warfarin and Gastrointestinal-Hemorrhage

Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug interactions are present with NOACs, it is unclear whether NOACs should also be preferred over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) using pharmacokinetically interacting drugs. Therefore, the benefit-risk profile of NOACs versus VKAs was investigated in AF patients treated with P-gp and/or CYP450-interacting drugs.. Using PubMed and Embase, randomized controlled trials and observational studies on the effectiveness and safety of NOACs versus VKAs in AF patients using P-gp and/or CYP450-interacting drugs were included. A meta-analysis was performed, calculating relative risks (RR) and 95% confidence intervals (CI) with the Mantel-Haenszel method.. Twelve studies were included, investigating 10,793 NOAC and 10,096 VKA users treated with P-gp/CYP3A4 inhibitors, whereas no studies on P-gp and/or CYP450-inducing drugs were identified. Compared to VKAs, NOACs were associated with a borderline non-significantly lower stroke or systemic embolism (stroke/SE) risk (RR 0.85, 95%CI (0.72-1.01)), significantly lower intracranial bleeding (RR 0.47, 95%CI (0.34-0.65)) and all-cause mortality risks (RR 0.87, 95%CI (0.79-0.95), but significantly higher gastrointestinal bleeding risk (RR 1.74, 95%CI (1.06-2.86)). Among AF patients using amiodarone, NOACs were associated with significantly lower stroke/SE (RR 0.71, 95%CI (0.54-0.93)) and intracranial bleeding risks (RR 0.51, 95%CI (0.29-0.88)), but significantly higher gastrointestinal bleeding risk (RR 2.15, 95%CI (1.24-3.72)) than VKAs.. The benefit-risk profile of NOACs compared to VKAs was preserved in AF patients using P-gp/CYP3A4 inhibitors, including amiodarone.

Topics: Administration, Oral; Amiodarone; Anticoagulants; ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Cytochrome P-450 CYP3A Inhibitors; Embolism; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Warfarin

Direct oral anticoagulants (DOACs), such as apixaban, edoxaban, rivaroxaban, or dabigatran, are an effective treatment for atrial fibrillation (AF) and deep venous thromboembolism. We hope to evaluate the safety of DOACs versus warfarin/low molecular weight heparin (LMWH) in improving bleeding events in patients with different severity of the liver disease.. We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the effects of DOACs in patients with liver cirrhosis. A random-effects model or fixed-effects model was selected to pool risk ratios (RR) and 95% confidence intervals (CI).. A total of 18 studies involving 41,447 participants was included in this meta-analysis. Compare with warfarin/ LMWH, the use of DOACs significantly reduced the incidence of all bleeding (RR: 0.76; 95%CI: 0.66 to 0.87), major bleeding (RR: 0.51; 95%CI: 0.28 to 0.91), intracranial hemorrhage (RR: 0.50; 95%CI: 0.31 to 0.81), and gastrointestinal bleeding (RR: 0.76, 95% CI: 0.60 to 0.97), and all-cause death in patients with liver disease (RR: 0.77; 95%CI: 0.62 to 0.95). Similar results were observed in atrial fibrillation patients with liver disease and cirrhosis subgroups. Furthermore, the pooled estimates of the Child-Turcotte-Pugh (CTP) class indicated that DOACs reduced the incidence of all bleeding (RR: 0.61; 95%CI: 0.45 to 0.82), gastrointestinal bleeding (RR 0.55; 95%CI: 0.37 to 0.83), and all-cause death (RR: 0.62; 95%CI: 0.49 to 0.79) in patients with mild to moderate cirrhosis.. Our study demonstrates that DOACs significantly reduce the risk of bleeding in patients with liver disease compared with warfarin/LMWH.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Liver Diseases; Venous Thromboembolism; Warfarin

Frail patients with atrial fibrillation (AF) are thought to be at a higher risk for cerebral infarction and death than patients who are not frail, making preventive interventions important. Anticoagulants should be used in frailty patients with AF. However, there are limited data about anticoagulants in frail patients with AF. Therefore, we concucted this meta-analysis to find the best anticoagulation strategy.. Systematic electronic searches were conducted on 4 July 2022 4 July 2022, in PubMed, Embase (Ovid), and Cochrane Library. Relevant and eligible cohort studies were included. A random-effects model was used to estimate the pooled Hazard ratio (HR) and 95% confidence intervals (CI). Furthermore, we performed a publication bias analysis and subgroup analysis to explore the source of heterogeneity.. 3 publications (10 cohorts, 188573 participants) met our inclusion criteria. The pooled analysis showed that ischemic strokes (HR: 0.75; 95%CI: 0.71 to 0.79;. NOAC was more effective and safety than warfarin in frail patients with AF.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Frail Elderly; Gastrointestinal Hemorrhage; Humans; Retrospective Studies; Stroke; Warfarin

The rising prevalence and the complexity of atrial fibrillation (AF) pose major clinical challenges. Stroke prevention is accompanied by non-negligible risks, making anticoagulant treatment an ongoing challenge for the clinician. Current guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention in most AF patients, mainly due to the ease of their use. However, assessing the bleeding risk in patients receiving oral anticoagulants remains-particularly in the case of DOACs-highly challenging. Using dose-adjusted warfarin increases threefold the risk of gastrointestinal bleeding (GIB). Although the overall bleeding risk appears to be lower, the use of DOACs has been associated with an increased risk of GIB compared to warfarin. Accurate bleeding (including GIB-specific) risk scores specific for DOACs remain to be developed. Until then, the assessment of bleeding risk factors remains the only available tool, although the extent to which each of these factors contributes to the risk of bleeding is unknown. In this paper, we aim to provide a comprehensive review of the bleeding risk associated with oral anticoagulant therapy in AF patients, with a highlight on the latest insights into GIB associated with oral anticoagulation; we emphasize questions that remain to be answered; and we identify hotspots for future research.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Stroke; Treatment Outcome; Warfarin

Oral anticoagulants (OACs) prevent stroke in patients with atrial fibrillation (AF). Several factors may cause OAC switching.. To examine the phenomenon of OAC switching in patients with AF, including all available evidence; frequency and patterns of switch, clinical outcomes, adherence, patient-reported outcomes, reasons for switch, factors associated with switch and evidence gaps.. Scoping review.. MEDLINE, Embase and Web of Science, up to January 2022.. Of the 116 included studies, 2/3 examined vitamin K antagonist (VKA) to direct-acting OAC (DOAC) switching. Overall, OAC switching was common and the definition of an OAC switch varied across. Switching from VKA to dabigatran was the most prevalent switch type, but VKA to apixaban has increased in recent years. Patients on DOAC switched more to warfarin than to other DOACs. OAC doses involved in the switches were hardly reported and patients were often censored after the first switch. Switching back to a previously taken OAC (frequently warfarin) occurred in 5%-21% of switchers.The risk of ischaemic stroke and gastrointestinal bleeding in VKA to DOAC switchers compared with non-switchers was conflicting, while there was no difference in the risk of other types of bleeding. The risk of ischaemic stroke in switchers from DOAC versus non-switchers was conflicting. Studies evaluating adherence found no significant changes in adherence after switching from VKA to DOAC, however, an increase in satisfaction with therapy were reported. Reasons for OAC switch, and factors associated with OAC switch were mostly risk factors for stroke and bleeding. Clinical outcomes, adherence and patient-reported outcomes were sparse for switches from DOACs.. OAC switching is common in patients with AF and patients often switch back to an OAC they have previously been on. There are aspects of OAC switching that have received little study, especially in switches from DOACs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Rivaroxaban; Stroke; Warfarin

This study aimed to comprehensively evaluate the risk of gastrointestinal bleeding (GIB) with statin monotherapy or with concomitant warfarin use.. PubMed, Web of Science, and EMBASE (via Scopus) were searched for observational studies that reported the risk of GIB in adults on statin therapy or with concomitant warfarin use until August 28, 2021.. Observational studies evaluating the risk of GIB in adults (age >18 years) on statin medication or concomitant use with warfarin were included.. In all, 14 studies with a total of 5 235 123 participants, reporting 48 677 GIB events (43 734 from statin users and 4943 from users of statin combined with warfarin), were included in the analyses. The pooled analysis revealed no difference in the risk of GIB with statin monotherapy (relative risk [RR]: 0.65; 95% CI: 0.42-1.02) or concomitant statin + warfarin use (RR: 0.97; 95% CI: 0.91-1.02). Prior use of statin was not associated with GIB risk (RR: 0.88; 95% CI: 0.63-1.22), whereas a shorter duration of statin use (<5 years) was associated with a lower risk of GIB (RR: 0.42; 95% CI: 0.18-0.97).. This analysis provides strong evidence on the association between statin use (with/without warfarin) and risk of GIB.. Statin alone or combined with warfarin was not significantly associated with either an increased or decreased risk of GIB. The GIB risk was significantly lower when statins were used for a short duration (<5 years). The putative relationship between statins and GIB in warfarin users warrant further investigation.

Topics: Adolescent; Adult; Anticoagulants; Gastrointestinal Hemorrhage; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Warfarin

Patients with atrial fibrillation (AF) require oral anticoagulation to prevent ischemic stroke. However, oral anticoagulation may cause bleeding, and patients with AF and a history of bleeding were excluded from pivotal trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. We therefore aimed to assess the efficacy and safety of NOACs compared with warfarin in patients with AF and a history of bleeding.. We conducted a systematic review of retrospective studies and clinical trials using the PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases to May 2021.. Overall, 56,697 patients from six studies were included. NOACs significantly reduced the risk of ischemic stroke (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59-0.91; p = 0.005), fatal ischemic stroke (HR 0.49, 95% CI 0.39-0.61; p < 0.001), all-cause mortality (HR 0.70, 95% CI 0.50-0.98; p = 0.04), major bleeding events (HR 0.75, 95% CI 0.67-0.84; p < 0.001), intracranial hemorrhage (ICH; HR 0.63, 95% CI 0.48-0.82; p < 0.001), fatal ICH (HR 0.33, 95% CI 0.20-0.56, p < 0.001), and gastrointestinal bleeding (HR 0.83, 95% CI 0.72-0.96; p = 0.01).. NOACs showed better efficacy and safety profile compared with warfarin in patients with AF and a history of bleeding. Randomized controlled trials are warranted to validate these findings.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

The objective of present study was to compare the safety and efficacy of resuming direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and prior gastrointestinal bleeding (GIB).. PubMed, Embase, Web of Science, and the Cochrane Library were searched from their inception until 2 June 2021 for observational cohort studies in patients with AF, who resumed VKAs or DOACs after a history of GIB. Studies that reported data on clinical outcomes including risk of recurrent GIB, thromboembolic events, or all-cause mortality were included. A network meta-analysis was performed to calculate the pooled hazard ratio (HR) and associated 95% credible intervals (CIs), using a random effects model in a Bayesian framework.. A total of 10 studies were included in the final analysis, including 59,244 AF patients with prior GIB, of whom 27,793 resumed DOACs, 24,635 resumed warfarin, and 6816 did not resume anticoagulation. Compared with no resumption of anticoagulation, resumption of warfarin was associated with an increased risk of recurrent GIB (HR 1.33, 95% CI: 1.06-1.70), but no increased risk of recurrent GIB was found with resumption of DOACs (HR 1.22, 95% CI: 0.88-1.71); among individual DOACs, only rivaroxaban was associated with an increased risk of recurrent GIB (HR 1.67, 95% CI: 1.16-2.65). Compared with no resumption of anticoagulation, resumption of DOACs and warfarin was associated with a significant reduction in all-cause mortality (HR 0.57, 95% CI: 0.40-0.84; HR 0.58, 95% CI: 0.44-0.79), but no statistically significant reduction in thromboembolic events (HR 0.69, 95% CI: 0.4-1.2; HR 0.83, 95% CI: 0.55-1.29).. In AF patients with prior GIB, resumption of DOACs may be safer, except for rivaroxaban.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Bayes Theorem; Gastrointestinal Hemorrhage; Humans; Network Meta-Analysis; Rivaroxaban; Stroke; Warfarin

The meta-analysis of randomized controlled trials has illustrated that the efficacy of low-dose non-vitamin K antagonist oral anticoagulants is inferior compared with standard-dose non-vitamin K antagonist oral anticoagulants, though they are still frequently prescribed for Asian patients with non-valvular atrial fibrillation. We aimed to further investigate the efficacy and safety of low-dose non-vitamin K antagonist oral anticoagulants by carrying out a meta-analysis of all relevant randomized controlled tri- als and cohort studies.. Cochrane Central Register of Controlled Trials, Embase, and MEDLINE were sys- tematically searched from the inception to September 9, 2021, for randomized controlled trials or cohorts that compared the efficacy and/or safety of low-dose non-vitamin K antagonist oral anticoagulants in Asian patients with non-valvular atrial fibrillation. The primary outcomes were stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage, and gastrointestinal hemorrhage. Hazard ratios and 95% CIs were estimated using the random-effect model.. Nineteen publications involving 371 574 Asian patients with non-valvular atrial fibrillation were included. Compared with standard-dose non-vitamin K antagonist oral anticoagulants, low-dose non-vitamin K antagonist oral anticoagulants showed compa- rable risks of stroke (hazard ratio, 1.18; 95% CI 0.98 to 1.42), major bleeding (hazard ratio, 1.00; 95% CI 0.83 to 1.21), intracranial hemorrhage (hazard ratio, 1.13; 95% CI 0.92 to 1.38), and gastrointestinal hemorrhage (hazard ratio, 1.07; 95% CI 0.87 to 1.31), though had a higher risk of mortality (hazard ratio, 1.34; 95% CI 1.05 to 1.71). Compared with warfarin, low-dose non-vitamin K antagonist oral anticoagulants were associated with lower risks of stroke (hazard ratio, 0.73; 95% CI 0.67 to 0.79), mortality (hazard ratio, 0.69; 95% CI 0.60 to 0.81), major bleeding (hazard ratio, 0.62; 95% CI 0.51 to 0.75), intracranial hemor- rhage (hazard ratio, 0.48; 95% CI 0.33 to 0.69), and gastrointestinal hemorrhage (hazard ratio, 0.78; 95% CI 0.65 to 0.93).. Low-dose non-vitamin K antagonist oral anticoagulants were superior to warfarin, and comparable to standard-dose non-vitamin K antagonist oral anticoagu- lants considering risks of stroke, major bleeding, intracranial hemorrhage, and gastroin- testinal hemorrhage. Further, high qualified studies are warranted.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Treatment Outcome; Warfarin

Patients with cancer are at higher risk of atrial fibrillation (AF). Currently there are no definitive data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in cancer patients with AF. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of NOACs compared with warfarin. A search through Pubmed/MEDLINE, Embase, and Cochrane library was done from the databases inception to March 2022. Studies that compared NOACs to warfarin in the setting of AF and cancer were included. The primary outcomes were the incidence of major bleeding and ischemic stroke/systemic embolism (SE). Secondary outcomes were major adverse cardiovascular event (MACE), intracranial bleeding, and Major gastrointestinal bleeding. Risk ratios (RRs) with 95% confidence intervals (CI) were used to report the outcomes. A total of 11 studies were included. We found that NOACs were associated with a lower incidence of major bleeding and combined ischemic stroke/SE in patients with AF and cancer compared with warfarin (RR 0.57; 95% CI 0.44-0.75, P < 0.0001 and RR 0.59; 95% CI 0.47-0.75, P < 0.0001, respectively). Also, there was lower incidence of Intracranial and major gastrointestinal bleeding in patients who received NOACs compared with warfarin (P < 0.0001). Network analyses revealed that apixaban and dabigatran were associated with reduction of major bleeding compared with warfarin. Among patients who diagnosed with AF and cancer, NOACs were associated with lower incidence of major bleeding ischemic stroke/SE compared with warfarin. Furthermore, NOACs were associated with lower gastrointestinal and intracranial bleeding.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Neoplasms; Network Meta-Analysis; Stroke; Treatment Outcome; Warfarin

Gastrointestinal bleeding (GIB) is the most common type of bleeding occurring in patients on oral anticoagulation. A meta-analysis of the landmark randomized controlled trials (RCTs) for patients with atrial fibrillation demonstrated that direct oral anticoagulants (DOACs) were associated with higher GIB rates compared to warfarin. However, significant heterogeneity existed between studies. While rivaroxaban, high-dose dabigatran, and high-dose edoxaban were associated with higher GIB rates than warfarin, GIB rates were similar between warfarin users and both apixaban and low-dose dabigatran users. Additionally, previous observational studies have yielded conflicting reports on whether GIB rates differ between warfarin and DOACs. Meta-analyses of observational studies demonstrated that warfarin is associated with lower rates of GIB compared to rivaroxaban, similar or lower rates compared to dabigatran, and higher rates compared to apixaban. Importantly, no RCT has compared individual DOACs directly and due to the different selection criteria of the initial RCTs, indirect comparisons between DOACs using these studies are unreliable. The best available information of comparisons between individual DOACs is therefore limited to observational studies. There is mounting evidence that suggests that rivaroxaban is associated with a higher risk of GIB compared to other DOACs. Finally, GIB induced by oral anticoagulation may have some positive aspects. Interestingly, there are studies that indicate oral anticoagulation facilitates colorectal cancer detection. Furthermore, results from RCTs and observational studies suggest that warfarin may even decrease the incidence of cancer.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Pyridones; Rivaroxaban; Stroke; Warfarin

Novel oral anticoagulants (NOACs) are drugs approved for the prevention and treatment of many thromboembolic cardiovascular conditions as a safer alternative to warfarin. We reviewed studies published in PubMed

Topics: Administration, Oral; Anticoagulants; Dabigatran; Gastrointestinal Hemorrhage; Humans; Warfarin

Data on the efficacy and safety of the combination of warfarin and dual-antiplatelet therapy compared with warfarin and mono-antiplatelet therapy (MAPT) in patients with left ventricular assist devices (LVAD) remains scarce. Single-center study of 130 consecutive patients with durable LVAD. Baseline demographics, antithrombotic and antiplatelet regimen, and outcomes were compared between patients receiving warfarin plus dual-antiplatelet therapy (Group 1) and warfarin plus MAPT (Group 2). Antiplatelet therapy was assessed at hospital discharge post-LVAD implant and included aspirin, clopidogrel and dipyridamole. Outcomes at 1-year were assessed in each group. All patients were on aspirin and warfarin. No significant differences with regards to age, gender or ethnicity were noted at baseline between the two groups. Group 1 was more likely to have higher lactate dehydrogenase LDH levels at discharge and a history of stroke. No significant differences in international normalized ratio INR, hemoglobin or hematocrit were noted at discharge. During the study period, 48 patients had gastrointestinal bleeding events: 28 of 68 (41.2%) in Group 1 vs 20 of 62 (32.2%) in Group 2 (P = 0.293). At 1year, no statistically significant differences were noted in gastrointestinal bleeding (Group 1=27.90% vs Group 2 = 25.80, P = 0.784), ischemic stroke (Group 1 = 8.8% vs group 2 = 6.5%, P = 0.612), hemorrhagic stroke (Group 1 = 4.4% vs group 2 = 3.2%, P = 0.725) or mortality (Group 1 = 5.9% vs Group 2 = 1.6%, P = 0.206). Rates of pump thrombosis however were lower in Group 1 (Group 1 = 0% vs Group 2 = 6.5%, P = 0.033). Our study showed a high prevalence of triple-therapy antithrombotic use in LVAD patients with no significant differences in bleeding, stroke or survival. However, the risk for pump thrombosis was lower at 1-year when compared to patient receiving MAPT.

Topics: Anticoagulants; Aspirin; Drug Therapy, Combination; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Heart-Assist Devices; Humans; Platelet Aggregation Inhibitors; Stroke; Thrombosis; Warfarin

Upper gastrointestinal (GI) bleeding is a common reason for hospital admission in older adult patients and carries a high morbidity and mortality if not properly managed. Risk factors include advanced age, Helicobacter pylori infection, medication use, smoking, and history of liver disease. Patients with known or suspected liver disease and suspected variceal bleeding should also receive antibiotics and somatostatin analogues. Risk stratification scores should be used to determine patients at highest risk for further decompensation. Upper endoscopy is both a diagnostic and therapeutic tool used in the management of upper GI bleeding. Endoscopy should be performed within 24 hours of presentation after appropriate resuscitation. Management of anticoagulation in upper GI bleeding largely depends on the indication for anticoagulation, the risk of continued bleeding with continuing the medication, and the risk of thrombosis with discontinuing the medication. A multidisciplinary approach to the decision of anticoagulation continuation is preferred when possible.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hematemesis; Humans; Melena; Peptic Ulcer; Peptic Ulcer Hemorrhage; Warfarin

Nonvalvular atrial fibrillation (NVAF) is the most common arrhythmia. It is of a high disability and death rate, and seriously affects quality of life. Although New oral anticoagulants (NOACs) are recommended for anticoagulation therapy of atrial fibrillation, they are not widely used for the high cost and limited availability. Warfarin is effective and economical. The risk of thromboembolism and anticoagulant hemorrhage is higher in patients >65 years with NVAF. So, it is of great clinical significance to explore the optimal anticoagulation intensity of warfarin in patients >65 years of China, and other ethnicities. Some studies suggested that low-intensity international normalized ratio (INR) has similar antithrombotic efficacy comparing to standard-intensity INR, whereas bleeding risk was significantly reduced. But others showed conflicting results. We pooled the efficacy and safety data of low- and standard-intensity warfarin therapy for patients over 65 years with NVAF by meta-analysis, as to evaluate optimal INR intensity of warfarin therapy in patients over 65 years. We identified 18 studies providing data of 2105 patients receiving anticoagulation therapy with warfarin. On meta-analysis (odds ratio [OR] [95% confidence interval {CI}]), low-intensity INR conferred similar efficacy to standard intensity INR on all thrombosis (1.28 [0.90 to 1.81]), stroke (1.09 [0.67 to 1.77]), other thromboembolism ([peripheral and pulmonary embolism] 2.26 [0.89 to 5.79]), and all cause death (1.38 [0.94 to 2.02]). Low-intensity INR conferred better safety profile than standard intensity INR in major bleeding (intracranial and gastrointestinal hemorrhage) (0.32 [0.19 to 0.52]), minor bleeding (gum, nasal cavity and conjunctival hemorrhage, skin ecchymosis, hematuria, hemoptysis) (0.30 [0.20 to 0.45]), and all bleeding (0.30 [0.22 to 0.40]). In conclusion, low-intensity INR (1.5 to 2.0) of warfarin therapy is as effective as standard intensity INR (2.0 to 3.0) therapy in reducing thromboembolic risk in patients>65 years with NVAF, and has a safer profile of bleeding.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Mortality; Patient Care Planning; Pulmonary Embolism; Stroke; Thromboembolism; Thrombosis; Warfarin

Direct oral anticoagulants (DOACs) are increasingly prescribed instead of warfarin for chronic anticoagulation for ease of dosing, fewer interactions, and less stringent monitoring. However, it is important to consider indications and comorbidities for which warfarin is still the preferred anticoagulant. This review aims to capture these clinical scenarios in which warfarin may still be preferred over DOACs.. We undertook a comprehensive literature search using the PubMed database. Key search terms were based on DOAC clinical trial exclusion criteria, as well as indications and conditions in which the use of DOACs for anticoagulation has suggested harm. Society guidelines and tertiary literature were used to inform expert opinion where necessary. Studies were included if they investigated the use of DOACs or warfarin in the identified indications or conditions.. Currently, evidence for the use of warfarin over DOACs for anticoagulation is strongest for patients with prosthetic valves, antiphospholipid syndrome, or a high risk of gastrointestinal bleeding. For several clinical situations, including mitral stenosis, obesity, altered gastrointestinal anatomy, pulmonary arterial hypertension, renal or hepatic impairment, and left ventricular thrombus, evidence is lacking but may eventually support the use of DOACs. Depending on indication and condition, appropriateness of DOAC use may vary by agent.. New evidence continues to support new indications and conditions in which DOACs may be appropriate to use for anticoagulation. There are key clinical scenarios, however, in which emerging literature continues to support warfarin as the preferred anticoagulant.

Topics: Anticoagulants; Antiphospholipid Syndrome; Atrial Fibrillation; Blood Coagulation; Comorbidity; Drug Interactions; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Humans; Liver Failure; Medication Adherence; Mitral Valve Stenosis; Overweight; Pulmonary Arterial Hypertension; Renal Insufficiency; Stroke; Warfarin

The relative risk of major gastrointestinal bleeding (GIB) among different direct oral anticoagulants (DOACs) is debatable. Randomized controlled trials (RCTs) comparing DOACs with each other are lacking. We performed network meta-analysis to assess whether the risk of major GIB differs based on type and dose of DOAC. Literature search of PubMed, EMBASE and Cochrane databases from inception to August 2019, limited to English publications, was conducted to identify RCTs comparing DOACs with warfarin or enoxaparin for any indication. Primary outcome of interest was major GIB risk. We used frequentist network meta-analysis through the random-effects model to compare DOACs with each other and DOACs by dose to isolate the impact on major GIB. Twenty-eight RCTs, including 139 587 patients receiving six anticoagulants, were selected. The risk of major GIB for DOACs was equal to warfarin. Comparison of DOACs with each other did not show risk differences. After accounting for dose, rivaroxaban 20 mg, dabigatran 300 mg and edoxaban 60 mg daily had 47, 40 and 22% higher rates of major GIB versus warfarin, respectively. Apixaban 5 mg twice daily had lower major GIB compared to dabigatran 300 mg (OR, 0.63; 95% CI, 0.44-0.88) and rivaroxaban 20 mg (OR, 0.60; 95% CI, 0.43-0.83) daily. Heterogeneity was low, and the model was consistent without publication bias (Egger's test: P = 0.079). All RCTs were high-quality with low risk of bias. DOACs at standard dose, except apixaban, had a higher risk of major GIB compared to warfarin. Apixaban had a lower rate of major GIB compared to dabigatran and rivaroxaban.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Gastrointestinal Hemorrhage; Humans; Network Meta-Analysis; Rivaroxaban; Stroke; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for stroke prevention in atrial fibrillation (AF) and the treatment and prevention of venous thromboembolism. There is an issue with safety, especially in clinically relevant bleeding. We performed a network meta-analysis to evaluate the risk of major gastrointestinal (GI) bleeding associated with NOACs.. Interventions were warfarin, enoxaparin, apixaban, dabigatran, edoxaban, and rivaroxaban. The primary outcome was the incidence of major GI bleeding. A subgroup analysis was performed according to the following indications: AF, deep venous thrombosis/pulmonary embolism, and postsurgical prophylaxis.. A total of 29 randomized controlled trials (RCTs) and 4 large observation population studies were included. Compared with warfarin, apixaban showed a decreased the risk of major GI bleeding (relative risk [RR] 0.54, 95% confidence interval [CI] 0.25-0.76), and rivaroxaban tended to increase this risk (RR 1.40, 95% CI 1.06-1.85). Dabigatran (RR 1.25, 95% CI 0.98-1.60), edoxaban (RR 1.07, 95% CI 0.69-1.65), and enoxaparin (RR 1.24, 95% CI 0.63-2.43) did not significantly increase the risk of GI bleeding than did warfarin. In the subgroup analysis, according to indications, apixaban showed a decreased risk of major GI bleeding (RR 0.50, 95% CI 0.34-0.74) than did warfarin in AF studies. Dabigatran (RR 2.36, 95% CI 1.55-3.60, and rivaroxaban (RR 1.75, 95% CI 1.10-6.41) increased the risk of major GI bleeding than did apixaban. An analysis of studies on venous thromboembolism or pulmonary embolism showed that no individual NOAC or enoxaparin was associated with an increased risk of major GI bleeding compared to warfarin.. Individual NOACs had varying profiles of GI bleeding risk. Results of analyses including only RCTs and those including both RCTs and population studies showed similar trends, but also showed several differences.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Enoxaparin; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Network Meta-Analysis; Observational Studies as Topic; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes.. MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug-drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.. Of 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56-1.94), many antimicrobials (OR = 1.63; 95% CI 1.45-1.83), NSAIDs including COX-2 NSAIDs (OR = 1.83; 95% CI 1.29-2.59), SSRIs (OR = 1.62; 95% CI 1.42-1.85), mirtazapine (OR = 1.75; 95% CI 1.30-2.36), loop diuretics (OR = 1.92; 95% CI 1.29-2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin-related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64-0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens.. This review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug-drug interactions leading to thromboembolic outcomes or death.

