Liver injury from direct oral anticoagulants

BACKGROUND Drug-induced liver injury(DILI)can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs.Direct-acting oral anticoagulants(DOACs)are non-vitamin K-based antagonists recently introduced and increasingly used for various clinical conditions.A meta-analysis of 29 randomised controlled trials and 152116 patients reported no increased risk of DILI with DOACs.However,it is challenging to predict the risk factors for DILI in individual patients with exclusion of patients with pre-existing liver disease from these studies.AIM To determine the risk factors and outcomes of patients who developed DILI secondary to DOACs by systematic review and meta-summary of recent case reports and series.METHODS A systematic search was conducted on multiple databases including PubMed,Science Direct,Reference Citation Analysis,and Google Scholar.The search terms included“Acute Liver Failure”OR“Acute-On-Chronic Liver Failure”OR“Acute Chemical and Drug Induced Liver Injury”OR“Chronic Chemical and Drug Induced Liver Injury”AND“Factor Xa Inhibitors”OR“Dabigatran”OR“Rivaroxaban”OR“apixaban”OR“betrixaban”OR“edoxaban”OR“Otamixaban”.The results were filtered for literature published in English and on adult patients.Only case reports and case studies reporting cases of DILI secondary to DOACs were included.Data on demographics,comorbidities,medication history,laboratory investigations,imaging,histology,management,and outcomes were extracted.RESULTS A total of 15 studies(13 case reports and 2 case series)were included in the analysis,comprising 27 patients who developed DILI secondary to DOACs.Rivaroxaban was the most commonly implicated DOAC(n=20,74.1%).The mean time to onset of DILI was 40.6 d.The most common symptoms were jaundice(n=15,55.6%),malaise(n=9,33.3%),and vomiting(n=9,33.3%).Laboratory investigations showed elevated liver enzymes and bilirubin levels.Imaging studies and liver biopsies revealed features of acute hepatitis and cholestatic injury.Most patients had a favourable outcome,and only 1 patient(3.7%)died due to liver failure.CONCLUSION DOACs are increasingly used for various clinical conditions,and DILI secondary to DOACs is a rare but potentially serious complication.Prompt identification and cessation of the offending drug are crucial for the management of DILI.Most patients with DILI secondary to DOACs have a favourable outcome,but a small proportion may progress to liver failure and death.Further research,including post-marketing population-based studies,is needed to better understand the incidence and risk factors for DILI secondary to DOACs.

Anticoagulant use before COVID-19 diagnosis prevent COVID-19 associated acute venous thromboembolism or not:A systematic review and meta-analysis

BACKGROUND Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019(COVID-19)patients.There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease.AIM To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients.METHODS A Literature search was performed on LitCovid PubMed,WHO,and Scopus databases from inception(December 2019)till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19.The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants.Secondary outcomes included COVID-19 disease severity,in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection,and mortality.The random effects models were used to calculate crude and adjusted odds ratios(aORs)with 95%confidence intervals(95%CIs).RESULTS Forty-six observational studies met our inclusion criteria.The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk[n=43851,9 studies,odds ratio(OR)=0.67(0.22,2.07);P=0.49;I2=95%].The association between prior anticoagulation and disease severity was non-significant[n=186782;22 studies,OR=1.08(0.78,1.49);P=0.64;I2=89%].However,pre-hospital anticoagulation significantly increased all-cause mortality risk[n=207292;35 studies,OR=1.72(1.37,2.17);P<0.00001;I2=93%].Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk[aOR=0.87(0.42,1.80);P=0.71],mortality[aOR=0.94(0.84,1.05);P=0.31],and disease severity[aOR=0.96(0.72,1.26);P=0.76].CONCLUSION Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events,improved survival,and lower disease severity in COVID-19 patients.

Compliance and adherence to oral anticoagulation therapy in elderly patients with atrial fibrillation in the era of direct oral anticoagulants

Thromboembolic complications represent a substantial problem in patients with atrial fibrillation （AF）. The prevalence of AF burden and associated arterial and venous thrombosis progressively increases with age. At the same time, representative national data regarding stroke incidence in AF patients aged 80 and older are limited.

Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection(ESD)for early-stage gastrointestinal tumors.The rate of post-ESD bleeding for gastric cancer is higher(around 5%-8%)than that for esophagus,duodenum and colon cancer(around 2%-4%).Although investigations into the risk factors for post-ESD bleeding have identified several procedure-,lesion-,physician-and patient-related factors,use of antithrombotic drugs,especially anticoagulants[direct oral anticoagulants(DOACs)and warfarin],is thought to be the biggest risk factor for post-ESD bleeding.In fact,the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%,which is higher than that in patients not receiving anticoagulants.However,because clinical guidelines for management of ESD in patients receiving DOACs differ among countries,it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice.Given that the pharmacokinetics(e.g.,plasma DOAC level at both trough and T_(max))and pharmacodynamics(e.g.,anti-factor Xa activity)of DOACs are related to risk of major bleeding,plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

Multicenter experience with photoselective vaporization of the prostate on men taking novel oral anticoagulants

Objective:Photoselective vaporization of the prostate(PVP)is a widely performed surgical procedure for benign prostatic obstruction.This approach has become particular favoured for men on anti-platelet and anticoagulation agents such as clopidogrel and warfarin but there is minimal published experience in the setting of novel oral anticoagulants(NOACs).This study was to examine the perioperative outcomes in men on NOACs undergoing PVP,with particular reference to perioperative morbidity.Methods:A retrospective analysis of PVP datasets was undertaken from three centres in Sydney(Australia),Toulouse(France)and Boston(USA).Subjects who had been treated whilst on NOACs without discontinuation or bridging were identified.Perioperative outcomes and treatment parameters were examined and morbidity recorded according to Clavien-Dindo(CD)classification.Results:There were a total of 20 subjects who had undergone PVP whilst NOACs had been continued during the perioperative period.The mean age was 776.5 years.The mean prostate volume,energy utilization and vaporisation time was 9456 mL,301211 kJ,and 3521 min respectively.The mean postoperative duration of catheterization and duration of hospitalization was 2.22.4 days and 2.42.4 days respectively.There was a single episode of urinary tract infection and four subjects required re-catheterisation for non-hematuric retentions.Conclusions:This study supports the safety of men on NOACs undergoing PVP.Whilst this study represents the largest experience of PVP in these men,larger studies are necessary to confirm the safety of PVP in this group of men undergoing BPH-related surgery.

Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuriafuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides （HfP） from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time （APTT）, prothrombin time （PT） and thrombin time （TT）. The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man： Rha： Glc A： Glc： Gal： Xyl： Fuc=0.083 6： 0.437： 0.134： 0： 1.182： 0.748： 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity ECs0 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that ofheparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

Current practice of anticoagulant in the treatment of splanchnic vein thrombosis secondary to acute pancreatitis

Background:Severe acute pancreatitis is a common diagnosis in emergency general surgery and can be a cause of significant morbidity and mortality.A consequence of severe acute pancreatitis is thrombus in the splanchnic veins.These thrombi can potentially lead to bowel ischemia or hepatic failure.However,another complication of severe acute pancreatitis is retroperitoneal bleeding.At this time,it is unclear if treating patients for splanchnic vein thrombosis in the context of severe acute pancreatitis is associated with any outcome benefit.A systematic review might clarify this question.Data sources:A two-fold search strategy(one broad and one precise)looked at all published literature.The review was registered on PROSPERO(ID:CRD42018102705).MEDLINE,EMBASE,PubMed,Cochrane and Web of Science databases were searched and potentially relevant papers were reviewed indepen-dently by two researchers.Any disagreement was reviewed by a third independent researcher.Primary outcome was reestablishment of flow in the thrombosed vein versus bleeding complications.Results:Of 1462 papers assessed,a total of 16 papers were eligible for inclusion.There were no ran-domized controlled trials,2 were case series,5 retrospective single-center studies and 9 case reports.There were a total of 198 patients in these studies of whom 92(46.5%)received anticoagulation therapy.The rates of recanalization of veins in the treated and non-treated groups was 14%and 11%and bleeding complications were 16%and 5%,respectively.However,the included studies were too heterogeneous to undertake a meta-analysis.Conclusions:The systematic review highlights the lack evidence addressing this clinical question.There-fore a randomized controlled trial would be appropriate to undertake.

