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World Journal of Gastroenterology 2023年第19期29卷 2916-2931页

作者： Mitsushige Sugimoto Masaki Murata Takashi Kawai Department of Gastroenterological Endoscopy Tokyo Medical University HospitalTokyo 160-0023Japan Department of Gastroenterology National Hospital Organization Kyoto Medical CenterKyoto 612-8555Japan

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.

关键词： Direct oral anticoagulants Gastrointestinal tumors Endoscopic submucosal dissection Delayed bleeding Adverse events anticoagulants

Liver injury from direct oral anticoagulants

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World Journal of Hepatology 2023年第6期15卷 841-849页

作者： Deven Juneja Prashant Nasa Ravi Jain Institute of Critical Care Medicine Max Super Specialty HospitalNew Delhi 110017India Critical Care Medicine NMC Specialty HospitalDubai 7832United Arab Emirates Internal Medicine College of Medicine and Health SciencesAl Ain 15551United Arab Emirates Critical Care Medicine Mahatma Gandhi Medical College and HospitalJaipur 302001RajasthanIndia

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 o

关键词： anticoagulants Direct-acting oral anticoagulants Drug induced liver injury Drug reactions Hepatotoxicity Novel oral anticoagulants

Non-vitamin K antagonist oral anticoagulants for COVID-19 thrombosis

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Journal of Acute Disease 2022年第6期11卷 212-221页

作者： Adel Khalifa Sultan Hamad Department of Electrophysiology Mohammed bin Khalifa bin Salman Al Khalifa Cardiac CentreAwaliKingdom of Bahrain

Thrombotic complications appear to be a major predictor of death in COVID-19 patients,and multiple studies have shown that anticoagulants can help to improve the outcome.The Food and Drug Administration’s acceptance of non-vitamin K antagonist oral anticoagulants(NOACs)has sparked much excitement about their potential as a replacement for existing oral anticoagulants.NOACs target a single clotting factor,often activated factor X or thrombin,and involve the coagulation factor Xa inhibitors including apixaban,edoxaban,and rivaroxaban,and the thrombin inhibitor dabigatran.COVID-19 is an infectious disease that causes thrombotic events by inducing a pro-inflammatory and prothrombotic condition.This article provides a comprehensive overview of the mechanism behind enhanced thrombogenicity accompanying COVID-19,the clinical range of NOACs,and the role of NOACs in treatment of COVID-19 based on recent investigations and clinical trials.

关键词： anticoagulants COVID-19 NOACs SARS-CoV-2 Thrombosis

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

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World Journal of Gastroenterology 2018年第14期24卷 1540-1549页

作者： Naohiro Yanagisawa Naoyoshi Nagata Kazuhiro Watanabe Tatsuhiro Iida Mariko Hamada Sakurako Kobayashi Takuro Shimbo Junichi Akiyama Naomi Uemura Department of Gastroenterology and Hepatology National Center for Global Health and MedicineTokyo 162-8655Japan Ohta Nishinouchi Hospital Fukushima 963-8022Japan Department of Gastroenterology and Hepatology National Center for Global Health and MedicineKohnodai HospitalChiba 272-8516Japan

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.

关键词： High-risk endoscopic procedures Novel oral anticoagulants Endoscopic guideline validation Postprocedure gastrointestinal bleeding

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

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World Journal of Gastrointestinal Oncology 2019年第10期11卷 866-876页

作者： Alejandro Recio-Boiles Sumana Veeravelli Jessica Vondrak Hani M Babiker Aaron J Scott Rachna T Shroff Hitendra Patel Emad Elquza Ali McBride Department of Medicine Hematology and Medical OncologyUniversity of Arizona Cancer CenterTucsonAZ 85724United States Department of Medicine Internal Medicine Residency ProgramUniversity of ArizonaTucsonAZ 85725United States UC San Diego Health Moores Cancer Center La JollaCA 92093United States University of Arizona College of Pharmacy TucsonAZ 85725United States

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

关键词： Direct oral anticoagulants Low molecular weight heparin Gastrointestinal cancer Venous thromboembolism Cancer associated thrombosis Clinical risk

Pancreatic cancer:A model cancer for the study of the therapeutic effects of anticoagulants

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World Journal of Gastrointestinal Oncology 2009年第1期1卷 38-40页

作者： Anthony Maraveyas The Queen's Centre for Oncology and Haematology Hull and York Medical SchoolCastle Hill Hospital

Cancer-related thromboembolic disease is a well recognized syndrome since first described by Armand Trousseau in 1865.Preventing the morbidity and mortality related to thromboembolism in these patients is becoming a priority research area with the advent of new anti-coagulants.It is only recently that randomized trials of improved quality are been undertaken to study this question.Many of these trials however are still not accounting for the heterogeneity of "cancer" in terms of anatomical site,histology,stage and treatment.This editorial review highlights why pancreatic cancer may serve as a model malignancy to study this question.