Topics: Anticoagulants; Drug Interactions; Gastrointestinal Hemorrhage; Humans; Pharmaceutical Preparations; Randomized Controlled Trials as Topic; Warfarin

Many concerns were raised about the outcome of non-vitamin K antagonist oral anticoagulants compared with warfarin in subjects with atrial fibrillation and liver disease. However, the reported relationship between their efficacy and safety was variable. This meta-analysis was performed to evaluate this relationship.. A systematic literature search up to July 2020 was performed and six studies included 50 074 subjects with atrial fibrillation and liver disease at the baseline with 32 229 non-vitamin K antagonist oral anticoagulant consumers and 18 920 warfarin consumers. They were reporting relationships between non-vitamin K antagonist oral anticoagulants and warfarin in subjects with atrial fibrillation and liver disease. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of the efficacy and safety of non-vitamin K antagonist oral anticoagulants compared with warfarin in subjects with atrial fibrillation and liver disease subjects using the dichotomous method with a random or fixed-effect model.. Non-vitamin K antagonist oral anticoagulants consumption was significantly related to lower all-cause mortality in subjects with atrial fibrillation and liver disease (OR, 0.90; 95% CI, 0.81-0.99, P = .03); lower intracranial haemorrhage (OR, 0.67; 95% CI, 0.55- 0.82, P < .001) and low stroke and system embolism (OR, 0.76; 95% CI, 0.68-0.86, P < .001) compared with warfarin consumption. However, non-vitamin K antagonist oral anticoagulants consumption was not significantly related to lower major bleeding in subjects with atrial fibrillation and liver disease (OR, 0.73; 95% CI, 0.52-1.02, P = .06); and gastrointestinal bleeding (OR, 0.93; 95% CI, 0.58-1.49, P = .77) compared with warfarin consumption.. Based on this meta-analysis, non-vitamin K antagonist oral anticoagulant consumption may have an independent lower risk relationship with all-cause mortality, intracranial haemorrhage, and stroke and system embolism compared with warfarin consumption in subjects with atrial fibrillation and liver disease. This relationship forces us to recommend non-vitamin K antagonist oral anticoagulant use in subjects with atrial fibrillation and liver disease for better outcomes and to avoid any possible complications. Further studies are required.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Liver Diseases; Stroke; Warfarin

To assess the risk of gastrointestinal bleeding and intracranial hemorrhage in patients with atrial fibrillation (AF) after the use of rivaroxaban or warfarin. To investigate the effects of rivaroxaban and warfarin on gastrointestinal and intracranial hemorrhage in patients with AF, we searched PubMed, Embase, and Medline from the establishment of databases up to 2020. We finally included 38 observational studies involving 1 312 609 patients for the assessment of intracranial hemorrhage, and 33 observational studies involving 1 332 956 patients for the assessment of gastrointestinal bleeding. The rates of intracranial hemorrhage were 0.55% in the rivaroxaban group versus 0.91% in the warfarin group (OR 0.59; 95% CI 0.53-0.66; p < .00001, I2 = 78%). The rates of gastrointestinal bleeding were 2.63% in patients with rivaroxaban versus 2.48% in those with warfarin (OR 1.06; 95% CI 0.96-1.17; p < .00001, I2 = 94%). Rivaroxaban could significantly reduce the risk of intracranial hemorrhage in patients with AF than warfarin, but the risk of gastrointestinal bleeding remained controversy due to no statistical significant difference. Notably, a subgroup analysis demonstrated that patients in rivaroxaban group with severe chronic renal diseases or undergoing hemodialysis exposed to less gastrointestinal hemorrhage risk than the group from warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Rivaroxaban; Stroke; Warfarin

 Warfarin use can trigger the occurrence of bleeding independently or as a result of a drug-drug interaction when used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs)..  This article examines the risk of bleeding in individuals exposed to concomitant warfarin and NSAID compared with those taking warfarin alone (Prospero Registry ID 145237)..  PubMed, EMBASE, Scopus, and Web of Science were searched. The primary outcome of interest was gastrointestinal bleeding and general bleeding. Summary effects were calculated to estimate average treatment effect using random effects models. Heterogeneity was assessed using Cochran's.  A total of 651 studies were identified, of which 11 studies met inclusion criteria for meta-analysis. The odds ratio (OR) for gastrointestinal bleeding when exposed to warfarin and an NSAID was 1.98 (95% confidence interval [CI]: 1.55-2.53). The risk of gastrointestinal bleeding was also significantly elevated with exposure to a COX-2 inhibitor and warfarin relative to warfarin alone (OR = 1.90, 95% CI: 1.46-2.46). There was an increased risk of general bleeding with the combination of warfarin with NSAIDs (OR = 1.58, 95% CI: 1.18-2.12) or COX-2 inhibitors (OR = 1.54, 95% CI: 0.86-2.78) compared with warfarin alone..  Risk of bleeding is significantly increased among persons taking warfarin and a NSAID or COX-2 inhibitor together as compared with taking warfarin alone. It is important to caution patients about taking these medications in combination.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Warfarin; Young Adult

Direct oral anticoagulants are being increasingly used in patients with non-valvular atrial fibrillation and venous thromboembolism, due to their improved efficacy/ safety ratio, a predictable anticoagulant effect without need for routine coagulation monitoring, and fewer food and drug interactions compared with vitamin K antagonists. Gastrointestinal bleeding remains a serious complication, whose management is challenging for gastroenterologists due to the lack of a standardized clinical approach. Clinical experience on periendoscopic management of these drugs is still limited and there is a paucity of clinical data supporting guidelines recommendations', and this ultimately turns out in different, unsubstantiated and potentially harmful practices of patient management. Present study will provide a thorough revision on the risk of GI bleeding for DOAC therapy and the identification of patient risk factors to individualize treatment. Moreover, the approach to management of DOACs in case of bleeding complications is discussed, and an algorithm of different strategies in presence or not of plasma level measurement is proposed. Finally the periendoscopic management for elective procedures will be reviewed, at the light of the guideline recommendations and new evidences from observational studies.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Humans; Risk Factors; Venous Thromboembolism; Warfarin

Novel oral anticoagulants are the cornerstone of therapy for non-valvular atrial fibrillation patients to lower the risk of ischaemic stroke. Given the lack of head-to-head comparisons among oral anticoagulants, a Bayesian analysis was used to evaluate their safety and efficacy based on studies from real-world practice.. The PubMed, Embase, Cochrane and Web of Science databases were searched for relevant studies. Bayesian analyses were conducted to estimate hazard ratios (HR) and 95% credible intervals (CrI) for the safety and efficacy of oral anticoagulants.. In the 22 studies included in our analysis, novel oral anticoagulants exhibited a clear advantage over warfarin in preventing ischaemic stroke, haemorrhagic stroke and, especially, intracranial haemorrhage. Incidence of major bleeding was lowest for apixaban, followed by dabigatran, warfarin and rivaroxaban. Gastrointestinal bleeding risk was lowest for apixaban, followed by warfarin, and was slightly lower for dabigatran than for rivaroxaban with no statistical difference (HR 1.05, 95% CrI 0.99-1.11). Ischaemic stroke risk was lowest for rivaroxaban, followed by apixaban, dabigatran and warfarin (HR 1.13, 95% CrI 1.07-1.20).. In real-world practice, apixaban may represent the optimal treatment in terms of safety and efficacy for patients with non-valvular atrial fibrillation. For patients with high risk of ischaemic events but low bleeding risk, rivaroxaban may be preferable.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Bayes Theorem; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Proportional Hazards Models; Pyrazoles; Pyridones; Risk; Rivaroxaban; Stroke; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) require dose reductions according to patient or clinical factors for patients with atrial fibrillation (AF). In this meta-analysis, we aimed to assess outcomes with reduced-dose NOACs when given as pre-specified in pivotal trials.. Aggregated data abstracted from Phase III trials comparing NOACs with warfarin in patients with AF were assessed by treatment using risk ratios (RRs) and 95% confidence intervals (CIs) stratified by patient eligibility for NOAC dose reduction. Irrespective of treatments, annualized rates of stroke or systemic embolism and major bleeding were higher in patients eligible for reduced-dose NOACs than in those eligible for full-dose NOACs (2.70% vs. 1.60% and 4.35% vs. 2.87%, respectively). Effects of reduced-dose NOACs compared with warfarin in patients eligible for reduced-dose NOACs on stroke or systemic embolism [RR 0.84 (95% CI 0.69-1.03)] and on major bleeding [RR 0.70 (95% CI 0.50-0.97)] were consistent with those of full-dose NOACs relative to warfarin in those eligible for full-dose NOACs [RR 0.86 (95% CI 0.77-0.96) for stroke or systemic embolism and RR 0.87 (95% CI 0.70-1.08) for major bleeding; interaction P, 0.89 and 0.26, respectively]. In addition, NOACs were associated with reduced risks of haemorrhagic stroke, intracranial haemorrhage, fatal bleeding, and death regardless of patient eligibility for NOAC dose reduction (interaction P > 0.05 for each).. Patients eligible for reduced-dose NOACs were at elevated risk of thromboembolic and haemorrhagic complications when treated with anticoagulants. NOACs, when appropriately dose-adjusted, had an improved benefit-harm profile compared with warfarin. Our findings highlight the importance of prescribing reduced-dose NOACs for indicated patient populations.

Topics: Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiazoles; Warfarin

Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the results remain controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of NOACs versus warfarin in this population. Methods and Results We systematically searched the PubMed and Embase databases until February 16, 2019 for studies comparing the effect of NOACs with warfarin in AF patients with cancer. Risk ratios (RRs) with 95% CIs were extracted and pooled by a random-effects model. Five studies involving 8908 NOACs and 12 440 warfarin users were included. There were no significant associations between cancer status and risks of stroke or systemic embolism, major bleeding, or death in AF patients. Compared with warfarin, NOACs were associated with decreased risks of stroke or systemic embolism (RR, 0.52; 95% CI, 0.28-0.99), venous thromboembolism (RR, 0.37, 95% CI, 0.22-0.63), and intracranial or gastrointestinal bleeding (RR, 0.65; 95% CI, 0.42-0.98) and with borderline significant reductions in ischemic stroke (RR, 0.63; 95% CI, 0.40-1.00) and major bleeding (RR, 0.73; 95% CI, 0.53-1.00). In addition, risks of efficacy and safety outcomes of NOACs versus warfarin were similar between AF patients with and without cancer. Conclusions In patients with AF and cancer, compared with warfarin, NOACs had lower or similar rates of thromboembolic and bleeding events and posed a reduced risk of venous thromboembolism.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

Peri-procedural heparin is recommended as bridging therapy for patients with high thromboembolic risk who need to withhold anticoagulant for endoscopic submucosal dissection (ESD) for gastric neoplasms. However, little is known about the bleeding risk from heparin-bridging therapy itself.. MEDLINE and EMBASE databases were searched through August 2017 for studies that compared the risk of post-ESD bleeding in patients who received heparin-bridging therapy in lieu of anticoagulant for gastric neoplasms and those who discontinued anticoagulant without receiving heparin. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effect model, generic inverse variance method. The between-study heterogeneity was quantified using the Q statistic and I. A total of four studies consisting of 350 patients were identified. A significantly increased risk of post-ESD bleeding among the bridged patients compared with the non-bridged patients was observed with the pooled RR of 2.99 (95% CI, 1.51 to 5.92). The statistical heterogeneity was insignificant with I. A significantly increased risk of post-ESD bleeding among patients who received heparin-bridging therapy in lieu of anticoagulant compared to patients who did not receive it was demonstrated in this study.

Topics: Aged; Endoscopy; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Male; Risk Factors; Stomach Neoplasms; Warfarin

Colonoscopy frequently is performed for patients who are taking aspirin, nonsteroidal anti-inflammatory drugs, antiplatelet agents, and other anticoagulants. These colonoscopies often involve polypectomy, which can be complicated by bleeding. The risks of precipitating thromboembolic complications if anticoagulants are stopped must be weighed against the risk of postpolypectomy bleeding if these agents are continued. This article systematically reviews the management of anticoagulation during elective and emergency colonoscopy. For patients undergoing colonoscopic polypectomy, the overall risk of postpolypectomy bleeding is <0.5%. Risk factors for postpolypectomy bleeding include large polyp size and anticoagulant use, especially warfarin and thienopyridines. For patients who do not stop aspirin or other nonsteroidal anti-inflammatory drugs prior to colonoscopy, the rate of postpolypectomy bleeding is not significantly different from that for patients who do not take those medications. For patients who continue thienopyridines and undergo polypectomy, the risk of delayed postpolypectomy bleeding is approximately 2.4%. Even for patients who interrupt warfarin, the risk of postpolypectomy bleeding is increased. The direct oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) have a rapid onset and offset of action, and periprocedural bridging generally is not necessary. For the thienopyridines, warfarin, and the direct oral anticoagulants, the decision to interrupt or continue these agents for endoscopy will involve considerable exercise of clinical judgment.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Colonic Polyps; Colonoscopy; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Pyridines; Risk Factors; Thromboembolism; Warfarin; Withholding Treatment

Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin.. For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs).. We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]).. Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with warfarin or low-molecular-weight heparin. These findings support the continued use of direct oral anticoagulants.. Leeds Teaching Hospitals Charitable Foundation.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Risk Factors; Warfarin

The choice for oral anticoagulant (OAC) therapy was previously limited to the vitamin K antagonists (VKAs). The advent of the direct oral anticoagulants (DOACs) brought with it the expectation that oral anticoagulation would become simpler (with the elimination of routine monitoring and introduction of a fixed-dose anticoagulant), and that the use of VKAs would be slowly phased out. Although DOACs have made anticoagulation more convenient and accessible, we are now faced with what can be described as a tyranny of choice, together with many unanswered questions relating to DOAC use. These include optimal DOAC selection and dosing, use in complex 'real-world' patients, the role for monitoring and issues surrounding adherence. Warfarin remains the anticoagulant of choice in certain scenarios (e.g. metallic heart valves). The future holds much excitement: clinical studies are underway to expand the indications for DOACs and experience continues to grow outside the trials setting.

Topics: Administration, Oral; Anticoagulants; Body Weight; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Gastrointestinal Hemorrhage; Humans; Medication Adherence; Venous Thromboembolism; Vitamin K; Warfarin; Women's Health

To evaluate current clinical evidence for management of oral anticoagulation therapy after gastrointestinal bleeding (GIB) with an emphasis on whether to, when to, and how to resume an anticoagulation therapy.. Relevant articles from MEDLINE, Cochrane Library, and EMBASE databases were identified from 1946 through May 20, 2017, using the keywords: gastrointestinal hemorrhage or gastrointestinal bleeding and antithrombotic therapy or anticoagulation therapy or warfarin or dabigatran or rivaroxaban or apixaban or edoxaban.. All English-language studies assessing management of oral anticoagulation therapy after GIB were evaluated.. A total of 9 studies were identified. Four retrospective cohort studies showed that resuming anticoagulation therapy was associated with significantly lower rate of thromboembolism (TE) in the general population. Meta-analyses and prospective cohort studies also supported this finding. Two retrospective cohort studies indicated an increase in GIB when anticoagulation reinitiation occurred in less than 7 days without a decrease in TE. Resuming therapy between 7 and 15 days did not demonstrate a significant increase in GIB or TE. A large retrospective study showed that apixaban was associated with the significantly lowest risk of GIB compared with both rivaroxaban and dabigatran.. Anticoagulation therapy resumption is recommended, with resumption being considered between 7 and 14 days following GIB regardless of the therapy chosen. Data for warfarin management after GIB should be applied with caution to direct oral anticoagulants (DOACs) because of the quicker onset and experimental nature of reversal agents. Apixaban may be a preferred option when restarting a DOAC therapy.

Topics: Anticoagulants; Dabigatran; Gastrointestinal Hemorrhage; Humans; Pyrazoles; Pyridones; Rivaroxaban; Thromboembolism; Warfarin

Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs.. We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods.. Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg).. Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bayes Theorem; Clinical Trials as Topic; Dabigatran; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Markov Chains; Middle Aged; Monte Carlo Method; Network Meta-Analysis; Odds Ratio; Pyridines; Randomized Controlled Trials as Topic; Risk; Thiazoles; Warfarin

Evidence from the real-world setting complements evidence coming from randomized controlled trials. We aimed to summarize all available evidence from high-quality real-world observational studies about efficacy and safety of nonvitamin-K oral anticoagulants compared with vitamin-K antagonists in patients with atrial fibrillation.. We searched PubMed and Web of Science until January 7, 2017 for observational nationwide or health insurance databases reporting matched or adjusted results comparing nonvitamin-K oral anticoagulants versus vitamin-K antagonists in patients with atrial fibrillation. Outcomes assessed included ischemic stroke, ischemic stroke or systemic embolism, any stroke or systemic embolism, myocardial infarction, intracranial hemorrhage, major hemorrhage, gastrointestinal hemorrhage, and death.. In 28 included studies of dabigatran, rivaroxaban, and apixaban compared with vitamin-K antagonists, all 3 nonvitamin-K oral anticoagulants were associated with a large reduction of intracranial hemorrhage (apixaban hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31-0.63; dabigatran HR, 0.42; 95% CI, 0.37-0.49; rivaroxaban HR, 0.64; 95% CI, 0.47-0.86); similar rates of ischemic stroke and ischemic stroke or systemic embolism (apixaban HR, 1.05; 95% CI, 0.75-1.19 and HR, 1.08; 95% CI, 0.95-1.22 / dabigatran HR, 0.96; 95% CI, 0.80-1.16 and HR, 1.17; 95% CI, 0.92-1.50 / rivaroxaban HR, 0.89; 95% CI, 0.76-1.04 and HR, 0.73; 95% CI, 0.52-1.04, respectively); apixaban and dabigatran with lower mortality (HR, 0.65; 95% CI, 0.56-0.75 and HR, 0.63; 95% CI, 0.53-0.75, respectively); apixaban with fewer gastrointestinal (HR, 0.63; 95% CI, 0.42-0.95) and major hemorrhages (HR, 0.55; 95% CI, 0.48-0.63); dabigatran and rivaroxaban with more gastrointestinal hemorrhages (HR, 1.20; 95% CI, 1.06-1.36 and HR, 1.24; 95% CI, 1.08-1.41, respectively); dabigatran and rivaroxaban with similar rate of myocardial infarction (HR, 0.96; 95% CI, 0.77-1.21 and HR, 1.02; 95% CI, 0.54-1.89, respectively).. This meta-analysis confirms the main findings of the randomized controlled trials of dabigatran, rivaroxaban, and apixaban in the real-world setting and, hence, strengthens their validity.

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Dabigatran; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Myocardial Infarction; Proportional Hazards Models; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Warfarin

Trial data for the benefits and risks of dabigatran versus warfarin in the treatment of nonvalvular atrial fibrillation are lacking. We sought to review real-world observational evidence for the comparative effectiveness and safety of these agents.. A systematic search of multiple databases was conducted from first available date to March 10, 2015 for longitudinal, observational studies comparing dabigatran with warfarin. Two reviewers evaluated studies for eligibility and extracted hazard ratios for ischemic stroke and gastrointestinal and intracranial bleeding. hazard ratios were pooled using random-effects meta-analysis. Metaregression was performed to assess treatment-effect heterogeneity. We identified 232 unique citations. Seven retrospective cohort studies met study eligibility criteria, with 348 750 patients and a mean follow-up of 2.2 years. In pooled analyses, dabigatran-150 mg was not superior to warfarin in preventing stroke (hazard ratio, 0.92; 95% confidence interval, 0.84-1.01; P=0.066), but had a significantly lower hazard of intracranial bleeding (0.44; 0.34-0.59; P<0.001). Dabigatran-150 mg had a significantly greater hazard of gastrointestinal bleeding than warfarin (1.23; 1.01-1.50; P=0.041), which was potentiated in studies of older (elderly) versus younger populations (median/mean age, ≥75 versus <75 years; β=1.53; 95% confidence interval, 1.10-2.14; P=0.020).. In real-world clinical practice, dabigatran is comparable with warfarin in preventing ischemic stroke among patients with nonvalvular atrial fibrillation. However, dabigatran is associated with a lower risk for intracranial bleeding relative to warfarin, but-particularly among the elderly-a greater risk for gastrointestinal bleeding. Bleeding outcomes from observational studies are consistent with those from the pivotal Randomized Evaluation of Long-Term Anticoagulation Therapy trial.

Topics: Age Factors; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Risk Factors; Stroke; Treatment Outcome; Warfarin

Particular concerns have been raised regarding the association between non-vitamin K antagonist oral anticoagulants (NOACs) and the risk of gastrointestinal bleeding (GIB); however, current findings are still inconclusive. We conducted a systematic review with a meta-analysis to examine the association between NOACs and GIB in real-life settings. We performed a systematic search of PubMed, EMBASE and CINAHL Plus up to September 2015. Observational studies that evaluated exposure to NOACs reporting GIB outcomes were included. The inverse variance method using the random-effects model was used to calculate the pooled estimates. Eight cohort studies were included in the primary meta-analysis, enrolling 1442 GIB cases among 106 626 dabigatran users (49 486 patient-years), and 184 GIB cases among 10 713 rivaroxaban users (4046 patient-years). The pooled incidence rates of GIB were 4.50 [95% confidence interval (CI) 3.17, 5.84] and 7.18 (95% CI 2.42, 12.0) per 100 patient-years among dabigatran and rivaroxaban users, respectively. The summary risk ratio (RR) was 1.21 (95% CI 1.05, 1.39) for dabigatran compared with warfarin, and 1.09 (95% CI 0.92, 1.30) for rivaroxaban. Subgroup analyses showed a dose-related effect of dabigatran, with a significantly higher risk of GIB for 150 mg b.i.d. (RR = 1.51, 95% CI 1.34, 1.70) but not for 75 mg b.i.d. or 110 mg b.i.d.. In addition, the use of proton pump inhibitors (PPIs)/histamine H2-receptor antagonists (H2RAs) influenced the association in dabigatran users, whereas this effect was modest among rivaroxaban users. In conclusion, our meta-analysis suggested a slightly higher risk of GIB with dabigatran use compared with warfarin, whereas no significant difference was found between rivaroxaban and warfarin for GIB risk.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Dose-Response Relationship, Drug; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors; Rivaroxaban; Warfarin

The management of stroke prevention among patients with atrial fibrillation (AF) has changed in the last few years. Despite the benefits of new oral anticoagulants (NOACs), decisions about the optimal agent remain a challenge. We provide a visual aid tool to guide clinicians and patients in the decision process of selecting oral anticoagulants for stroke prevention.. We created visual plots representing benefits of warfarin versus NOACs from a meta-analysis comprising 58,541 participants. Visual plots (Cates plots) were created using software available at nntonline.net. The primary outcome was stroke or systemic embolism during the study period.. In the chosen meta-analysis, 29,312 participants received a NOAC and 29,229 participants received warfarin. For every 1000 patients with AF, 38 would have a stroke or systemic embolic event in the warfarin group compared to 31 in the NOAC group (RR .81; 95% CI .73-.91). Fifteen patients would develop an intracranial hemorrhage in the warfarin group compared to 7 in the NOAC group (RR .48; 95% CI .39-.59). Conversely, 25 patients would develop gastrointestinal bleeding in the NOAC group compared to 20 in the warfarin group (RR 1.25; 95% CI 1.01-1.55).. For every 1000 treated individuals with AF, NOACs would prevent stroke or systemic embolism in 7 additional patients and cerebral hemorrhage in 8 additional patients compared to warfarin. On the other hand, 5 more patients would develop gastrointestinal bleeding with NOACs compared to warfarin. These data are visually shown in Cates plots, facilitating conversations with patients regarding anticoagulation decisions.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Audiovisual Aids; Decision Support Techniques; Embolism; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Odds Ratio; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Software; Stroke; Treatment Outcome; Warfarin

New oral anticoagulants represent an alternative to standard therapy with vitamin K antagonists but data regarding gastrointestinal bleeding are still unclear.. To investigate if new oral anticoagulants are associated with an enhanced risk of gastrointestinal bleeding vs warfarin in patients with atrial fibrillation.. Meta-analysis of phase three randomized controlled trials to compare the incidence of gastrointestinal bleeding in atrial fibrillation patients treated with new oral anticoagulants (apixaban, dabigatran, edoxaban and rivaroxaban) vs warfarin.. Four studies including 71,302 patients were selected. Compared with warfarin, new oral anticoagulants significantly increased gastrointestinal bleeding (RR: 1.23; 95% CI 1.03-1.46; p=0.01). Rivaroxaban (RR: 1.46; 95% CI 1.2-1.8; p<0.001) and high dosages of edoxaban (RR: 1.22; 95% CI 1.01-1.47; p=0.038) and dabigatran (RR: 1.50; 95% CI 1.20-1.88; p<0.001) significantly increased gastrointestinal bleeding while a null effect was detected with apixaban.. This meta-analysis suggests that rivaroxaban and high dosages of dabigatran and edoxaban should be avoided in patients at high risk of gastrointestinal bleeding.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thiazoles; Warfarin

Acute gastrointestinal bleeding represents the most common adverse event associated with the use of oral anticoagulant therapy. Due to increasing prescription of anticoagulants worldwide, gastroenterologists are more and more called to deal with bleeding patients taking these medications. Their management is challenging because several issues have to be taken into account, such as the severity of bleeding, the intensity of anticoagulation, the patient's thrombotic risk and endoscopy findings. The recent introduction into the marketplace of new direct oral anticoagulants, for whom specific reversal agents are still lacking, further contributes to make the decision-making process even more demanding. Available evidence on this topic is limited and practice guidelines by gastroenterology societies only marginally address key issues for clinicians, including when and how to reverse coagulopathy, the optimal timing of endoscopy and when and how to resume anticoagulation thereafter. The present paper reviews the evidence in the literature and provides practical algorithms to support clinicians in the management of patients on anticoagulants who present with acute gastrointestinal bleeding.