Gastrointestinal bleeding in patients on novel oral anticoagulants:Risk,prevention and management

Novel oral anticoagulants(NOACs), which include direct thrombin inhibitor(dabigatran) and direct factor Xa inhibitors(rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding(GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran(150 mg b.i.d), rivaroxaban and high-dose edoxaban(60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.

Preparation of low molecular weight Sargassum fusiforme polysaccharide and its anticoagulant activity

Heparin has been used as an anticoagulant drug for many years, but it has significant side ef fects. In the search for good substitutes, low molecular weight(MW) polysaccharides from S argassum fusiforme have been examined and confi rmed to possess biological activities. Here, S. fusiforme polysaccharides(SFP) were extracted and subjected to a hydrogen peroxide(H_2O_2) oxidation method for the preparation of low-MW SFP(LSFP). The effects of temperature, pH, and H_2O_2 concentration on the degradation process were also examined. Several LSFP of 36, 9, 5.7, and 2.7 kDa were obtained under different conditions, and their anticoagulant activities studied in vitro. The results showed that SFP and LSFP prolonged activated partial thromboplastin(APTT), prothrombin(PT) and thrombin times(TT) significantly, indicating that these low MW polysaccharides possessed anticoagulant activity in the intrinsic, extrinsic, and common coagulation pathways. As these ef fects were related to the MW of the polysaccharides in APTT and TT but not in PT, the contents of the monosaccharide fucose and sulfate and the polysaccharide MW could have exerted combined ef fects. The details of this mechanism require further verifi cation.

In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants

AIM To verify the validity of the endoscopy guidelines for patients taking warfarin or direct oral anticoagulants(DOAC).METHODS We collected data from 218 patients receiving oral anticoagulants(73 DOAC users, 145 warfarin users) and 218 patients not receiving any antithrombotics(age-and sexmatched controls) who underwent polypectomy.(1) We evaluated post-polypectomy bleeding(PPB) risk in patients receiving warfarin or DOAC compared with controls;(2) we assessed the risks of PPB and thromboembolism between three AC management methods: Discontinuing AC with heparin bridge(HPB)(endoscopy guideline recommendation), continuing AC, and discontinuing AC without HPB.RESULTS PPB rate was significantly higher in warfarin users and DOAC users compared with controls(13.7% and 13.7% vs 0.9%, P < 0.001), but was not significantly different between rivaroxaban(13.2%), dabigatran(11.1%), and apixaban(13.3%) users. Two thromboembolic events occurred in warfarin users, but none in DOAC users. Compared with the continuing anticoagulant group, the discontinuing anticoagulant with HPB group(guideline recommendation) had a higher PPB rate(10.8% vs 19.6%, P = 0.087). These findings were significantly evident in warfarin but not DOAC users. One thrombotic event occurred in the discontinuing anticoagulant with HPB group and the discontinuing anticoagulant without HPB group; none occurred in the continuing anticoagulant group.CONCLUSION PPB risk was similar between patients taking warfarin and DOAC. Thromboembolism was observed in warfarin users only. The guideline recommendations for HPB should be re-considered.

Real-world characteristics of hospitalized frail elderly patients with atrial fibrillation： can we improve the current prescription of anticoagulants？

Background In elderly patients, especially those older than 80 years, atrial fibrillation （AF） is associated with an almost 25% in- creased risk of stroke. Stroke prophylaxis with anticoagulants is therefore highly recommended. The prevalence of factors that have been associated with a lower rate of prescription and adherence to anticoagulant therapy in these patients is little known. The objective of this study was to explore the clinical characteristics of elderly subjects, with and without AF, consecutively admitted to an acute geriatric unit, discussing factors that may decrease the persistence on stroke prophylaxis therapy. We also highlight possible strategies to overcome the barriers conditioning the current underuse of oral anticoagulants in this segment of the population. Methods A retrospective observational study was performed on a cohort of elderly patients with and without AF admitted to the Acute Geriatric Unit of San Gerardo Hospital （Monza, Italy）. Results Compared to patients without AF （n = 1216）, those with AF （n = 403） had a higher Charlson Comorbidity Index （3 vs. 2, P 〈 0.001）, number of administered drugs （4 vs. 3, P 〈 0.001）, rate of heart failure （36.5% vs. 12%, P 〈 0.001） and chronic kidney disease （20.6 vs. 13.2, P 〈 0.001）. Many patients with AF were frail （54%） or pre-frail （29%）. Conclusions Elderly patients with AF have higher rates of conditions that affect adherence to traditional anticoagulant therapy （vitamin K antagonists, VKA）. New direct oral anticoagulants （DOAs） can help overcome this problem. In order to prescribe the most appropriate VKA or DOAs, with the best efficacy/safety profile and the highest compliance, a comprehensive geriatric assessment should always accompany the scores for thrombotic and hemorrhagic risk stratification.

