Seven previously unreported sesquiterpenes including three rare 5/5/6-fused tricyclic gymnomitrane-type sesquiterpenes(1-3),an ent-longipinane-type sesquiterpene(4),a cuparane-type sesquiterpene(5),and two chamigrane-...Seven previously unreported sesquiterpenes including three rare 5/5/6-fused tricyclic gymnomitrane-type sesquiterpenes(1-3),an ent-longipinane-type sesquiterpene(4),a cuparane-type sesquiterpene(5),and two chamigrane-type sesquiterpenes(6 and 7),along with a known chamigrane-type sesquiterpene xylariterpenoid C(8)were isolated from the hydrothermal vent sediment derived fungus Penicillium sp.JWM79-5-1.Their structures were identified on the basis of 1D and 2D NMR,in conjunction with Mosher’s method,X-ray crystallography,and electronic circular dichroism(ECD).The antithrombotic activity of compounds 1-6 and 8 was evaluated in arachidonic acid(AA)-induced zebrafish thrombosis model in vivo.The results revealed compound 1 with potent antithrombotic activity in a concentration-dependent manner.Further,the pro-angi-ogenic activities of compounds 1-6 and 8 were evaluated in a transgenic zebrafish model that expresses vegfr2,the receptor for the angiogenic factor VEGF,tagged with the green fluorescence protein(vegfr2-GFP)through detecting the length of both intersegmental vessels(ISVs)and subintestinal veins(SIVs).The results revealed that compound 1 exhibited a potent antithrombotic activity while 3 revealed a potent pro-angiogenic activity.These findings strongly support drug development of these compounds in cardiovascular disease treatment.展开更多
Objective:EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen,an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome.Its composition,anticoagulant ...Objective:EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen,an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome.Its composition,anticoagulant and fibrinolytic activities,and relevant mechanisms have been confirmed through in vitro experiments.However,whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown.This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro.Methods:The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl3.Then,the protein bands of EPF3 incubated with simulated gastric fluid(SGF),simulated intestinal fluid(SIF),and homogenate of Caco-2 cells(HC2C)were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability.Finally,the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer.Results:EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid.It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl3.EPF3 was stable in SIF and HC2C and unstable in SGF.The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent.The efflux ratio was less than1.2 during transport,and the transport behavior was not affected by inhibitors.EPF3 could reversibly reduce the expression of tight junction-related proteins,including zonula occludens-1,occludin,and claudin-1 in Caco-2 cells.Conclusion:EPF3 could play a thrombolytic and antithrombotic role in zebrafish.It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction.This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation.Please cite this article as:Zhong WL,Yang JQ,Liu H,Wu YL,Shen HJ,Li PY,Du SY.Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong(Pheretima vulgaris Chen)and its transport mechanism in Caco-2 monolayer through cell bypass pathway.J Integr Med.2025;23(4):415–428.展开更多
Thrombosis,the process of blood clot formation in blood vessels,is an important protective mechanism for avoiding excessive blood spillage when an individual is exposed to trauma.The body has both a thrombosis inhibit...Thrombosis,the process of blood clot formation in blood vessels,is an important protective mechanism for avoiding excessive blood spillage when an individual is exposed to trauma.The body has both a thrombosis inhibition and a thrombus removal system,which interact in a balanced manner.If these mechanisms become unbalanced,and too many clots form and block the lumen,thrombosis occurs.Thrombosis is currently the leading cause of death from disease in humans and is one of the most common events leading to many cardiovascular diseases.Antithrombotic drugs are an integral part of the pharmacological treatment regimens,and interventional strategies are currently recom-mended for thrombotic complications in patients with thrombosis.Despite major advances in these therapies,the high risk associated with thrombosis and bleeding remains,because of the complex interplay among patient comorbidities,drug combinations,multifaceted dose adjustments,and care settings.Detailed assessment of the effects of bleeding and thrombosis is necessary to establish optimal treatment plans for patients with thrombosis.This study retrospec-tively evaluated methods for assessing the risk of bleeding/ischemia in thrombosis and the individualized use of these methods.展开更多
Objective To describe the long-term antithrombotic management patterns(AMPs)and clinical outcomes of Chinese patients with acute coronary syndrome(ACS).Methods This was an observational,multicenter,longitudinal cohort...Objective To describe the long-term antithrombotic management patterns(AMPs)and clinical outcomes of Chinese patients with acute coronary syndrome(ACS).Methods This was an observational,multicenter,longitudinal cohort extension study of Chinese patients who had completed the EPICOR Asia 2-year follow-up study post-hospitalization for an ACS event.Changes in AMP and clinical outcomes for up to 5 years post-ACS event were evaluated.Results Overall,2334 patients with ACS were enrolled at 49 sites.The mean age was 61.6 years and 76.3%were men.By study end,2093 patients completed the 3-year follow-up.At baseline(2 years post-ACS event),72.4%of patents received one antiplatelet(AP)medication,with aspirin being the preferred one.A small proportion of patients(21.5%)was treated with two or more APs(2+AP),and even fewer patients(6.1%)did not receive any AP medication at baseline.Upon study completion,the proportion of patients without AP therapy increased to 13.6%,while the percentage of patients on one AP and 2+AP decreased to 69.3%and 17.1%,respectively.Numerically,a higher incidence of clinical events(composite of all-cause mortality,myocardial infarction,stroke)was observed for the 2+AP(13.2%)subgroup than for the no AP(10.5%)and one AP(8.6%)subgroups.Furthermore,the 2+AP subgroup exhibited the greatest number of bleeding events,outpatient visits,and hospitalization rates.Unlike myocardial infarction or stroke,bleeding events prompted an adjustment in AMP.Conclusion Most patients in China received at least one AP medication up to 5 years after an ACS event.展开更多
To investigated the relationship between postoperative bleeding following gastric endoscopic submucosal dissection (ESD) and individual antithrombotic agents. METHODSA total of 2488 gastric neoplasms in 2148 consecuti...To investigated the relationship between postoperative bleeding following gastric endoscopic submucosal dissection (ESD) and individual antithrombotic agents. METHODSA total of 2488 gastric neoplasms in 2148 consecutive patients treated between May 2001 and June 2016 were studied. The antithrombotic agents were categorized into antiplatelet agents, anticoagulants, and other antithrombotic agents, and we included combination therapies [e.g., dual antiplatelet therapy (DAPT)]. The risk factors associated with post-ESD bleeding, namely, antithrombotic agents overall, individual antithrombotic agents, withdrawal or continuation of antithrombotic agents, and bleeding onset period (during the first six days or thereafter), were analyzed using univariate and multivariate analyses. RESULTSThe en bloc resection and complete curative resection rates were 99.2% and 91.9%, respectively. Postoperative bleeding occurred in 5.1% cases. Bleeding occurred in 10.3% of the patients administered antithrombotic agents. Being male (P = 0.007), specimen size (P < 0.001), and antithrombotic agent used (P < 0.001) were independent risk factors for postoperative bleeding. Heparin bridging therapy (HBT) (P = 0.002) and DAPT/multidrug combinations (P < 0.001) were independent risk factors associated with postoperative bleeding. The bleeding rate of the antithrombotic agent continuation group was significantly higher than that of the withdrawal group (P < 0.01). Bleeding within postoperative day (POD) 6 was significantly higher in warfarin (P = 0.015), and bleeding after POD 7 was significantly higher in DAPT/multidrug combinations (P = 0.007). No thromboembolic events were reported. CONCLUSIONWe must closely monitor patients administered HBT and DAPT/multidrug combinations after gastric ESD, particularly those administered multidrug combinations after discharge.展开更多
