Anticoagulation and antiplatelets as prophylaxis for hepatic artery thrombosis after liver transplantation

Hepatic artery thrombosis(HAT) is the most serious vascular complication after liver transplantation. Multiple risk factors have been identified to impact its development. Changes in haemostasis associated with end stage liver disease and the disturbance of the coagulation and anticoagulation cascades play an important role in development of this lethal complication. Early recognition and therapeutic intervention is mandatory to avoid its consequences. Pharmacological prophylaxis, by the use of antiplatelet or anticoagulant agents, is an important tool to reduce its incidence and prevent graft loss. Only a few studies have shown a clear benefit of antiplatelet agents in reducing HAT occurrence, however, these studies are limited by being retrospective and by inhomogeneous populations. The use of anticoagulants such as heparin is associated with an improvement in the outcomes mainly when used for a high-risk patients like living related liver recipients. The major concern when using these agents is the tendency to increase bleeding complications in a setting of already unstable haemostasis. Hence, monitoring of their administration and careful selection of patients to be treated are of great importance. Well-designed clinical studies are still needed to further explore their effects and to formulate proper protocols that can be implemented safely.

Risk factors and outcomes of peptic ulcer bleed in a Pakistani population:A single-center observational study

BACKGROUND Peptic ulcer disease(PUD)remains a significant healthcare burden,contributing to morbidity and mortality worldwide.Despite advancements in therapies,its prevalence persists,particularly in regions with widespread nonsteroidal antiinflammatory drugs(NSAIDs)use and Helicobacter pylori infection.AIM To comprehensively analyse the risk factors and outcomes of PUD-related upper gastrointestinal(GI)bleeding in Pakistani population.METHODS This retrospective cohort study included 142 patients with peptic ulcer bleeding who underwent upper GI endoscopy from January to December 2022.Data on demographics,symptoms,length of stay,mortality,re-bleed,and Forrest classification was collected.RESULTS The mean age of patients was 53 years,and the majority was men(68.3%).Hematemesis(82.4%)and epigastric pain(75.4%)were the most common presenting symptoms.Most patients(73.2%)were discharged within five days.The mortality rates at one week and one month were 10.6%and 14.8%,respectively.Re-bleed within 24 h and seven days occurred in 14.1%and 18.3%of patients,respectively.Most ulcers were Forrest class(FC)Ⅲ(72.5%).Antiplatelet use was associated with higher mortality at 7 and 30 d,while alternative medications were linked to higher 24-hour re-bleed rates.NSAID use was associated with more FCⅢulcers.Re-bleed at 24 h and 7 d was strongly associated with one-week or one-month mortality.CONCLUSION Antiplatelet use and rebleeding increase the risk of early mortality in PUD-related upper GI bleeding,while alternative medicines are associated with early rebleeding.

Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity

BACKGROUND Hepatocellular carcinoma(HCC)is the most common malignant liver disease in the world.Platelets(PLTs)are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases.Aspirin is the most classic antiplatelet agent.However,the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study.AIM To explore the impact of the antiplatelet effect of aspirin on the development of HCC.METHODS Platelet-rich plasma,platelet plasma,pure platelet,and platelet lysate were prepared,and a coculture model of PLTs and HCC cells was established.CCK-8 analysis,apoptosis analysis,Transwell analysis,and real-time polymerase chain reaction(RT-PCR)were used to analyze the effects of PLTs on the growth,metastasis,and inflammatory microenvironment of HCC.RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways.Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo,and the effect of PLTs on the progression of HCC RESULTS PLTs significantly promoted the growth,invasion,epithelial-mesenchymal transition,and formation of an inflammatory microenvironment in HCC cells.Activated PLTs promoted HCC progression by activating the mitogenactivated protein kinase/protein kinase B/signal transducer and activator of transcription three(MAPK/AKT/STAT3)signaling axis.Additionally,aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation.CONCLUSION PLTs play an important role in the pathogenesis of HCC,and aspirin can affect HCC progression by inhibiting platelet activity.These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

Early antiplatelet therapy used for acute ischemic stroke and intracranial hemorrhage

In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.