Rate of anticoagulant use, and factors associated with not prescribing anticoagulant in older Thai adults with non-valvular atrial fibrillation: A multicenter registry

Objectives To investigate the rate of anticoagulant use,the reasons for not prescribing anticoagulant,and the factors associated with non-prescription of anticoagulant in older Thai adults with non-valvular atrial fibrillation.Methods A multicenter registry of patients with non-valvular atrial fibrillation was conducted during 2014 to 2017 in Thailand.Demographic,medical history,antithrombotic medication,non-antithrombotic medication,and laboratory data were collected and analyzed.Data were compared between the older adult (≥ 65 years) and younger adult (< 65 years) groups.The reasons why anticoagulant was not prescribed were collected,and predictive factors were identified.Results A total of 3218 patients (1873 males) with an average age of 67.3 ± 11.3 years were included.Almost two-thirds (61.0%) of patients were in the older adult group.Anticoagulant was prescribed in 2422 patients (75.3%): 81.4% in the older adult group and 65.7% in the younger adult group.The three main reasons for not prescribing anticoagulant were already taking antiplatelets,patient refusal,and bleeding risk.These reasons were more common in older adults as compared to younger adults.Multivariate analysis revealed current use of antiplatelets to be the most important factor that predict the non-prescription of anticoagulant in older population.Conclusions The prevalence of anticoagulant prescription among older Thai adults with atrial fibrillation is 81.4%.Taking antiplatelet drugs was found to be the strongest reason that predicts the non-prescription of anticoagulant in this patient population.A guideline should be developed to optimize the use of anticoagulant and antiplatelet in older adults.

Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation

Background The efficacy and safety of non-vitamin K antagonist oral anticoagulants （NOACs） and warfarin in Asian octogenarian atrial fibrillation （AF） patients have not been established in a real-world setting. We aimed to evaluate the efficacy and safety of NOACs and warfarin in Korean octogenarian patients. Methods A total of 293 consecutive patients aged 〉 80 years with non-valvular AF who had taken either NOACs 048 cases, 50.5%） or warfarin （145 cases, 49.5%） were retrospectively reviewed. The efficacy outcome was the com- posite of stroke or systemic embolism. The safety outcome was major bleeding. Results The follow-up duration was 375 patient-years （ 172 patient-years with NOACs and 203 patient-years with warfarin）. Patients on NOACs were slightly older （P = 0.006） and had slightly higher HAS-BLED scores （P = 0.034）. The efficacy of both anticoagulants was high （1.16% for NOACs vs. 2.98% for warfarin per 100 pa- tient-years, P = 0.46）. The safety outcome was relatively high in both NOACs and warfarin groups （8.96% vs. 12.46%, P = 0.29）. The effi- cacy and safety outcomes tended to decrease non-significantly in low dose NOACs than in common dose NOACs or warfarin （0.85% vs. 1.84% vs. 2.98% in efficacy outcome, P = 0.69; and 6.97% vs. 13.29% vs. 12.46% in safety outcome, P = 0.34）. Conclusions NOACs were highly effective for prevention of stroke or systemic embolism in Asian octogenarian AF patients. However, major bleeding occurred excessively high in both anticoagulant groups. Further study is required on the optimal anticoagulant regimen in octogenarian population.

Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism

BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulation treatment have an associated increase rate.GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants(DOAC),especially with active cancer therapies.AIM To evaluate patient risk factors,effectiveness(VTE)and safety(MB)of DOACs and low molecular weight heparin(LMWH)in patients with active GICA-VTE.METHODS A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed.Inclusion criteria included active GI cancer diagnosed at any stage or treatment+/-6 mo of VTE diagnosis,whom were prescribed 6 mo or more of DOACs or LMWH.The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events.Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.RESULTS A total of 144 patients were prescribed anticoagulation,in which 106 fulfilled inclusion criteria apixaban(27.3%),rivaroxaban(34.9%)and enoxaparin(37.7%),and 38 were excluded.Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event,with 62%males,80%Caucasian,70%stage IV,pancreatic cancer(40.5%),30%Khorana Score(≥3 points),and 43.5%on active chemotherapy.Sixty-four percent of patients completed anticoagulation therapy(range 1 to 43 mo).Recurrent VTE at 6 mo was noted in 7.5%(n=3),6.8%(n=2)and 2.7%(n=1)of patients on enoxaparin,apixaban and rivaroxaban,respectively(all P=NS).MB at 6 mo were 5%(n=2)for enoxaparin,6.8%(n=2)for apixaban and 21.6%(n=8)for rivaroxaban(overall P=0.048;vs LMWH P=0.0423;all other P=NS).Significant predictors of a primary or secondary outcome for all anticoagulation therapies included:Active systemic treatment(OR=5.1,95%CI:1.3-19.3),high Khorana Score[≥3 points](OR=5.5,95%CI:1.7-17.1),active smoker(OR=6.7,95%CI:2.1-21.0),pancreatic cancer(OR=6.8,95%CI:1.9-23.2),and stage IV disease(OR=9.9,95%CI:1.2-79.1).CONCLUSION Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.

The effect of cryotherapy application before versus after subcutaneous anticoagulant injection on pain intensity and hematoma formation: A quasi-experimental design

Objective:To investigate the effect of cryotherapy application before versus after subcutaneous anticoagulant injection(SCAI)on pain intensity and hematoma formation.Methods:A quasi-experimental design was utilized.A convenient sample of 105 adult patients,who were admitted to one of the biggest teaching hospitals in Cairo and receiving SCAI,were recruited over a period of six months.Patients were randomly allocated into three groups:A Control group who received the routine hospital care(G1,n=35)and two intervention group who received cryotherapy for 5-min(G2:cryotherapy applied before SCAI,n=35;G3:cryotherapy applied after SCAI,n=35).Demographic and medical history data sheet,Pain Numeric Rating Scale and Hematoma Formation and Size Assessment Scale were used to collect the data.Results:The pain intensity among the patients in the two intervention groups(G2:Median=1.0;G3:Median=0)was significantly lower than in the control group(G1,Median=3.0).No significant difference was found between G2 and G3(P=0.728).Applying cryotherapy after SCAI(G3)decreased the frequency of hematoma formation(48hrs=31.4%&72hrs=28.5%)compared to applying it before injection(G2,100%)or not applying it(G1,100%).The size of hematoma in G3 was smaller than that in G2(P<0.01).Conclusion:Applying cryotherapy significantly decreased pain intensity and hematoma occurrence/size.Applying cryotherapy after injection was more effective in preventing hematoma formation and decreasing its size than applying it before injection.

Quantitation of bivalirudin,a novel anticoagulant peptide,in human plasma by LC-MS/MS:Method development,validation and application to pharmacokinetics

A rapid and sensitive method based on liquid chromatographtandem mass spectrometry （LC-MS/MS） for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and reextracted with dichloromethane, after which the analyte and triptorelin as an internal standard （IS） were separated on a 300SB-Cl8 column （150 mm x 4.6 mm i.d., 5 gm particle size） using 0.1% formic acid：methanol （45：55, v/v） as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization （ESI） interface, was operated in the positive ion mode, and the multiplereaction monitoring （MRM） transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5 - 249.3, respectively. The lower limit of quantification （LLOQ） was 1 ng/mL for 100 ng/mL plasma sample and the assay was linear over the concentration range 1 1000 ng/mL. The accuracy was within a range from -0.4% to 0.5% in terms of relative error （RE） and the intra- and inter-day precisions in terms of relative standard deviation （RSD） were 〈2.92 and 〈 3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin （0.5 mg/kg） to Chinese volunteers.

