warfarin and Stomach-Ulcer

Acute arterial thromboembolism to the renal arteries can be treated promptly by local thrombolysis, conventional surgical thrombectomy, or anticoagulation.. We report a patient who presented with acute loin pain as a result of atrial fibrillation-related thromboembolism to the right renal artery supplying his horseshoe kidney. He was already on warfarin treatment with international normalized ratio of 1.7 and had acute bleeding from malignant peptic ulcer disease, so thrombolysis was contraindicated.. He underwent timely endovascular revascularization with aspiration thrombectomy, with good clinical and radiological consequence. He subsequently underwent curative partial gastrectomy and made a steady recovery.. Early endovascular target-directed therapy such as intra-arterial thrombolysis and mechanical aspiration in combination with intravenous heparin therapy will result in renal salvage.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Computed Tomography Angiography; Fused Kidney; Gastrectomy; Humans; International Normalized Ratio; Male; Peptic Ulcer Hemorrhage; Renal Artery Obstruction; Stomach Ulcer; Thrombectomy; Thromboembolism; Treatment Outcome; Warfarin

In this study, lafutidine (LAF) was used as a model compound to investigate the binding mechanism between antiulcer drugs and human serum albumin (HSA) through various techniques, including STD-NMR, WaterLOGSY-NMR, (1)H NMR relaxation times, tr-NOESY, molecule docking calculation, FT-IR spectroscopy, and CD spectroscopy. The analyses of STD-NMR, which derived relative STD (%) intensities, and WaterLOGSY-NMR, determined that LAF bound to HSA. In particular, the pyridyl group of LAF was in close contact with HSA binding pocket, whereas furyl group had a secondary binding. Competitive STD-NMR and WaterLOGSY-NMR experiments, with warifarin and ibuprofen as site-selective probes, indicated that LAF preferentially bound to site II in the hydrophobic subdomains IIIA of HSA. The bound conformation of LAF at the HSA binding site was further elucidated by transferred NOE effect (tr-NOESY) experiment. Relaxation experiments provided quantitative information about the relationship between the affinity and structure of LAF. The molecule docking simulations conducted with AutoDock and the restraints derived from STD results led to three-dimensional models that were consistent with the NMR spectroscopic data. The presence of hydrophobic forces and hydrogen interactions was also determined. Additionally, FT-IR and CD spectroscopies showed that LAF induced secondary structure changes of HSA.

Topics: Acetamides; Binding Sites; Circular Dichroism; Humans; Magnetic Resonance Spectroscopy; Molecular Docking Simulation; Piperidines; Protein Binding; Protein Domains; Protein Structure, Secondary; Protons; Pyridines; Serum Albumin; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Stomach Ulcer; Warfarin

There is a lack of consensus regarding the risk of postoperative hemorrhage in patients on antithrombotic therapy who undergo endoscopic submucosal dissection (ESD).We examined postoperative bleeding rates and risk factors for postoperative hemorrhage from post-ESD gastric ulcers in patients on antithrombotic therapy.. The subjects of this study were 833 patients who underwent ESD of gastric tumors. Of these, 743 were not on antithrombotic therapy and 90 were on some form of antithrombotic therapy (46 on low-dose aspirin (LDA) only, 23 on LDA + thienopyridine, and 21 on LDA + warfarin). All patients commenced proton pump inhibitor (PPI) therapy immediately postoperatively. Antiplatelet agents were discontinued for 7 days preoperatively and postoperative Day 1, and anticoagulants for 5 days preoperatively and postoperative Day 1.. The postoperative bleeding rate in the antithrombotic group was 23.3%, significantly higher than the 2.0% observed in the non-antithrombotic group. Significant differences were seen in patients in the antithrombotic group with and without postoperative bleeding according to ESD duration (p = 0.041), PPI + mucosal protective agent combination therapy (p = 0.039), and LDA + warfarin combination therapy (p < 0.001). Multivariate analysis of these factors yielded odds ratios of 1.04 for ESD duration, 14.83 for LDA + warfarin combination therapy, and 0.27 for PPI + mucosal protective agent combination therapy.. The risk of postoperative hemorrhage following gastric ESD was higher in patients with antithrombotic therapy than in those without that therapy. Among these patients, LDA + warfarin combination therapy and longer ESD duration were significant risk factors for postoperative bleeding. On the contrary, a mucosal protective agent to PPI therapy, lowering the odds ratio for postoperative bleeding, which suggests that the addition of a mucosal protective agent might be effective in preventing post-ESD hemorrhage in patients on antithrombotic therapy.