Topics: Acenocoumarol; Acute Disease; Algorithms; Anticoagulants; Coagulants; Dabigatran; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Humans; Rivaroxaban; Vitamin K; Warfarin

For patients undergoing colonoscopy with polypectomy, current guidelines recommend temporary cessation of blood-thinning medications. The data regarding periprocedural management of these medications are sparse.. To perform a systematic review and meta-analysis to determine the risk of post-polypectomy bleeding (PPB) in patients taking anti-platelet, anti-coagulant and/or thienopyridine medications.. We searched Pubmed, Scopus, Web of Science, Biosis and Proceedings First from 1970 to 2015. PPB was defined as overt haemorrhage or drop in haemoglobin of at least 2 g/dL.. Of 1490 articles identified, we included 3 papers and 1 abstract with patients on aspirin and/or NSAIDs, 1 paper on warfarin, 2 abstracts on clopidogrel, and 2 papers on clopidogrel plus aspirin and/or NSAIDs. While the rate of immediate PPB on aspirin and/or NSAIDs was not increased (OR = 1.1, 95% CI 0.7-1.9, P = 0.7), the risk of delayed PPB was increased (OR = 1.7, 95% CI 1.0-2.4, P = 0.0009, I(2)  = 60%) but rendered non-significant with elimination of a small study. There was an elevated risk of delayed PPB on clopidogrel (OR = 9.7, 95% CI 3.1-30.8, P = 0.0, I(2)  = 0). There was an increased risk of delayed PPB in patients on clopidogrel + aspirin and/or NSAIDs (OR = 3.4, 95% CI 1.3-8.8, P = 0.01, I(2)  = 0). Based on a single study on warfarin, the PPB rate was elevated. There were no data regarding PPB and usage of the newer anti-coagulant agents.. Usage of aspirin or NSAIDs does not increase risk of post-polypectomy bleeding. Clopidogrel and warfarin should be discontinued in the periprocedural period to prevent the occurrence of post-polypectomy bleeding.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Blood Coagulation Disorders; Colonic Polyps; Colonoscopy; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Pyridines; Risk Factors; Warfarin

Gastrointestinal bleeding (GIB) is a potentially fatal and avoidable medical condition that poses a burden on global health care costs. The rate of major GIB related to the use of some direct acting oral anticoagulant drugs (DOACs), is higher than that detected in warfarin users. Current strategies in the treatment of GIBs in patients receiving warfarin or DOACs (vitamin K, activated charcoal; hemodialysis; recombinant factor VIIa; [activated] prothrombin complex concentrates) including indications for the treatment of bleeding based on different degrees of severity of the episodes, is reported in this article. Potential preventive strategies to mitigate the risk of GIBs (e.g. upper endoscopy/biopsy, colon cancer screening; eradication of Helicobacter pylori prior to starting anticoagulation; use of proton-pump inhibitors, identification of risk factors for bleeding) are also reported as well as the fact that some of them have not been tested so far in patients receiving DOACs. Antidotes that experimentally reverse the anti-coagulant effect of dabigatran (Idarucizumab; BI 655075; Boehringer Ingelheim); of rivaroxaban, apixaban, or edoxaban (Andexanet alfa, r-Antidote, PRT064445; Portola Pharmaceuticals) or of all DOACs (Aripazine, PER-977, ciraparantag; Perosphere Inc.) are discussed. Likewise, population pharmacokinetics modeling related to the rate of major DOACs-related GIBs is presented. It is also emphasized that the occurrence of GIB reflects the presence of patients at the highest risk for adverse outcomes. Finally, the implications of the concept that patient characteristics and the severity of illness (i.e. comorbidities) exert a greater impact on the risk of GIB than the type of antithrombotic agent employed, are analyzed.

Topics: Anticoagulants; Dabigatran; Gastrointestinal Hemorrhage; Humans; Proton Pump Inhibitors; Pyrazoles; Pyridones; Warfarin

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Databases, Pharmaceutical; Gastrointestinal Hemorrhage; Humans; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Embolism; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K; Warfarin

Anticoagulants are effective at preventing and treating thrombosis, but can cause bleeding. For decades, vitamin K antagonists (VKAs) have been the only available oral anticoagulants. The development of non-VKA oral anticoagulants (NOACs), which inhibit either factor Xa or thrombin stoichiometrically, has provided alternatives to VKAs for several indications. The results of recent large-scale randomised controlled trials comparing NOACs with VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation (AF) have produced some unexpected results. As a group, NOACs showed similar efficacy as warfarin, but a reduced risk of major bleeding. The reduction in bleeding with NOACs was greatest with intracranial hemorrhage. In contrast, the relative risk of gastro-intestinal bleeding was increased with some NOACs. In this review, we explore the potential mechanisms as well as the implications of these organ-specific bleeding patterns.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation Factors; Endothelium, Vascular; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intestinal Absorption; Intracranial Hemorrhages; Organ Specificity; Randomized Controlled Trials as Topic; Stroke; Thrombophilia; Thromboplastin; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Endoscopy; Gastrointestinal Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Warfarin

To quantify the novel oral anticoagulant (NOAC)-related gastrointestinal bleeding, summarize the management strategies and highlight the knowledge gaps.. Dabigatran, rivaroxaban and apixaban differ from warfarin with their fixed oral dose and no requirement for routine monitoring. Patients at highest risk of thromboembolism benefit most from NOACs; however, there is a clinically significant risk for NOAC-related gastrointestinal bleeding. The management of NOACs in the acute and elective setting differs from that used with warfarin.. The magnitude of gastrointestinal risk is still unclear because of paucity of literature. Current risk-stratification models are incomplete and cannot be used solely to predict future risk. The periendoscopic management requires an understanding of drug half-life, metabolism and patient's ability to excrete the agent. Acute bleeding management relies on fluid resuscitation to promote renal excretion of active metabolite, withholding the doses and timely management of endoscopic stigmata. The administration of coagulation factors (fresh frozen plasma, prothrombin complex concentrates or recombinant activated FVII) is more successful in reversing the activity of the upstream inhibitors of coagulation (rivaroxaban and apixaban) than dabigatran which is a direct thrombin inhibitor.

Topics: Administration, Oral; Anticoagulants; Biomedical Research; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Humans; Risk Assessment; Warfarin

Glucocorticosteroids are still very important part of the treatment of chronic inflammatory disorders. Their use is often accompanied by unpleasant adverse effects, problems associated with withdrawal during their long-term use and interactions with concomitantly administered drugs. One of the important interactions that may often occur in clinical practice is interaction with warfarin. Despite the fact that as glucocorticosteroids so warfarin are used for many years and seem to be completely known, their co-administration is still accompanied by uncertainties. The interaction may have pharmacodynamic or pharmacokinetic character and both types result in increased risk of bleeding. The pharmacodynamic interaction can be expected to increase a risk of gastrointestinal bleeding to which a gastrotoxicity of glucocorticosteroids contributes. A pharmacokinetic interaction is considered to influence a hepatic metabolism of warfarin and to increase its availability. The exact mechanism is still not fully understood. Manifestations of both types of interactions are taken up with a delay. Co-administration requires increased attention and close monitoring of international normalized ratio. At higher doses of glucocorticosteroids proton pump inhibitors are also effective in prevention of gastrotoxicity.

Topics: Anti-Inflammatory Agents; Anticoagulants; Autoimmune Diseases; Drug Interactions; Gastrointestinal Hemorrhage; Glucocorticoids; Humans; Warfarin

Oral anticoagulation is the mainstay of therapy for stroke prevention in patients with atrial fibrillation (AF). Vitamin K antagonists such as warfarin have many drawbacks that reduce their uptake, safety and effectiveness. The ROCKET AF trial compared rivaroxaban (20 mg/day; 15 mg/day in patients with creatinine clearance 30-49 ml/min) with dose-adjusted warfarin (international normalized ratio 2-3) in 14,264 patients with AF and a prior history of stroke or at least two other additional risk factors for stroke. The ROCKET AF trial demonstrated the noninferiority of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism, with a similar rate of major bleeding and a substantial reduction in intracranial hemorrhage. These results, in conjunction with its convenient once-daily dosing regimen, make rivaroxaban an attractive alternative to warfarin for stroke prevention in AF.

Topics: Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Morpholines; Rivaroxaban; Stroke; Thiophenes; Warfarin

Spontaneous intestinal hematoma is a rare complication of anticoagulant therapy. The authors reported three cases of intramural and submucosal small bowel hematoma resulting from warfarin administration. The first patient presented with abdominal pain, had intramural hematoma at jejunum, the most common site of intramural small bowel hematoma. Another patient who had submucosal duodenal hematoma presented with massive upper gastrointestinal bleeding, a rare manifestation of small bowel hematoma. The third patient presented with intramural ileal hematoma that caused abdominal pain and palpable mass after a short period of warfarin therapy. Typical findings on abdominal computerized tomography yielded the diagnosis. All patients rapidly improved after conservative treatment. The history of anticoagulant use with prolonged INR value in patients presented with abdominal pain should alert physicians to search for this entity. It is extremely important to recognize this syndrome in order to avoid an unnecessary operation since the outcome is usually excellent after conservative treatment.

Topics: Abdominal Pain; Aged; Anticoagulants; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; International Normalized Ratio; Male; Risk Factors; Thailand; Time Factors; Warfarin

Elderly patients as a group may present more of a challenge in managing warfarin therapy because of alterations in pharmacokinetics from other medications, diet, and disease; pharmacodynamic changes; increased risk for hemorrhage; and difficulty in monitoring. The elderly, however, may derive the most benefit from warfarin therapy for certain indications, such as the prevention of stroke in atrial fibrillation or recurrent events following deep venous thrombosis. Warfarin can be managed as effectively as in other populations with careful attention to these issues.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Cerebral Hemorrhage; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Geriatric Assessment; Humans; Male; Maximum Tolerated Dose; Monitoring, Physiologic; Prothrombin Time; Risk Assessment; Treatment Outcome; Warfarin

This review examines ulcers and gastrointestinal bleeding with low-dose aspirin, focusing on randomized placebo-controlled trials. The single endoscopic trial assessing ulcers showed no significant difference in 12-week ulcer incidence: 6% of 381 given placebo vs. 7% of 387 given 81 mg enteric-coated aspirin. The relative risk of major gastrointestinal bleeding with low-dose aspirin in a meta-analysis of placebo-controlled trials of vascular protection was 2.07 (95% CI: 1.61-2.66). The absolute rate increase with aspirin above placebo was 0.12% per year (95% CI: 0.07-0.19%) with a number-needed-to-harm of 833 patients (95% CI: 526-1429). A meta-analysis of aspirin 50-1500 mg daily reported an odds ratio for any gastrointestinal bleeding of 1.68 (95% CI: 1.51-1.88) with an number-needed-to-harm at 1 year of 247. The relative risk of hospitalization for upper gastrointestinal bleeding with low-dose aspirin in a large Danish cohort study was 2.6 (95% CI: 2.2-2.9) with an absolute annual incidence of 0.6%. Factors that may increase the risk of gastrointestinal bleeding include prior history of ulcers or gastrointestinal bleeding, corticosteroid use, anticoagulant therapy and addition of a non-aspirin non-steroidal anti-inflammatory drug. When determining whether low-dose aspirin is appropriate for an individual patient, the cardiovascular benefit must be weighed against the potential for clinical events such as gastrointestinal bleeding.

Topics: Adrenal Cortex Hormones; Aging; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cardiovascular Diseases; Cyclooxygenase 2 Inhibitors; Drug Administration Schedule; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Factors; Ulcer; Warfarin

Topics: Anticoagulants; Drug Monitoring; Female; Gastrointestinal Hemorrhage; Humans; Middle Aged; Necrosis; Patient Education as Topic; Skin Diseases; Warfarin

Topics: Administration, Oral; Anti-Inflammatory Agents; Anticoagulants; Biotransformation; Blood Coagulation; Coumarins; Drug Interactions; Gastrointestinal Hemorrhage; Humans; Warfarin

Portal vein thrombosis (PVT) and acute variceal bleeding (AVB) are frequent complications of cirrhosis. The efficacy, safety, and timing of anticoagulant treatment in cirrhotic patients with PVT and AVB are contentious issues. We aimed to establish the safety and efficacy of initiating nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy early after esophageal variceal band ligation within PVT patients having cirrhosis and AVB. Cirrhotic patients having AVB and PVT who underwent EVL were included and randomly allocated to either the NWS therapy group (1-month nadroparin calcium by subcutaneous injection following 5-month warfarin through oral administration, n = 43) or the control group (without any anticoagulation therapy, n = 43). The primary endpoint was the rate of PVT recanalization. Secondary endpoints included major bleeding events mainly referring to variceal rebleeding (5-day failure, 14-day, 4-week, 6-week, and 6-month rebleeding rates) and mortality after EVL. The overall recanalization (complete and partial) rate in the NWS therapy group was significantly higher than that in the control group (67.4% vs. 39.5%, P = 0.009). Low Child-Pugh score (P = 0.039, OR: 0.692, 95% CI 0.488-0.982), D-dimer < 2.00 ug/mL (P = 0.030, OR: 3.600, 95% CI 1.134-11.430), and NWS anticoagulation therapy (P = 0.002, OR: 4.189, 95% CI 1.660-10.568) were the predictors of PVT recanalization through univariate analysis of binary logistic regression. NWS anticoagulation therapy (P = 0.003, OR: 4.506, 95% CI 1.687-12.037) was the independent factor of recanalization through multivariate analysis. Nobody bled except for variceal rebleeding. Five-day failure and 14-day rebleeding were zero. There were no significantly different in 4-week (2.3% vs. 4.7%, P = 1.000), 6-week (4.7% vs. 9.3%, P = 0.672) and 6-month rebleeding (18.6% vs. 20.9%, P = 0.787) between the two groups. There was no mortality during six months follow-up. Low serum albumin (P = 0.011, OR: 0.844, 95% CI 0.741-0.962), high MELD score (P = 0.003, OR: 1.564, 95% CI 1.167-2.097) and Child-Pugh score (P = 0.006, OR: 1.950, 95% CI 1.206-3.155) were predictors of rebleeding by univariate analysis of binary logistic regression analysis. The Child-Pugh score (7 [6-8] vs. 6 [5-7], P = 0.003) and albumin levels (33.93 ± 5.30 vs. 37.28 ± 4.32, P = 0.002) were improved in the NWS therapy group at six months. In PVT patients with cirrhosis and AVB, starting NWS anticoagulation therapy early after EVL wa

Topics: Albumins; Anticoagulants; Esophageal and Gastric Varices; Fibrosis; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Nadroparin; Portal Vein; Treatment Outcome; Venous Thrombosis; Warfarin

This study compares the safety and efficacy of a fixed dose of 4-factor prothrombin complex concentrate (4FPCC) to the FDA-approved variable dosing for reversal of warfarin-induced anticoagulation.. This was a single-center, prospective, open-label, randomized controlled trial with subjects randomized to 4FPCC at a fixed dose of 1500 IU or the FDA-approved variable dosing regimen. The primary efficacy outcome (reversal success) was defined as a post-intervention international normalized ratio (INR) of less than or equal to 1.5. Given that 4FPCC is the standard of care for reversal of warfarin-induced anticoagulation an active-controlled approach was employed with the two dosing regimens compared based on efficacy, cost, and safety outcomes.. 71 subjects (34 in the fixed dose group and 37 in the variable dose group) completed the study. There were no significant differences in age, gender, weight, initial INR, or indication for 4FPCC administration between the two treatment groups. Reversal success in the fixed-dose group was 61.8%, while in the variable dose group reversal success was 89.2%. Reversal success in the fixed-dose group was significantly lower than the rate of reversal success in the variable dose group (27.4% lower, p = 0.011).. The results of this study provide evidence that fixed dosing results in lower reversal success rates as compared to variable dosing of 4FPCC for warfarin-induced anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Emergencies; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Warfarin

A history of gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) may impact decisions about anticoagulation treatment. We sought to determine whether prior GIB in patients with AF taking anticoagulants was associated with an increased risk of stroke or major hemorrhage.. We analyzed key efficacy and safety outcomes in patients with prior GIB in ARISTOTLE. Centrally adjudicated outcomes according to GIB history were analyzed using Cox proportional hazards models adjusted for randomized treatment and established risk factors.. In patients with AF on oral anticoagulants, prior GIB was associated with an increased risk of subsequent major GIB but not stroke, intracranial bleeding, or all-cause mortality. For the key outcomes of stroke, hemorrhagic stroke, death, and major bleeding, we found no evidence that the treatment effect (apixaban vs. warfarin) was modified by a history of GIB.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Mortality; Proportional Hazards Models; Pyrazoles; Pyridones; Risk; Risk Factors; Severity of Illness Index; Stroke; Treatment Outcome; Warfarin

In the Japanese clinical setting, the prevalence, potential cofounders of gastrointestinal (GI) bleeding from anticoagulant therapy, including direct oral anticoagulants (DOACs) and warfarin, and prognosis after GI bleeding are unclear.Methods and Results:We examined about GI bleeding from anticoagulant therapy using data from the SAKURA AF Registry, a prospective multicenter registry in Japan. Among 3,237 enrollees, 48.8% (n=1,561) were warfarin users and 51.2% (n=1,676) DOAC users. GI bleeding was identified in 68 patients (2.1%). No incidental differences in GI bleeding were observed between the DOAC and warfarin users (32 [1.9%] patients [0.67 events per 100 person-years] vs. 36 [2.3%] patients [0.75 events per 100 person-years], respectively; P=0.43). Multivariate Cox proportional hazard model analysis revealed that creatinine (hazard ratio [HR] 1.379, 95% confidence interval [CI] 1.091-1.743 P=0.007) and hemoglobin (HR 0.814, 95% CI 0.705-0.941, P=0.005) remained independent determinants of GI bleeding. Patients experiencing GI bleeding events had a higher risk of all-cause death (18%) than those without GI bleeding (6%) (P=0.045).. GI bleeding was strongly associated with anemia and renal impairment. Patients experiencing GI bleeding had higher risk for all-cause death than those without GI bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Prevalence; Proportional Hazards Models; Prospective Studies; Registries; Retrospective Studies; Risk Factors; Survival Rate; Tokyo; Treatment Outcome; Warfarin

The impact of different types of extracranial bleeding events on health-related quality of life and health-state utility among patients with atrial fibrillation is not well understood.. The ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation. Data from the EuroQol-5D (EQ-5D-3L) questionnaire, prospectively collected at 3-month intervals for up to 48 months, were used to estimate the impact of different categories of bleeding events on health-state utility over 12 months following the event. Longitudinal mixed-effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores (-0.029 [-0.044 to -0.014;. All categories of bleeding events were associated with negative impacts on health-state utility in patients with atrial fibrillation. Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months; clinically relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months.. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Embolism; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Health Status; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Pyridines; Quality of Life; Risk Factors; Stroke; Surveys and Questionnaires; Thiazoles; Time Factors; Treatment Outcome; Warfarin

Gastrointestinal (GI) bleeding in patients receiving anticoagulation agents can be caused by occult malignancies. We investigated the proportions and features of major GI bleeding (MGIB) events related to occult GI cancers in patients receiving anticoagulation therapy.. We analyzed data from the Randomized Evaluation of Long Term Anticoagulant Therapy study (conducted between December 2005 and March 2009 in 951 clinical centers in 44 countries worldwide), which compared the abilities of dabigatran vs warfarin to prevent stroke and systemic embolism in 18,113 patients with atrial fibrillation. Two blinded gastroenterologists independently reviewed source documents of MGIB events (n = 595) that occurred during the study period. We collected data on MGIB events caused by previously unidentified GI malignancies, and compared characteristics of MGIB events in patients who received dabigatran vs warfarin (primary end point), and in patients with bleeding from cancer, vs patients bleeding from a nonmalignant or unidentified source.. Of 546 unique MGIB events, 44 (8.1%) were found to be from GI cancers (34 of 398 MGIB events in dabigatran users and 10 of 148 MGIB events in warfarin users; P = .60). Colorectal cancer accounted for 35 of 44 of all cancers identified. There were more colorectal cancer-associated MGIB events in the dabigatran group (30 of 34) than in the warfarin group (5 of 10) (P = .02), but more gastric cancer-associated MGIB events in the warfarin group (5 of 10) than in the dabigatran group (1 of 34) (P = .001). There were no differences in the short-term outcomes of cancer-related MGIB events in the dabigatran vs the warfarin group, but 75% of all cancer-related MGIB events required at least 1 blood transfusion and the mean hospital stay was 10.1 days. Compared with MGIB events from a nonmalignant or unidentified source, MGIB from cancer occurred sooner (343.0 vs 223.1 d; P = .003), but the bleeding was more likely to be chronic (for >7 d) (27.3% vs 63.6%; P < .001).. In evaluating data from a study of the effects of anticoagulation therapy, we found approximately 1 of every 12 MGIB events to be related to an occult cancer. Approximately two thirds of cancer-related MGIB presents with chronic bleeding, and morbidity, and resource utilization is high.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chemoprevention; Dabigatran; Embolism; Female; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Male; Prevalence; Prospective Studies; Stroke; Warfarin

To date, there have been few studies evaluating outcomes of patients with atrial fibrillation (AF) who have experienced gastrointestinal (GI) hemorrhages. We examined short- and long-term mortality of major GI hemorrhage in patients with AF on and off warfarin in recent clinical care. We evaluated this association in the large Anticoagulation and Risk Factors in Atrial fibrillation (ATRIA) and ATRIA-Cardiovascular Research Network (CVRN) California community-based cohorts of patients with AF (study years 1996 to 2003 and 2006 to 2009, respectively), where all events were clinician adjudicated. We used proportional hazards regression with propensity score adjustment to estimate the short- (30 days) and long-term (>30 days for 1 year) mortality rate ratio for patients using warfarin compared with those who were not using warfarin at the time of GI hemorrhage. In the 414 ATRIA participants with major GI hemorrhage, 54% were taking warfarin at the time of the hemorrhage; in the 361 ATRIA-CVRN participants with major GI hemorrhage, 58% were taking warfarin. Warfarin use at the time of GI hemorrhage was not associated with 30-day mortality in the ATRIA cohort but was associated with significantly reduced 30-day mortality in the ATRIA-CVRN cohort (adjusted mortality rate ratio [95% confidence interval], ATRIA 0.97 [0.54 to 1.74]; ATRIA-CVRN 0.38 [0.17 to 0.83]). There was a modest suggestion of lower mortality on warfarin after 30 days in both cohorts. In conclusion, our study demonstrates that GI hemorrhages on warfarin are certainly no worse and may be less life threatening than those occurring off warfarin. These findings are in stark contrast to the deleterious effect of warfarin on mortality from intracranial hemorrhage and add another factor favoring anticoagulation in clinical decision making for patients with AF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; California; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Survival Rate; Thromboembolism; Warfarin

Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation.. This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of the ROCKET AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial.. The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors.. Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use.. In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Double-Blind Method; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Internationality; Male; Rivaroxaban; Treatment Outcome; Warfarin

High International Normalized Ratio (INR) level resulting from warfarin use increases the risk of gastrointestinal hemorrhages. We aimed to compare the efficacy of prothrombin complex concentrates (PCC) and fresh frozen plasma (FFP) at lowering the INR level, decreasing active hemorrhages visible by endoscopy, and shortening the length of stay at the emergency department (ED).. This study is a prospective cohort study of consecutive patents with gastrointestinal hemorrhages that received either PCC or FFP. With strict exclusion criteria, only patients over 18 years of age with a high INR level (>2.1) due to warfarin usage were included.. A total of 40 patients (18 female) were included in the study, 20 each in the PCC and FFP groups. For the PCC group, the mean INR levels at the second and sixth hours were lower than those for the FFP group (second hour INR: 1.53 vs 4.50, P<.01, sixth hour INR: 1.52 vs 2.41, P<.01). Seven patients experienced active bleeding (Forrest 1) in the FFP group, whereas no patient experienced active bleeding in the PCC group based on the Forrest classification (35% vs 0%, P<.01), and only 3 patients in the FFP group underwent invasive/surgical treatment (15% vs 0%, P<.01). The ED length of stay was lower for the PCC group (1.62 days vs 3.46 days, P<.01).. For patients experiencing a gastrointestinal hemorrhage, INR levels were reversed more quickly, there was less active bleeding on endoscopy, and the ED length of stay was lower in the PCC group than in the FFP group.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Blood Transfusion; Emergency Service, Hospital; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Plasma; Prospective Studies; Treatment Outcome; Warfarin

Warfarin reduces the incidence of thromboembolism but increases the risk of gastrointestinal bleeding (GIB). GIB during warfarin anticoagulation is rarely evaluated in Asian patients.. This study aimed at investigating the incidence, risk factors, management, and outcome of GIB in Taiwanese patients treated with warfarin.. We analyzed a cohort of warfarin anticoagulated patients between July 1993 and May 2012. Clinical data were retrieved in a chart-reviewing manner.. A total of 401 warfarin anticoagulated patients were enrolled. The incidence of GIB was 3.9% per patient-years. Multivariate analysis with Cox regression showed that age >65 years old (RR: 2.5, 95% CI: 1.2-5.5), a mean international normalized ratio >2.1 (RR: 2.1, 95% CI: 1.0-4.2), a history of GIB (RR: 5.1, 95% CI: 1.9-13.5), and cirrhosis (RR: 6.9, 95% CI: 2.0-24.5) were independent factors predicting GIB. 27.3% of the GIB patients had rebleeding after restarting warfarin while thromboembolic events were found in 16.7% of the patients discontinuing warfarin therapy.. Warfarin was associated with a significant incidence of GIB in Taiwanese patients. The intensity of anticoagulation should be monitored closely during warfarin therapy, especially in patients with risk factors of GIB.

Topics: Aged; Aged, 80 and over; Anticoagulants; Asian People; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Taiwan; Thromboembolism; Warfarin

The comparison of anticoagulants dabigatran and warfarin might be most equitable in vitamin K antagonist (VKA)-naive patients.. Warfarin and 2 doses of dabigatran-110 mg BID (D110) and 150 mg BID (D150)-were compared in a balanced population of VKA-naive (≤62 days of lifetime VKA exposure, with 33% never prescribed a VKA) and VKA-experienced patients with atrial fibrillation (n=18 113). For VKA-naive and -experienced patients assigned warfarin, the time in therapeutic range (international normalized ratio 2.0 to 3.0) was 62% and 67%, respectively, and 61% and 66% for those never and ever prescribed a VKA. In VKA-naive patients, stroke and systemic embolism rates were 1.57%, 1.07%, and 1.69% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.65); D150 was superior (P=0.005). Major bleeding rates were 3.11%, 3.34%, and 3.57% per year, respectively. D110 and D150 were similar to warfarin (P=0.19 and P=0.55). Intracranial bleeding rates were 0.19%, 0.33%, and 0.73% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 and P=0.005). In VKA-experienced patients, stroke and systemic embolism rates were 1.51%, 1.15%, and 1.74% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.32); D150 was superior (P=0.007). Major bleeding rates were 2.66%, 3.30%, and 3.57% per year, respectively. D110 was lower than warfarin (P=0.003); D150 was similar (P=0.41). Intracranial bleeding rates were 0.26%, 0.32%, and 0.79% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 for both). Results were similar for patients never on a VKA.. Previous VKA exposure does not influence the benefits of dabigatran at either dose compared with warfarin.. http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Embolism; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyridines; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

Use of proton pump inhibitor (PPI) reduces the risk of gastrointestinal (GI) bleeding, and is generally recommended for high GI risk patients taking nonsteroidal anti-inflammatory agents. Aspirin and/or anticoagulants have been identified as increasing the risk of GI bleeding, whereby use of PPI could reduce this risk. The use of PPI in routine practice is not well defined, especially in patients with acute coronary syndromes (ACS) who require one or several antithrombotic drugs.. We analyzed the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI) 22 trial database, which enrolled patients who had been hospitalized for ACS. Patients were to be treated with aspirin, and received clopidogrel and/or warfarin at the discretion of the treating physician. We analyzed the use of PPI at baseline, which was not specified in the protocol, according to prior known GI risk factors.. Of the 4162 patients enrolled, 781 (18.8%) received PPI during the course of this study. The use ranged from 14% to 67% across the number of GI risk factors of 0 to > or =4 (P < 0.0001). Individual factors most associated with increased use of PPI were a prior GI event (RR = 2.3, P < 0.001) and use of anticoagulants (RR = 1.49, P < 0.001), but not dual antiplatelet therapy.. Use of PPI following ACS is modest, although it did increase with an increasing number of previously identified GI risk factors. Further, larger studies are warranted to validate prior, or identify new, risk factors as predictors of long-term bleeding, and improve awareness of GI bleeding risk such that use of PPI could be optimized.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Clopidogrel; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Proton Pump Inhibitors; Risk Factors; Ticlopidine; Treatment Outcome; Warfarin

Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy.. To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalization ratio,<1.5] plus 325 mg/d of enteric-coated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin.. Among the 63 at high risk of stroke, abnormal values (>2mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean ( +/- SD) values were more for those randomly assigned to receive combined therapy (1.7 +/- 3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0 +/- 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (+/- SD) HemoQuant value of 0.8 +/- 0.7mg of hemoglobin per gram of stool 1 month after entry in the study.. Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Drug Therapy, Combination; Feces; Female; Gastrointestinal Hemorrhage; Hemoglobins; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Thrombosis; Warfarin

Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk.. We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death.. Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history.. Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.