A new method for the determination of antithrombotic activity of egg white protein hydrolysate （EWPH） was developed using a microplate reader. Reaction was carried out at 37℃and pH 7.2 with fibrinogen concentration...A new method for the determination of antithrombotic activity of egg white protein hydrolysate （EWPH） was developed using a microplate reader. Reaction was carried out at 37℃and pH 7.2 with fibrinogen concentration 0.1%. Microplate reading was conducted at 405 nm. Inhibition rate of EWPH on thrombin activity showed linearity （R2 = 0.9971）, when the inhibition rate was in the range of 10-90%. The lower limit of detection （LLD, at 99.7% probability） and the biological limit of detection （BLD, at 99.7% probability） of the method were 10.643 and 40 mg/mL, respectively. The repeatability standard deviation （R.S.D.） was 1.08%. The standard deviation of the method was ±0.027 AT-U.展开更多
AIM: To evaluate the risk factors for postoperative bleeding after gastric endoscopic submucosal dissection(ESD) based on the latest guidelines.METHODS: A total of 262 gastric neoplasms were treated by ESD at our cent...AIM: To evaluate the risk factors for postoperative bleeding after gastric endoscopic submucosal dissection(ESD) based on the latest guidelines.METHODS: A total of 262 gastric neoplasms were treated by ESD at our center during a 2-year period from October 2012. We analyzed the data of these cases retrospectively to identify the risk factors for postESD bleeding.RESULTS: Of the 48(18.3%) cases on antithrombotic treatment, 10 were still receiving antiplatelet drugs perioperatively, 13 were on heparin replacement after oral anticoagulant withdrawal, and the antithrombotic therapy was discontinued perioperatively in 25 cases. Postoperative bleeding occurred in 23 cases(8.8%). The postoperative bleeding rate in the heparin replacement group was 61.5%, significantly higher than that in the non-antithrombotic therapy group(6.1%). Univariate analysis identified history of antithrombotic drug use, heparin replacement, hemodialysis, cardiovascular disease, diabetes mellitus, elevated prothrombin timeinternational normalized ratio, and low hemoglobin level on admission as risk factors for post ESD bleeding. Multivariate analysis identified only heparin replacement(OR = 13.7, 95%CI: 1.2-151.3, P = 0.0329) as a significant risk factor for post-ESD bleeding.CONCLUSION: Continued administration of antiplatelet agents, based on the guidelines, was not a risk factor for postoperative bleeding after gastric ESD; however, heparin replacement, which is recommended after withdrawal of oral anticoagulants, was identified as a significant risk factor.展开更多
AIM To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. METHODS All clinical data of ...AIM To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. METHODS All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t- or χ2-test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the differencewas compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. RESULTS A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups(70.8 ± 11.4 vs 62.4 ± 12.0, P < 0.001; 8(8.2%) vs 15(21.7%), P < 0.05; 65(66.3%) vs 13(18.8%), P < 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant(P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients in the continuing group, and the risk of death and developing acute cardiovascular disease was higher in patients in the discontinuing group(log-rank test, P = 0.000 for both). Furthermore, COX regression multivariate analysis revealed that the hazard ratio(HR) for recurrent bleeding was 2.986(95%CI: 067-8.356, P = 0.015) in the continuing group, while HR for death or acute cardiovascular disease was 5.216(95%CI: 1.035-26.278, P = 0.028).CONCLUSION After the occurrence of peptic ulcer bleeding, continuing antithrombotics increases the risk of recurrent bleeding events, while discontinuing antithrombotics would increase the risk of death and developing cardiovascular disease. This suggests that clinicians should comprehensively consider the use of antithrombotics after peptic ulcer bleeding.展开更多
This is the first report on a polysaccharide(RCJ2-Ib)isolated from Rosa Chinensis Flos.RCJ2-Ib was obtained through the extraction with water,precipitation with ethanol,separation with DEAE-52 column and purification ...This is the first report on a polysaccharide(RCJ2-Ib)isolated from Rosa Chinensis Flos.RCJ2-Ib was obtained through the extraction with water,precipitation with ethanol,separation with DEAE-52 column and purification with DEAE-Sepharose Fast Flow column and Sephadex G100 column.GC,FT-IR and NMR analyses revealed that RCJ2-Ib(3.3 k Da)was a 1,4-linked polymannuronic acid containing substantialβ-Danomers units.The anticoagulant effect of RCJ2-Ib evaluated by using rabbit ear venous blood and an acute blood stasis rat model showed that RCJ2-Ib had obvious anticoagulant activity in regulating endogenous and exogenous coagulation pathways and reducing serum thromboxane B2 and endothelin-1.In addition,RCJ2-Ib could also increase the number of Lactobacillus and Escherichia coli.As a result,RCJ2-Ib has the potential to inhibit thrombosis and maintain the intestinal environment.展开更多
The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical charact...The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical character on their antithrombotic activity and the possible mechanism. Both LMW fucoidan fractions exhibited favorable antithrombotic activity in an Fecl3-induced arterial thrombosis. The antithrombotic activity of LMW fucoidan was related with decrease of TXB2 and whole blood viscosity and hematocrit. LMW fucoidan showed a correlation between anticoagulant, antiaggregant and antithrombotic effects in vivo. For LMW fucoidan, antithrombotic activity required high dose of 5-10 nmol kg-1, concomitantly with increase in anticoagulant activity and inhibition of platelet aggregation. Administration of LMW fucoidan significantly promoted the 6-keto-PGF1α content and decreased the TXB2 content, indicating its inhibition of tissue factor pathway and regulation of metabolism of arachidonic acid. By comparison, highly sulfated fucoidan LF2 with Mw 3900 seemed to be a more suitable choice for antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic risk in vivo.展开更多
BACKGROUND There are few reports on major gastrointestinal(GI)bleeding among patients receiving an antithrombotic.AIM To describe clinical characteristics,bleeding locations,management and inhospital mortality related...BACKGROUND There are few reports on major gastrointestinal(GI)bleeding among patients receiving an antithrombotic.AIM To describe clinical characteristics,bleeding locations,management and inhospital mortality related to these events.METHODS Over a three-year period,we prospectively identified 1080 consecutive adult patients admitted in two tertiary care hospitals between January 1,2013 and December 31,2015 for major GI bleeding while receiving an antithrombotic.The bleeding events were medically validated.Clinical characteristics,causative lesions,management and fatalities were described.The distribution of antithrombotics prescribed was compared across the bleeding lesions identified.RESULTS Of 576 patients had symptoms of upper GI bleeding and 504 symptoms of lower GI bleeding.No cause was identified for 383(35.5%)patients.Gastro-duodenal ulcer was the first causative lesion in the upper tract(209 out of 408)and colonic diverticulum the first causative lesion in the lower tract(120 out of 289).There was a larger proportion of direct oral anticoagulant use among patients with lower GI than among those with upper GI lesion locations(P=0.03).There was an independent association between gastro-duodenal ulcer and antithrombotic use(P=0.03),taking account of confounders and proton pump inhibitor coprescription.Pair wise comparisons pointed to a difference between vitamin K antagonist,direct oral anticoagulants,and antiplatelet agents in monotherapy vs dual antiplatelet agents.CONCLUSION We showed a higher rate of bleeding lesion identification and suggested a different pattern of antithrombotic exposure between upper and lower GI lesion locations and between gastro-duodenal ulcer and other identified upper GI causes of bleeding.Management was similar across antithrombotics and in-hospital mortality was low(5.95%).展开更多