Distribution of gene polymorphisms associated with aspirin antiplatelet in the Han NSTEMI population

Objective:To analyze the genotype and allele distribution characteristics of GPⅢa PLA2(rs5918),PEAR1(rs12041331),and PTGS1(rs10306114)genes related to the antiplatelet pharmacological effects of aspirin,providing reference for individualized treatment of Chinese Han NSTEMI patients.Methods:A total of 107 Han patients with NSTEMI in Beijing Luhe Hospital affiliated to Capital Medical University from January 2016 to December 2022 were selected as the research subjects.The genotypes of GPⅢa PLA2(rs5918),PEAR1(rs12041331)and PTGS1(rs10306114)were detected by fluorescence staining in situ hybridization.The frequency distribution and allele distribution of genotype were analyzed.The results were analyzed whether there were statistical differences in the distribution of related alleles between the Han NSTEMI population and some populations in the 1000 Genomes database.Results:In the Han NSTEMI population,the genotype frequencies of GPⅢa PLA2(rs5918)locus were TT 97.20%,TC 2.80%and CC 0%,the allele frequencies were T 98.60%and C 1.40%.The genotype frequencies of PEAR1(rs12041331)locus were GG 42.06%,GA 44.86%and AA 13.08%,the allele frequencies were G 64.49%and A 35.51%.The genotypes at the PTGS1(rs10306114)locus were all AA(100%),no AG or GG genotype was found.Conclusion:In the NSTEMI population of Han nationality,the mutation at GPⅢa PLA2(rs5918)site related to aspirin antiplatelet pharmacology is rare,and there is no mutation at PTGS1(rs10306114)site.Wild homozygotes are dominant in these two gene loci,while mutations in PEAR1(rs12041331)are more common.Some of the findings in this study are similar to those in previous reports or other populations included in the relevant database;however,some results differ from previous reports or other populations。

Efficacy and safety of aspirin antiplatelet therapy within 48 h of symptom onset in patients with acute stroke

BACKGROUND Aspirin is a widely used antiplatelet agent that reduces the risk of recurrent ischemic stroke and other vascular events.However,the optimal timing and dose of aspirin initiation after an acute stroke remain controversial.AIM To evaluate the efficacy and safety of aspirin antiplatelet therapy within 48 h of symptom onset in patients with acute stroke.METHODS We conducted a randomized,open-label,controlled trial in 60 patients with acute ischemic or hemorrhagic stroke who were admitted to our hospital within 24 h of symptom onset.Patients were randomly assigned to receive either aspirin 300 mg daily or no aspirin within 48 h of stroke onset.The primary outcome was the occurrence of recurrent stroke,myocardial infarction,or vascular death within 90 d.The secondary outcomes were functional outcomes at 90 d measured using the modified Rankin Scale(mRS),incidence of bleeding complications,and mortality rate.RESULTS The mean age of the patients was 67.8 years and 55%of them were male.The median time from stroke onset to randomization was 12 h.The baseline characteristics were well balanced between the two groups.The primary outcome occurred in 6.7%of patients in the aspirin group and 16.7%of patients in the no aspirin group(relative risk=0.40,95%confidence interval:0.12-1.31,P=0.13).The mRS score at 90 d was significantly lower in the aspirin group than in the no aspirin group(median,2 vs 3,respectively;P=0.04).The incidence of bleeding complications was similar between the groups(6.7%vs 6.7%,P=1.00).The mortality rates were also comparable between the two groups(10%vs 13.3%,P=0.69).CONCLUSION Aspirin use is associated with favorable functional outcomes but does not significantly reduce the risk of recurrent vascular events.Its acceptable safety profile is comparable to that of no aspirin.Further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings.

Dissolvable polymeric microneedles loaded with aspirin for antiplatelet aggregation

To reduce mucosal damage in the gastrointestinal tract caused by aspirin,we developed a dissolvable polymeric microneedle(MN)patch loaded with aspirin.Biodegradable polymers provide mechanical strength to the MNs.The MN tips punctured the cuticle of the skin and dissolved when in contact with the subcutaneous tissue.The aspirin in the MN patch is delivered continuously through an array of micropores created by the punctures,providing a stable plasma concentration of aspirin.The factors affecting the stability of aspirin during MNs fabrication were comprehensively analyzed,and the hydrolysis rate of aspirin in the MNs was less than 2%.Compared to oral administration,MN administration not only had a smoother plasma concentration curve but also resulted in a lower effective dose of antiplatelet aggregation.Aspirin-loaded MNs were mildly irritating to the skin,causing only slight erythema on the skin and recovery within 24 h.In summary,aspirin-loaded MNs provide a new method to reduce gastrointestinal adverse effects in patients requiring aspirin regularly.