Topics: Aged; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Double-Blind Method; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Research Design; Warfarin

To investigate the suitability of treatment with low dose aspirin or warfarin, or both, as possible prophylaxis against cardiovascular disease by determining the effect on gastric mucosal bleeding.. Randomised crossover trial.. Academic department of therapeutics.. Twenty healthy male volunteers aged 19-22.. On separate occasions and in randomised order all subjects received aspirin 75 mg, warfarin, or aspirin 75 mg combined with warfarin. Each treatment was given for 12 days or (when warfarin was used) for longer if necessary until the international normalised ratio of the prothrombin time was stable at 1.4-1.6.. Loss of blood over 10 minutes into gastric washings.. Bleeding over 10 minutes into gastric washings under baseline conditions and after five days, and at end of each regimen of treatment. Aspirin 75 mg increased bleeding from 0.60 (95% confidence interval 0.36 to 0.99) microliters/10 minutes to 1.26 (0.71 to 2.25) microliters/10 minutes at five days, with no evidence of either progressive change or adaptation thereafter. Warfarin had no effect on bleeding either alone or when combined with aspirin.. Aspirin 75 mg causes gastric mucosal bleeding. Low dose warfarin neither induces gastric mucosal bleeding nor enhances that caused by aspirin.

Topics: Adult; Aspirin; Cohort Studies; Drug Synergism; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Male; Random Allocation; Warfarin

Topics: Aged; Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Male; Multiple Myeloma; Warfarin

While overall gastrointestinal bleeding (GIB) rates have been extensively compared between warfarin and direct oral anticoagulants (DOACs), it is still unclear whether upper and lower GIB rates differ between these types of drugs. This study aimed to compare upper and lower GIB rates between warfarin and DOACs in a nationwide cohort.. Data on all patients in Iceland who received a prescription for oral anticoagulation from 2014 to 2019 were collected and their personal identification numbers linked to the electronic medical record system of the National University Hospital of Iceland and the 4 regional hospitals in Iceland. Inverse probability weighting was used to yield balanced study groups and rates of overall, major, upper, and lower GIB were compared using Cox regression. All GIB events were manually confirmed by chart review.. Warfarin was associated with higher rates of upper GIB (1.7 events per 100 person-years vs 0.8 events per 100 person-years; hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.26-3.59) but similar rates of lower GIB compared with DOACs. Specifically, warfarin was associated with higher rates of upper GIB compared with apixaban (HR, 2.63; 95% CI, 1.35-5.13), dabigatran (5.47; 95% CI, 1.87-16.05), and rivaroxaban (HR, 1.74; 95% CI, 1.00-3.05). Warfarin was associated with higher rates of major GIB compared with apixaban (2.3 events per 100 person-years vs 1.5 events per 100 person-years; HR, 1.79; 95% CI, 1.06-3.05), but otherwise overall and major GIB rates were similar in warfarin and DOAC users.. Warfarin was associated with higher rates of upper but not overall or lower GIB compared with DOACs. Warfarin was associated with higher rates of major GIB compared with apixaban.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Gastrointestinal Hemorrhage; Humans; Retrospective Studies; Stroke; Warfarin

Direct oral anticoagulants (DOACs) used in nonvalvular atrial fibrillation (NVAF) are dose-reduced in elderly and patients with impaired renal function. Only reduced dose dabigatran is concluded as having similar stroke risk reduction and lower risk of major bleeding than warfarin in the pivotal studies. In clinical practice, reduced dose is prescribed more often than expected making this an important issue. The objective of this study was to compare effectiveness and safety between reduced dose DOACs and high TTR warfarin treatment (TTR ≥ 70%) in NVAF. A Swedish anticoagulation registry was used in identifying eligible patients from July 2011 to December 2017. The study cohort consisted of 40,564 patients with newly initiated DOAC (apixaban, dabigatran, or rivaroxaban) (11,083 patients) or warfarin treatment (29,481 patients) after exclusion of 374,135 patients due to not being warfarin or DOAC naïve, not being prescribed reduced dose, having previous mechanical heart valve (MHV), or being under 18 years old. The median durations of follow up were 365, 419, 432 and 473 days for apixaban, dabigatran, rivaroxaban and warfarin, respectively. Warfarin TTR identified from Auricula was 70.0%. Endpoints (stroke and major bleeding) and baseline characteristics were collected from hospital administrative registers using ICD-10 codes. Cohorts were compared using weighted adjusted Cox regression after full optimal matching based on propensity scores. DOACs are associated with lower risk of major bleeding (HR with 95% CI) 0.85 (0.78-0.93), intracranial bleeding HR 0.64 (0.51-0.80), hemorrhagic stroke HR 0.68 (0.50-0.92), gastrointestinal bleeding HR 0.81 (0.69-0.96) and all-cause stroke HR 0.87 (0.76-0.99), than warfarin. Apixaban and dabigatran are associated with lower risk of major bleeding, HR 0.70 (0.63-0.78) and HR 0.80 (0.69-0.94), and rivaroxaban is associated with lower risk of ischemic stroke, HR 0.73 (0.59-0.96), with higher major bleeding risk, HR 1.31 (1.15-1.48), compared to warfarin. Apixaban is associated with higher all-cause mortality compared to warfarin, HR 1.12 (1.03-1.21). DOACs are associated with lower risk of major bleeding and all-cause stroke, than high quality warfarin treatment, with exception of rivaroxaban that carried higher risk of major bleeding and lower risk of stroke or systemic embolism. In this large observational registry-based NVAF cohort, DOACs are preferred treatment in patients with indication for DOAC dose reduction, even

Topics: Administration, Oral; Adolescent; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Pyridones; Rivaroxaban; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Renal Dialysis; Risk Factors; Warfarin

The guide for the use of genotype-guided warfarin dosing in patients for the treatment of non-valvular atrial fibrillation (AF) is still lacking.. We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients.. Our study consisted of 508 newly recruited and 471 existing Chinese AF patients. Among the total 979 patients, 585 patients received their dose of warfarin determined by a genetic and clinical factor (gene group), while the remaining 394 patients whose dosing was determined empirically in control group. We incorporated CYP2C9 and VKORC1 genotypes into the gene group. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcomes were the percentage of time in the therapeutic range (%TTR) and INR during 12-month follow-up. Secondary safety outcome included bleeding and thrombotic events.. Compared with the control group, the average TTR of the gene group was higher [68.4 ± 20.6% vs 48.5 ± 21.6%, P < 0.001]. The average INR monitoring times to reach the therapeutic time in the gene group was lower (P < 0.001). The risk ratios (RR) for cumulative incidence of total bleeding events, minor bleeding events, gastrointestinal bleeding, and intracerebral bleeding events were not significantly different between the two groups (P > 0.05). Comparing to the analysis using existing 471 patients, the analysis using total 979 patients showed that the gene group experienced a lower (RR 0.4 (95% CI 0.2 to 0.8), P = 0.008) incidence of cumulative ischemic stroke.. Genotype-guided warfarin administration increases the average TTR, reaches higher TTR levels in the early anticoagulant phase, and significantly reduces the risk of ischemic stroke events.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Cytochrome P-450 CYP2C9; East Asian People; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Ischemic Stroke; Pharmacogenetics; Treatment Outcome; Vitamin K Epoxide Reductases; Warfarin

Background Patients with aortic stenosis (AS) have been underrepresented in the trials evaluating direct oral anticoagulants (DOACs) in atrial fibrillation (AF). We aimed to assess whether AS impacts outcomes in patients with AF and estimate the effects of DOACs versus warfarin in patients with AF and AS. Methods and Results The registry-based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covered all patients with AF diagnosed during 2007 to 2018 in Finland. Hazard ratios (HRs) of first-ever gastrointestinal bleeding, intracranial bleeding, any bleeding, ischemic stroke, and death were estimated with cause-specific hazards regression adjusted for anticoagulant exposure variables. We identified 183 946 patients (50.5% women; mean age, 71.7 [SD, 13.5] years) with incident AF without prior bleeding or ischemic stroke, of whom 5231 (2.8%) had AS. The crude incidence rate of all outcomes was higher in patients with AS than in patients without AS. After propensity score matching, AS was associated with the hazard of any bleeding, gastrointestinal bleeding, and death but not with intracranial bleeding or ischemic stroke (adjusted HRs, 1.36 [95% CI, 1.25-1.48], 1.63 [95% CI, 1.43-1.86], 1.32 [95% CI, 1.26-1.38], 0.96 [95% CI, 0.78-1.17], and 1.11 [95% CI, 0.99-1.25], respectively). Among patients with AS, DOACs were associated with a lower risk of ischemic stroke when compared with warfarin, while bleeding and mortality did not differ between DOACs and warfarin. Conclusions AS is associated with substantially higher risk of gastrointestinal bleeding in patients with AF. DOACs may be more effective in preventing ischemic stroke than warfarin in patients with AF and AS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Stroke; Male; Stroke; Warfarin

Direct oral anticoagulants (DOACs) are increasingly used in renal transplant recipients (RTR), but relatively understudied in this population. We assess the safety of post-transplant anticoagulation with DOACs compared to warfarin.. We conducted a retrospective study of RTRs at the Mayo Clinic sites (2011-present) that were anticoagulated for greater than 3 months excluding the 1st month post-transplant. The main safety outcomes were bleeding and all-cause mortality. Concomitant antiplatelet and interacting drugs were noted. DOAC dose adjustment was assessed according to common US prescribing practices, guidelines, and/or FDA labeling.. The median follow-up was longer for RTRs on warfarin (1098 days [IQR 521, 1517]) than DOACs (449 days [IQR 338, 942]). Largely, there were no differences in baseline characteristics and comorbidities between RTRs on DOACs (n = 208; apixaban 91.3%, rivaroxaban 8.7%) versus warfarin (n = 320). There was no difference in post-transplant use of antiplatelets, immunosuppressants, most antifungals assessed, or amiodarone. There was no significant difference in incident major bleeding (8.4 vs. 5.3%, p = 0.89), GI bleeding (4.4% vs. 1.9%, p = 0.98), or intra-cranial hemorrhage (1.9% vs. 1.4%, p = 0.85) between warfarin and DOAC. There was no significant difference in mortality in the warfarin group compared to DOACs when adjusted for follow-up time (22.2% vs. 10.1%, p = 0.21). Rates of post-transplant venous thromboembolism, atrial fibrillation or stroke were similar between the two groups. 32% (n = 67) of patients on DOACs were dose reduced, where 51% of those reductions were warranted. 7% of patients that were not dose reduced should have been.. DOACs did not have inferior bleeding or mortality outcomes compared to warfarin in RTRs. There was greater use of warfarin compared to DOACs and a high rate of improper DOAC dose reduction.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Kidney Transplantation; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

To investigate risks of hospitalization for upper gastrointestinal bleeding (UGIB) in H. pylori-eradicated patients newly started on warfarin or direct oral anti-coagulants (DOACs).. We identified all patients who had previously received H. pylori eradication therapy or were found to have no H. pylori on endoscopy and were then newly started on warfarin or DOACs from a population-based electronic healthcare database. Primary analysis was the risk of UGIB between warfarin and DOACs users in H. pylori-eradicated patients. Secondary analysis included the UGIB risk between H. pylori-eradicated and H. pylori-negative patients who were newly started on warfarin or DOACs. The hazard ratio (HR) of UGIB was approximated by pooled logistic regression model incorporating the inverse propensity of treatment weightings with time-varying covariables.. Among H. pylori-eradicated patients, DOACs had a significantly lower risk of UGIB (HR: 0.26, 95% CI 0.09-0.71) compared with warfarin. In particular, lower UGIB risks with DOACs were observed among older (≥65 years) patients, female, those without a history of UGIB or peptic ulcer, or ischemic heart disease, and non-users of acid-suppressive agents or aspirin. Secondary analysis showed no significant difference in UGIB risk between H. pylori-eradicated and H. pylori-negative patients newly started on warfarin (HR: 0.63,95% CI 0.33-1.19) or DOACs (HR: 1.37, 95% CI 0.45-4.22).. In H. pylori-eradicated patients, new users of DOACs had a significantly lower risk of UGIB than new warfarin users. Furthermore, the risk of UGIB in new warfarin or DOACs users was comparable between H. pylori-eradicated and H. pylori-negative patients.

Topics: Administration, Oral; Anticoagulants; Cohort Studies; Female; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Hospitalization; Humans; Retrospective Studies; Warfarin

This study aimed to analyze the factors influencing warfarin-related major gastrointestinal bleeding (GIB) and to develop a score that would provide a reference for assessing the risk of major GIB associated with warfarin treatment.. This was a retrospective analysis of clinical and follow-up data from warfarin-treated patients. Scores were analyzed using logistic regression. The area under the subject working characteristic curve (AUC), sensitivity, specificity, and Hosmer-Lemeshow test were used to evaluate the scoring performance.. A total of 1591 patients who met the requirements for warfarin use were included in this study, and 46 developed major GIB. After univariate analysis as well as multivariate logistic regression analysis, nine factors were found to be associated with increased risk of major GIB, namely age ≥ 65 years, history of peptic ulcer, history of major bleeding, abnormal liver function, abnormal renal function, cancer, anemia, labile international normalized ratio, and combination of antiplatelet agents/non-steroidal anti-inflammatory drugs. The Alfalfa-Warfarin-GIB score was constructed using these nine factors. The AUC and Bootstrap method-corrected AUC of the Alfalfa-Warfarin-GIB score were 0.916 (95% CI: 0.862-0.970, P < 0.001) and 0.919 (95% CI: 0.860-0.967, P < 0.001), respectively, which were higher than those of the HAS-BLED score (AUC = 0.868, 95% CI: 0.812-0.924, P < 0.001).. Based on nine risk factors, the Alfalfa-Warfarin-GIB score was constructed to predict the risk of warfarin-related major GIB. The newly developed Alfalfa-Warfarin-GIB score has a better predictive value than the HAS-BLED score and may be an effective tool to help reduce the occurrence of major GIB in patients on warfarin.

Topics: Aged; Anticoagulants; Gastrointestinal Hemorrhage; Humans; Medicago sativa; Retrospective Studies; Risk Factors; Warfarin

To investigate the efficacy and safety outcomes of warfarin and direct oral anticoagulants in Asian octogenarians. A retrospective study was undertaken in 270 patients aged 80 years old and above, between 15 July 2015 and 21 December 2017, prescribed oral anticoagulation (OAC) with warfarin or direct oral anticoagulant (DOAC). Data collection included demographics, bleeding events, cessation of anticoagulation, mortality and hospital utilization up to 2 years post prescription. Thrombotic and embolic events within 30 days of anticoagulation cessation were reviewed. Data was analysed according to initial prescription of either warfarin or DOAC. There were 134 patients on warfarin and 136 patients on DOAC, of which majority of them were on anticoagulation for atrial fibrillation. In the warfarin group, there was a higher rate of minor bleeding events leading to permanent cessation (12.7 vs. 2.9%, P  = 0.035) compared with DOAC. Mortality rate at 2 years was higher in the warfarin group than DOAC (40.3 vs. 28.7%, P  = 0.044). There was no difference in major bleeding events, risk of gastrointestinal bleed or ICH between the two groups. There was no difference in rate of thrombotic and embolic events after cessation of anticoagulation and hospital utilization over 2 years was similar in both groups. In Asian octogenarians on anticoagulation, DOAC appears to have benefit over warfarin in terms of minor bleeding risk and mortality.

Topics: Administration, Oral; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Gastrointestinal Hemorrhage; Humans; Octogenarians; Retrospective Studies; Stroke; Warfarin

Evidence for direct oral anticoagulants (DOACs) in patients with cirrhosis is limited. Few patients with Child-Turcotte-Pugh (CTP) class B and C cirrhosis have been studied.. To compare major bleeding rates in patients with cirrhosis receiving a DOAC versus warfarin.. A retrospective cohort study was conducted in adults with cirrhosis receiving a DOAC versus warfarin for venous thromboembolism, portal-vein thrombosis, or atrial fibrillation. The primary outcome was the rate of major bleeding. Secondary outcomes included time to major bleeding, clinically relevant nonmajor bleeding, all bleeding, gastrointestinal bleeding, intracranial bleeding, and new thromboembolic events. The study was approved by the Ochsner Health System Institutional Review Board.. A total of 44 patients receiving a DOAC and 41 patients receiving warfarin were included. Major bleeding occurred in 4 patients receiving a DOAC and 6 patients receiving warfarin (9.1% vs 14.6%;. Treatment with DOACs in patients with cirrhosis was associated with a similar rate of major bleeding compared with warfarin. Inclusion of CTP class C patients in future studies remains valuable to evaluate safety and efficacy of DOACs in this population.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Retrospective Studies; Thrombosis; Venous Thromboembolism; Warfarin

Direct oral anticoagulants such as dabigatran are the preferred anticoagulant in treating atrial fibrillation (AF) patients due to their effectiveness and safety. Whether this applies to severely obese patients needs to be determined.. To compare the effectiveness and safety of dabigatran with warfarin among AF patients with severe obesity.. Retrospective cohort study.. Not applicable.. Primary effectiveness outcome was composite thromboembolism including transient ischemic attack, ischemic stroke, or systemic embolism. Primary safety outcome was composite bleeding including gastrointestinal bleeding, intracranial bleeding, or other bleeding. Secondary outcomes included the individual outcomes and all-cause mortality. Propensity score matching (PSM) was performed to create a 1:1 matched cohort and Cox proportional hazards model was used to estimate the hazard ratio (HR) of each outcome for dabigatran users compared to warfarin users.. A total of 6848 patients receiving either dabigatran or warfarin were identified. In a 1:1 matched cohort, dabigatran users had a HR of 0.71 (95% confidence interval (CI): 0.56-0.91) for composite thromboembolism, a HR of 1.24 (95%CI: 1.07-1.42) for composite bleeding, and a HR of 0.57 (95% CI: 0.45-0.71) for all-cause mortality when compared to warfarin users.. Among AF patients with a BMI >40kg/m

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Gastrointestinal Hemorrhage; Humans; Obesity, Morbid; Retrospective Studies; Stroke; Thromboembolism; Treatment Outcome; Warfarin

Hypertrophic cardiomyopathy (HCM) patients with nonvalvular atrial fibrillation (AF) have an increased risk of suffering thromboembolic events. Vitamin K antagonists (VKA) are recommended as therapy but there is still limited data regarding the efficacy of prescribing non-vitamin K antagonist oral anticoagulants (NOACs). This retrospective study investigates the effectiveness and safety of NOAC administration in patients with HCM and AF. A total of 124 patients with HCM and AF on an oral anticoagulant therapy were recruited between January 2015 and December 2019; these patients were followed up until March 31, 2020. Kaplan-Meier analysis was used to compare the clinical outcomes in patients treated with NOACs versus warfarin. The Cox model was used to estimate the risk of clinically relevant bleeding. Our study included 124 patients, of which 48 (38.7%) received warfarin and 76 (61.3%) received NOACs. Survival analysis showed the patients undergoing NOACs had a lower risk of clinically relevant bleeding (log-rank P = 0.039) over a period of 53.6 months. The median time in therapeutic range (TTR) score was 50% (interquartile range: 40.43 to 57.08%). A total of nine patients (18.75%) had a good TTR with a median score of 66.35% (interquartile range: 64.58 to 77.75%). The incidence of death by all causes, cardiovascular death and thromboembolism were similar between NOAC and warfarin-treated patients (log-rank P = 0.239, log-rank P = 0.386, and log-rank P = 0.257, respectively). Patients treated with NOACs showed a significant reduction in the risk of clinical (P = 0.011) and gastrointestinal bleeding (P = 0.032). Cox multiple regression analysis showed age (HR 1.13, 95% CI 1.03-1.24; P = 0.013) and warfarin therapy (HR 7.37, 95% CI 1.63-33.36; P = 0.010) were independent predictors of clinically relevant bleeding. Compared to warfarin, NOACs were associated with a lower incidence of clinically relevant bleeding in HCM patients with AF, as demonstrated by the similar incidence of death by all causes, cardiovascular death and thromboembolic events.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Retrospective Studies; Stroke; Thromboembolism; Warfarin

Data on the use of activated prothrombin complex concentrate (aPCC) for the management of warfarin associated major bleeding is sparse. The objective of the study was to assess the achievement of effective clinical hemostasis using aPCC in patients presenting with major bleeding while on warfarin. We also assessed the safety of the drug. This retrospective study was conducted at a tertiary care teaching center in the USA where patients with major bleeding while receiving warfarin, and received aPCC were included. Efficacy of aPCC in achieving effective hemostasis was assessed according to the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria. Efficacy was also assessed by achieving INR < 1.5 after treatment. The primary safety endpoint was the occurrence of any thromboembolic complications. A total of 67 patients were included in the study. The most common site for bleeding was intracerebral hemorrhage (n = 37, 55.2%), followed by gastrointestinal bleed (n = 26, 38.8%). Clinical hemostasis was achieved in 46 (68.7%) patients and of the 21 (31.3%) patients who did not achieve clinical hemostasis, 16 died. Thirty nine (58.2%) patients achieved INR < 1.5. Five (7.5%) patients developed thromboembolic complications. This study suggests that the use of aPCCs is effective in achieving effective hemostasis in patients on warfarin presenting with major bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Cerebral Hemorrhage; Coagulants; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Carbazochrome sodium sulfonate (CSS) is conventionally administered to prevent post-endoscopic submucosal dissection (ESD) bleeding in many institutions, but research on its preventive efficacy is lacking. Therefore, we investigated the risk of post-ESD bleeding and the preventive efficacy of CSS administration.. We retrospectively reviewed 304 lesions in 259 patients with gastric neoplasms who underwent ESD at Asahikawa Medical University Hospital from 2014 to 2021. In the CSS group, CSS 100 mg/day was intravenously infused with maintenance fluid replacement on postoperative days 0-2. The risk factors of post-ESD bleeding, including CSS administration, were investigated.. The overall rate of post-ESD bleeding was 4.6% (14/304). The univariate analysis showed that atrial fibrillation (Af), warfarin intake, heparin replacement, and tumor location in the lower third were significant risk factors for increasing the likelihood of postoperative bleeding. In the multivariate analysis, Af (odds ratio [OR] 3.83, 95% CI 1.02-14.30; p < 0.05), heparin replacement (OR 4.60, 95% CI 1.02-20.70; p < 0.05), and tumor location in the lower third of the stomach (OR 6.67, 95% CI 1.43-31.00; p < 0.05) were independent factors for post-ESD bleeding. Post-ESD bleeding was observed in 5.2% (9/174) of the CSS group and 3.8% (5/130) of the non-CSS group, with no significant difference between the two groups (p = 0.783). Additionally, CSS was not shown to have preventive effects in groups with higher-risk factors, such as Af diagnosis, warfarin use, heparin replacement, and tumor location in the lower third of the stomach.. CSS administration was not effective for the prevention of the post-ESD bleeding in the overall patient population as well as in higher-risk patients. This suggests that the administration of CSS for post-ESD bleeding prevention may need to be reconsidered.

Topics: Adrenochrome; Endoscopic Mucosal Resection; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Heparin; Humans; Postoperative Hemorrhage; Retrospective Studies; Risk Factors; Stomach Neoplasms; Warfarin

Direct oral anticoagulants (DOACs) have been used for both primary and secondary prevention of cerebral infarction in older patients with atrial fibrillation (AF). However, whether DOACs are more effective and safer than warfarin for secondary prevention of cerebral infarction in older patients with AF remains unclear.. Using the Japanese Diagnosis Procedure Combination database, we identified patients with AF who were hospitalized for cerebral infarction from January 1, 2015 to March 31, 2019 and were aged ≥75 years at admission. We performed propensity score-stabilized inverse probability of treatment weighting analyses to balance measured confounders between patients with AF receiving DOACs and those receiving warfarin after discharge. The primary outcomes were 365-day readmission for (a) benefit: cerebral infarction or (b) harm: bleeding events after discharge. The secondary outcomes were 365-day readmission for intracranial bleeding or gastrointestinal bleeding after discharge as well as all-cause death during readmission. Using a Fine-Gray model, we compared the subdistribution hazard ratios (SHRs) of readmission between the DOAC group and warfarin group.. We identified 101,389 eligible patients, including 80,726 patients receiving DOACs and 20,663 patients receiving warfarin. After the propensity score-stabilized inverse probability of treatment weighting, the adjusted SHRs of readmission (95% confidence interval [CI]) for cerebral infarction, bleeding events, and intracranial bleeding in the DOAC group as compared with the warfarin group were 0.76 (0.71-0.81), 0.78 (0.68-0.90), and 0.69 (0.57-0.82), respectively. There was no significant difference in readmission for gastrointestinal bleeding (SHR, 1.01; 95% CI, 0.72-1.41) between the DOAC and warfarin groups.. In this retrospective nationwide study, DOACs were more effective and safer than warfarin for preventing reinfarction and bleeding events in patients with AF aged ≥75 years who have a history of cerebral infarction.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cerebral Infarction; Gastrointestinal Hemorrhage; Humans; Retrospective Studies; Secondary Prevention; Stroke; Warfarin

Both suburothelial hemorrhage and intestinal mural hemorrhage are very rare causes of abdominal pain and gross hematuria. Com-puted tomography (CT) is very valuable in both diagnoses. We present left suburothelial hemorrhage and intestinal mural hemorrhage with CT findings, in a case of Coumadin use for mitral valve replacement.