Objective The optimal antithrombotic regimen for patients on oral anticoagulation （OAC） after acute coronary syndrome （ACS） and percutaneous coronary intervention （PCI） remains debated. This study sought to eval...Objective The optimal antithrombotic regimen for patients on oral anticoagulation （OAC） after acute coronary syndrome （ACS） and percutaneous coronary intervention （PCI） remains debated. This study sought to evaluate the efficacy and safety of OAC plus clopidogrel with or without aspirin in a real-world setting. Methods We retrospectively analyzed data from an international, multi-center registry be- tween 2003 and 2014 （n = 15,401）. Patients with ACS and receiving OAC after PCI were screened. The composite primary endpoint was 1-year all-cause death, re-infarction, or severe bleeding. Results The final analysis enrolled 642 patients including 62 patients （9.7%） with OAC and clopidogrel （dual therapy）, and 580 patients （90.3%） with the combination of aspirin, OAC and clopidogrel （triple therapy）. Pa- tients on triple therapy were more often female and were more likely to have comorbidities. There was no significant difference regarding the primary end point between dual therapy with triple therapy patients [17.74% vs. 17.24%; unadjusted hazard ratio （HR）： 1.035; 95% confi- dence interval （CI）： 0.556-1.929; adjusted HR： 1.026; 95% CI： 0.544-1.937]. However, the re-infarction rate was significantly higher in dual therapy than triple therapy patients （14.52% vs. 5.34%; unadjusted HR： 2.807; 95% CI： 1.329-5.928; adjusted HR： 2.333; 95% CI： 1.078-5.047）. In addition, there was no difference between two regimes in all-cause death and severe bleeding. Conclusions In real-life patients with ACS following PCI and with an indication of OAC, triple therapy was not associated with an increased rate of adverse out- comes compared to dual therapy. Moreover, it decreased risk of re-infarction and did not increase risk of severe bleeding.展开更多
Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previou...Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previous works have shown that it is possible to develop potent thrombin receptor antagonists to compete effectively with the receptor’s internal “tethered” ligand to block platelet activation. Vorapaxar (SCH 530348) from Schering-Plough (now Merck) and atopaxar (E5555) from Eisai have been advanced to human clinical trials. Recently, the pivotal phase III clinical trial results for vorapaxar were published. In this article we review these results plus the phase II results from atopaxar. Several newly described thrombin receptor antagonists from the literature will also be discussed. The phase III results from vorapaxar demonstrated that a thrombin receptor antagonist can achieve efficacy in addition to current standard- of-care in treating atherothrombotic patients, especially those with previous myocardial infarction (MI). However, the increased moderate and severe bleeding, especially intracranial bleeding, point to the limitations of current thrombin receptor antagonists. Future thrombin receptor antagonists that can improve on the efficacy and bleeding profile of current ones should have a promising place in meeting the unmet medical need in treating atherothrombotic patients using current standard therapy.展开更多
Age is an important prognostic factor in the outcome of acute coronary syndromes （ACS）. A substantial percentage of patients who ex- perience ACS is more than 75 years old, and they represent the fastest-growing seg...Age is an important prognostic factor in the outcome of acute coronary syndromes （ACS）. A substantial percentage of patients who ex- perience ACS is more than 75 years old, and they represent the fastest-growing segment of the population treated in this setting. These pa- tients present different patterns of responses to pharmacotherapy, namely, a higher ischemic and bleeding risk than do patients under 75 years of age. Our aim was to identify whether the currently available ACS ischemic and bleeding risk scores, which has been validated for the general population, may also apply to the elderly population. The second aim was to determine whether the elderly benefit more from a spe- cific pharmacological regimen, keeping in mind the numerous molecules of antiplatelet and antithrombotic drugs, all validated in the general population. We concluded that the GRACE （Global Registry of Acute Coronary Events） risk score has been extensively validated in the elderly. However, the CRUSADE （Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early imple- mentation of the ACC/AHA Guidelines） bleeding score has a moderate correlation with outcomes in the elderly. Until now, there have not been head-to-head scores that quantify the ischemic versus hemorrhagic risk or scores that use the same end point and timeline （e.g., ischemic death rate versus bleeding death rate at one month）. We also recommend that the frailty score be considered or integrated into the current existing scores to better quantify the overall patient risk. With regard to medical treatment, based on the subgroup analysis, we identified the drugs that have the least adverse effects in the elderly while maintaining optimal efficacy.展开更多
Endoscopic submucosal dissection(ESD) is minimally invasive and thus has become a widely accepted treatment for gastric neoplasms,particularly for patients with comorbidities.Antithrombotic agents are used to prevent ...Endoscopic submucosal dissection(ESD) is minimally invasive and thus has become a widely accepted treatment for gastric neoplasms,particularly for patients with comorbidities.Antithrombotic agents are used to prevent thrombotic events in patients with comorbidities such as cardio-cerebrovascular diseases and atrial fibrillation.With appropriate cessation,antithrombotic therapy does not increase delayed bleeding in low thrombosis-risk patients.However,high thrombosisrisk patients are often treated with combination therapy with antithrombotic agents and occasionally require the continuation of antithrombotic agents or heparin bridge therapy(HBT) in the perioperative period.Dual antiplatelet therapy(DAPT),a representative combination therapy,is frequently used after placement of drug-eluting stents and has a high risk of delayed bleeding.In patients receiving DAPT,gastric ESD may be postponed until DAPT is no longer required.HBT is often required for patients treated with anticoagulants and has an extremely high bleeding risk.The continuous use of warfarin or direct oral anticoagulants may be possible alternatives.Here,we show that some antithrombotic therapies in high thrombosis-risk patients increase delayed bleeding after gastric ESD,whereas most antithrombotic therapies do not.The management of high thrombosis-risk patients is crucial for improved outcomes.展开更多