关键词： Pancreatic Cancer Vascular Thromboembolism Vascular thromboembolic disease Heparin anticoagulants

Efficacy and safety of non-vitamin K antagonist oral anticoagulants post-kidney transplantation

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World Journal of Transplantation 2019年第6期9卷 134-144页

作者： Muhammad A Bukhari Abdulrahman Al-Theaby Mohammed Tawhari Ali Al-Shaggag Ryan Pyrke Azim Gangji Darin Treleaven Christine Ribic Department of Medicine Taif UniversityTaif 26311Saudi Arabia Department of Transplantation King Abdulaziz Medical CityRiyadh 11159Saudi Arabia Department of Nephrology and Transplantation King Fahad Specialist Hospital Dammam 15215Saudi Arabia Department of Nephrology McMaster UniversityHamiltonON L8N 4A6Canada

BACKGROUND Novel oral anticoagulants(NOACs)were developed as alternatives to vitamin K antagonists,primarily warfarin,as they do not require routine monitoring and have limited drug-drug and drug-food interactions.However,the efficacy and safety of these agents in kidney transplantation are not well studied.AIM To assess the profile and safety of NOACs for patients who had kidney transplantation,and to provide recommendations and guidelines on therapeutic strategies in these patients.METHODS This was a retrospective study carried out among adult patients who were actively on the following NOACs(apixaban,rivaroxaban or dabigatran)in our renal transplantation program from December 2015 to December 2016.The patients were identified primarily through electronic medical record system(patient data linkage).Data on the clinical and laboratory profile of the patients were retrieved and analyzed with SPSS 22.0.RESULTS Complete data on 42 renal transplant patients were retrieved:59.5%males,90.5%were whites and 66.7%were older than 60 years old.The mean duration since renal transplantation of the patients was 8.8±7.4 years.The most common risk factors for the development of end-stage renal disease in the subjects were hypertension(19.0%),polycystic kidney disease(19.0%),followed by diabetic nephropathy(16.7%)and chronic glomerulonephritis(16.7%).The main indications for NOACs use in the cohort were atrial fibrillation in 25 patients(59.5%)and venous thromboembolism in 10 patients(23.8%).Overall,29 patients(69%)were treated with apixaban,10 patients(23.8%)with rivaroxaban and 3 patients(7.14%)with dabigatran.No(0%)thromboembolic events were observed during the one-year period,but 3(7.1%)bleeding events occurred in the cohort consisting of 1 patient treated with rivaroxaban 15 mg daily and 2 patients who received apixaban 2.5 mg twice daily.There were no significant changes in serum tacrolimus level three days after the initiation of NOACs among patients treated with tacrolimus(pre-and post-NOACs tacrolimus levels were 7.2516

关键词： Novel oral anticoagulants Adult patients Kidney transplantation Renal outcomes Efficacy

Gallbladder hemorrhage–An uncommon surgical emergency:A case report

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World Journal of Clinical Cases 2022年第27期10卷 9734-9742页

作者： Maria Rosaria Valenti Andrea Cavallaro Maria Di Vita Antonio Zanghi Giovanni Longo Trischitta Alessandro Cappellani Department of Surgery University of Catania Medical SchoolUniversity of CataniaCatania 95123Italy

BACKGROUND Gallbladder hemorrhage is a life-threatening disorder.Trauma(accidental or iatrogenic such as a percutaneous biopsy or cholecystectomy surgery),cholelithiasis,biliary tract parasitosis,vasculitis,vascular malformations,autoimmune and neoplastic diseases and coagulopathies have been described as causes of hemorrhage within the lumen of the gallbladder.The use of nonsteroidal anti-inflammatory drugs and anticoagulants may represent a risk factor.CASE SUMMARY We report the case of a 76-year-old male patient.An urgent contrast computed tomography scan demonstrated relevant distension of the gallbladder filled with hyperdense non-homogeneous content.The gallbladder walls were of regular thickness.Near the anterior wall a focus of suspected active bleeding was observed.Due to the progressive decrease in hemoglobin despite three blood transfusions,this was an indication for urgent surgery.CONCLUSION Early diagnosis of this potentially fatal pathology is essential in order to plan a strategy and eventually proceed with urgent surgical treatment.

关键词： Gallbladder Hemorrhage anticoagulants Cholecystectomy Surgery Case report

Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view

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世界心脏病学杂志:英文版(电子版) 2023年第8期15卷 375-394页

作者： Maurizio Giuseppe Abrignani Alberto Lombardo Annabella Braschi Nicolo Renda Vincenzo Abrignani Operative Unit of Cardiology P.Borsellino HospitalASP TrapaniMarsala 91025TrapaniItaly Operative Unit of Cardiology S.Antonio Abate HospitalASP TrapaniErice 91100TrapaniItaly Department of Psychology Educational Science and Human MovementUniversity of PalermoPalermo 90100Italy Department of Direction CTA SalusGibellina 91024TrapaniItaly Operative Unit of Internal Medicine with Stroke Care Department of Health PromotionMother and Child CareInternal Medicine and Medical Specialties(ProMISE)“G.D’Alessandro”University of PalermoPalermo 90100Italy