Topics: Gastrointestinal Hemorrhage; Humans; Tomography, X-Ray Computed; Warfarin

Topics: Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestine, Small; Warfarin

Whether antithrombotic drugs increase the risk of post-esophageal endoscopic resection bleeding is unknown. This study examined the effect of antithrombotic drugs, aspirin, thienopyridine, direct oral anticoagulants (DOAC), and warfarin, on post-esophageal endoscopic resection bleeding.. We enrolled 957 patients (1202 esophageal tumors) treated with endoscopic resection and classified them based on antithrombotic drug use as no use, aspirin, thienopyridine, DOAC, and warfarin. Patients using antiplatelet drugs (i.e. aspirin and thienopyridine) were further sub-classified based on their continued or discontinued use before endoscopic resection. The bleeding rates were compared between these groups to assess the effects of antithrombotic drug use and interruption of antiplatelet therapy on post-esophageal endoscopic resection bleeding.. The post-endoscopic resection bleeding rate was 0.3% (95% CI, 0.1-1) in the group without antithrombotic drug use, 4.5% (95% CI, 0.1-23) in the aspirin-continued group, 2.9% (95% CI, 0.1-15) in the aspirin-discontinued group, 0% (95% CI, 0-78) in the replaced thienopyridine with aspirin group, 0% (95% CI, 0-26) in the thienopyridine-discontinued group, 13% (95% CI, 1.6-38) in the DOAC group, and 0% (95% CI, 0-45) in the warfarin group. The post-endoscopic resection bleeding rate in the DOAC group was significantly higher than that in the group without antithrombotic drugs (P = 0.003). The post-endoscopic resection bleeding rates did not differ between the other groups.. Our results suggest that discontinuing aspirin is not necessary for esophageal endoscopic resection while we must be careful regarding DOAC.

Topics: Anticoagulants; Aspirin; Endoscopic Mucosal Resection; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Retrospective Studies; Risk Factors; Thienopyridines; Warfarin

Patients with end-stage kidney disease (ESKD) are at significantly increased risk for both thrombosis and bleeding relative to those with normal renal function. The optimal therapy of venous thromboembolism (VTE) in patients with ESKD is unknown.. To compare the safety and effectiveness of apixaban relative to warfarin in patients with ESKD and acute VTE.. New-user, active-comparator retrospective United States population-based cohort with inverse probability of treatment weighting, using the United States Renal Data System data from 2014 to 2018. We included adults with ESKD on hemodialysis or peritoneal dialysis who were newly initiated on apixaban or warfarin for an acute VTE.. The coprimary outcomes were major bleeding, recurrent VTE, and all-cause mortality within 6 months of anticoagulant initiation. Secondary outcomes were intracranial hemorrhage and gastrointestinal bleeding. The primary analyses were based on intent-to-treat defined by the first drug received and accounted for competing risks of death. Sensitivity analyses included varied follow-up time, as-treated analyses, and dose-specific apixaban subgroups.. The apixaban and warfarin cohorts included 2302 and 9263 patients, respectively. Apixaban was associated with a lower risk of major bleeding (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.70-0.94), intracranial bleeding (HR 0.69, 95% CI 0.48-0.98), and gastrointestinal bleeding (HR 0.82, 95% CI 0.69-0.96). Recurrent VTE and all-cause mortality were not significantly different between the groups.. Apixaban was associated with a lower risk of bleeding relative to warfarin when used to treat acute VTE in patients with ESKD on dialysis.

Topics: Adult; Anticoagulants; Cohort Studies; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Retrospective Studies; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

Although warfarin is the most effective treatment approved to prevent atrial fibrillation-associated stroke, it remains underused in clinical practice due to patient noncompliance. Therefore, novel oral anticoagulants (NOACs) have been developed.. This study aimed to identify bleeding complications in patients who were taking oral anticoagulants and compare the rates of major and minor bleeding events between NOACs and warfarin groups.. We conducted a retrospective, observational study of warfarin- and NOAC-treated patients who presented to an emergency department between January 2015 and December 2019 with bleeding events. We compared patients with major and minor bleeding in terms of age, gender, comorbid diseases, type of anticoagulant, and site of bleeding.. An electronic search yielded 95 (21.9%) cases of patients taking a NOAC (i.e., dabigatran [19], rivaroxaban [45], apixaban [29], or edoxaban [6]) and 354 taking warfarin. There were no significant differences between the warfarin and NOACs groups in the frequency of minor bleeding complications. Similarly, there were no significant differences between the groups in the frequency of major bleeding complications. No significant difference in intracranial bleeding was seen between the NOACs- and warfarin-treated patients, although the incidence of gastrointestinal bleeding was significantly higher in the NOACs (P = 0.102 and P = 0.021, respectively).. Our findings indicate that rates of major and minor bleeding complications in patients taking NOACs are similar to those in patients taking warfarin. While warfarin was associated with fewer complications than NOACs in terms of gastrointestinal bleeding, the risk of intracranial bleeding, was similar between the groups.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Emergency Service, Hospital; Gastrointestinal Hemorrhage; Humans; Retrospective Studies; Stroke; Warfarin

Performing percutaneous renal biopsy procedures in lupus nephritis (LN) and nephrotic syndrome presents a unique challenge to the nephrologist because of the risk of bleeding from the procedure and the hypercoagulable state in hypoalbuminemia. The management of a patient with venous thrombosis with perinephric hematoma post renal biopsy can be difficult if occurred.. We are presenting a case of perinephric hematoma following percutaneous renal biopsy in a 23-year-old man with lupus nephritis, nephrotic syndrome, and lower limbs deep vein thrombosis (DVT). The patient developed persistent frank haematuria, flank pain and acute urinary retention post-procedure. We have withheld his oral warfarin three days before the procedure, and no anticoagulation was given subsequently. Initial CT Angiography (CTA) renal showing stable hematoma and no visible evidence of vascular injury. Three weeks later, the patient still has persistent frank haematuria and a repeated CTA renal revealed new bilateral renal vein thrombosis. Considering the high risk of worsening symptomatic venous thrombosis, we gave subcutaneous enoxaparin sodium and restart oral warfarin despite ongoing haematuria. The frank haematuria resolved within two days of anticoagulation with no radiological evidence of worsening of the perinephric hematoma. The follow-up ultrasonography a month later showed resolution of the hematoma and renal vein thrombosis with no adverse effect.. Our experience, in this case, highlighted the importance of case selection for percutaneous renal biopsy among high-risk patients. Additionally, a prolonged frank haematuria in post-renal biopsy with nephrotic syndrome warranted a reassessment, as a clinical presentation of post-procedure perinephric hematoma and renal vein thrombosis can overlap. We also demonstrated that restarting anticoagulation earlier than four weeks in a patient with renal vein thrombosis and post-renal biopsy perinephric hematoma can be safe in the selective case.

Topics: Adult; Biopsy; Enoxaparin; Gastrointestinal Hemorrhage; Hematoma; Hematuria; Humans; Kidney Diseases; Lupus Nephritis; Male; Nephrotic Syndrome; Renal Veins; Ureteral Diseases; Venous Thrombosis; Warfarin; Young Adult

Spontaneous intramural small-bowel hematoma (SISBH) is a rare complication of anticoagulation therapy. Presentation of SISBH can vary from mild abdominal pain to an acute abdomen.. A 70-year-old woman was brought to the emergency department because of severe abdominal pain for 1 day. She had a medical history of coronary artery disease and paroxysmal atrial fibrillation and was receiving anticoagulation therapy with warfarin for 3 years.. Computed tomography disclosed disproportional dilatation of the segmental small bowel and near-total obstruction of the intestinal lumen at the level of the jejunum, indicating an acute abdomen.. We performed laparoscopic exploration and found a segmental distal jejunum was tense, heavy, firm, and discolored with a blue hue. Histopathological examination of the resected jejunum revealed diffuse hemorrhage and necrosis at the mucosa and submucosal layers, indicating SISBH.. The patient had an uneventful recovery and was discharged in a relatively stable condition.. Warfarin-induced SISBH presenting as an acute abdomen is an emergency condition that needs early diagnosis and timely management. Surgical intervention may be indicated for intestinal obstruction, ischemia, perforation, peritonitis, and intra-abdominal hemorrhage.

Topics: Abdomen, Acute; Abdominal Pain; Aged; Anticoagulants; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Warfarin

To evaluate the comparison of direct-acting oral anticoagulants (DOACs) and warfarin for their effects on major bleeding and hospital outcomes in patients with acute nonvariceal upper gastrointestinal bleeding (NVUGIB).. An observational study.. Tekirdag Namik Kemal University Hospital, Hitit University Erol Olçok Education and Research Hospital, between January and December 2021.. Adult patients prescribed warfarin and DOACs were followed up for one year. Their length of hospital stay, need for intensive care unit admission, need for red blood cell transfusion, and major bleeding rates were compared.. Thirty-two patients (61.5%) were user of DOACs (DOAC group), and 20 patients (38.5%) were users of warfarin (warfarin group). No statistically significant difference was determined between patients in warfarin group and DOAC group for the number of packed red blood cells transfused [median 3 (0-6) units, 3 (0-10) units, p=0.229, respectively], length of hospital stay [median 5 days (3-10), and 4.5 days (2-20), p=0.739, respectively], rate of intensive care unit admission [(n=9, 45%; and n=10 (31%), p=0.623, respectively] and the occurrence of major bleeding events (warfarin-70%; DOACs-78%; p=0.529).. Major bleeding episodes and hospital outcomes of acute NVUGIB were similar between patients receiving warfarin and DOACs.. Direct-acting oral anticoagulants, Warfarin, Gastrointestinal bleeding, Outcome, Mortality.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hospitals; Humans; Retrospective Studies; Warfarin

Limited data exist on the management of anticoagulation after hospitalization for gastrointestinal bleeding (GIB) and the risks of recurrent GIB and thromboembolism in patients who are prescribed warfarin vs direct oral anticoagulants (DOACs). The purpose of this study was to assess the risk of recurrent GIB and thromboembolism with resumption of anticoagulation after GIB.. This was a retrospective analysis of adults with atrial fibrillation prescribed warfarin or DOACs and subsequently hospitalized for GIB. We used claims data from IBM MarketScan Databases from January 2008 through December 2017. Multivariable time-varying regression was used to determine the risks of recurrent GIB and thromboembolism within 6 months of the index hospitalization.. There were 2991 patients hospitalized for GIB on anticoagulants (warfarin, n = 1872; rivaroxaban, n = 676; dabigatran, n = 293; and apixaban, n = 250). Of warfarin users, 46% (n = 869) resumed warfarin after discharge compared with 43% (n = 483) of DOAC users who resumed DOACs. In the regression analysis modeling time-varying coefficients for anticoagulant use, warfarin resumption was associated with an increased risk of recurrent GIB (hazard ratio [HR], 2.12; 95% CI, 1.43-3.14; P = .0002) compared with no anticoagulant resumption, whereas there was no association with DOAC resumption and recurrent bleeding (HR, 1.43; 95% CI, 0.81-2.52; P = .22). Rivaroxaban was the only individual DOAC that was associated with recurrent GIB (HR, 2.73; 95% CI, 1.43-5.20; P = .002). Both warfarin (HR, 0.61; 95% CI, 0.39-0.96; P = .033) and DOAC (HR, 0.52; 95% CI, 0.28-0.98; P = .044) resumption as a class was associated with a decreased risk of thromboembolism.. Either warfarin or DOAC resumption after hospitalization for GIB was associated with a decreased risk of thromboembolism, whereas warfarin and rivaroxaban resumption were associated with an increased risk of recurrent GIB.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Gastrointestinal Hemorrhage; Humans; Retrospective Studies; Warfarin

There were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort.. We performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020. Patients who received an oral anticoagulant and had undergone colonoscopy with polypectomy were identified. Propensity-score models with inverse probability of treatment weighting were developed for the warfarin-DOAC and between-DOAC comparisons. The primary outcome was clinically significant delayed PPB, defined as repeat colonoscopy requiring haemostasis within 30 days. The secondary outcomes were 30-day blood transfusion requirement and new thromboembolic event.. Apixaban was associated with lower PPB risk than warfarin (adjusted HR (aHR) 0.39, 95% CI 0.24 to 0.63, p<0.001). Dabigatran (aHR 2.23, 95% CI 1.04 to 4.77, adjusted p (ap)=0.035) and rivaroxaban (aHR 2.72, 95% CI 1.35 to 5.48, ap=0.002) were associated with higher PPB risk than apixaban. In subgroup analysis, apixaban was associated with lower PPB risk in patients aged ≥70 years and patients with right-sided colonic polyps.For thromboembolic events, apixaban was associated with lower risk than warfarin (aHR 0.22, 95% CI 0.11 to 0.45, p<0.001). Dabigatran (aHR 2.60, 95% CI 1.06 to 6.41, ap=0.033) and rivaroxaban (aHR 2.96, 95% CI 1.19 to 7.37, ap =0.013) were associated with higher thromboembolic risk than apixaban.. Apixaban was associated with a significantly lower risk of PPB and thromboembolism than warfarin, dabigatran and rivaroxaban, particularly in older patients with right-sided polyps.

Topics: Aged; Anticoagulants; Blood Transfusion; Cohort Studies; Colonic Polyps; Colonoscopy; Dabigatran; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hong Kong; Humans; Male; Postoperative Complications; Pyrazoles; Pyridones; Retrospective Studies; Risk Assessment; Rivaroxaban; Thromboembolism; Warfarin

The risk of gastrointestinal bleeding (GIB) can be mitigated by proton pump inhibitor (PPI) co-therapy in patients with atrial fibrillation (AF) treated with anticoagulants. We aimed to evaluate the effect of PPIs on the risk of GIB in Asian patients with AF, treated with oral anticoagulants (OACs), and with a prior history of upper GIB.. Using a nationwide claims database, OAC-naïve patients with AF and a history of upper GIB before initiating OAC treatment between January 2010 and April 2018 were included. Patients were categorized into 10 groups according to the index OAC (warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban) and whether or not they received PPI co-therapy, and were followed up for incidence of major GIB.. Among a total of 42,048 patients, 40% were prescribed PPIs as co-therapy with OACs. Over a median 0.6 years (interquartile ranges 0.2-1.7 years) of follow-up, rivaroxaban use without PPIs showed the highest crude incidence of major GIB (2.62 per 100 person-years), followed by the use of warfarin without a PPI (2.20 per 100 person-years). Compared to the patients without PPI use, PPI co-therapy was associated with a significantly lower risk of major GIB, by 40% and 36%, in the rivaroxaban and warfarin groups, respectively. In dabigatran, apixaban, and edoxaban users, PPI co-therapy did not show a significant reduction in the risk of major GIB.. Among patients with AF receiving anticoagulant treatment and with a prior history of upper GIB, PPI co-therapy was associated with a significant reduction in the risk of major GIB in patients treated with rivaroxaban and warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Proton Pump Inhibitors; Rivaroxaban; Stroke; Upper Gastrointestinal Tract; Warfarin

Gastrointestinal bleeding is the most common bleeding complication during anticoagulant therapy. A reliable bleeding risk score can help the clinician assess risk of bleeding in individual patients and select the anticoagulant regimen. This study retrospectively analyzed the data of patients with atrial fibrillation who received anticoagulant therapy from July 2015 to December 2018 at two centers-the Fujian Medical University Union Hospital and Fuzhou Second Hospital Affiliated to Xiamen University. Demographic data, clinical findings, and laboratory results were collected from the hospital records. Patients were followed up for 6 months. The performance of four bleeding risk scores (New Score, RIETE Score, Cuschieri et al. Score, de Groot et al. Score) for prediction of gastrointestinal bleeding was assessed using the area under the curve. A total of 3462 patients (mean age, 66.3 ± 11.5 years; 59.6% males; 1055 direct oral anticoagulants users and 2407 warfarin users) were followed up for 6 months. While 99/3462 (2.9%) patients had gastrointestinal bleeding. The area under the curves for the New, RIETE, Cuschieri et al., de Groot et al. scores were 0.652 (95% CI 0.576-0.728), 0.862 (95% CI 0.809-0.914), 0.606 (95% CI 0.527-0.685), and 0.873 (95% CI 0.816-0.929), respectively. Among the four BRSs evaluated, the RIETE score and the de Groot et al. score appear to have the good predictive value, while the NEW score and the Cuschieri et al. score did not sufficiently predict gastrointestinal bleeding risk within the study Chinese population.

Topics: Aged; Anticoagulants; Atrial Fibrillation; China; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Warfarin

Topics: Aspirin; Blood Transfusion; Clopidogrel; Colonic Diseases; Colonoscopy; Combined Modality Therapy; Drug Therapy, Combination; Endoscopy, Digestive System; Equipment Design; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Hemostatic Techniques; Humans; Ileocecal Valve; Male; Middle Aged; Reoperation; Thrombosis; Warfarin

To evaluate comparative effectiveness and safety of non-vitamin-K antagonist oral anticoagulants (NOACs) versus warfarin in Medicare beneficiaries with non-valvular atrial fibrillation (NVAF) and comorbid diabetes mellitus (DM).. A retrospective cohort study using 2014-2016 5% national Medicare data was undertaken. NVAF patients with DM aged ≥65 years having at least one prescription for NOACs or warfarin between July 2014 and December 2015 were included in the study. Propensity score matching was used to balance demographic and baseline clinical characteristics of patients in two treatment groups. Cardiovascular outcomes including stroke/systemic embolism (SE) and myocardial infarction (MI) were evaluated to measure effectiveness. Assessment of safety outcomes included intracranial hemorrhage (ICH), major gastrointestinal bleeding (MGB), bleeding from other sites (OB) and all-cause mortality. Stratified Cox proportional hazards models were used to estimate hazard ratios for the outcomes in the matched cohort.. The matched sample consisted of 4582 patients (2291 pairs). Compared to warfarin, NOACs had a significantly lower risk of stroke/SE (hazard ratio (HR): 0.373, 95% confidence interval (CI): 0.247-0.564,. Oral anticoagulation therapy with NOACs was found to be more effective than warfarin therapy among older adults with NVAF and comorbid DM.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Gastrointestinal Hemorrhage; Humans; Medicare; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin

There is inadequate information on the risk of gastrointestinal (GI) bleeding in patients who are under rivaroxaban and warfarin therapy in Iran. Determining the risk of GI bleeding in patients receiving these two drugs can help to select a more appropriate anti-coagulation prophylaxis in high-risk patients.. The aim of this study was to compare the incidence of GI bleeding in patients with atrial fibrillation (AF) and concomitant bleeding risk factors receiving either warfarin or rivaroxaban.. In this observational study, 200 patients with AF and bleeding risk factors who referred to Imam Hossein Hospital (Tehran, Iran) were included. The patients were under treatment with either warfarin or rivaroxaban. The incidence of GI bleeding was compared between the two groups monthly for one year.. GI bleedings were observed in 61% and 34% of patients treated with warfarin and rivaroxaban, respectively (P = 0.001).Melena was the most common type of GI bleeding in both groups. History of hypertension, history of stroke, consumption of anti-platelet drugs, NSAID consumption, and history of alcohol consumption were associated with more frequent GI bleeding only in warfarin group.. The incidence of GI bleeding was lower in AF patients who received rivaroxaban compared to those treated with warfarin. Also, GI bleeding risk does not change according to the consumption of other anti-coagulant drugs and underlying history of hypertension or stroke in patients received rivaroxaban. Therefore, rivaroxaban is suggested as the choice of prophylaxisin patients with AF and concomitant coagulopathy.

Topics: Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Humans; Iran; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Limited data support the benefits of non-vitamin K oral anticoagulants (NOACs) among atrial fibrillation patients with prior gastrointestinal bleeding (GIB). We aimed to evaluate the effectiveness and safety of NOACs compared with those of warfarin among atrial fibrillation patients with prior GIB.. Oral anticoagulant-naive individuals with atrial fibrillation and prior GIB between January 2010 and April 2018 were identified from the Korean claims database. NOAC users were compared with warfarin users by balancing covariates using the inverse probability of treatment weighting method. The primary outcomes were ischemic stroke, major bleeding, and the composite outcome (combined ischemic stroke and major bleeding). Fatal events from each outcome were evaluated as secondary outcomes.. A total of 42 048 patients were included (24 781 in the NOAC group and 17 267 in the warfarin group). The mean time from prior GIB to the initiation of oral anticoagulant was 3.1±2.6 years. After inverse probability of treatment weighting, baseline characteristics were balanced between the two groups (mean age, 72 years; men, 56.8%; and mean CHA. NOACs were associated with lower risks of ischemic stroke and major bleeding than warfarin among atrial fibrillation patients with prior GIB.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Stroke; Male; Middle Aged; Retrospective Studies; Thromboembolism; Warfarin

The usage of direct oral anticoagulants (DOACs) to prevent and treat thromboembolic events is gradually increasing. We aimed to evaluate the outcomes of patients taking DOACs after polypectomy. We retrospectively reviewed 131 patients taking DOACs and 270 taking clopidogrel who underwent polypectomy between November 2010 and December 2017. The risk of delayed postpolypectomy bleeding (PPB) was evaluated and compared. A total of 989 polyps were removed (320 polyps in the DOAC and 669 polyps in the clopidogrel group). DOACs and clopidogrel were discontinued for 2.8 ± 1.7 days and 5.8 ± 2.5 days before polypectomy, respectively. DOACs and clopidogrel were restarted on 1.6 ± 2.9 days and 1.7 ± 1.1 days after polypectomy, respectively. According to per polyp analysis, delayed PPB rate was 1.6% in both groups (p = 0.924). Logistic regression analysis was performed after propensity score matching and revealed that DOACs did not increase the delayed PPB risk compared to clopidogrel (OR 0.929, 95% CI 0.436-1.975, p = 0.847). With the majority following the antithrombotic discontinuation guidelines, the incidence of delayed PPB was 3.1% in the patients taking DOACs. The delayed PPB risk was not greater in those taking DOACs than in those taking clopidogrel.

Topics: Administration, Oral; Aged; Anticoagulants; Clopidogrel; Colonic Polyps; Colonoscopy; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Thromboembolism; Ticlopidine; Warfarin

Real-world predictors of major bleeding (MB) have been well-studied among warfarin users, but not among all direct oral anticoagulant (DOAC) users diagnosed with atrial fibrillation (AF). Thus, our goal was to build a predictive model of MB for new users of all oral anticoagulants (OAC) with AF.. We identified patients hospitalized for any cause and discharged alive in the community from 2011 to 2017 with a primary or secondary diagnosis of AF in Quebec's RAMQ and Med-Echo administrative databases. Cohort entry occurred at the first OAC claim. Patients were categorized according to OAC type. Outcomes were incident MB, gastrointestinal bleeding (GIB), non-GI extracranial bleeding (NGIB) and intracranial bleeding within 1 year of follow-up. Covariates included age, sex, co-morbidities (within 3 years before cohort entry) and medication use (within 2 weeks before cohort entry). We used logistic-LASSO and adaptive logistic-LASSO regressions to identify MB predictors among OAC users. Discrimination and calibration were assessed for each model and a global model was selected. Subgroup analyses were performed for MB subtypes and OAC types.. Our cohort consisted of 14,741 warfarin, 3,722 dabigatran, 6,722 rivaroxaban and 11,196 apixaban users aged 70-86 years old. The important MB predictors were age, prior MB and liver disease with ORs ranging from 1.37-1.64. The final model had a c-statistic of 0.63 (95% CI 0.60-0.65) with adequate calibration. The GIB and NGIB models had similar c-statistics of 0.65 (95% CI 0.63-0.66) and 0.67 (95% CI 0.64-0.70), respectively.. MB and MB subtype predictors were similar among DOAC and warfarin users. The predictors selected by our models and their discriminative potential are concordant with published data. Thus, these models can be useful tools for future pharmacoepidemiologic studies involving older oral anticoagulant users with AF.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hospitalization; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridones; Regression Analysis; Rivaroxaban; Warfarin

Direct oral anticoagulants (DOACs) are increasingly used in place of warfarin, but evidence about their effectiveness and safety in patients with valvular atrial fibrillation (AF) remains limited.. To assess the effectiveness and safety of DOACs compared with warfarin in patients with valvular AF.. New-user retrospective propensity score-matched cohort study.. U.S.-based commercial health care database from 1 January 2010 to 30 June 2019.. Adults with valvular AF who were newly prescribed DOACs or warfarin.. The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial or gastrointestinal bleeding.. Among a total of 56 336 patients with valvular AF matched on propensity score, use of DOACs (vs. warfarin) was associated with lower risk for ischemic stroke or systemic embolism (hazard ratio [HR], 0.64 [95% CI, 0.59 to 0.70]) and major bleeding events (HR, 0.67 [CI, 0.63 to 0.72]). The results for the effectiveness and safety outcomes remained consistent for apixaban (HRs, 0.54 [CI, 0.47 to 0.61] and 0.52 [CI, 0.47 to 0.57], respectively) and rivaroxaban (HRs, 0.74 [CI, 0.64 to 0.86] and 0.87 [CI, 0.79 to 0.96], respectively); with dabigatran, results were consistent for the major bleeding outcome (HR, 0.81 [CI, 0.68 to 0.97]) but not for effectiveness (HR, 1.03 [CI, 0.81 to 1.31]).. Relatively short follow-up; inability to ascertain disease severity.. In this comparative effectiveness study using practice-based claims data, patients with valvular AF who were new users of DOACs had lower risks for ischemic stroke or systemic embolism and major bleeding than new users of warfarin. These data may be used to guide risk-benefit discussions regarding anticoagulant choices for patients with valvular AF.. None.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Comparative Effectiveness Research; Dabigatran; Embolism; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Male; Propensity Score; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Treatment Outcome; Warfarin

The optimal anticoagulant for end-stage renal disease patients for stroke prophylaxis is unknown. The efficacy and safety of warfarin in this population are debatable. In addition, real-world evidence of direct oral anticoagulants in patients with end-stage renal disease is limited. The aim of this study was to evaluate the clinical outcomes of rivaroxaban compared with warfarin in Taiwanese patients with end-stage renal disease with nonvalvular atrial fibrillation in a real-world setting.. This was a retrospective population-based cohort study conducted using Taiwan's National Health Insurance Research Database. Patients with nonvalvular atrial fibrillation and end-stage renal disease who started on rivaroxaban or warfarin between February 2013 and September 2017 were eligible to participate in the study. The inverse probability of treatment weighting approach was used to balance baseline characteristics. Bleeding and thromboembolic outcomes were compared using competing risk analyses. The study population consisted of 3358 patients (173 and 3185 patients on rivaroxaban and warfarin, respectively). In the rivaroxaban group, 50.8%, 38.7%, and 10.4% of the patients received 10, 15, and 20 mg of the drug, respectively. The cumulative incidence of major bleeding was similar between the two groups; however, the gastrointestinal bleeding rate was lower in the rivaroxaban group (adjusted subdistribution hazard ratio [SHR]: 0.56, 95% confidence interval [CI]: 0.34-0.91) than in the warfarin group. Furthermore, the composite risk of ischemic stroke or systemic embolism was significantly lower in the rivaroxaban group (adjusted SHR: 0.36, 95% CI: 0.17-0.79). Similar findings were observed for patients who received 10 mg of rivaroxaban.. In Taiwanese patients with end-stage renal disease and nonvalvular atrial fibrillation, rivaroxaban may be associated with a similar risk of major bleeding but a lower risk of thromboembolism compared with warfarin. The potential benefit of 10 mg of rivaroxaban in this population requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Taiwan; Thromboembolism; Warfarin; Young Adult