BACKGROUND Postoperative delayed bleeding(PDB) after gastric endoscopic submucosal dissection(ESD) is the most common adverse event in patients receiving antithrombotics even with second-look endoscopy. Moreover, with...BACKGROUND Postoperative delayed bleeding(PDB) after gastric endoscopic submucosal dissection(ESD) is the most common adverse event in patients receiving antithrombotics even with second-look endoscopy. Moreover, with the increasing prevalence of cardiovascular and cerebrovascular diseases in an aging population with associated lifestyle-related diseases, an increasing number of patients receive antithrombotics. Several attempts have been made to prevent PDB in aging population;however, a consensus has yet to be reached.AIM To examine the efficacy of third-look endoscopy(TLE) for PDB prevention.METHODS One hundred patients with early gastric neoplasms receiving antithrombotics were prospectively enrolled and subjected to ESD with TLE between February 2017 and July 2019. The primary endpoint was PDB rate, which was compared with our preset threshold. Furthermore, we divided the bleeding period into early-and late-onset PDB(E-PDB and L-PDB, respectively) and analyzed its rate. As a secondary analysis, we compared PDB rates with those of a historical control group, using propensity score matching, and calculated the PDB rates per antithrombotic agent use in each group.RESULTS In total, 96 patients and 114 specimens were finally evaluated. The overall PDB rate was 7.9%(9/114) [90%CI: 4.7-13.1, P = 0.005], while the late-and early-onset PDB rates(L-PDB and E-PDB) were 5.3% [90%CI: 2.7-9.9, P < 0.0001] and 2.6% [90%CI: 1.1-6.4, P = 0.51], respectively. Propensity score matching generated 58 matched pairs for TLE and control groups. No differences were found in overall PDB incidence(10.3% vs 20.7%, P = 0.12), whereas L-PDB occurrence significantly differed(5.2% vs 17.2%, P = 0.04) between groups. Considering antithrombotics' use, the overall PDB rate was higher for direct oral anticoagulants and multiple antithrombotics in the control group, while L-PDB incidence was lower in the TLE group for these agents(8.7% vs 23.1% and 5.0% vs 29.4%, respectively).CONCLUSION TLE for gastric ESD reduces overall PDB, and especially L-PDB incidence, among patients receiving antithrombotics.展开更多
To assess the impact of laparoscopic liver resection (LLR) on surgical blood loss (SBL), especially in patients with antithrombotics for thromboembolic risks. METHODSConsecutive 258 patients receiving liver resection ...To assess the impact of laparoscopic liver resection (LLR) on surgical blood loss (SBL), especially in patients with antithrombotics for thromboembolic risks. METHODSConsecutive 258 patients receiving liver resection at our institution between 2010 and 2016 were retrospectively reviewed. Preoperative antithrombotic therapy (ATT; antiplatelets and/or anticoagulation) was regularly used in 100 patients (ATT group, 38.8%) whereas not used in 158 (non-ATT group, 61.2%). Our perioperative management of high thromboembolic risk patients included maintenance of preoperative aspirin monotherapy for patients with antiplatelet therapy and bridging heparin for patients with anticoagulation. In both ATT and non-ATT groups, outcome variables of patients undergoing LLR were compared with those of patients receiving open liver resection (OLR), and the independent risk factors for increased SBL were determined by multivariate analysis. RESULTSThis series included 77 LLR and 181 OLR. There were 3 thromboembolic events (1.2%) in a whole cohort, whereas increased SBL (≥ 500 mL) and postoperative bleeding complications (BCs) occurred in 66 patients (25.6%) and 8 (3.1%), respectively. Both in the ATT and non-ATT groups, LLR was significantly related to reduced SBL and low incidence of BCs, although LLR was less performed as anatomical resection. Multivariate analysis showed that anatomical liver resection was the most significant risk factor for increased SBL [risk ratio (RR) = 6.54, P < 0.001] in the whole cohort, and LLR also had the significant negative impact (RR = 1/10.0, P < 0.001). The same effects of anatomical resection (RR = 15.77, P < 0.001) and LLR (RR = 1/5.88, P = 0.019) were observed when analyzing the patients in the ATT group. CONCLUSIONLLR using the two-surgeon technique is feasible and safely performed even in the ATT-burdened patients with thromboembolic risks. Independent from the extent of liver resection, LLR is significantly associated with reduced SBL, both in the ATT and non-ATT groups.展开更多
BACKGROUND There is no consensus on the antithrombotic treatment strategy for patients with coronary artery ectasia(CAE).CASE SUMMARY This case reports the dynamic observation of a patient for 48 mo after a diagnosis ...BACKGROUND There is no consensus on the antithrombotic treatment strategy for patients with coronary artery ectasia(CAE).CASE SUMMARY This case reports the dynamic observation of a patient for 48 mo after a diagnosis of CAE with acute myocardial infarction(AMI).The first antithrombotic agents used were aspirin(100 mg/d)and clopidogrel(75 mg/d).During the sixth month of observation,a second AMI occurred involving the same culprit vessel;therefore,antithrombotic agents were changed to aspirin(100 mg/d)and ticagrelor(90 mg twice per day).Twelve months after the second AMI,an attempt to reduce the dosage ticagrelor failed;therefore the original dose was continued.The CAE was relatively stable during the following 4 years.CONCLUSION This case indicates that a combination of aspirin and ticagrelor may be more effective for CAE patients with AMI than aspirin and clopidogrel.展开更多
Transcatheter aortic valve implantation （TAVI） carries a significant thromboembolic and concomitant bleeding risk, not only during the procedure but also during the periprocedural period. Many issues concerning opti...Transcatheter aortic valve implantation （TAVI） carries a significant thromboembolic and concomitant bleeding risk, not only during the procedure but also during the periprocedural period. Many issues concerning optimal antithrombotic therapy after TAVI are still under debate. In the present review, we aimed to identify all relevant studies evaluating antithrombotic therapeutic strategies in relation to clinical outcomes after the procedure. Four randomized control trials （RCT） were identified analyzing the post-TAVI antithrombotic strategy with all of them utilizing aspirin lifelong plus clopidogrel for 3-6 months. Seventeen registries have been identified, with a wide variance among them regarding baseline characteristics, while concerning antiplatelet therapy, clopidogrel duration was ranging from 3-12 months. Four non-randomized trials were identified, comparing single vs. dual antiplatelet therapy after TAVI, in respect of investigating thromboembolic outcome events over bleeding complications. Finally, limited data from a single RCT and a retrospective study exist with regards to anticoagulant treatment during the procedure and the optimal antithrombotic therapy when concomitant atrial fibrillation. In conclusion, due to the high risk and frailty of the treated population, antithrombotic therapy after TAVI should be carefully evaluated. Diminishing ischaemic and bleeding complications remains the main challenge in these patients with further studies to be needed in this field.展开更多
A new rapid and sensitive high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of atorvastatin—an antihyperlipidemic drug along with most commonly prescribed drug...A new rapid and sensitive high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of atorvastatin—an antihyperlipidemic drug along with most commonly prescribed drugs (antihyperlipidemic, antihypertensive, antidiabetic, antithrombotic) in bulk and marketed combined formulations. The chromatographic separation was carried out by gradient elution mode with acetonitrile as organic modifier and 0.1% triethylamine acetate (TEAA) buffer pH 5 at a flow rate of 1 mL/min and a diode array detector at wavelength 230 nm was employed for detection of the analytes. Calibration curves were linear in the range of 5-150 mg/mL for all the drugs with correlation coefficients of determination (r 2 values)Z0.999. Limits of detection (LODs) and Limits of quantification (LOQs) ranged from 0.1 to 0.27 mg/mL and 0.3 to 0.89 mg/mL respectively. Intra-day and inter-day precision was studied at three concentration levels (20, 60 and 100 mg/mL). The intra-day and inter-day RSD for all compounds was less than 2.0%. The accuracy for all compounds was found to be between 98% and 102%. Thus, the performance of the method described allows its use in quantification of atorvastatin along with 9 most commonly prescribed drugs available in market as atorvastatin combined dosage forms.展开更多
基金supported by grants from Guangdong Provincial Key R&D Program(2023B1111050011)National Key Research and Development Program of China(Grant Number 2022YFC2804101)to J.S.T.,Guangdong Basic and Applied Basic Research Foundation(No.2023A1515010432)+2 种基金Guangzhou Basic and Applied Basic Research Foundation(No.2025A04J5239)to D.M.T.High-level Talents Special Program of Zhejiang(No.2022R52036)to B.W.Meanwhilesupported by The High Performance Public Computing Service Platform of Jinan University.