Topics: Adenoma; Aged; Anti-Ulcer Agents; Anticoagulants; Aspirin; Carcinoma; Case-Control Studies; Clopidogrel; Dissection; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Proton Pump Inhibitors; Retrospective Studies; Risk Factors; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer; Thienopyridines; Ticlopidine; Warfarin

Between 3% and 40% of patients surviving an episode of upper gastrointestinal bleeding (UGIB) experience a recurrence within 1 year. Aim To characterize further the recurrence rate of UGIB and to investigate the role of long-term acid suppressive therapy in its secondary prevention.. Recurrent cases of UGIB were identified among patients registered in The Health Improvement Network in the UK. A nested case-control analysis provided relative risk (RR) estimates of factors associated with recurrence.. Of 1287 patients included, 67 (5.2%) were identified with a recurrent UGIB episode, corresponding to a recurrence rate of 17.5 per 1000 person-years during a mean follow-up of 3 years. The greatest risk of recurrence was in patients prescribed the oral anticoagulant warfarin (RR: 5.38; 95% confidence interval: 2.02-14.36). Use of a single proton pump inhibitor (PPIs) was associated with a reduced risk of recurrence (RR: 0.51; 95% confidence interval: 0.26-0.99), even in patients taking warfarin, while current use of H(2)-receptor antagonists was not. After the first episode of UGIB, use of nonsteroidal anti-inflammatory drugs and aspirin was greatly reduced, preventing estimation of the risk associated with these drugs.. Long-term PPI therapy reduces the risk of UGIB recurrence.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Case-Control Studies; Duodenal Ulcer; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Risk Factors; Secondary Prevention; Stomach Ulcer; Treatment Outcome; Warfarin

Traditional nonaspirin, nonsteroidal anti-inflammatory drugs (tNSAIDs) have been associated with a 3- to 5-fold increased risk in upper gastrointestinal complications (UGIC). Whether use of selective inhibitors of cyclooxygenase-2 (COXIBs) will translate into a clinically relevant reduced toxicity has not been widely investigated in the general population.. We conducted a nested case control study using The Health Improvement Network Database identifying 1561 cases of UGIC between January 2000 and 2005. A random sample of 10,000 controls was frequency matched to the cases by age, sex, and calendar year.. The adjusted relative risk (RR) of UGIC associated with current use was 3.7 (95% CI: 3.1-4.3) for tNSAIDs and 2.6 (95% CI: 1.9-3.6) for COXIBs. Daily dose was a predictor of increased risk for both tNSAIDs and COXIBs. Users of tNSAIDs with a prolonged plasma half-life or slow release formulations had an augmented risk of UGIC. Overall, the estimate of RR associated with COXIBs was 0.8 (95% CI: 0.6-1.1) compared with current use of tNSAIDs, and, among nonusers of aspirin, the corresponding estimate of RR associated with COXIBs was 0.6 (95% CI: 0.4-0.9).. COXIBs present a better upper gastrointestinal safety than tNSAIDs, although the risk of UGIC for an individual drug is determined by its daily dose and plasma drug exposure in addition to its selectivity for cyclooxygenase-2. Also, concomitant use of aspirin is a strong effect modifier of COXIBs that negates the superior gastrointestinal safety over tNSAIDs in the absence of aspirin use.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Anticoagulants; Aspirin; Case-Control Studies; Cohort Studies; Cyclooxygenase 2 Inhibitors; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Interactions; Duodenal Ulcer; Gastrointestinal Diseases; Half-Life; Humans; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Retrospective Studies; Risk Assessment; Risk Factors; Steroids; Stomach Ulcer; Time Factors; United Kingdom; Upper Gastrointestinal Tract; Warfarin