Atrial fibrillation is a major cause of death and disability due to stroke. Vitamin K antagonist drugs are effective for prevention, but they have a narrow therapeutic range and multiple pharmacological interactions. In recent years, new therapeutic alternatives have been searched to minimize complications. The main objective is to evaluate the risk of gastrointestinal bleeding in anticoagulated patients and compare the classic treatment with new anticoagulants.. We conducted a retrospective cohort study to determine the risk of gastrointestinal bleeding in patients treated with acenocoumarol/dabigatran/rivaroxaban, between 2012 and 2016. We compared the classic with the new anticoagulant group, and a multivariate logistic regression analysis was used to determinate the risk factors of gastrointestinal bleeding.. A total of 1213 patients were selected, 52.7% male patients, a mean age of 72.6 years old (± 14.563). 73.6% had atrial fibrilation. 14.5% of patients used acetylsalicylic acid, and 4% clopidogrel. 67.2% had a high-risk CHADS-2 Score, and 36.9% a high-risk HAS-BLED Score. We determined a 5.6% (68) of gastrointestinal bleeding, without differences according to anticoagulant used. The multivariate model showed a greater risk for digestive hemorrhage in patients with a previous hemorrhagic event (odds ratio [OR] = 2.422 95% confidence interval [CI]: 1.101-5.327) and the concomitant therapy with clopidogrel (OR = 2.373 95% CI: 0.996-5.652).. No differences were found in the risk of gastrointestinal bleeding between the different anticoagulants. A previous gastrointestinal bleeding were considered independent risk factor. The HAS-BLED score should be taken into account to make clinical decisions about to prescribe anticoagulant treatment.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clopidogrel; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Retrospective Studies; Rivaroxaban; Warfarin

Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs.. Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013-2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke.. During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65-0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation.. In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Ischemic Stroke; Male; Middle Aged; Proton Pump Inhibitors; Republic of Korea; Risk; Rivaroxaban; Upper Gastrointestinal Tract; Warfarin

Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions.. To compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin.. This retrospective cohort study included patients with NVAF who were 75 years and older; had stage III to V CKD; had an HAS-BLED score of 3 or greater; used corticosteroids, antiplatelets, or NSAIDs; or had GI conditions. Data were collected from the Centers for Medicare & Medicaid Services and 4 commercial insurance databases between January 1, 2012, and September 30, 2015. Data analysis was conducted from January 2012 to September 2015.. New prescription for apixaban, dabigatran, rivaroxaban, or warfarin between January 1, 2013, and September 30, 2015 (identification period).. Six propensity score-matched cohorts were created to compare between study drugs. For the primary objective, Cox models were used to estimate stroke and/or SE and MB hazard ratios (HRs).. A total of 381 054 patients (187 489 [49.2%] women) with NVAF and at least 1 high-risk GI bleeding factor were identified (HAS-BLED score ≥3: 284 527 [74.7%]; aged ≥75 years: 252 835 [66.4%]; corticosteroid, antiplatelet, or NSAID therapy: 107 675 [28.3%]; prior GI bleeding conditions: 74 818 [19.6%]; and stage III-V CKD: 56 892 [14.9%]). All NOACs were associated with a lower risk of stroke and/or SE vs warfarin (apixaban: HR, 0.60; 95% CI, 0.52-0.68; dabigatran: HR, 0.75; 95% CI, 0.64-0.88; rivaroxaban: HR, 0.79; 95% CI, 0.73-0.86). Compared with warfarin, apixaban and dabigatran were associated with a lower risk of MB (apixaban: HR, 0.59; 95% CI, 0.56-0.63; dabigatran: HR, 0.78; 95% CI, 0.70-0.86), while rivaroxaban was associated with a higher risk (HR, 1.11; 95% CI, 1.05-1.16).. In this study of patients with NVAF and high risk of GI bleed, NOACs were associated with lower rates of stroke and/or SE, but NOACs had varying risks of MB compared with warfarin. These results may help inform treatment options in this patient population.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Treatment Outcome; United States; Warfarin

Little is known about the risk factors for post endoscopic submucosal dissection (post-ESD) bleeding with anticoagulant therapy.. We aimed to investigate the risk factors for post-ESD bleeding for early gastric cancer (EGC) with an emphasis on anticoagulant therapy.. We retrospectively analyzed 2355 EGCs, including 137 lesions in patients treated under anticoagulants. Clinicopathological findings were evaluated between lesions in patients with and without anticoagulant therapy with propensity score matching analysis. The factors associated with post-ESD bleeding were analyzed with multivariate analysis with a logistic regression method.. After propensity score matching, post-ESD bleeding was significantly more frequent in lesions of patients with than without anticoagulant therapy (11.7% vs 1.5%, respectively; P = 0.001). A univariate analysis revealed that anticoagulant therapy, heparin bridge therapy, undifferentiated type, deep submucosal invasion, and resected specimen size were associated with post-ESD bleeding. A multivariate analysis revealed anticoagulant therapy (OR 23.1, 95% CI 3.61-147.52) and resected specimen size (OR 1.03, 95% CI 1.00-1.06) to be independent factors associated with post-ESD bleeding.. Anticoagulant therapy and resected specimen size were risk factors associated with post-ESD bleeding for EGC.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Endoscopic Mucosal Resection; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Logistic Models; Male; Middle Aged; Neoplasm Invasiveness; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Propensity Score; Retrospective Studies; Risk Factors; Stomach Neoplasms; Tumor Burden; Warfarin

More clinical data are required on the safety of direct oral anticoagulants (DOACs). Although patients treated with warfarin and DOACs have a similar risk of bleeding, short-term mortality after a gastrointestinal bleeding (GIB) episode in DOAC-treated patients has not been clarified. The objective of this study was to assess differences in 30-day mortality in patients treated with DOACs or warfarin admitted to the emergency department (ED) for GIB. This was a multicentre retrospective study conducted over 2 years. The study included patients evaluated at three different EDs for GIB. The baseline characteristics were included. Subsequently, we assessed the differences in past medical history and clinical data between the two study groups (DOAC and warfarin users). Differences between the two groups were evaluated using Kaplan-Meier curves. Among the 284 patients presenting GIB enrolled in the study period, 39.4% (112/284) were treated with DOACs and 60.6% (172/284) were treated with warfarin. Overall, 8.1% (23/284) of patients died within 30 days. Among the 172 warfarin-treated patients, 8.7% (15/172) died within 30 days from ED evaluation. In the 112 DOAC-treated patients, the mortality rate was 7.1% (8/112). The Cox regression analysis, adjusted for possible clinical confounders, and the Kaplan-Meier curves did not outline differences between the two treatment groups. The present study shows no differences between DOACs and warfarin in short-term mortality after GIB.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Italy; Male; Mortality; Retrospective Studies; Statistics, Nonparametric; Treatment Outcome; Warfarin

The Safety of Oral Anticoagulants Registry (SOAR) was designed to describe the evaluation and management of patients with oral anticoagulant (OAC)-related major bleeding or bleeding concerns who present to the emergency department (ED) with acute illness or injury. Patients in the ED are increasingly taking anticoagulants, which can cause bleeding-related complications as well as impact the acute management of related or unrelated clinical issues that prompt presentation. Modifications of emergency evaluation and management due to anticoagulation have not previously been studied.. This was a multicenter observational in-hospital study of patients who were judged to be experiencing an active OAC effect and had (a) an obvious bleeding event or (b) were deemed at risk for serious bleeding spontaneously, after injury, or during an indicated invasive procedure. Diagnostic testing, therapies employed, and clinical outcomes were collected.. Thirty-one US hospitals contributed data to SOAR. Of 1513 subjects, acute hemorrhage (AH) qualified 78%, while 22% had a bleeding concern (BC). Warfarin was the index OAC in 37.3%, dabigatran in 13.3%, and an anti-Factor X. Care of anticoagulated patients in the acute care setting is inconsistent, reflecting the diversity of presentation. As the prevalence of OAC use increases with the aging of the US population, further study and targeted educational efforts are needed to drive more evidence-based care of these patients.

Topics: Aged; Aged, 80 and over; Dabigatran; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Registries; Warfarin

Although direct oral anticoagulants (DOACs) carry a lower bleeding risk compared with warfarin, gastrointestinal bleeds (GIB) are a known complication. There are limited data observing outcomes associated with resuming DOACs following a GIB.. The purpose of this study was to evaluate practice patterns and clinical outcomes of patients admitted with an index GIB while receiving DOAC therapy.. This retrospective, single-system study included adult patients receiving DOAC therapy prior to admission and hospitalized with an index GIB between January 1, 2013, and October 31, 2018. Patient exclusion criteria were a history of immune thrombocytopenia purpura or inflammatory bowel disease; discharge to hospice; leaving against medical advice; or death during hospitalization. The primary objective was 90-day readmission for a recurrent GIB.. There were 57 patients included for analysis; 37 patients had DOAC therapy held >7 days, 18 patients resumed DOAC therapy within 7 days, and 2 patients switched to warfarin. The majority of patients received rivaroxaban (59.6%) prior to admission for atrial fibrillation (71.9%), were admitted with a major GIB (66.7%), and required a blood transfusion (61.4%). The rates of recurrent GIB were 2.5% (n = 1) and 5.6% (n = 1) for those who had their DOAC held and resumed, respectively (. Resuming anticoagulation within 7 days of admission for an index GIB was not associated with a recurrent GIB within 90 days of discharge.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Middle Aged; Patient Readmission; Recurrence; Retrospective Studies; Rivaroxaban; Treatment Outcome; Warfarin

Black patients are under-represented in randomized trials evaluating oral anticoagulants in non-valvular atrial fibrillation (NVAF). We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in African Americans with NVAF.. We performed an analysis using Optum® De-Identified Electronic Health Record (EHR) data from 1/1/2012-9/30/2018. We included adult African American patients with a diagnosis of NVAF who were anticoagulant-naïve during the 12-months prior to initiation of rivaroxaban or warfarin. Patients receiving rivaroxaban were 1:1 propensity score matched to warfarin patients. Our primary effectiveness and safety outcomes were the 2-year incidence rates (%/year) of stroke or systemic embolism (SSE) and major bleeding using an intention-to-treat approach. Cohorts were compared using doubly-robust Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).. We matched 4102 rivaroxaban and 4102 warfarin users with a median (interquartile range) available follow-up of 2.0 (0.9, 2.0) years. Median CHA2DS2-VASc and HASBLED scores were 3 (2, 4) and 2 (1, 3). Rivaroxaban use was associated with a lower risk of SSE (1.99 versus 2.48, HR = 0.77, 95%CI = 0.60-0.99), ischemic stroke (1.84 versus 2.37, HR = 0.76, 95%CI = 0.59-0.98) and major bleeding (4.22 versus 4.98, HR = 0.84, 95%CI = 0.70-0.99). No differences in intracranial hemorrhage or gastrointestinal bleeding were observed. Neither sensitivity analyses utilizing an on-treatment methodology nor inverse probability-of-treatment weighting showed significant differences in SSE or major bleeding between rivaroxaban and warfarin users.. Rivaroxaban appeared at least as effective and safe as warfarin when used to manage African American patients with NVAF in routine practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Black or African American; Embolism; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Incidence; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

Trials and past observational work compared dabigatran and warfarin in patients with atrial fibrillation, but few reported estimates of absolute harm and benefit under real-world adherence patterns, particularly in older adults that may have differing benefit-harm profiles. We aimed to estimate risk differences for ischemic stroke, death, and gastrointestinal bleeding after initiating dabigatran and warfarin in older adults (a) when patients adhere to treatment and (b) under real-world adherence patterns.. In a 20% sample of nationwide Medicare claims from 2010 to 2015, we identified beneficiaries aged 66 years and older initiating warfarin and dabigatran. We followed individuals from initiation until death or October 2015 (initial treatment, IT) and separately censored individuals' follow-up after drug switches and gaps in supply (on-treatment, OT). We applied inverse probability of treatment and standardized morbidity ratio weights, as well as inverse probability of censoring weights, to estimate two-year risk differences (RDs) for dabigatran vs warfarin.. We identified 10,717 dabigatran and 74,891 warfarin initiators. Weighted OT RDs suggested decreased ischemic stroke risk for dabigatran vs warfarin; IT RDs indicated increased or no change in ischemic stroke risk. Regardless of follow-up approach and weighting strategy, risk of death appeared lower and risk of gastrointestinal bleeding appeared higher when comparing dabigatran vs warfarin.. Dabigatran use was associated with lower risks of mortality and ischemic stroke in routine care when older adults stayed on treatment. IT analyses suggested that these benefits may be diminished under real-world patterns of switching and discontinuation.

Topics: Age Factors; Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Dabigatran; Drug-Related Side Effects and Adverse Reactions; Female; Gastrointestinal Hemorrhage; Health Services for the Aged; Humans; Male; Medicare; Risk Factors; Stroke; United States; Warfarin

Results from trials and nonexperimental studies are often directly compared, with little attention paid to differences between study populations. When target and trial population data are available, accounting for these differences through transporting trial results to target populations of interest provides useful perspective. We aimed to compare two-year risk differences (RDs) for ischemic stroke, mortality, and gastrointestinal bleeding in older adults with atrial fibrillation initiating dabigatran and warfarin when using trial transport methods versus nonexperimental methods.. We identified Medicare beneficiaries who initiated warfarin or dabigatran from a 20% nationwide sample. To transport treatment effects observed in the randomized evaluation of long-term anticoagulation trial, we applied inverse odds weights to standardize estimates to two Medicare target populations of interest, initiators of: (1) dabigatran and (2) warfarin. Separately, we conducted a nonexperimental study in the Medicare populations using standardized morbidity ratio weighting to control measured confounding.. Comparing dabigatran to warfarin, estimated two-year RDs for ischemic stroke were similar with trial transport and nonexperimental methods. However, two-year mortality RDs were closer to the null when using trial transport versus nonexperimental methods for the dabigatran target population (transported RD: -0.57%; nonexperimental RD: -1.9%). Estimated gastrointestinal bleeding RDs from trial transport (dabigatran initiator RD: 1.8%; warfarin initiator RD: 1.9%) appeared more harmful than nonexperimental results (dabigatran initiator RD: 0.14%; warfarin initiator RD: 0.57%).. Differences in study populations can and should be considered quantitatively to ensure results are relevant to populations of interest, particularly when comparing trial with nonexperimental findings. See video abstract: http://links.lww.com/EDE/B703.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Medicare; Mortality; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; United States; Warfarin

Topics: Endoscopy; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Humans; Thromboembolism; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used in patients with atrial fibrillation (AF) because of their effectiveness in preventing stroke and their better safety, compared with warfarin. However, there are concerns for an increased risk of bleeding associated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective serotonin reuptake inhibitors (SSRIs) with NOACs. In this study, we aimed to evaluate the risk of bleeding events in individuals taking concomitant NSAIDs or SSRIs with NOACs after being diagnosed with AF.. A nested case-control analysis to assess the safety of NSAIDs and SSRIs among NOAC users with AF was performed using data from Korean National Health Insurance Service from January 2012 to December 2017. Among patients who were newly prescribed NOACs, 1233 cases hospitalized for bleeding events were selected, and 24660 controls were determined.. The risk of bleeding events was higher in patients receiving concomitant NSAIDs [adjusted odds ratio (aOR) 1.41; 95% confidence interval (CI) 1.24-1.61] or SSRIs (aOR 1.92; 95% CI 1.52-2.42) with NOACs, compared to no use of either drug, respectively. The risk of upper gastrointestinal bleeding was higher in patients receiving concomitant NSAIDs or SSRIs without proton pump inhibitors (PPIs) (NSAIDs: aOR 2.47; 95% CI 1.26-4.83, SSRI: aOR 10.8; 95% CI 2.41-2.48) compared to no use.. When NSAIDs or SSRIs are required for NOAC users with AF, physicians need to monitor bleeding events and consider the use of PPIs, especially for combined use of both drugs or when initiating NOACs treatment.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Middle Aged; Selective Serotonin Reuptake Inhibitors; Stroke; Warfarin

The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited.. We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years.. Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated.. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively).. NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.

Topics: Aged, 80 and over; Atrial Fibrillation; Brain Ischemia; Databases, Factual; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Republic of Korea; Stroke; Thiazoles; Vitamin K; Warfarin

Previous studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal.. This was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications.. A total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC.. A fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.

Topics: Aged; Aged, 80 and over; Blood Coagulation Factors; Chi-Square Distribution; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Warfarin

: Upper tract gastrointestinal system (GIS) bleeding is considered as an important cause of morbidity and mortality despite modern and advanced endoscopic interventions. In patients with thrombotic state and vitamin D deficiency, vitamin D analogs and vitamin D receptor activators have been determined as adjunctive anticoagulant treatment in previous studies. However, these studies did not evaluate or reveal the possible bleeding diathesis. In this article, we evaluated the vitamin D status in patients with warfarin treatment and upper tract GIS bleeding. A total of 75 patients with a definite diagnosis of upper tract GIS bleeding who had a treatment of warfarin and current vitamin D measurement; and a total of 75 control patients without any recent or prior GIS bleeding who had a treatment of warfarin and current vitamin D measurement were enrolled to the study. GIS bleeding group had a proportionally higher vitamin D treatment (29.3 vs. 17.3%). In GIS bleeding group, the prevalence of vitamin D level less than 20 ng/ml was significantly lower (66.7 vs. 82.7%; P = 0.024) and the prevalence of vitamin D level at least 30-100 ng/ml was significantly higher (25.3 vs. 10.7%; P = 0.019). According to a subgroup analysis; in patients with a vitamin D level at least 30-100 ng/ml, major bleeding rate was significantly higher compared with other patients. There was not a significant difference regarding mortality between the groups. Our study is the first which represents the possible bleeding effect of elevated vitamin D levels and vitamin D treatment in patients with warfarin treatment.

Topics: Aged; Anticoagulants; Case-Control Studies; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Vitamin D; Warfarin

The purpose of the study was to examine the association between the type of preceding oral anticoagulant use (warfarin or direct oral anticoagulants [DOACs]) and in-hospital mortality among patients admitted with gastrointestinal bleeding.. In this observational cohort study, all patients admitted with a first-time gastrointestinal bleeding from January 2011 to March 2017 while receiving any oral anticoagulant therapy prior to admission were identified using data from Danish nationwide registries. The risk of in-hospital mortality according to type of oral anticoagulation therapy was examined by multivariable logistic regression models.. Among 5,774 patients admitted with gastrointestinal bleeding (median age, 78 years [25th-75th percentile, 71-85 years]; 56.8% men), 2,038 (35.3%) were receiving DOACs and 3,736 (64.7%) were receiving warfarin prior to admission. The unadjusted in-hospital mortality rates were 7.5% for DOAC (7.2% for dabigatran, 6.4% for rivaroxaban, and 10.1% for apixaban) and 6.5% for warfarin. After adjustment for baseline demographic and clinical characteristics, there was no statistically significant difference in in-hospital mortality between prior use of any DOAC and warfarin (unadjusted odds ratio [OR] 1.18 [95% CI 0.95-1.45], adjusted OR 0.97 [95% CI 0.77-1.24]). Similar results were found for each individual DOAC as compared with warfarin (dabigatran: unadjusted OR 1.12 [95% CI 0.84-1.49], adjusted OR 0.96 [95% CI 0.71-1.30]); rivaroxaban: unadjusted OR 0.98 [95% CI 0.71-1.37], adjusted OR 0.84 [95% CI 0.59-1.21]; and apixaban: unadjusted OR 1.62 [95% CI 0.84-1.49], adjusted OR 1.22 [95% CI 0.83-1.79]).. Among patients admitted with gastrointestinal bleeding, there was no statistically significant difference in in-hospital mortality between prior use of DOAC and warfarin.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Cohort Studies; Dabigatran; Denmark; Female; Gastrointestinal Hemorrhage; Hospital Mortality; Humans; Logistic Models; Male; Pyrazoles; Pyridones; Rivaroxaban; United States; Vitamin K; Warfarin

A 73-year-old man presented for evaluation of weakness and black tarry stools that occurred 1 day prior to admission. His medical history is significant for diabetes mellitus, stage 3 chronic kidney disease and deep vein thrombosis on warfarin. He was admitted to the hospital and was found to have acute kidney injury and gastrointestinal bleeding due to a supratherapeutic International Normalized Ratio. His hospital course was complicated by persistent decline in his renal function. He was given intravenous fluid resuscitation, fresh frozen plasma and packed red blood cells for his acute blood loss anaemia. Urinalysis was consistent with acute tubular necrosis. Given the persistent rise in creatinine, a kidney biopsy was obtained, and was significant for mild inflammatory changes, without evidence of vasculitis or allergic interstitial nephritis. Histopathological examination with tissue fixation revealed cholesterol embolisation. Given that he had no recent endovascular procedure or instrumentation, this atheroembolic event was attributed to his warfarin use.

Topics: Aged; Anticoagulants; Diagnosis, Differential; Embolism, Cholesterol; Gastrointestinal Hemorrhage; Humans; Male; Muscle Weakness; Nephritis, Interstitial; Venous Thrombosis; Warfarin

Newly published guidelines of the Japanese Gastroenterological Endoscopy Society (JGES) suggest to consider endoscopic procedures with high risk of bleeding without stopping warfarin and with stopping direct oral anticoagulants (DOACs) only on the day of the procedure. In this study, we aimed to test the validity of these recommendations.. We retrospectively reviewed medical records of 344 patients with anticoagulant therapy who underwent hot-snare polypectomy between January 2012 and October 2018. Patients (n = 132) with interruption of anticoagulants (3-7 days for warfarin and 2-3 days for DOACs before the procedure) and without heparin-bridging were excluded. Among the remaining 212 patients, the incidence of post-polypectomy bleeding was compared between the following 2 patient groups: patients who had interruption of anticoagulants with heparin-bridging (HB group, n = 139) and patients treated according to the new JGES guideline (FG group, n = 73).. The rate of post-polypectomy bleeding (PPB) in FG group (9.6%) was not significantly different from that in HB group (12.9%, p = 0.5). In subgroup analysis, the incidence of bleeding in patients with warfarin (12.2%) and with DOAC (6.3%) in FG group was not significantly different from corresponding figures in HB group (14.2%, 0%). In multivariate analysis, number of resected polyps was associated with PPB, but the administration of anticoagulants according to the new guidelines was not a significant risk factor for PPB (p = .98).. Our study affirms the recommendations of JGES for the management of anticoagulants in patients who undergo colonic polypectomy regarding post-polypectomy bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Colonic Polyps; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Multivariate Analysis; Risk Factors; Treatment Outcome; Warfarin

A 74-year-old woman receiving long-term anticoagulation with warfarin for chronic atrial fibrillation presented with severe acute abdominal pain, diarrhoea and vomiting. Initial laboratory workup revealed a deranged coagulation profile. Computed tomography of the abdomen and pelvis demonstrated spontaneous distal jejunal intramural haematoma with associated reactive ileus. No overt pneumatosis intestinalis, intraperitoneal free gas or haemoperitoneum was seen. Based on clinical and imaging findings, a diagnosis of over-anticoagulation complicated by small bowel intramural haematoma was made. The patient was managed non-operatively with analgesia, cessation of warfarin and reversal therapy with vitamin K. Warfarin therapy was recommenced upon resolution of symptoms and optimisation of coagulation status. The clinical presentation, radiological features and overall management of anticoagulation-induced bleeding are further discussed in this article.

Topics: Abdominal Pain; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Ileus; International Normalized Ratio; Intestinal Obstruction; Intestines; Male; Middle Aged; Risk Factors; Tomography, X-Ray Computed; Warfarin

Heparin bridging therapy (HBT) is indeed related to a high frequency of bleeding after endoscopic mucosal resection (EMR). In this study, our aim was to investigate clinical impact of management of oral anticoagulants without HBT in bleeding after colonic EMR.. From data for patients who underwent consecutive colonic EMR, the relationships of patient factors and procedural factors with the risk of bleeding were analysed. Our management of antithrombotic agents was based on the shortest cessation as follows: the administration of warfarin was generally continued within the therapeutic range, and direct oral anticoagulants (DOACs) were not administered on the day of the procedure. We calculated bleeding risks after EMR in patients who used antithrombotic agents and evaluated whether perioperative management of anticoagulants without HBT was beneficial for bleeding.. A total of 1734 polyps in 825 EMRs were analysed. Bleeding occurred in 4.0% of the patients and 1.9% of the polyps. The odds ratios for bleeding using multivariate logistic regression analysis were 3.67 in patients who used anticoagulants and 4.95 in patients who used both anticoagulants and antiplatelet agents. In patients with one-day skip of DOACs, bleeding occurred in 6.5% of the polyps, and there were no significant differences in bleeding risk between HBT and continuous warfarin or one-day skip DOACs.. The use of oral anticoagulants was related to bleeding after colonic EMR, and perioperative management of oral anticoagulants based on the shortest cessation without HBT would be clinically acceptable.

Topics: Administration, Oral; Aged; Anticoagulants; Colonic Polyps; Drug Administration Schedule; Endoscopic Mucosal Resection; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Heparin; Humans; Japan; Male; Middle Aged; Perioperative Care; Platelet Aggregation Inhibitors; Retrospective Studies; Warfarin

The US Food and Drug Administration's Sentinel System was established to monitor safety of regulated medical products. Sentinel investigators identified known associations between drugs and adverse events to test reusable analytic tools developed for Sentinel. This test case used a comparator with a different indication.. We tested the ability of Sentinel's reusable analytic tools to identify the known association between warfarin and gastrointestinal bleeding (GIB). Statins, expected to have no effect on GIB, were the comparator. We further explored the impact of analytic features, including matching ratio and stratifying Cox regression analyses, on matched pairs.. This evaluation included data from 14 Sentinel Data Partners. New users of warfarin and statins, aged 18 years and older, who had not received other anticoagulants or had recent GIB were matched on propensity score using 1:1 and 1:n variable ratio matching, matching statin users with warfarin users to estimate the average treatment effect in warfarin-treated patients. We compared the risk of GIB using Cox proportional hazards regression, following patients for the duration of their observed continuous treatment or until a GIB. For the 1:1 matched cohort, we conducted analyses with and without stratification on matched pair. The variable ratio matched cohort analysis was stratified on the matched set.. We identified 141,398 new users of warfarin and 2,275,694 new users of statins. In analyses stratified on matched pair/set, the hazard ratios (HR) for GIB in warfarin users compared with statin users were 2.78 (95% confidence interval [CI] 2.36-3.28) in the 1:1 matched cohort and 3.10 (95% CI 2.76-3.49) in the variable ratio matched cohort. The HR was lower in the analysis of the 1:1 matched cohort not stratified by matched pair (2.22, 95% CI 1.97-2.49), and highest early in treatment. Follow-up for warfarin users tended to be shorter than for statin users.. This study identified the expected GIB risk with warfarin compared with statins using an analytic tool developed for Sentinel. Our findings suggest that comparators with different indications may be useful in surveillance in select circumstances. Finally, in the presence of differential censoring, stratification by matched pair may reduce the potential for bias in Cox regression analyses.