文摘Seven previously unreported sesquiterpenes including three rare 5/5/6-fused tricyclic gymnomitrane-type sesquiterpenes(1-3),an ent-longipinane-type sesquiterpene(4),a cuparane-type sesquiterpene(5),and two chamigrane-type sesquiterpenes(6 and 7),along with a known chamigrane-type sesquiterpene xylariterpenoid C(8)were isolated from the hydrothermal vent sediment derived fungus Penicillium sp.JWM79-5-1.Their structures were identified on the basis of 1D and 2D NMR,in conjunction with Mosher’s method,X-ray crystallography,and electronic circular dichroism(ECD).The antithrombotic activity of compounds 1-6 and 8 was evaluated in arachidonic acid(AA)-induced zebrafish thrombosis model in vivo.The results revealed compound 1 with potent antithrombotic activity in a concentration-dependent manner.Further,the pro-angi-ogenic activities of compounds 1-6 and 8 were evaluated in a transgenic zebrafish model that expresses vegfr2,the receptor for the angiogenic factor VEGF,tagged with the green fluorescence protein(vegfr2-GFP)through detecting the length of both intersegmental vessels(ISVs)and subintestinal veins(SIVs).The results revealed that compound 1 exhibited a potent antithrombotic activity while 3 revealed a potent pro-angiogenic activity.These findings strongly support drug development of these compounds in cardiovascular disease treatment.
基金supported by grants from the Fundamental Research Funds for the Central Universities(No.2020-JYB-ZDGG-032)National Natural Science Foundation of China(No.82104352)。
文摘Objective:EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen,an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome.Its composition,anticoagulant and fibrinolytic activities,and relevant mechanisms have been confirmed through in vitro experiments.However,whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown.This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro.Methods:The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl3.Then,the protein bands of EPF3 incubated with simulated gastric fluid(SGF),simulated intestinal fluid(SIF),and homogenate of Caco-2 cells(HC2C)were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability.Finally,the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer.Results:EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid.It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl3.EPF3 was stable in SIF and HC2C and unstable in SGF.The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent.The efflux ratio was less than1.2 during transport,and the transport behavior was not affected by inhibitors.EPF3 could reversibly reduce the expression of tight junction-related proteins,including zonula occludens-1,occludin,and claudin-1 in Caco-2 cells.Conclusion:EPF3 could play a thrombolytic and antithrombotic role in zebrafish.It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction.This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation.Please cite this article as:Zhong WL,Yang JQ,Liu H,Wu YL,Shen HJ,Li PY,Du SY.Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong(Pheretima vulgaris Chen)and its transport mechanism in Caco-2 monolayer through cell bypass pathway.J Integr Med.2025;23(4):415–428.
基金supported by the Beijing Municipal Medical Research Institutes Pilot Reform Project(grant number 2021-07).
文摘Thrombosis,the process of blood clot formation in blood vessels,is an important protective mechanism for avoiding excessive blood spillage when an individual is exposed to trauma.The body has both a thrombosis inhibition and a thrombus removal system,which interact in a balanced manner.If these mechanisms become unbalanced,and too many clots form and block the lumen,thrombosis occurs.Thrombosis is currently the leading cause of death from disease in humans and is one of the most common events leading to many cardiovascular diseases.Antithrombotic drugs are an integral part of the pharmacological treatment regimens,and interventional strategies are currently recom-mended for thrombotic complications in patients with thrombosis.Despite major advances in these therapies,the high risk associated with thrombosis and bleeding remains,because of the complex interplay among patient comorbidities,drug combinations,multifaceted dose adjustments,and care settings.Detailed assessment of the effects of bleeding and thrombosis is necessary to establish optimal treatment plans for patients with thrombosis.This study retrospec-tively evaluated methods for assessing the risk of bleeding/ischemia in thrombosis and the individualized use of these methods.
基金provided by Isuru Wijesoma from MediTech Media(Singapore),which was funded by AstraZeneca in accordance with Good Publication Practice(GPP3)guidelines。
文摘Objective To describe the long-term antithrombotic management patterns(AMPs)and clinical outcomes of Chinese patients with acute coronary syndrome(ACS).Methods This was an observational,multicenter,longitudinal cohort extension study of Chinese patients who had completed the EPICOR Asia 2-year follow-up study post-hospitalization for an ACS event.Changes in AMP and clinical outcomes for up to 5 years post-ACS event were evaluated.Results Overall,2334 patients with ACS were enrolled at 49 sites.The mean age was 61.6 years and 76.3%were men.By study end,2093 patients completed the 3-year follow-up.At baseline(2 years post-ACS event),72.4%of patents received one antiplatelet(AP)medication,with aspirin being the preferred one.A small proportion of patients(21.5%)was treated with two or more APs(2+AP),and even fewer patients(6.1%)did not receive any AP medication at baseline.Upon study completion,the proportion of patients without AP therapy increased to 13.6%,while the percentage of patients on one AP and 2+AP decreased to 69.3%and 17.1%,respectively.Numerically,a higher incidence of clinical events(composite of all-cause mortality,myocardial infarction,stroke)was observed for the 2+AP(13.2%)subgroup than for the no AP(10.5%)and one AP(8.6%)subgroups.Furthermore,the 2+AP subgroup exhibited the greatest number of bleeding events,outpatient visits,and hospitalization rates.Unlike myocardial infarction or stroke,bleeding events prompted an adjustment in AMP.Conclusion Most patients in China received at least one AP medication up to 5 years after an ACS event.