Little is known about the site and nature of bleeding lesions related to low-dose aspirin and other antithrombotic agents.. To describe the mucosal abnormalities in patients presenting with upper gastrointestinal bleeding while being treated with these drugs.. The endoscopic findings and clinical details were analysed in all patients presenting with haematemesis and/or melaena at a single centre during three calendar years. Associations between endoscopic findings and risk factors, including the intake of non-steroidal anti-inflammatory drugs, low-dose aspirin (75 mg daily) and other antithrombotic drugs including warfarin, clopidogrel, and dipyridamole, were assessed by logistic regression analysis.. In 674 upper gastrointestinal bleeders, we found that the odds ratio for the presence of erosive oesophagitis in aspirin users was 2 (95% CI, 1-3; P = 0.03) and 3 (2-5; P = 0.0003) in patients taking other antithrombotic agents. In 41 patients with oesophagitis and taking these drugs, 36 (88%) had cardiovascular disease and only 4 (10%) had peptic symptoms.. Erosive oesophagitis is common in patients with upper gastrointestinal bleeding taking low-dose aspirin or antithrombotic agents, and could potentially be confused with the coexisting heart disease.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Clopidogrel; Dipyridamole; Drug Administration Schedule; Drug Therapy, Combination; Duodenal Ulcer; Endoscopy, Gastrointestinal; Esophagitis; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Hematemesis; Humans; Intestinal Mucosa; Male; Middle Aged; Platelet Aggregation Inhibitors; Stomach Ulcer; Ticlopidine; Warfarin

To compare the frequency and outcome of upper gastrointestinal haemorrhage (UGH) patients who had undergone cardiac surgery with a control group of vascular surgery patients.. Patients who had undergone cardiac or vascular surgery from January 1999 to December 2000 were identified from departmental records. The inclusion criteria used were haematemesis and/or melaena in the post-operative period.. Only 20 of the 2274 (0.9%) cardiac operations were complicated by UGH compared to eight of 708 (1.1%) vascular operations. Among those with UGH, 90% of the cardiac and 43% of the vascular patients were taking aspirin, warfarin or both. The mean interval between surgery and the UGH was 9.6 days (range 1-30) for the cardiac and 6 days (range 0-15) for the vascular patients. Duodenal and gastric ulcers were the most common cause of UGH (60%) in the cardiac group. Despite endoscopic intervention, more than one third of ulcer associated haemorrhages required surgical over-sewing, but none of the patients who had surgery died. The overall mortality on the cardiac surgery patients who experienced UGH was 15%, significantly higher than the 2.3% for the whole cardiac surgery group during the study period (P = 0.00075, OR = 8, 95% confidence interval 2.3-28). However, even this mortality is less than that of general inpatients who suffer UGH (33%).. Cardiac and vascular surgical patients have similar low post-operative rate of UGH. Post-operative UGH is associated with increased mortality after primary surgery. Early surgical intervention appears to be life saving in those patients who are too ill to compensate for the haemodynamic disturbance of untreated UGH.

Topics: Aged; Aspirin; Cardiac Surgical Procedures; Coronary Artery Bypass; Duodenal Ulcer; Female; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Postoperative Hemorrhage; Smoking; Stomach Ulcer; Time Factors; Vascular Surgical Procedures; Warfarin

Topics: Aged; Ciprofloxacin; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Stomach Ulcer; Warfarin

Carbenoxolone is a potent ulcer-healing drug which is extensively bound to plasma proteins and therefore has the potential for displacement interaction. However, carbenoxolone has been shown to be bound to human serum albumin in vitro at a different class of binding site to many other drugs and does not potentiate the pharmacological activity of warfarin, tolbutamide, chlorpropamide or phenytoin in the rat. In the present study four volunteers each received a single 100 mg dose of Biogastrone and the plasma half-life of carbenoxolone was determined. The procedure was repeated with a concurrent dose of either warfarin 10 mg, tolbutamide 500 mg, chlorpropamide 250 mg or phenytoin 100 mg. Chlorpropamide appeared to delay the absorption of carbenoxolone but no effects were observed with the other drugs. The study with concomitant chlorpropamide treatment was repeated with 6 gastric ulcer patients on an established Biogastrone regimen. In these patients the delayed absorption of carbenoxolone was confirmed although no changes in the glucose-lowering activity of chlorpropamide were evident. Further investigations into this findings are in progress.

Topics: Carbenoxolone; Chlorpropamide; Drug Interactions; Glycyrrhetinic Acid; Half-Life; Humans; Phenytoin; Protein Binding; Stomach Ulcer; Tolbutamide; Warfarin