Prolonged dual antiplatelet therapy after drug-eluting stent implantation improves long-term prognosis for acute coronary syndrome:five-year results from a large cohort study

BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of China.METHODS:We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013.Patients were divided into four groups based on DAPT duration:standard DAPT group(11-13 months,n=1,568)and prolonged DAPT groups(13-18 months[n=308],18-24 months[n=2,125],and>24 months[n=1,186]).Baseline characteristics and 5-year clinical outcomes were recorded.RESULTS:Baseline characteristics were similar across the four groups.Among the four groups,those with prolonged DAPT(18-24 months)had the lowest incidence of major adverse cardiovascular and cerebrovascular events(MACCEs)(14.1%vs.11.7%vs.9.6%vs.24.2%,P<0.001),all-cause death(4.8%vs.3.9%vs.2.1%vs.2.6%,P<0.001),cardiac death(3.1%vs.2.6%vs.1.4%vs.1.9%,P=0.004),and myocardial infarction(MI)(3.8%vs.4.2%vs.2.5%vs.5.8%,P<0.001).The incidence of bleeding was not different among the four groups(9.9%vs.9.4%vs.11.0%vs.9.4%,P=0.449).Cox multivariable analysis showed that prolonged DAPT(18-24 months)was an independent protective factor for MACCEs(hazard ratio[HR]0.802,95%confidence interval[CI]0.729-0.882,P<0.001),all-cause death(HR 0.660,95%CI 0.547-0.795,P<0.001),cardiac death(HR 0.663,95%CI 0.526-0.835,P<0.001),MI(HR 0.796,95%CI 0.662-0.957,P=0.015),and target vessel revascularization(HR 0.867,95%CI 0.755-0.996,P=0.044).Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs.CONCLUSION:For patients with ACS after DES,appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.

Perioperative thromboprophylaxis in liver transplant patients

Improvements in surgical and anesthetic procedures have increased patient survival after liver transplantation(LT). However, the perioperative period of LT can still be affected by several complications. Among these, thromboembolic complications(intracardiac thrombosis, pulmonary embolism, hepatic artery and portal vein thrombosis) are relatively common causes of increased morbidity and mortality. The benefit of thromboprophylaxis in general surgical patients has already been established, but it is not the standard of care in LT recipients. LT is associated with a high bleeding risk, as it is performed in a setting of already unstable hemostasis. For this reason, the role of routine perioperative prophylactic anticoagulation is usually restricted. However, recent data have shown that the bleeding tendency of cirrhotic patients is not an expression of an acquired bleeding disorder but rather of coexisting factors(portal hypertension, hypervolemia and infections). Furthermore, in cirrhotic patients, the new paradigm of ‘‘rebalanced hemostasis' ' can easily tip towards hypercoagulability because of the recently described enhanced thrombin generation, procoagulant changes in fibrin structure and platelet hyperreactivity. This new coagulation balance, along with improvements in surgical techniques and critical support, has led to a dramatic reduction in transfusion requirements, and the intraoperative thromboembolic-favoring factors(venous stasis, vessels clamping, surgical injury) have increased the awareness of thrombotic complications and led clinicians to reconsider the limited use of anticoagulants or antiplatelets in the postoperative period of LT.