Topics: Adolescent; Adult; Aged; Anticoagulants; Female; Gastrointestinal Hemorrhage; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pharmacovigilance; United States; United States Food and Drug Administration; Warfarin; Young Adult

The purpose of the study is to evaluate the impact of validation on the identification of major bleeding events in The Health Improvement Network (THIN) database in patients receiving anticoagulant therapy.. Patients aged 2 to 89 years with a first prescription for an anticoagulant (rivaroxaban or warfarin) between 2012 and 2015 were identified in THIN. Major bleeding events, defined as bleeding events necessitating hospitalization or referral to accident and emergency services or a specialist clinic, were identified using a 2-step ascertainment process based on read codes only, and then validated using a 2-step process requiring manual review of patients' records.. The positive predictive value for the ascertainment of major intracranial (IC) bleeds using only read codes was 96.9%, compared with 70.4% for gastrointestinal (GI) bleeds and 64.1% for urogenital (UG) bleeds. The incidence rate of major IC bleeding events was therefore similar when it was calculated before and after validation (0.32 per 100 person-years and 0.31 per 100 person-years, respectively). The incidence rate of major GI bleeds identified using read codes alone was reduced following validation from 2.05 to 0.94 per 100 person-years, and that of major UG bleeds decreased from 2.45 to 1.11 per 100 person-years.. Major GI and UG bleeding events ascertained from THIN using read codes require validation using additional information to prevent outcome misclassification. The absence of validation may lead to overestimated incidence rates of major bleeding for GI and UG bleeds.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Emergency Service, Hospital; Female; Female Urogenital Diseases; Gastrointestinal Hemorrhage; Hospitalization; Humans; Incidence; Intracranial Hemorrhages; Male; Male Urogenital Diseases; Middle Aged; Predictive Value of Tests; Primary Health Care; Registries; Risk Assessment; Risk Factors; Rivaroxaban; Validation Studies as Topic; Warfarin; Young Adult

Essentials Uncertainty remains about antiplatelets for vascular access patency in hemodialysis patients. 95 971 people under hemodialysis were followed in a claims database in Taiwan. Aspirin reduced vascular access failure rate and did not increase major bleeding rate. Clopidogrel, Aggrenox, and warfarin might increase major bleeding rate. SUMMARY: Background Dialysis adequacy is a major determinant of survival for patients with end-stage renal disease. Good vascular access is essential to achieve adequate dialysis. Objectives This study evaluated the impacts of different drugs on the vascular access failure rate of an arteriovenous fistula or an arteriovenous graft and the rate of major bleeding in hemodialysis patients. Patients and methods We studied patients with end-stage renal disease registered in the Taiwan National Health Insurance program from 1 January 1997 to 31 December 2012. A total of 95 971 patients were enrolled in our study. Vascular access dysfunction was defined as the need for thrombectomy or percutaneous angioplasty. Major bleeding was defined as emergency department visits or hospitalization with a primary diagnosis of gastrointestinal bleeding or intracerebral hemorrhage. The adjusted odds ratios between person-quarters with or without antiplatelet or oral anticoagulant use were calculated using a generalized estimating equation. Results The odds ratio of vascular access failure was 0.21 (0.11-0.39) for aspirin, 0.76 (0.74-0.79) for clopidogrel, 0.67 (0.59-0.77) for dipyridamole, 0.67 (0.53-0.86) for Aggrenox and 0.96 (0.90-1.03) for warfarin. The highest odds ratio for intracerebral hemorrhage was 5.33 (1.25-22.72) in younger patients using Aggrenox. The highest odds ratio for gastrointestinal bleeding was 1.34 (1.10-1.64) for clopidogrel. Conclusion Antiplatelet agents, but not warfarin, might reduce the vascular access thrombosis rate. The gastrointestinal bleeding rate was increased in the group using clopidogrel. Aggrenox should be used with caution in young individuals because it might increase the rate of intracerebral hemorrhage.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arteriovenous Shunt, Surgical; Aspirin; Aspirin, Dipyridamole Drug Combination; Blood Vessel Prosthesis Implantation; Clopidogrel; Databases, Factual; Female; Gastrointestinal Hemorrhage; Graft Occlusion, Vascular; Humans; Intracranial Hemorrhages; Kidney Failure, Chronic; Male; Middle Aged; Platelet Aggregation Inhibitors; Protective Factors; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Taiwan; Thrombosis; Treatment Failure; Warfarin; Young Adult

Use of direct-acting oral anticoagulants (DOACs) is increasing, but little is known about the associated risks in patients undergoing colonoscopy with polypectomy. We aimed to determine the risk of post-polypectomy complications in patients prescribed DOACs.. We performed a retrospective analysis using Optum's de-identified Clinformatics Data Mart Database (2003-2016) (a de-identified administrative database from a large national insurance provider) to identify adults who underwent colonoscopy with polypectomy or endoscopic mucosal resection (EMR) from January 1, 2011, through December 31, 2015. We collected data from 11,504 patients prescribed antithrombotic agents (1590 DOAC, 3471 warfarin, and 6443 clopidogrel) and 599,983 patients not prescribed antithrombotics of interest (controls). We compared 30-day post-polypectomy complications, including gastrointestinal bleeding (GIB), cerebrovascular accident (CVA), myocardial infarction (MI), and hospital admissions, of patients prescribed DOACs, warfarin, or clopidogrel vs controls.. Post-polypectomy complications were uncommon but occurred in a significantly higher proportion of patients receiving any antithrombotic vs controls (P < .001). The percentage of patients in the DOAC group with GIB was 0.63% (95% CI, 0.3%-1.2%) vs 0.2% (95% CI, 0.2%-0.3%) in controls. The percentage of patients with CVA in the DOAC group was 0.06% (95% CI, 0.01%-0.35%) vs 0.04% (95% CI, 0.04%-0.05%) in controls. After we adjusted for bridge anticoagulation, EMR, Charlson comorbidity index (CCI), and CHADS. In our retrospective analysis of a large national dataset, we found that patients prescribed DOACs did not have significantly increased adjusted odds of post-polypectomy GIB, MI, CVA, or hospital admission. Bridge anticoagulation, higher CHADS

Topics: Aged; Anticoagulants; Case-Control Studies; Clopidogrel; Colonic Polyps; Colonoscopy; Endoscopic Mucosal Resection; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Risk Factors; Stroke; Warfarin

This retrospective study investigated the efficacy and safety of prothrombin complex concentrates (PCCs) for management of major bleeding events (MBE) in 344 patients receiving the anticoagulants rivaroxaban, apixaban or warfarin during the period January 2016 to April 2018. Median (range) PCC dose was 2000 units (1000-4500). Intracranial haemorrhage (ICH) was the most common indication (137/344, 39·8%) for PCC use followed by gastrointestinal bleeding (93/344, 27%). ICH patients more frequently received rivaroxaban (62·5%) or apixaban (52·5%) compared to warfarin (34·5%), P = 0·002; and visceral bleeding patients received warfarin more frequently (24·2%) than rivaroxaban (5%) or apixaban (10%), P = 0·003. Median rivaroxaban and apixaban levels were 230 ng/ml (47-759) and 159 ng/ml (45-255). Median International Normalised Ratio pre- and post-PCC in patients on warfarin were 3·4 (1·9-15·4) and 1·2 (1·0-1·9). Blood products use was the same between groups. Thirty-day mortality and re-bleeding rates in patients with ICH were 35% (P = 0·50) and 18% (P = 0·90) with no differences between the groups. Thrombosis occurred in 4·1% patients within 30 days with no difference between groups. Two of 91 (2·2%) patients with ICH only (both on warfarin) had ischaemic strokes within 30 days post-PCC. In conclusion, there was no difference in the safety (thrombosis) or efficacy (30-day mortality, re-bleeding) in use of PCC for MBE in patients on warfarin, rivaroxaban or apixaban.

Topics: Aged; Aged, 80 and over; Blood Coagulation Factors; Disease-Free Survival; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Survival Rate; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Drug Monitoring; Female; Gastrointestinal Hemorrhage; Humans; Male; Michigan; Middle Aged; Program Evaluation; Proton Pump Inhibitors; Quality Improvement; Quality Indicators, Health Care; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; Warfarin

Among patients with nonvalvular atrial fibrillation (NVAF) who have sustained an upper gastrointestinal bleed (UGIB), the benefits and harms of oral anticoagulation change over time. Early resumption of anticoagulation increases recurrent bleeding, while delayed resumption exposes patients to a higher risk of ischemic stroke. We therefore set out to estimate the expected benefit of resuming anticoagulation as a function of time after UGIB among patients with NVAF.. We created a decision-analytic model estimating discounted quality-adjusted life-years when patients with NVAF resume anticoagulation on each day following UGIB. We simulated from a health system perspective over a lifelong time horizon.. Peak utility for warfarin was achieved by resumption 41 days after hemostasis from the index UGIB. Resumption between days 32 and 51 produced greater than 99.9% of the peak utility. Peak utility for apixaban was achieved by resumption 32 days after the index UGIB. Resumption between days 21 and 47 produced greater than 99.9% of the peak utility. Of input parameters, results were most sensitive to underlying stroke risk. Specifically, across the range of CHA. For patients with NVAF following UGIB, warfarin is optimally restarted approximately six weeks following hemostasis, and apixaban is optimally restarted approximately one month following hemostasis. Modest changes to this timing based on probability of thromboembolic stroke are reasonable.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Computer Simulation; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Stroke; Time Factors; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestine, Small; Male; Middle Aged; Tomography, X-Ray Computed; Warfarin

Background and Purpose- Hypertrophic cardiomyopathy patients with atrial fibrillation are at increased risk of stroke, and anticoagulation is strongly recommended. However, limited data are available regarding the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) for primary prevention of stroke. Methods- Using the Korean Health Insurance Review and Assessment Service database, we identified 2397 patients with hypertrophic cardiomyopathy and nonvalvular atrial fibrillation on oral anticoagulation from 2013 to 2016 without history of ischemic stroke, intracranial hemorrhage (ICH), or gastrointestinal bleeding (992 on warfarin and 1405 on NOACs). Inverse probability of treatment weighting with propensity scores was used to balance covariates between treatment groups. Risk for ischemic stroke, ICH, gastrointestinal bleeding, death, and their composite outcome associated with NOAC use was assessed with warfarin use as the reference. Results- During a mean follow-up of 1.6 years, the incidence rates of ischemic stroke, ICH, gastrointestinal bleeding, death, and composite outcome were all significantly lower in the NOAC than in the warfarin group (stroke, 2.8 versus 5.0; ICH, 0.5 versus 1.3; gastrointestinal bleeding, 2.3 versus 3.0; death, 3.0 versus 5.1; composite, 7.5 versus 12.5 events per 100 person-years). NOACs were associated with significantly lower risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.32-0.68), ICH (HR, 0.31; 95% CI, 0.14-0.69), gastrointestinal bleeding (HR, 0.62; 95% CI, 0.40-0.96), death (HR, 0.45; 95% CI, 0.31-0.65), and the composite outcome (HR, 0.48; 95% CI, 0.38-0.61) than warfarin. The same trend was observed regardless of the NOAC dose and across various high-risk subgroups. In analysis of individual NOACs, all NOACs were associated with lower risks of ischemic stroke and composite outcome. Conclusions- NOACs showed superior effectiveness and safety versus warfarin in the primary prevention of stroke versus warfarin in real-world Asian hypertrophic cardiomyopathy with atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Primary Prevention; Stroke; Treatment Outcome; Warfarin

To compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures.. Using the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups.. In the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk.. The risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure.

Topics: Aged; Anticoagulants; Endoscopy, Gastrointestinal; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Japan; Male; Middle Aged; Retrospective Studies; Risk Assessment; Thromboembolism; Warfarin

: In patients with inherited bleeding disorders undergoing surgery, we recommend assessment of individual risk for venous thromboembolism, taking into account the nature of the surgery and anaesthetic, type and severity of bleeding disorder, age, BMI, history of thrombosis, the presence of malignancy and other high-risk comorbidities. Venous thromboembolism risk should be balanced against the increased bleeding risk associated with anticoagulant use in patients with known bleeding disorders (Grade 1C). In these patients undergoing major surgery, we recommend against routine postoperative use of pharmacological thromboprophylaxis, especially for patients with haemophilia A and B (Grade 1B). Glomerular filtration rate should be assessed before initiation of each direct oral anticoagulant, and also at least once a year or more frequently as needed, such as postoperatively before the resumption of therapeutic direct oral anticoagulant administration, when it is suspected that renal function could decline or deteriorate (Grade 1C). Reduced dosages of low molecular weight heparins may be used relatively safely during transient severe (<50 × 10 l) thrombocytopaenia (Grade 2C). Monitoring of anti-Xa levels may be used to adjust the doses of low molecular weight heparin in patients with moderate or severe thrombocytopaenia (Grade 2C). The delay between major gastrointestinal bleeding and resuming warfarin should be at least 7 days (Grade 2C). For patients at a high risk of thromboembolism and with a high bleeding risk after surgery, we consider that administering a reduced dose of direct oral anticoagulant on the evening after surgery and on the following day (first postoperative day) after surgery is a good practice (Grade 2B).

Topics: Administration, Oral; Age Factors; Aged; Anesthesiology; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Clinical Trials, Phase III as Topic; Critical Care; Dose-Response Relationship, Drug; Drug Administration Schedule; Europe; Gastrointestinal Hemorrhage; Glomerular Filtration Rate; Heparin, Low-Molecular-Weight; Humans; Perioperative Care; Platelet Count; Risk Factors; Societies, Medical; Surgical Procedures, Operative; Time Factors; Venous Thromboembolism; Warfarin

Direct-acting oral anticoagulants (DOACs), which have gained approval for stroke prevention in nonvalvular atrial fibrillation and treatment of venous thromboembolism, have become increasingly preferred over warfarin given their predictable pharmacodynamics, lack of required monitoring, and superior outcomes. Direct-acting oral anticoagulants have been shown to be associated with an increased frequency of gastrointestinal bleeding compared with warfarin, but the severity and characteristics of gastrointestinal bleeding in these patients is poorly understood.. We retrospectively evaluated electronic medical records of patients with gastrointestinal bleeding (n = 8496) from 2010-2016. We identified 61 patients with gastrointestinal bleeding episodes while treated with DOACs (rivaroxaban, dabigatran, or apixaban) and 123 patients with gastrointestinal bleeding while taking warfarin. We randomly selected a control group of 296 patients with gastrointestinal bleeding who were not receiving anticoagulation treatment from the same sample. Outcomes included the need for hospitalization, blood transfusion, endoscopic or surgical intervention, and 30-day mortality.. The DOAC and warfarin groups were similar in terms of age and underlying comorbidity (assessed using the Charlson Comorbidity Index), but the DOAC group had greater concomitant aspirin use. Gastrointestinal bleeding was classified as upper (n = 186), lower (n = 88), anorectal (n = 183), small bowel (n = 9), and indeterminate (n = 14). After adjusting for differences in baseline variables, the DOAC group had fewer hospitalizations and required fewer transfusions than the warfarin group. The DOAC and control groups were not statistically different for all outcomes. There were no significant mortality differences among groups.. Although prior studies have shown a higher frequency of gastrointestinal bleeding in patients treated with DOACs compared with warfarin, our data suggest that gastrointestinal bleeding in patients taking DOACs may be less severe. These differences occurred despite significantly greater concomitant aspirin use in the DOAC group compared with warfarin users.

Topics: Administration, Oral; Aged; Anticoagulants; Arteriovenous Malformations; Aspirin; Blood Transfusion; Case-Control Studies; Dabigatran; Diverticulum; Endoscopy, Gastrointestinal; Female; Gastrointestinal Hemorrhage; Hemorrhoids; Hospitalization; Humans; Male; Middle Aged; Peptic Ulcer; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Warfarin

Balancing the risks for thromboembolism and postpolypectomy bleeding in patients requiring anticoagulation and antiplatelet agents is challenging. We investigated the incidence and risk factors for postpolypectomy bleeding on anticoagulation, including heparin bridge and other antithrombotic therapy.. We performed a retrospective cohort and case control study at 2 tertiary-care medical centers from 2004 to 2012. Cases included male patients on antithrombotics with hematochezia after polypectomy. Nonbleeding controls were matched to cases 3 to 1 by antithrombotic type, study site, polypectomy technique, and year of procedure. Our outcomes were the incidence and risk factors for postpolypectomy bleeding.. There were 59 cases and 174 matched controls. Postpolypectomy bleeding occurred in 14.9% on bridge anticoagulation. This was significantly higher than the overall incidence of bleeding on antithrombotics at 1.19% (95% confidence interval, 0.91%-1.54%) (59/4923). We identified similarly low rates of bleeding in patients taking warfarin (0.66%), clopidogrel (0.84%), and aspirin (0.92%). Patients who bled tended to have larger polyps (13.9 vs 7.3 mm; P < .001) and more polyps ≥2 cm (41% vs 10%; P < .001). Bleeding risk was increased with restarting antithrombotics within 1 week postpolypectomy (odds ratio [OR] 4.50; P < .001), having polyps ≥2 cm (OR 5.94; P < .001), performing right-sided cautery (OR 2.61; P = .004), and having multiple large polyps (OR 2.92; P = .001). Among patients on warfarin, the presence of bridge anticoagulation was an independent risk factor for postpolypectomy bleeding (OR 12.27; P = .0001).. We conclude that bridge anticoagulation is associated with a high incidence of postpolypectomy bleeding and is an independent risk factor for hemorrhage compared with patients taking warfarin alone. A higher threshold to use bridge anticoagulation should be considered in patients with an elevated bleeding risk.

Topics: Aged; Anticoagulants; Aspirin; Case-Control Studies; Clopidogrel; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Female; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Retrospective Studies; Risk Factors; Thromboembolism; Ticlopidine; Time Factors; Warfarin

The US Food and Drug Administration's Sentinel system developed tools for sequential surveillance.. In patients with non-valvular atrial fibrillation, we sequentially compared outcomes for new users of rivaroxaban versus warfarin, employing propensity score matching and Cox regression. A total of 36 173 rivaroxaban and 79 520 warfarin initiators were variable-ratio matched within 2 monitoring periods.. Statistically significant signals were observed for ischemic stroke (IS) (first period) and intracranial hemorrhage (ICH) (second period) favoring rivaroxaban, and gastrointestinal bleeding (GIB) (second period) favoring warfarin. In follow-up analyses using primary position diagnoses from inpatient encounters for increased definition specificity, the hazard ratios (HR) for rivaroxaban vs warfarin new users were 0.61 (0.47, 0.79) for IS, 1.47 (1.29, 1.67) for GIB, and 0.71 (0.50, 1.01) for ICH. For GIB, the HR varied by age: <66 HR = 0.88 (0.60, 1.30) and 66+ HR = 1.49 (1.30, 1.71).. This study demonstrates the capability of Sentinel to conduct prospective safety monitoring and raises no new concerns about rivaroxaban safety.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Atrial Fibrillation; Brain Infarction; Factor Xa Inhibitors; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pilot Projects; Prospective Studies; Rivaroxaban; United States; United States Food and Drug Administration; Warfarin

Although bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) remains problematic, especially in patients taking anticoagulants, there are differing views on the ideal and optimal management for these patients. This study investigated the risk of bleeding after ESD in patients taking anticoagulants.. We enrolled 61 consecutive patients taking anticoagulants (anticoagulant group) and 968 patients taking no antithrombotic agents (non-antithrombotic group) treated with ESD for EGC between December 2010 and October 2016. We analyzed the risk factors for bleeding after ESD in relation to the various clinical factors.. Incidences of bleeding after ESD were significantly higher (14%; 11/76) in the anticoagulant group compared to the non-antithrombotic group (3%; 40/1,167). Moreover, bleeding after ESD was significantly more common in patients in the warfarin monotherapy group (14%; 5/37) and in the direct oral anticoagulant (DOAC) monotherapy group (22%; 4/18), compared to the non-antithrombotic group. Multivariate analysis revealed that dialysis, the use of anticoagulants, and an operation time ≥75 min were independent risk factors for bleeding after ESD.. Our data suggest that patients who take warfarin and receive heparin bridging, and those who take DOAC medication, are prone to bleeding after ESD for EGC.

Topics: Aged; Aged, 80 and over; Anticoagulants; Drug Substitution; Endoscopic Mucosal Resection; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Heparin; Humans; Incidence; Male; Middle Aged; Postoperative Hemorrhage; Retrospective Studies; Risk Factors; Stomach Neoplasms; Stroke; Warfarin

To assess the association between anticoagulation, ischaemic stroke, gastrointestinal and cerebral haemorrhage, and all cause mortality in older people with atrial fibrillation and chronic kidney disease.. Propensity matched, population based, retrospective cohort analysis from January 2006 through December 2016.. The Royal College of General Practitioners Research and Surveillance Centre database population of almost 2.73 million patients from 110 general practices across England and Wales.. Patients aged 65 years and over with a new diagnosis of atrial fibrillation and estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73m. Receipt of an anticoagulant prescription within 60 days of atrial fibrillation diagnosis.. Ischaemic stroke, cerebral or gastrointestinal haemorrhage, and all cause mortality.. 6977 patients with chronic kidney disease and newly diagnosed atrial fibrillation were identified, of whom 2434 were on anticoagulants within 60 days of diagnosis and 4543 were not. 2434 pairs were matched using propensity scores by exposure to anticoagulant or none and followed for a median of 506 days. The crude rates for ischaemic stroke and haemorrhage were 4.6 and 1.2 after taking anticoagulants and 1.5 and 0.4 in patients who were not taking anticoagulant per 100 person years, respectively. The hazard ratios for ischaemic stroke, haemorrhage, and all cause mortality for those on anticoagulants were 2.60 (95% confidence interval 2.00 to 3.38), 2.42 (1.44 to 4.05), and 0.82 (0.74 to 0.91) compared with those who received no anticoagulation.. Giving anticoagulants to older people with concomitant atrial fibrillation and chronic kidney disease was associated with an increased rate of ischaemic stroke and haemorrhage but a paradoxical lowered rate of all cause mortality. Careful consideration should be given before starting anticoagulants in older people with chronic kidney disease who develop atrial fibrillation. There remains an urgent need for adequately powered randomised trials in this population to explore these findings and to provide clarity on correct clinical management.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebral Hemorrhage; England; Female; Gastrointestinal Hemorrhage; Humans; Male; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; Wales; Warfarin

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person-years of exposure to warfarin-only and 60,253 years of exposure to warfarin-with-statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin-with-statin compared to warfarin-only and to allow multiple episodes per patient and time-dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable-adjusted RR = 0.98, 95% CI 0.89-1.07) or to simvastatin (RR = 1.01, 95% CI 0.91-1.11) with warfarin compared to exposure to warfarin-only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.

Topics: Aged; Anticoagulants; Drug Interactions; Female; Finland; Gastrointestinal Hemorrhage; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Risk Factors; Simvastatin; Thromboembolism; Treatment Outcome; Warfarin

The use of anticoagulants is a contributor to gastrointestinal (GI) bleeding. Most bleeding patients on anticoagulant therapy such as warfarin commonly have basic lesions existing in their GI mucosa.. We report a case of major GI bleeding following the use of anticoagulants in a patient with hookworm infection.. The patient was diagnosed with nephrotic syndrome with pulmonary embolism.. He was treated with anticoagulants and suffered from acute major GI bleeding during the treatment. Capsule endoscopy revealed many hookworms in the lumen of jejunum where fresh blood was seen coming from the mucosa.. The patient was successfully rescued and cured with albendazole.. Latent hookworm infection can be a cause of massive small-bowel hemorrhage in patients on anticoagulant therapy and anthelmintic treatment is the key to stop bleeding.

Topics: Albendazole; Anthelmintics; Anticoagulants; Atrial Fibrillation; Capsule Endoscopy; Diagnosis, Differential; Diagnostic Errors; Gastrointestinal Hemorrhage; Hookworm Infections; Humans; Jejunum; Male; Middle Aged; Treatment Outcome; Warfarin

Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis.. Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF).. Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR 1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively).. In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.

Topics: Administration, Oral; Angiodysplasia; Anticoagulants; Antithrombins; Atrial Fibrillation; Colon; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intestinal Mucosa; Odds Ratio; Randomized Controlled Trials as Topic; Rectum; Retrospective Studies; Risk Factors; Treatment Outcome; Warfarin

We report on a woman with lower gastrointestinal bleeding under effective oral anticoagulation with both phenprocoumon and apixaban (with intention to switch to the latter) as well as the antiplatelet agent acetylsalicylic acid for aortic bifurcation kissing stents after stent thrombosis. Our patient presented with weakness and rectal bleeding. Upon examination, she looked anemic and had sinus tachycardia (104 beats per minute). The digital rectal examination revealed bright red blood mixed with clots. We established the diagnosis of lower gastrointestinal bleeding that originated from angiodysplasia in the cecum. The patient was stabilized with fluid resuscitation and transfusion. The bleeding source was treated endoscopically. Phenprocoumon had already been stopped and apixaban was paused immediately. Further intervention regarding coagulation was not needed.. Anticoagulation is an important risk factor for gastrointestinal bleeding. Switching from phenprocoumon (or warfarin) to a non-vitamin K oral anticoagulant (NOAC) should be monitored closely using the international normalized ratio. Apixaban or other NOAC are currently not approved for arterial stent thrombosis and there is no evidence for efficacy. Therefore, off-label use requires careful consideration of the risks and benefits.