文摘To investigated the relationship between postoperative bleeding following gastric endoscopic submucosal dissection (ESD) and individual antithrombotic agents. METHODSA total of 2488 gastric neoplasms in 2148 consecutive patients treated between May 2001 and June 2016 were studied. The antithrombotic agents were categorized into antiplatelet agents, anticoagulants, and other antithrombotic agents, and we included combination therapies [e.g., dual antiplatelet therapy (DAPT)]. The risk factors associated with post-ESD bleeding, namely, antithrombotic agents overall, individual antithrombotic agents, withdrawal or continuation of antithrombotic agents, and bleeding onset period (during the first six days or thereafter), were analyzed using univariate and multivariate analyses. RESULTSThe en bloc resection and complete curative resection rates were 99.2% and 91.9%, respectively. Postoperative bleeding occurred in 5.1% cases. Bleeding occurred in 10.3% of the patients administered antithrombotic agents. Being male (P = 0.007), specimen size (P < 0.001), and antithrombotic agent used (P < 0.001) were independent risk factors for postoperative bleeding. Heparin bridging therapy (HBT) (P = 0.002) and DAPT/multidrug combinations (P < 0.001) were independent risk factors associated with postoperative bleeding. The bleeding rate of the antithrombotic agent continuation group was significantly higher than that of the withdrawal group (P < 0.01). Bleeding within postoperative day (POD) 6 was significantly higher in warfarin (P = 0.015), and bleeding after POD 7 was significantly higher in DAPT/multidrug combinations (P = 0.007). No thromboembolic events were reported. CONCLUSIONWe must closely monitor patients administered HBT and DAPT/multidrug combinations after gastric ESD, particularly those administered multidrug combinations after discharge.
文摘A new method for the determination of antithrombotic activity of egg white protein hydrolysate （EWPH） was developed using a microplate reader. Reaction was carried out at 37℃and pH 7.2 with fibrinogen concentration 0.1%. Microplate reading was conducted at 405 nm. Inhibition rate of EWPH on thrombin activity showed linearity （R2 = 0.9971）, when the inhibition rate was in the range of 10-90%. The lower limit of detection （LLD, at 99.7% probability） and the biological limit of detection （BLD, at 99.7% probability） of the method were 10.643 and 40 mg/mL, respectively. The repeatability standard deviation （R.S.D.） was 1.08%. The standard deviation of the method was ±0.027 AT-U.
文摘AIM: To evaluate the risk factors for postoperative bleeding after gastric endoscopic submucosal dissection(ESD) based on the latest guidelines.METHODS: A total of 262 gastric neoplasms were treated by ESD at our center during a 2-year period from October 2012. We analyzed the data of these cases retrospectively to identify the risk factors for postESD bleeding.RESULTS: Of the 48(18.3%) cases on antithrombotic treatment, 10 were still receiving antiplatelet drugs perioperatively, 13 were on heparin replacement after oral anticoagulant withdrawal, and the antithrombotic therapy was discontinued perioperatively in 25 cases. Postoperative bleeding occurred in 23 cases(8.8%). The postoperative bleeding rate in the heparin replacement group was 61.5%, significantly higher than that in the non-antithrombotic therapy group(6.1%). Univariate analysis identified history of antithrombotic drug use, heparin replacement, hemodialysis, cardiovascular disease, diabetes mellitus, elevated prothrombin timeinternational normalized ratio, and low hemoglobin level on admission as risk factors for post ESD bleeding. Multivariate analysis identified only heparin replacement(OR = 13.7, 95%CI: 1.2-151.3, P = 0.0329) as a significant risk factor for post-ESD bleeding.CONCLUSION: Continued administration of antiplatelet agents, based on the guidelines, was not a risk factor for postoperative bleeding after gastric ESD; however, heparin replacement, which is recommended after withdrawal of oral anticoagulants, was identified as a significant risk factor.
基金Supported by Shanghai Health and Family Planning Commission Foundation,No.201440430
文摘AIM To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. METHODS All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t- or χ2-test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the differencewas compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. RESULTS A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups(70.8 ± 11.4 vs 62.4 ± 12.0, P < 0.001; 8(8.2%) vs 15(21.7%), P < 0.05; 65(66.3%) vs 13(18.8%), P < 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant(P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients in the continuing group, and the risk of death and developing acute cardiovascular disease was higher in patients in the discontinuing group(log-rank test, P = 0.000 for both). Furthermore, COX regression multivariate analysis revealed that the hazard ratio(HR) for recurrent bleeding was 2.986(95%CI: 067-8.356, P = 0.015) in the continuing group, while HR for death or acute cardiovascular disease was 5.216(95%CI: 1.035-26.278, P = 0.028).CONCLUSION After the occurrence of peptic ulcer bleeding, continuing antithrombotics increases the risk of recurrent bleeding events, while discontinuing antithrombotics would increase the risk of death and developing cardiovascular disease. This suggests that clinicians should comprehensively consider the use of antithrombotics after peptic ulcer bleeding.
基金supported by Research on Precision Nutrition and Health Food,Department of Science and Technology of Henan Province(CXJD2021006)Key Project in Science and Technology Agency of Henan Province(202102110283 and 202102110149)。
文摘This is the first report on a polysaccharide(RCJ2-Ib)isolated from Rosa Chinensis Flos.RCJ2-Ib was obtained through the extraction with water,precipitation with ethanol,separation with DEAE-52 column and purification with DEAE-Sepharose Fast Flow column and Sephadex G100 column.GC,FT-IR and NMR analyses revealed that RCJ2-Ib(3.3 k Da)was a 1,4-linked polymannuronic acid containing substantialβ-Danomers units.The anticoagulant effect of RCJ2-Ib evaluated by using rabbit ear venous blood and an acute blood stasis rat model showed that RCJ2-Ib had obvious anticoagulant activity in regulating endogenous and exogenous coagulation pathways and reducing serum thromboxane B2 and endothelin-1.In addition,RCJ2-Ib could also increase the number of Lactobacillus and Escherichia coli.As a result,RCJ2-Ib has the potential to inhibit thrombosis and maintain the intestinal environment.
基金supported in part by the Notional Natural Science Foundation of China (No.30800858)the Shandong Natural Science Foundation (No.ZR2010 CQ020)
文摘The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical character on their antithrombotic activity and the possible mechanism. Both LMW fucoidan fractions exhibited favorable antithrombotic activity in an Fecl3-induced arterial thrombosis. The antithrombotic activity of LMW fucoidan was related with decrease of TXB2 and whole blood viscosity and hematocrit. LMW fucoidan showed a correlation between anticoagulant, antiaggregant and antithrombotic effects in vivo. For LMW fucoidan, antithrombotic activity required high dose of 5-10 nmol kg-1, concomitantly with increase in anticoagulant activity and inhibition of platelet aggregation. Administration of LMW fucoidan significantly promoted the 6-keto-PGF1α content and decreased the TXB2 content, indicating its inhibition of tissue factor pathway and regulation of metabolism of arachidonic acid. By comparison, highly sulfated fucoidan LF2 with Mw 3900 seemed to be a more suitable choice for antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic risk in vivo.
基金National Clinical Research Hospital Program of the French Ministry of Health,No.PHRC-12-009-0243.