colorectal 癌症阶段特征上的 antiplatelet 治疗的影响

AIM:To evaluate whether antiplatelet medication leads to an earlier stage colorectal cancer(CRC) diagnosis.METHODS:From January 2002 until March 2010,patients that presented to our institution with the initial diagnosis of CRC and were submitted to an open curative CRC resection or a palliative procedure were retrospectively reviewed.Exclusion criteria were the use of antithrombotic medication,i.e.,coumarins,and appendiceal malignancies.Data acquired from medical files included age,gender,past medical history,antithrombotic treatment received prior to endoscopic diagnosis,preoperative imaging staging,location of the tumor,surgical and final histopathological report.Patients that did not receive any antithrombotic medication prior to the endoscopic diagnosis comprised the control group of the study,while patients that were on antiplatelet medication comprised the antiplatelet group.Primary end point was a comparison of CRC stage in the two groups of the study.CRC presenting symptoms and the incidence of each cancer stage in the two groups were also evaluated.RESULTS:A total of 387 patients with the diagnosis of CRC were submitted to our department for further surgical treatment.Ninety-eight patients(25.32%),with a median age of 71 years(range 52-91 years),were included in the antiplatelet group,while 289(74.67%) patients,with a median age of 67 years(range 4190 years),were not in any thrombosis prophylaxis medication(control group).Thirty-one patients were treated with some kind of palliative procedure,either endoscopic,such as endoscopic stent placement,or surgical,such as de-compressive colostomy or deviation.Coronary disease(77.55%-76 patients),stroke recurrence prevention(14.28%-14 patients) and peripheral arterial disease(8.16%-8 patients) were the indications for the administration of antiplatelet treatment(aspirin,clopidogrel,ticlopidine or dipyridamole) in the antiplatelet group.All patients on aspirin treatment received a dosage of 100 mg/d,while the minimum prophylactic dosages were also used for the rest of the antiplatelet drugs.Investigation of an iron deficiency anemia(147 patients),per rectum blood loss(84 patients),bowel obstruction and/or perforation(81 patients),bowel habits alterations(32 patients),nonspecific symptoms,such as weight loss,intermittent abdominal pain and fatigue,(22 patients) or population screening(21 patients) were the indications for the endoscopic investigation in both groups.Bleeding,either chronic presenting as anemia or acute was significantly higher(P = 0.002) for the antiplatelet arm of the study(71 patients-72.4% of the antiplatelet group vs 160 patients-55.3% of the control group).The mean tumor,node and metastasis stage was 2.57 ± 0.96 for the control group,2.27 ± 0.93 for the antiplatelet group(P = 0.007) and 2.19 ± 0.92 for the subgroup of patients taking aspirin(P = 0.003).The incidence of advanced disease(stage Ⅳ) was lower for the antiplatelet group of the study(P = 0.033).CONCLUSION:The adverse effect of bleeding that is justifiably attached to this drug category seems to have a favorable impact on the staging characteristics of CRC.

Heparin bridge therapy and post-polypectomy bleeding

AIM To identify risk factors for post-polypectomy bleeding(PPB), focusing on antithrombotic agents. METHODS This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. RESULTS PPB occurred in 29(3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210(26.6%)patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB(P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB(P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. CONCLUSION Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants.

Bleeding risk with clopidogrel and percutaneous endoscopic gastrostomy

AIM To compare bleeding within 48 h in patients undergoing percutaneous endoscopic gastrostomy(PEG) with or without clopidogrel.METHODS After institutional review board approval, a retrospective study involving a single center was conducted on adult patients having PEG(1/08-1/14). Patients were divided into two groups: Clopidogrel group consisting of those patients taking clopidogrel within 5 d of PEG and the non-clopidogrel group including those patients not taking clopidogrel within 5 d of the PEG.RESULTS Three hundred and nineteen PEG patients were found. One hundred and sixty-eight males and 151 females with mean body mass index 28.47 ± 9.75 kg/m2 and mean age 65.03 ± 16.11 years were identified. Thirtythree patients were on clopidogrel prior to PEG with 286 patients not on clopidogrel. No patients in either group developed hematochezia, melena, or hematemesiswithin 48 h of percutaneous endoscopic gastrostomy(PEG). No statistical differences were observed between the two groups with 48 h for hemoglobin decrease of > 2 g/dL(2 vs 5 patients; P = 0.16), blood transfusions(2 vs 7 patients; P = 0.24), and repeat endoscopy for possible gastrointestinal bleeding(no patients in either group). CONCLUSION Based on the results, no significant post-procedure bleeding was observed in patients undergoing PEG with recent use of clopidogrel.

