervention, and clinically relevant outcomes. After data extraction and quality appraisal we developed recommendations to stop the prescribing of specific drugs in older adults following the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. RESULTS: Overall, 2385 records were screened leading to an inclusion of 35 articles reporting on 22 systematic reviews and meta-analyses, 11 randomised controlled trials, and two observational studies. Mean ages ranged from 57.0 to 84.6 years. Ten studies included a subgroup analysis by age. Overall, based on the evaluated evidence, three recommendations were formulated. First, the use of acetylsalicylic acid (ASA) for primary prevention of cardiovascular disease (CVD) in older people cannot be recommended due to an uncertainty in the risk-benefit ratio (weak recommendation; low quality of evidence). Secondly, the combination of ASA and clopidogrel in patients without specific indications should be avoided (strong recommendation; moderate quality of evidence). Lastly, to improve the effectiveness and reduce the risks of stroke prevention therapy in older people with atrial fibrillation (AF) and a CHA2DS2-VASc score of ≥ 2, the use of ASA for the primary prevention of stroke should be discontinued in preference for the use of oral anticoagulants (weak recommendation; low quality of evidence). CONCLUSIONS: The use of ASA for the primary prevention of CVD and the combination therapy of ASA and clopidogrel for the secondary prevention of vascular events in older people may not be justified. The use of oral anticoagulants instead of ASA in older people with atrial fibrillation may be recommended. Further high quality studies with older adults are needed The PRIMA-eDS study was supported by a grant from the European Commission within the 7th Framework Programme (Grant No. 305388–2). The work of YVM was also supported by a grant from the NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre. The publication charge was funded by the University of Witten/Herdecke