文摘BACKGROUND There are few reports on major gastrointestinal(GI)bleeding among patients receiving an antithrombotic.AIM To describe clinical characteristics,bleeding locations,management and inhospital mortality related to these events.METHODS Over a three-year period,we prospectively identified 1080 consecutive adult patients admitted in two tertiary care hospitals between January 1,2013 and December 31,2015 for major GI bleeding while receiving an antithrombotic.The bleeding events were medically validated.Clinical characteristics,causative lesions,management and fatalities were described.The distribution of antithrombotics prescribed was compared across the bleeding lesions identified.RESULTS Of 576 patients had symptoms of upper GI bleeding and 504 symptoms of lower GI bleeding.No cause was identified for 383(35.5%)patients.Gastro-duodenal ulcer was the first causative lesion in the upper tract(209 out of 408)and colonic diverticulum the first causative lesion in the lower tract(120 out of 289).There was a larger proportion of direct oral anticoagulant use among patients with lower GI than among those with upper GI lesion locations(P=0.03).There was an independent association between gastro-duodenal ulcer and antithrombotic use(P=0.03),taking account of confounders and proton pump inhibitor coprescription.Pair wise comparisons pointed to a difference between vitamin K antagonist,direct oral anticoagulants,and antiplatelet agents in monotherapy vs dual antiplatelet agents.CONCLUSION We showed a higher rate of bleeding lesion identification and suggested a different pattern of antithrombotic exposure between upper and lower GI lesion locations and between gastro-duodenal ulcer and other identified upper GI causes of bleeding.Management was similar across antithrombotics and in-hospital mortality was low(5.95%).
文摘Objective The optimal antithrombotic regimen for patients on oral anticoagulation （OAC） after acute coronary syndrome （ACS） and percutaneous coronary intervention （PCI） remains debated. This study sought to evaluate the efficacy and safety of OAC plus clopidogrel with or without aspirin in a real-world setting. Methods We retrospectively analyzed data from an international, multi-center registry be- tween 2003 and 2014 （n = 15,401）. Patients with ACS and receiving OAC after PCI were screened. The composite primary endpoint was 1-year all-cause death, re-infarction, or severe bleeding. Results The final analysis enrolled 642 patients including 62 patients （9.7%） with OAC and clopidogrel （dual therapy）, and 580 patients （90.3%） with the combination of aspirin, OAC and clopidogrel （triple therapy）. Pa- tients on triple therapy were more often female and were more likely to have comorbidities. There was no significant difference regarding the primary end point between dual therapy with triple therapy patients [17.74% vs. 17.24%; unadjusted hazard ratio （HR）： 1.035; 95% confi- dence interval （CI）： 0.556-1.929; adjusted HR： 1.026; 95% CI： 0.544-1.937]. However, the re-infarction rate was significantly higher in dual therapy than triple therapy patients （14.52% vs. 5.34%; unadjusted HR： 2.807; 95% CI： 1.329-5.928; adjusted HR： 2.333; 95% CI： 1.078-5.047）. In addition, there was no difference between two regimes in all-cause death and severe bleeding. Conclusions In real-life patients with ACS following PCI and with an indication of OAC, triple therapy was not associated with an increased rate of adverse out- comes compared to dual therapy. Moreover, it decreased risk of re-infarction and did not increase risk of severe bleeding.
文摘Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previous works have shown that it is possible to develop potent thrombin receptor antagonists to compete effectively with the receptor’s internal “tethered” ligand to block platelet activation. Vorapaxar (SCH 530348) from Schering-Plough (now Merck) and atopaxar (E5555) from Eisai have been advanced to human clinical trials. Recently, the pivotal phase III clinical trial results for vorapaxar were published. In this article we review these results plus the phase II results from atopaxar. Several newly described thrombin receptor antagonists from the literature will also be discussed. The phase III results from vorapaxar demonstrated that a thrombin receptor antagonist can achieve efficacy in addition to current standard- of-care in treating atherothrombotic patients, especially those with previous myocardial infarction (MI). However, the increased moderate and severe bleeding, especially intracranial bleeding, point to the limitations of current thrombin receptor antagonists. Future thrombin receptor antagonists that can improve on the efficacy and bleeding profile of current ones should have a promising place in meeting the unmet medical need in treating atherothrombotic patients using current standard therapy.
文摘Age is an important prognostic factor in the outcome of acute coronary syndromes （ACS）. A substantial percentage of patients who ex- perience ACS is more than 75 years old, and they represent the fastest-growing segment of the population treated in this setting. These pa- tients present different patterns of responses to pharmacotherapy, namely, a higher ischemic and bleeding risk than do patients under 75 years of age. Our aim was to identify whether the currently available ACS ischemic and bleeding risk scores, which has been validated for the general population, may also apply to the elderly population. The second aim was to determine whether the elderly benefit more from a spe- cific pharmacological regimen, keeping in mind the numerous molecules of antiplatelet and antithrombotic drugs, all validated in the general population. We concluded that the GRACE （Global Registry of Acute Coronary Events） risk score has been extensively validated in the elderly. However, the CRUSADE （Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early imple- mentation of the ACC/AHA Guidelines） bleeding score has a moderate correlation with outcomes in the elderly. Until now, there have not been head-to-head scores that quantify the ischemic versus hemorrhagic risk or scores that use the same end point and timeline （e.g., ischemic death rate versus bleeding death rate at one month）. We also recommend that the frailty score be considered or integrated into the current existing scores to better quantify the overall patient risk. With regard to medical treatment, based on the subgroup analysis, we identified the drugs that have the least adverse effects in the elderly while maintaining optimal efficacy.
文摘Endoscopic submucosal dissection(ESD) is minimally invasive and thus has become a widely accepted treatment for gastric neoplasms,particularly for patients with comorbidities.Antithrombotic agents are used to prevent thrombotic events in patients with comorbidities such as cardio-cerebrovascular diseases and atrial fibrillation.With appropriate cessation,antithrombotic therapy does not increase delayed bleeding in low thrombosis-risk patients.However,high thrombosisrisk patients are often treated with combination therapy with antithrombotic agents and occasionally require the continuation of antithrombotic agents or heparin bridge therapy(HBT) in the perioperative period.Dual antiplatelet therapy(DAPT),a representative combination therapy,is frequently used after placement of drug-eluting stents and has a high risk of delayed bleeding.In patients receiving DAPT,gastric ESD may be postponed until DAPT is no longer required.HBT is often required for patients treated with anticoagulants and has an extremely high bleeding risk.The continuous use of warfarin or direct oral anticoagulants may be possible alternatives.Here,we show that some antithrombotic therapies in high thrombosis-risk patients increase delayed bleeding after gastric ESD,whereas most antithrombotic therapies do not.The management of high thrombosis-risk patients is crucial for improved outcomes.