Anticoagulation and antiplatelet management in gastrointestinal endoscopy: A review of current evidence

The role of endoscopic procedures,in both diagnostic and therapeutic purposes is continually expanding and evolving rapidly.In this context,endoscopists will encounter patients prescribed on anticoagulant and antiplatelet medications frequently.This poses an increased risk of intraprocedural and delayed gastrointestinal bleeding.Thus,there is now greater importance on optimal pre,peri and post-operative management of anticoagulant and/or antiplatelet therapy to minimise the risk of post-procedural bleeding,without increasing the risk of a thromboembolic event as a consequence of therapy interruption.Currently,there are position statements and guidelines from the major gastroenterology societies.These are available to assist endoscopists with an evidenced-based systematic approach to anticoagulant and/or antiplatelet management in endoscopic procedures,to ensure optimal patient safety.However,since the publication of these guidelines,there is emerging evidence not previously considered in the recommendations that may warrant changes to our current clinical practices.Most notably and divergent from current position statements,is a growing concern regarding the use of heparin bridging therapy during warfarin cessation and its associated risk of increased bleeding,suggestive that this practice should be avoided.In addition,there is emerging evidence that anticoagulant and/or antiplatelet therapy may be safe to be continued in cold snare polypectomy for small polyps(<10 mm).

Secondary prevention of ischaemic stroke

In spite of a documented reduction in incidence in highincome countries over the last decades, stroke is still a leading cause of death and disability worldwide. With the ageing of the population stroke-related economic burden is expected to increase, because of residual disability and its complications, such as cognitive impairment, high risk of falls and fractures, depression and epilepsy. Furthermore, because of the substantial rate of early and long-term vascular recurrences after the first event, secondary prevention after cerebral ischaemia is a crucial issue. This is even more important after minor stroke and transient ischaemic attack(TIA), in order to reduce the risk of potentially more severe and disabling events. To accomplish this aim, acute long-term medical and surgical treatments as well aslifestyle modifications are strongly recommended. However, apart from the well-established indications to thrombolysis, studies in acute phase after a first stroke or TIA are scarce and evidence is lacking. More trials are available for long-term secondary prevention with different classes of drugs, including antithrombotic medications for ischaemic events of arterial and cardiac origin, especially related to atrial fibrillation(antiplatelets and anticoagulants, respectively), lipid lowering agents(mainly statins), blood pressure lowering drugs, surgical and endovascular revascularization procedures.

Percutaneous Coronary Interventional Treatment for Coronary Artery Disease and the Role of Antiplaplatelets Therapy: A Review of the Literature

Uses of balloon catheters or BMS for the treatment of coronary artery lesions shows good short-term results but long-term follow up revealed restenosis in up to 20%-30% of patients. Thus new improvements to balloons and stents are always necessary to achieve the best results from percutaneous coronary intervention (PCI). Drug-eluting stents (DES) improved the principles of bare metal stents (BMS) by local drug release to inhibit neointimal growth. DES reduced the incidence of in-stent restenosis. These benefits and lower costs compared to surgical treatment make the DES an attractive alternative for the treatment of coronary artery disease. Different components of DES which include the polymers, drugs and the stents underwent progressive evolution, and these led to development of new generations of DES with variable types of drugs and polymers to fully absorbable stents. The concern of stent thrombosis still an issue and dual antiplatlets therapy (DAPT) is mandatory for variable time ranging from one month to one year. This article discusses the main available clinical trials in the developments of BMS, DES and the comparison between both with a prospective look at future technologies in the field, in addition to reviewing the current guideline in the uses of DAPT after PCI.

Premorbid Use of Clopidogrel Portends Worse Outcomes in Patients Treated Surgically for Intracranial Hemorrhage