Efficacy and safety of novel anticoagulants in the elderly

Atrial fibrillation and venous thromboembolism （VTE） are common disorders associated with maleficent thrombotic events, particularly in the elderly patients. Polypharmacy, co-morbidities, and altered pharmacokinetics, often present in these patients, render the use of antico-agulants quite challenging. Novel oral anticoagulants （NOACs） have recently emerged as alternatives to Vitamin K Antagonists （VKAs） and are gradually increasing their popularity mainly because of their fewer drug and food interactions and ease of use. Their effectiveness and safety has been weU-established in the general population but the balance between benefit and harm in the elderly is still unclear. Routine use in these patients is uncommon. Accumulating data have shown that the benefit of NOACs is consistent among all age groups, featuring equal or greater efficacy in preventing thrombotic events. Excess bleedings were lower with NOACs in comparison to VKAs, but bleeding patterns were disparate among them and head to head comparison is not available. The present review highlights on the efficacy and safety of novel anticoagulants in the elderly population.

Structural Analysis and Anticoagulant Activity of Polysaccharides from Opuntia milpa alta

[Objective] To analyze the components and structure of Opuntia milpa alta polysaccharides, and to study its anticoagulant activity. [Method] The crude polysaccharides （CP） were prepared from Opuntia milpa alta using hot water extraction and ethanol precipitation method, purified by anion-exchange chromatography and gel filtration chromatography to study its monosaccharide composition, weight-average molecular weight distribution and main chain structure. And a preliminary study was conducted on the anticoagulant activity of polysaccharide components. [Result] The polysaccharide components WSP1, WSP2a and WSP3 were obtained from CP by the anion-exchange chromatography and gel filtration chromatography. WSP1 was mainly composed of galactose with a weight-average molecular weight of 2.32×106. WSP2a consisted of rhamnose, arabinose, xylose, mannose, glucose, galactose, glucuronic acid and galacturonic acid, the contents were 6.3%, 32.3%, 12.9%, 1.5%, 4.8%, 37.1%, 0.64% and 4.4%, respectively. WSP3 mainly composed of arabinose, xylose, rhamnose and trace of glucose, mannose, uronic acid. The weight-average molecular weight of WSP2a and WSP3 was 1.24×106 and 7.92×106, respectively. WSP2 prolonged the activated partial thromboplatin time （APTT） and thrombin time （TT）, while had no significant effect on the prothrombin time （PT） in vitro, indicating that anticoagulant activity of WSP2 functions by affecting the intrinsic coagulation system. The test of inhibition to the conversion of fibrinogen into thrombin showed that WSP2a and WSP3 had obvious anticoagulant activity. Methylation analysis indicated that the main chain of WSP2a was constituted of 1, 4-GalA, 1, 2-Rha and 1, 2, 4-Rha. [Conclusion] This study provided experimental basis for the optimization and development of polysaccharide resources from cactus

Management of antiplatelet or anticoagulant therapy in endoscopy: A review of literature

Endoscopic procedures hold a basal risk of bleeding that depends on the type of procedure and patients’comorbidities.Moreover,they are often performed in patients taking antiplatelet and anticoagulants agents,increasing the potential risk of intraprocedural and delayed bleeding.Even if the interruption of antithrombotic therapies is undoubtful effective in reducing the risk of bleeding,the thromboembolic risk that follows their suspension should not be underestimated.Therefore,it is fundamental for each endoscopist to be aware of the bleeding risk for every procedure,in order to measure the risk-benefit ratio for each patient.Moreover,knowledge of the proper management of antithrombotic agents before endoscopy,as well as the adequate timing for their resumption is essential.This review aims to analyze current evidence from literature assessing,for each procedure,the basal risk of bleeding and the risk of bleeding in patients taking antithrombotic therapy,as well as to review the recommendation of American society for gastrointestinal endoscopy,European society of gastrointestinal endoscopy,British society of gastroenterology,Asian pacific association of gastroenterology and Asian pacific society for digestive endoscopy guidelines for the management of antithrombotic agents in urgent and elective endoscopic procedures.