Aspirin,other antiplatelet agents,and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases.A concomitant proton pump inhibitor(PPI)treatment is often prescribed in these patients,as gastrointestinal complications are relatively frequent.On the other hand,a potential increased risk of cardiovascular events has been suggested in patients treated with PPIs;in particular,it has been discussed whether these drugs may reduce the cardiovascular protection of clopidogrel,due to pharmacodynamic and pharmacokinetic interactions through hepatic metabolism.Previously,the concomitant use of clopidogrel and omeprazole or esomeprazole has been discouraged.In contrast,it remains less known whether PPI use may affect the clinical efficacy of ticagrelor and prasugrel,new P2Y12 receptor antagonists.Current guidelines recommend PPI use in combination with antiplatelet treatment in patients with risk factors for gastrointestinal bleeding,including advanced age,concurrent use of anticoagulants,steroids,or non-steroidal anti-inflammatory drugs,and Helicobacter pylori(H.pylori)infection.In patients taking oral anticoagulant with risk factors for gastrointestinal bleeding,PPIs could be recommended,even if their usefulness deserves further data.H.pylori infection should always be investigated and treated in patients with a history of peptic ulcer disease(with or without complication)treated with antithrombotic drugs.The present review summarizes the current knowledge regarding the widespread combined use of platelet inhibitors,anticoagulants,and PPIs,discussing consequent clinical implications.

关键词： Antithrombotic drugs anticoagulants Aspirin Clopidogrel Gastrointestinal bleeding Proton pump inhibitors

Perioperative coagulation activation after permanent pacemaker placement

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World Journal of Cardiology 2023年第4期15卷 174-183页

作者： Roman Kalinin Igor Suchkov Vladislav Povarov Nina Mzhavanadze Olga Zhurina Department of Cardiovascular Endovascular Surgery and Diagnostic RadiologyRyazan State Medical UniversityRyazan 390026Russia Department of Surgical Treatment of Cardiac Arrhythmias and Cardiac Pacing Ryazan State"Regional Clinical Cardiology Dispensary"Ryazan 390026Russia Scientific and Clinical Center for Hematology Oncology and ImmunologyRyazan State Medical UniversityRyazan 390026Russia

BACKGROUND Bradyarrhythmias are typically treated with permanent pacemakers(PM). The elimination of bradyarrhythmia by PM implantation improves the patient’s quality of life and prognosis, but it can also result in a number of sequalae. It is still unclear how PM implantation affects the hemostasis system’s parameters and how such parameters relate to different consequences after PM placement.AIM To assess the blood coagulation factor activity in PM patients throughout the perioperative period.METHODS Patients treated in the Department of Surgical Therapy of Cardiac Arrhythmias and Pacing at the Ryazan State "Regional Clinical Cardiology Dispensary" from April 2020 to December 2021 were included in the study. Before surgery, 7 and 30 d after PM placement, peripheral venous blood samples were withdrawn to measure the level of blood coagulation factor Ⅰ(FⅠ) and the activity of blood coagulation factors Ⅱ(FⅡ), Ⅴ(FⅤ), Ⅶ(FⅦ), Ⅷ(FⅧ), ⅸ(Fⅸ), ⅹ(Fⅹ), Ⅺ(FⅪ), Ⅻ(FⅫ). We used an automatic coagulometer Sysmex CA 660(Sysmex Europe, Germany) and reagents from Siemens(Siemens Healthcare Diagnostics Products GmbH, Germany).RESULTS The study included 146 patients. The activity of factors FⅤ [147.7(102.1-247.55)% vs 103.85(60-161.6)% vs 81.8(67.15-130.65)%, P = 0.002], FⅧ [80.4(60.15-106.25)% vs 70.3(48.5-89.1)% vs 63.7(41.6-88.25)%, P = 0.039], Fⅸ [86.2(70.75-102.95)% vs 75.4(59.2-88.3)% vs 73.9(56.45-93.05)%, P = 0.014], Fⅹ [188.9(99.3-308.18)% vs 158.9(83.3-230)% vs 127.2(95.25-209.35)%, P = 0.022], FⅪ [82.6(63.9-103.6)% vs 69.75(53.8-97.6)% vs 67.3(54.25-98.05)%, P = 0.002], FⅫ [87.6(67.15-102.3)% vs 78.9(63.4-97.05)% vs 81.2(62.15-97.4)%, P < 0.001] decreased at 7 and 30 d after surgery;FⅡ activity [157.9(109.7-245.25)% vs 130(86.8-192.5)% vs 144.8(103.31-185.6)%, P = 0.021] decreased at 7 d and increased at 30 d postoperatively. There were no statistically significant changes in the FVII activity within 30 d after PM placement [182.2(85.1-344.8)% vs 157.2(99.1-259)% vs 108.9(74.9-219.8)%, P = 0.128]. Subgroup analysis revealed

关键词： Hemostasis Blood coagulation Cardiac pacemaker anticoagulants Postoperative complications