Background: Widespread use of antiplatelet and anticoagulation medications (APACs) can be a difficult challenge in the presence of a neurosurgical emergency. Premorbid use of APACs, particularly clopidogrel, has been shown to affect outcomes in patients with stroke and traumatic brain injury. Objective: We hypothesized that pre-morbid clopidogrel use in patients with intracranial hemorrhage necessitating surgical intervention would lead to a greater risk of death and need for re-operation than those taking other APACs. Methods: Retrospective single institution review was conducted from January, 2010 through November, 2012 for intracranial hemorrhages necessitating surgical evacuation. Acute, subacute and chronic subdural, epidural and intraparenchymal hemorrhages were included. Results: 185 of 410 patients that required surgery for intracranial hemorrhage were on APACs. Overall mortality rate was 33%, with a 37% mortality rate in the APAC group. Overall reoperation rate was 7.5%, and 13% in the APAC group. Chi-square testing demonstrated significance between mortality and clopidogrel use (p = 0.0038), but not in APAC, warfarin or aspirin groups. There was statistical significance between the need for reoperation and APAC use (p = 0.002), aspirin use (p = 0.0097), and clopidogrel use (p = 0.0152), but not warfarin. Multivariate regression demonstrated only clopidogrel use is associated with higher mortality (p = 0.05) and need for reoperation (p = 0.0206). Conclusion: APAC use in the setting of intracranial hemorrhage necessitating surgical evacuation have higher intraoperative blood loss, need for transfusion and risk for adverse cardiac events. Premorbid clopidogrel use is associated with an increased risk in mortality and need for reoperation.

Clinical importance of aspirin and clopidogrel resistance

Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked "aspirin and/or clopidogrel resistance", as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel.

Current status of high on-treatment platelet reactivity in patients with coronary or peripheral arterial disease:Mechanisms,evaluation and clinical implications

Antiplatelet therapy with aspirin or clopidogrel or both is the standard care for patients with proven coronary or peripheral arterial disease,especially those undergoing endovascular revascularization procedures. However,despite the administration of the antiplatelet regiments,some patients still experience recurrent cardiovascular ischemic events. So far,it is well documented by several studies that in vitro response of platelets may be extremely variable. Poor antiplatelet effect of clopidogrel or high on-treatment platelet reactivity(HTPR) is under investigation by numerous recent studies. This review article focuses on methods used for the ex vivo evaluation of HTPR,as well as on the possible underlying mechanisms and the clinical consequences of this entity. Alternative therapeutic options and future directions are also addressed.

Feasibility of gastric endoscopic submucosal dissection with continuous low-dose aspirin for patients receiving dual antiplatelet therapy

BACKGROUND Endoscopic submucosal dissection(ESD) for gastric neoplasms during continuous low-dose aspirin(LDA) administration is generally acceptable according to recent guidelines. This retrospective study aimed to investigate the effect of continuous LDA on the postoperative bleeding after gastric ESD in patients receiving dual antiplatelet therapy(DAPT).AIM To investigate the feasibility of gastric ESD with continuous LDA in patients with DAPT.METHODS A total of 597 patients with gastric neoplasms treated with ESD between January2010 and June 2017 were enrolled. The patients were categorized according to type of antiplatelet therapy(APT).RESULTS The postoperative bleeding rate was 6.9%(41/597) in all patients. Patients were divided into the following two groups: no APT(n = 443) and APT(n = 154). APT included single-LDA(n = 95) and DAPT(LDA plus clopidogrel, n = 59)subgroups. In the single-LDA and DAPT subgroups, 56 and 39 patients were received continuous LDA, respectively. The bleeding rate with continuous singleLDA(10.7%) was similar to that with discontinuous single-LDA(10.3%)(P >0.99). Although the bleeding rate with continuous LDA in patients receiving DAPT(23.1%) was higher than that with discontinuous LDA in patients receiving DAPT(5.0%), no significant difference was observed(P = 0.141).CONCLUSION The bleeding rate with continuous LDA in patients receiving DAPT was not statistically different from that with discontinuous LDA in patients receiving DAPT. Therefore, continuous LDA administration may be acceptable for ESD in patients receiving DAPT, although patients should be carefully monitored for possible bleeding.

Design, Synthesis, and Activities of Novel Derivativesof Isophthalamide and Benzene-1,3-disulfonamide

Based on the antiplatelet aggregation mechanism and the bioisosterism principle of the reference drug picotamide, thirteen novel derivatives of arylamide and arylsulfonamide were designed and prepared. The biological activities of these derivatives were investigated. The chemical structures of the target compounds were confirmed by ^1H NMR and IR. The in vitro activities of antiplatelet aggregation of the thirteen target compounds were assessed by Bore＇s method. Compounds 2b and 8h have significant antiplatelet aggregation activities, which are superior to the corresponding activity of Picotamide.