文摘BACKGROUND Postoperative delayed bleeding(PDB) after gastric endoscopic submucosal dissection(ESD) is the most common adverse event in patients receiving antithrombotics even with second-look endoscopy. Moreover, with the increasing prevalence of cardiovascular and cerebrovascular diseases in an aging population with associated lifestyle-related diseases, an increasing number of patients receive antithrombotics. Several attempts have been made to prevent PDB in aging population;however, a consensus has yet to be reached.AIM To examine the efficacy of third-look endoscopy(TLE) for PDB prevention.METHODS One hundred patients with early gastric neoplasms receiving antithrombotics were prospectively enrolled and subjected to ESD with TLE between February 2017 and July 2019. The primary endpoint was PDB rate, which was compared with our preset threshold. Furthermore, we divided the bleeding period into early-and late-onset PDB(E-PDB and L-PDB, respectively) and analyzed its rate. As a secondary analysis, we compared PDB rates with those of a historical control group, using propensity score matching, and calculated the PDB rates per antithrombotic agent use in each group.RESULTS In total, 96 patients and 114 specimens were finally evaluated. The overall PDB rate was 7.9%(9/114) [90%CI: 4.7-13.1, P = 0.005], while the late-and early-onset PDB rates(L-PDB and E-PDB) were 5.3% [90%CI: 2.7-9.9, P < 0.0001] and 2.6% [90%CI: 1.1-6.4, P = 0.51], respectively. Propensity score matching generated 58 matched pairs for TLE and control groups. No differences were found in overall PDB incidence(10.3% vs 20.7%, P = 0.12), whereas L-PDB occurrence significantly differed(5.2% vs 17.2%, P = 0.04) between groups. Considering antithrombotics' use, the overall PDB rate was higher for direct oral anticoagulants and multiple antithrombotics in the control group, while L-PDB incidence was lower in the TLE group for these agents(8.7% vs 23.1% and 5.0% vs 29.4%, respectively).CONCLUSION TLE for gastric ESD reduces overall PDB, and especially L-PDB incidence, among patients receiving antithrombotics.
文摘To assess the impact of laparoscopic liver resection (LLR) on surgical blood loss (SBL), especially in patients with antithrombotics for thromboembolic risks. METHODSConsecutive 258 patients receiving liver resection at our institution between 2010 and 2016 were retrospectively reviewed. Preoperative antithrombotic therapy (ATT; antiplatelets and/or anticoagulation) was regularly used in 100 patients (ATT group, 38.8%) whereas not used in 158 (non-ATT group, 61.2%). Our perioperative management of high thromboembolic risk patients included maintenance of preoperative aspirin monotherapy for patients with antiplatelet therapy and bridging heparin for patients with anticoagulation. In both ATT and non-ATT groups, outcome variables of patients undergoing LLR were compared with those of patients receiving open liver resection (OLR), and the independent risk factors for increased SBL were determined by multivariate analysis. RESULTSThis series included 77 LLR and 181 OLR. There were 3 thromboembolic events (1.2%) in a whole cohort, whereas increased SBL (≥ 500 mL) and postoperative bleeding complications (BCs) occurred in 66 patients (25.6%) and 8 (3.1%), respectively. Both in the ATT and non-ATT groups, LLR was significantly related to reduced SBL and low incidence of BCs, although LLR was less performed as anatomical resection. Multivariate analysis showed that anatomical liver resection was the most significant risk factor for increased SBL [risk ratio (RR) = 6.54, P < 0.001] in the whole cohort, and LLR also had the significant negative impact (RR = 1/10.0, P < 0.001). The same effects of anatomical resection (RR = 15.77, P < 0.001) and LLR (RR = 1/5.88, P = 0.019) were observed when analyzing the patients in the ATT group. CONCLUSIONLLR using the two-surgeon technique is feasible and safely performed even in the ATT-burdened patients with thromboembolic risks. Independent from the extent of liver resection, LLR is significantly associated with reduced SBL, both in the ATT and non-ATT groups.
基金Supported by National Natural Science Foundation of China,No. 81600276
文摘BACKGROUND There is no consensus on the antithrombotic treatment strategy for patients with coronary artery ectasia(CAE).CASE SUMMARY This case reports the dynamic observation of a patient for 48 mo after a diagnosis of CAE with acute myocardial infarction(AMI).The first antithrombotic agents used were aspirin(100 mg/d)and clopidogrel(75 mg/d).During the sixth month of observation,a second AMI occurred involving the same culprit vessel;therefore,antithrombotic agents were changed to aspirin(100 mg/d)and ticagrelor(90 mg twice per day).Twelve months after the second AMI,an attempt to reduce the dosage ticagrelor failed;therefore the original dose was continued.The CAE was relatively stable during the following 4 years.CONCLUSION This case indicates that a combination of aspirin and ticagrelor may be more effective for CAE patients with AMI than aspirin and clopidogrel.
文摘Transcatheter aortic valve implantation （TAVI） carries a significant thromboembolic and concomitant bleeding risk, not only during the procedure but also during the periprocedural period. Many issues concerning optimal antithrombotic therapy after TAVI are still under debate. In the present review, we aimed to identify all relevant studies evaluating antithrombotic therapeutic strategies in relation to clinical outcomes after the procedure. Four randomized control trials （RCT） were identified analyzing the post-TAVI antithrombotic strategy with all of them utilizing aspirin lifelong plus clopidogrel for 3-6 months. Seventeen registries have been identified, with a wide variance among them regarding baseline characteristics, while concerning antiplatelet therapy, clopidogrel duration was ranging from 3-12 months. Four non-randomized trials were identified, comparing single vs. dual antiplatelet therapy after TAVI, in respect of investigating thromboembolic outcome events over bleeding complications. Finally, limited data from a single RCT and a retrospective study exist with regards to anticoagulant treatment during the procedure and the optimal antithrombotic therapy when concomitant atrial fibrillation. In conclusion, due to the high risk and frailty of the treated population, antithrombotic therapy after TAVI should be carefully evaluated. Diminishing ischaemic and bleeding complications remains the main challenge in these patients with further studies to be needed in this field.
基金the Department of Pharmaceuticals (Ministry of Chemicals and Fertilizers),New Delhi,for grant of a MS(Pharm.) fellowship
文摘A new rapid and sensitive high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of atorvastatin—an antihyperlipidemic drug along with most commonly prescribed drugs (antihyperlipidemic, antihypertensive, antidiabetic, antithrombotic) in bulk and marketed combined formulations. The chromatographic separation was carried out by gradient elution mode with acetonitrile as organic modifier and 0.1% triethylamine acetate (TEAA) buffer pH 5 at a flow rate of 1 mL/min and a diode array detector at wavelength 230 nm was employed for detection of the analytes. Calibration curves were linear in the range of 5-150 mg/mL for all the drugs with correlation coefficients of determination (r 2 values)Z0.999. Limits of detection (LODs) and Limits of quantification (LOQs) ranged from 0.1 to 0.27 mg/mL and 0.3 to 0.89 mg/mL respectively. Intra-day and inter-day precision was studied at three concentration levels (20, 60 and 100 mg/mL). The intra-day and inter-day RSD for all compounds was less than 2.0%. The accuracy for all compounds was found to be between 98% and 102%. Thus, the performance of the method described allows its use in quantification of atorvastatin along with 9 most commonly prescribed drugs available in market as atorvastatin combined dosage forms.