Topics: Anticoagulants; Female; Gastrointestinal Hemorrhage; Humans; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Warfarin

Topics: Anticoagulants; Gastrointestinal Hemorrhage; Humans; Risk; Warfarin

The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction) compared higher-dose edoxaban regimen (HD-ER) and lower-dose edoxaban regimen with well-managed warfarin in 21 105 patients with atrial fibrillation. The risk factors and clinical impact of gastrointestinal bleeding (GIB) in this trial have not been described in detail.. MGIB occurred more frequently with HD-ER than warfarin. The rates of life-threatening or fatal GIB were low and similar with both HD-ER and warfarin. Clinical outcomes were generally favorable. The correlation between dose, trough edoxaban level, and the risk of GIB risk suggests GIB is exposure-related.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00781391.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Dose-Response Relationship, Drug; Drug Monitoring; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pyridines; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Thiazoles; Time Factors; Treatment Outcome; Warfarin

Clinical variables including hypertension could be linked with major bleeding events and death beyond vitamin K antagonist (warfarin) or direct oral anti-coagulants (DOACs) treatment strategy.. Subgroup analysis of major bleeding (primary endpoint) associated with clinical variables, site of bleeding, ongoing antithrombotics, reversal treatment or blood transfusion, outcomes (secondary endpoints) was performed in patients with bleeding events submitted to hard 5:1 propensity-score matching for hypertension.. Enrolled patients were 2,792 (mean age, 65.6 ± 19.9 years) during 2-year survey including 166,000 visits, of 200,000 inhabitants catchment area; 8,239 patients received warfarin and 3,797 DOACs. Hypertension account for 1,077 (39%) patients; major bleeding for 474 (17%); death for 29 (1%), and 72 (3%) on 1-month and 1-year, respectively. Hypertension, age, glucose, cancer, ischemic vascular disease, and CHA2D2VASc score were more likely to link with major bleeding. On multivariate analysis, only age (odds ratio [OR], 1.02; P < 0.001), CHA2DS2VASc score ≥ 2 (OR, 2.14; P = 0.001), and glucose (OR, 1.01; P = 0.005) were predictors of major bleeding. Kaplan-Meier analysis demonstrated patients with hypertension as compared with patients without showed 60% versus 20% death on 1-month (P < 0.001). Warfarin compared with DOACs was more likely to present with major bleeding (0.7% versus 0.2%; OR, 2.8; P = 0.005). Receiver operator characteristics analysis showed high value (0.61) of age and glucose over creatinine and systolic arterial pressure (P = NS).. Four in 10 patients with major bleeding showed hypertension; of these 8 in 10 will die within 1 month. Warfarin compared with DOACs was more likely to present with major bleeding.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Blood Glucose; Blood Transfusion; Cardiovascular Diseases; Creatinine; Dabigatran; Emergency Service, Hospital; Epistaxis; Female; Gastrointestinal Hemorrhage; Hematuria; Hemoptysis; Hemorrhage; Humans; Hypertension; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prognosis; Propensity Score; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Severity of Illness Index; Sex Factors; Thiazoles; Warfarin

Topics: Capsule Endoscopy; Chronic Disease; Gastrointestinal Hemorrhage; Humans; Intestine, Small; Warfarin

Background Patients with impaired liver function ( ILF ) were excluded from clinical trials that investigated non-vitamin K antagonist oral anticoagulants ( NOAC s) for stroke prevention in patients with atrial fibrillation. The aim of this study was to evaluate the efficacy and safety of NOAC s in atrial fibrillation patients with ILF . Methods and Results A cohort study based on electronic medical records was conducted from 2009 to 2016 at a multicenter healthcare provider in Taiwan and included 6451 anticoagulated atrial fibrillation patients (aged 76.7±7.0 years, 52.5% male). Patients were classified into 2 subgroups: patients with normal liver function (n=5818) and patients with ILF (n=633, 9.8%). Cox regression analysis was performed to investigate the risks of thromboembolism, bleeding, and death associated with use of NOAC s and warfarin in patients with normal liver function and ILF , respectively. In patients with normal liver function, compared with warfarin therapy (n=2928), NOAC therapy (n=4048) was associated with significantly lower risks of stroke or systemic embolism (adjusted hazard ratio: 0.75; 95% confidence interval, 0.65-0.88; P<0.001) and death (adjusted hazard ratio: 0.69; 95% confidence interval, 0.60-0.80; P<0.001) with no difference in major bleeding or gastrointestinal bleeding. In patients with ILF , compared with warfarin therapy (n=394), NOAC therapy (n=342) was associated with significantly lower risk of death (adjusted hazard ratio: 0.64; 95% confidence interval, 0.49-0.83; P<0.001), but no difference in stroke or systemic embolism, major bleeding, or gastrointestinal bleeding. Conclusions In atrial fibrillation patients with ILF , NOAC therapy and warfarin therapy were associated with similar risks of stroke or systemic embolism, major bleeding, and gastrointestinal bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Cohort Studies; Dabigatran; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hepatic Insufficiency; Humans; Male; Proportional Hazards Models; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Thiazoles; Thromboembolism; Warfarin

Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment.. To compare the incidence of hospitalization for upper gastrointestinal tract bleeding in patients using individual anticoagulants with and without PPI cotherapy, and to determine variation according to underlying gastrointestinal bleeding risk.. Retrospective cohort study in Medicare beneficiaries between January 1, 2011, and September 30, 2015.. Apixaban, dabigatran, rivaroxaban, or warfarin with or without PPI cotherapy.. Hospitalizations for upper gastrointestinal tract bleeding: adjusted incidence and risk difference (RD) per 10 000 person-years of anticoagulant treatment, incidence rate ratios (IRRs).. There were 1 643 123 patients with 1 713 183 new episodes of oral anticoagulant treatment included in the cohort (mean [SD] age, 76.4 [2.4] years, 651 427 person-years of follow-up [56.1%] were for women, and the indication was atrial fibrillation for 870 330 person-years [74.9%]). During 754 389 treatment person-years without PPI cotherapy, the adjusted incidence of hospitalization for upper gastrointestinal tract bleeding (n = 7119) was 115 per 10 000 person-years (95% CI, 112-118). The incidence for rivaroxaban (n = 1278) was 144 per 10 000 person-years (95% CI, 136-152), which was significantly greater than the incidence of hospitalizations for apixaban (n = 279; 73 per 10 000 person-years; IRR, 1.97 [95% CI, 1.73-2.25]; RD, 70.9 [95% CI, 59.1-82.7]), dabigatran (n = 629; 120 per 10 000 person-years; IRR, 1.19 [95% CI, 1.08-1.32]; RD, 23.4 [95% CI, 10.6-36.2]), and warfarin (n = 4933; 113 per 10 000 person-years; IRR, 1.27 [95% CI, 1.19-1.35]; RD, 30.4 [95% CI, 20.3-40.6]). The incidence for apixaban was significantly lower than that for dabigatran (IRR, 0.61 [95% CI, 0.52-0.70]; RD, -47.5 [95% CI,-60.6 to -34.3]) and warfarin (IRR, 0.64 [95% CI, 0.57-0.73]; RD, -40.5 [95% CI, -50.0 to -31.0]). When anticoagulant treatment with PPI cotherapy (264 447 person-years; 76 per 10 000 person-years) was compared with treatment without PPI cotherapy, risk of upper gastrointestinal tract bleeding hospitalizations (n = 2245) was lower overall (IRR, 0.66 [95% CI, 0.62-0.69]) and for apixaban (IRR, 0.66 [95% CI, 0.52-0.85]; RD, -24 [95% CI, -38 to -11]), dabigatran (IRR, 0.49 [95% CI, 0.41-0.59]; RD, -61.1 [95% CI, -74.8 to -47.4]), rivaroxaban (IRR, 0.75 [95% CI, 0.68-0.84]; RD, -35.5 [95% CI, -48.6 to -22.4]), and warfarin (IRR, 0.65 [95% CI, 0.62-0.69]; RD, -39.3 [95% CI, -44.5 to -34.2]).. Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper gastrointestinal tract bleeding was the highest in patients prescribed rivaroxaban, and the lowest for patients prescribed apixaban. For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Dabigatran; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Proton Pump Inhibitors; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Upper Gastrointestinal Tract; Warfarin

A historical cohort analysis of the Japan medical data center (JMDC) claims databases was performed to compare the incidence rates of bleeding events with warfarin (WF) versus direct oral anticoagulant (DOAC) treatment in patients with non-valvular atrial fibrillation. The aim of this study is to clarify the risk factors for bleeding events in younger patients newly treated with WF or DOAC in clinical practice setting. Patients who newly initiated WF or DOAC treatment from April 2012 to March 2015 were selected from the JMDC claims database. A 1:1 propensity score matching analysis was used for new users of WF or DOAC. Kaplan-Meier curves were generated to depict the time to bleeding event (total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage) during the follow-up period. Cox proportional regression models were used to estimate the hazard ratios for total bleeding events caused by oral anticoagulants. Overall, 2,046 patients (503 WF and 1,543 DOAC) were included. After applying propensity score matching, Kaplan-Meier analysis of the WF and DOAC groups displayed comparable incidences of total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage. Cox proportional hazards modeling showed that the use of WF was not associated with total bleeding events compared with DOAC (hazard ratio: 1.21, 95% confidence interval: 0.93-1.54,

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Child; Child, Preschool; Databases, Factual; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Infant; Infant, Newborn; Intracranial Hemorrhages; Japan; Male; Middle Aged; Time Factors; Warfarin; Young Adult

Topics: Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestine, Small; Male; Middle Aged; Warfarin

Oral anticoagulants (OACs) effectively reduce the risk of stroke in atrial fibrillation (AF). Three non-vitamin K antagonist OACs (NOACs) are introduced in regular care based on promising results compared with warfarin in randomized trials. This study compares outcomes with NOAC vs. warfarin treatment in OAC naïve AF patients in routine care, including primary care, in a large region with decentralized anticoagulant treatment.. Population-based cohort study. Individuals with non-valvular AF who initiated treatment with NOAC (n = 9279) or warfarin (n = 12 919) from 2012 to 2015 were identified in the Stockholm administrative health data register (population 2.2 million). Adjusted Cox regression analyses were performed to evaluate TIA/ischaemic or unspecified stroke/death, and severe bleeds (co-primary endpoints); and secondarily for components of the composites. NOAC patients were younger (72.9 vs. 74.1 years) and had lower CHA2DS2VASc scores (3.42 vs. 3.68) than warfarin patients. NOAC vs. warfarin treatment was associated with similar risks for TIA/ischaemic or unspecified stroke/death [hazard ratio (HR) 0.94; 0.85-1.05] and severe bleeds (HR 1.02; 0.88-1.19); lower risks of intracranial bleeds (HR 0.72; 0.53-0.97) or haemorrhagic stroke (HR 0.56; 0.34-0.93), but a higher risk for gastrointestinal bleeds (HR 1.28; 1.04-1.59). The advantages with NOAC treatment were most pronounced with standard dose in patients below 80 years, and with dose reduction in patients aged 80 and above.. This population-based cohort study of routine care indicates similar or better effectiveness and safety with NOAC compared with warfarin treatment. NOACs were associated with fewer intracranial bleeds, but more gastrointestinal bleeds.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Registries; Risk Factors; Stroke; Sweden; Time Factors; Treatment Outcome; Warfarin

To evaluate whether resumption of warfarin after hospitalization for lower gastrointestinal bleeding (LGIB) is associated with improved 90-day and 6-month survival.. LGIB is a common complication for patients on warfarin. There is limited data to guide clinicians on the optimal management of warfarin following hospitalization for LGIB.. We identified patients hospitalized with LGIB while on warfarin using a validated, machine-learning algorithm. Patients were classified as those who had warfarin resumed at discharge and those who did not. Univariate and multivariate Cox proportional hazards were used to determine whether resuming warfarin was associated with improved 90-day and 6-month mortality.. In total, 607 patients were admitted with warfarin-associated LGIB. A total of 403 (66.4%) patients had warfarin held at discharge. Discontinuation of warfarin was associated with an increased 90-day and 6-month mortality on univariate analysis [hazard ratio (HR), 2.07, 95% confidence interval (CI), 1.04-4.58, P=0.04; HR, 1.78, 95% CI, 1.02-3.27, P=0.04]. On multivariate regression adjusting for age, comorbidities, and transfusion requirement, only a higher Charlson Index was associated with increased 90-day mortality (HR, 1.18, 95% CI, 1.07-1.29, P=<0.001). At 6 months, only older age was associated with an increased mortality on multivariate regression (HR, 1.02, 95% CI, 1.00-1.05, P=0.02), with no significantly increased mortality risk with holding warfarin (HR, 1.48, 95% CI, 0.84-2.78, P=0.18) CONCLUSIONS:: There was no association between resumption of warfarin at discharge following hospitalization for LGIB and either 90-day or 6-month mortality on multivariate analysis. Mortality in LGIB was largely driven by age and comorbidities.

Topics: Age Factors; Aged; Anticoagulants; Comorbidity; Data Mining; Data Warehousing; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Machine Learning; Male; Middle Aged; Patient Discharge; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Warfarin

Aspirin increases the risk of gastrointestinal bleeding.. To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.. Low-dose (75-325 mg daily) aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.. A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 2.06-3.65), NSAIDs (HR: 8.61, 95% CI: 3.28-22.58), steroids (HR: 10.50, 95% CI: 1.98-55.57), SSRIs (HR: 11.71, 95% CI: 1.40-97.94), PPIs (HR: 8.47, 95% CI: 2.26-31.71), and H2RAs (HR: 10.83, 95% CI: 2.98-39.33) were significantly associated with LGIB.. The risk of LGIB was higher in low-dose aspirin users than in aspirin nonusers in this nationwide cohort. Low-dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Case-Control Studies; Clopidogrel; Comorbidity; Cyclooxygenase 2 Inhibitors; Databases, Factual; Dose-Response Relationship, Drug; Female; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Incidence; Male; Middle Aged; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors; Renal Insufficiency, Chronic; Risk Factors; Selective Serotonin Reuptake Inhibitors; Taiwan; Ticlopidine; Warfarin; Young Adult

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Craniocerebral Trauma; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Stroke; Thiazoles; Warfarin

Anticoagulant management of acute gastrointestinal bleeding (GIB) during the pre-endoscopic period has not been fully addressed in American, European, or Asian guidelines. This study sought to evaluate the risks of rebleeding and thromboembolism in anticoagulated patients with acute GIB.. Baseline, endoscopy, and outcome data were reviewed for 314 patients with acute GIB: 157 anticoagulant users and 157 age-, sex-, and important risk-matched non-users. Data were also compared between direct oral anticoagulants (DOACs) and warfarin users.. Between anticoagulant users and non-users, of whom 70% underwent early endoscopy, no endoscopy-related adverse events or significant differences were found in the rate of endoscopic therapy need, transfusion need, rebleeding, or thromboembolism. Rebleeding was associated with shock, comorbidities, low platelet count and albumin level, and low-dose aspirin use but not HAS-BLED score, any endoscopic results, heparin bridge, or international normalized ratio (INR) ≥ 2.5. Risks for thromboembolism were INR ≥ 2.5, difference in onset and pre-endoscopic INR, reversal agent use, and anticoagulant interruption but not CHA2DS2-VASc score, any endoscopic results, or heparin bridge. In patients without reversal agent use, heparin bridge, or anticoagulant interruption, there was only one rebleeding event and no thromboembolic events. Warfarin users had a significantly higher transfusion need than DOACs users.. Endoscopy appears to be safe for anticoagulant users with acute GIB compared with non-users. Patient background factors were associated with rebleeding, whereas anticoagulant management factors (e.g. INR correction, reversal agent use, and drug interruption) were associated with thromboembolism. Early intervention without reversal agent use, heparin bridge, or anticoagulant interruption may be warranted for acute GIB.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Endoscopy; Female; Gastrointestinal Hemorrhage; Heparin; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Risk Factors; Thromboembolism; Treatment Outcome; Warfarin

Patients on warfarin plus antiplatelet/NSAID regimens are likely to benefit from the gastroprotective effect of PPIs. For patients taking warfarin alone, it's a different story.

Topics: Anticoagulants; Atrial Fibrillation; Drug Administration Schedule; Drug Therapy, Combination; Gastroesophageal Reflux; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Proton Pump Inhibitors; Risk Factors; Warfarin

Long-acting anticoagulant rodenticides, also called superwarfarins, are known for their greater potency, longer half-life and delayed onset of symptoms. Cases of superwarfarin poisoning can pose a diagnostic and clinical challenge due to a wide array of presentations and prolonged severe coagulopathy requiring months of high-dose oral vitamin K therapy. The most common presentation of long-acting anticoagulant rodenticide poisoning is mucocutaneous bleeding, with other common presentations including haematuria, gingival bleeding, epistaxis and gastrointestinal bleeding. We discuss a case of deliberate self-poisoning with long-acting anticoagulant rodenticides presenting with haematuria and coagulation values above measurable limits. This case is important as it required immediate and maintenance therapy in order to prevent profound bleeding, as well as the evaluation of the patient's psychosocial factors to ensure medical compliance and to prevent refractory complications or repeated self-harm.

Topics: Abdominal Pain; Anticoagulants; Antifibrinolytic Agents; Anxiety Disorders; Blood Coagulation; Blood Coagulation Disorders; Chronic Pain; Comorbidity; Delayed-Action Preparations; Gastrointestinal Hemorrhage; Hematuria; Humans; Male; Middle Aged; Referral and Consultation; Suicide, Attempted; Treatment Outcome; Vitamin K; Warfarin

To determine the incidence and severity of bleeding events requiring hospitalization among patients with atrial fibrillation (AF) receiving anticoagulants (dabigatran or warfarin) or antiplatelet agents (eg, aspirin and clopidogrel).. This was a single-center, retrospective cohort study involving 1494 patients with AF hospitalized from November 1, 2010, to November 1, 2011, with prior warfarin, dabigatran, or antiplatelet therapy.. Overall bleeding events in the dabigatran group compared to the warfarin group were 24% and 12%, respectively ( P = .004). Of these events, individually, there were no significant differences in major (56% vs 58%, P = .88), life-threatening (25% vs 36%, P = .38), or minor bleeding (44% vs 42%, P = .06). Gastrointestinal (GI) bleeding occurred more in the dabigatran group compared to the warfarin group ( P = .02). Intracranial bleeding occurred in 15% of patients in the warfarin group and did not occur at all in the dabigatran group. Warfarin patients had significantly more overall bleeding events compared to antiplatelet therapy ( P < .001), with an increasing trend seen in major bleeding ( P = .06). GI bleeding, however, favored the warfarin group over the antiplatelet group (48% vs 73%, P = .04).. Anticoagulation with dabigatran was associated with an overall increased occurrence of bleeding requiring hospital admission compared to warfarin. GI bleeding was more prevalent with dabigatran and antiplatelets than with warfarin. There were more intracranial hemorrhages seen in the warfarin group.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cohort Studies; Dabigatran; Gastrointestinal Hemorrhage; Hemorrhage; Hospitalization; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Retrospective Studies; Warfarin

The aim of this study was to review and describe the use of Prothrombinex by a physician-led retrieval service based remote from a hospital blood bank.. This is a retrospective observational study. Patients to whom Prothrombinex was administered by the retrieval team were identified from the retrieval service patient database. The paper case cards of the identified patients were then manually reviewed and the data matched to patients in the state-wide electronic laboratory record.. Between 1 January 2010 and 30 November 2013 38 cases were identified. For 28 the indication was warfarinisation associated with life-threatening bleeding (most commonly intracranial or gastrointestinal tract). In the remaining 10 cases, Prothrombinex was used to treat coagulopathy associated with liver disease or massive haemorrhage. The median time saved by the retrieval team administering PTX-VF, rather than waiting to the receiving centre, was 120 min (interquartile range: 85-195 min). The median dose of PTX-VF administered was 23.25 IU/kg (interquartile range: 20-33 IU/kg). Paired international normalised ratios (INRs) were available for 33 of the 38 patients. In the warfarin group, all patients had an improvement in their INR and 21 of 25 had correction of their INR. In the non-warfarin group, the effect on INR was more variable.. Prothrombinex is a clinically useful product that can be relatively easily stored and used by retrieval services, even if they are based in isolation from a hospital blood bank. More research is required to look at the utility of Prothrombinex for non-warfarin-related bleeding in the pre-hospital and retrieval environment.

Topics: Adult; Aged; Anticoagulants; Blood Banks; Blood Coagulation Disorders; Blood Coagulation Factors; Emergency Service, Hospital; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Liver Diseases; Male; Middle Aged; Retrospective Studies; Statistics, Nonparametric; Time-to-Treatment; Warfarin

Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics.. The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180days of concomitant use.. Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin+gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use.. Among warfarin-treated persons, the use of fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH.

Topics: Aged; Anticoagulants; Cohort Studies; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Humans; Hypolipidemic Agents; Incidence; Insurance Benefits; Intracranial Hemorrhages; Male; Medicare; Middle Aged; Propensity Score; United States; Warfarin

Effectiveness data on novel oral anticoagulants (NOACs) versus warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) by prior warfarin use are limited.. We used data from the US MarketScan databases from 2009 to 2012. NVAF patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users. Propensity score-adjusted Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for relevant endpoints in NOACs versus warfarin users. Separate analyses were conducted to compare anticoagulant-naïve users of NOACs and those switching from warfarin.. Among 32,918 dabigatran, 3301 rivaroxaban, and 109,447 warfarin users with NVAF, 225 intracranial bleeds, 1035 ischemic strokes, 958 myocardial infarctions, and 1842 gastrointestinal bleeds were identified. Compared to warfarin users, patients initiating NOACs had similar ischemic stroke rates and lower intracranial bleeding rates, while the gastrointestinal bleeding rate was higher in dabigatran users than warfarin users. Associations of dabigatran with ischemic stroke risk differed between anticoagulant-naïve initiators and patients switching from warfarin; dabigatran was associated with lower ischemic stroke rates in naïve users (HR 0.65, 95% CI 0.52-0.82) but not in switchers (HR 1.20, 95% CI 0.95-1.51), compared to warfarin. Risk of stroke and bleeding was not different between rivaroxaban and warfarin users.. Real-world effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in published clinical trials. However, harms and benefits of switching from warfarin to dabigatran need to be evaluated.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Rivaroxaban; Warfarin

Direct oral anticoagulants (DOACs) have shown noninferiority to warfarin for stroke prevention in nonvalvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to be addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase.. Study based on reports of suspected ADRs held in VigiBase as at December 2014, in which a DOAC or warfarin were administered in patients with nonvalvular AF and listed as suspected/interacting drugs. Medical Dictionary for Regulatory Activities was used to classify ADRs. Reporting odds ratio (ROR) with 95% confidence interval were calculated. Results with P ≤ 0.05 were statistically significant.. We retrieved 32 972 reports. We identified 204 ADRs with a ROR >1 (P ≤ 0.05) and we focused on 105 reactions. Positive ROR emerged for DOACs and gastrointestinal haemorrhage compared with warfarin [(1.6 (1.47-1.75)], but no disproportionality with cerebral haemorrhage was found [0.31 (0.28-0.34)]. We identified other potential signals that have not been associated with DOACs previously.. As well as premarketing authorization clinical trial studies, we found a reduced risk of intracranial haemorrhage, but an increased risk of gastrointestinal haemorrhage in patients treated with DOACs compared to warfarin. We provide new data and we highlight several differences between the three novel oral anticoagulants, in the rate and type of ADRs occurred.

Topics: Administration, Oral; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Child; Child, Preschool; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Humans; Infant; Infant, Newborn; Male; Middle Aged; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stroke; Warfarin; World Health Organization; Young Adult

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Gastrointestinal Hemorrhage; Humans; Neoplasms; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Data Collection; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Observational Studies as Topic; Patient Selection; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Registries; Rivaroxaban; Stroke; Warfarin

Early reports suggested that the risk of gastrointestinal bleeding (GIB) was higher for patients on non-vitamin K antagonist oral anticoagulants (NOACs) than for those on warfarin. We compared the incidence of GIB in our patients on NOACs with those on warfarin.. We used our VA pharmacy database to identify patients taking NOACs (dabigatran, rivaroxaban, and apixaban) or warfarin between January 2011 and June 2015, and used the VistA system to identify those who were hospitalized for GIB. We included only patients with clinically significant GIB, defined as documented GI blood loss with a hemoglobin drop ≥2 g/dl, hemodynamic instability, and/or need for endoscopic evaluation, angiography, or surgery.. We identified 803 patients on NOACs and 6,263 on warfarin. One hundred and fifty-eight patients on warfarin had GIB (2.5%), compared with only five patients (0.6%) on NOACs (odds ratio=4.13; 95% confidence interval: 1.69-10.09). Blood transfusion for GIB was significantly more common in patients on warfarin than on NOACs (64.6% vs. 20%, P=0.04). Within 90 days of GIB hospitalization, 12 patients (7.6%) in the warfarin group died, whereas there were no deaths in the NOAC group.. In our patients, the incidence of GIB for those on warfarin was more than four times that for those on NOACs. Blood transfusions for GIB were more common in warfarin patients, and no NOAC patients died of GIB. In contrast to early reports, our findings suggest that the risk of GIB and subsequent complications is considerably lower for patients on NOACs than for patients on warfarin.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Blood Transfusion; Dabigatran; Female; Gastrointestinal Hemorrhage; Hemoglobins; Humans; Incidence; Male; Pulmonary Embolism; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Stroke; Warfarin

We report the case of 23-year-old man with mitral valve regurgitation and Glanzmann thrombasthenia, who underwent mechanical mitral valve replacement. Warfarin therapy was devastating, causing bilateral hemothorax, pericardial effusion, gastrointestinal bleeding, and hematuria. Redo mitral valve replacement with a biological prosthesis was required to resolve this critical situation. To our knowledge, this is the first report of mitral valve replacement in Glanzmann thrombasthenia, highlighting the danger of oral anticoagulation in this pathology.

Topics: Administration, Oral; Anticoagulants; Bioprosthesis; Blood Coagulation; Device Removal; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hematuria; Humans; Male; Mitral Valve; Mitral Valve Insufficiency; Pericardial Effusion; Postoperative Hemorrhage; Prosthesis Design; Reoperation; Risk Factors; Thrombasthenia; Treatment Outcome; Warfarin; Young Adult

New oral anticoagulants (NOACs) are now clinically available. However, few studies have demonstrated which patients with non-valvular atrial fibrillation (NVAF) actually receive NOACs in a clinical setting. We analyzed 182 NVAF patients who received oral anticoagulants. Clinical backgrounds and the risk of stroke, systemic embolism, and bleeding associated with oral anticoagulants were investigated. Seventy-three (40 %) patients were treated with NOACs and 109 (60 %) patients were treated with warfarin. A significantly lower mean number of bleeding risk factors was observed among the patients treated with NOACs than among those treated with warfarin (P = 0.010). Of the bleeding risk factors, NOACs were significantly less frequently prescribed in patients with a bleeding history and elderly subjects (>65 years) than in those who received warfarin (P < 0.001 and P = 0.029). A multivariate logistic regression analysis revealed that CHF and bleeding history were independently and significantly associated with the administration of NOACs (P = 0.047 and P = 0.003). The rate of a history of intracranial hemorrhage was comparable between the patients treated with NOACs and those treated with warfarin (P = 1.000). Significantly lower rates of a history of gastrointestinal and other minor bleeding were observed in the patients who received NOACs versus those who received warfarin (P = 0.001 and P = 0.026). NOACs were less frequently prescribed in patients with a history of bleeding, especially those with a history of gastrointestinal bleeding in a clinical setting.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chi-Square Distribution; Drug Prescriptions; Drug Utilization Review; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Patient Selection; Practice Patterns, Physicians'; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

In elderly patients (≥ 75 years), evidence of dabigatran efficacy is lacking and increased vigilance is warranted. We aimed to assess dabigatran effectiveness and safety in elderly patients in real-world practice. We conducted a population-based study using administrative databases, in Quebec (1999-2013). Dabigatran users (110/150 mg) were compared with matched warfarin users with regard to stroke and bleeding events. Age was categorised into < 75 or ≥ 75 years. Propensity score adjusted models were used. The cohort consisted of 15,918 dabigatran users and 47,192 matched warfarin users, with 67.3% being elderly patients. The elderly predominantly used the lower dose (80.1%) while younger patients mainly used the higher dose (80.0%). In multivariable analyses adjusted for propensity score, the risk of stroke in elderly patients using dabigatran, was no different than the risk in warfarin users (HR 1.05, 95% CI: 0.93, 1.19) regardless of dabigatran dose. However, dabigatran was associated with lower rates of intracranial haemorrhage (HR 0.60, 95% CI: 0.47-0.76) and higher rates of gastrointestinal bleeding (HR 1.30 95% CI: 1.14-1.50) when compared to warfarin. Based on real-life experience, dabigatran can offer an alternative to warfarin in elderly patients, with fewer intracranial bleeding events. However, caution is warranted for gastrointestinal bleeding.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Blood Coagulation; Dabigatran; Databases, Factual; Drug Utilization Review; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Multivariate Analysis; Propensity Score; Proportional Hazards Models; Quebec; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

The U.S. Food and Drug Administration recently approved a four-factor prothrombin complex concentrate (4-PCC) for warfarin reversal. The literature supporting its use over three-factor prothrombin complex concentrate (3-PCC) is limited.. Our objective was to retrospectively compare the efficacy of 3-PCC to 4-PCC in reversing warfarin in patients who were actively bleeding.. We conducted a single-center, retrospective cohort analysis of adult patients who received 3-PCC or 4-PCC for international normalized ratio (INR) reversal. Our study excluded patients not actively bleeding and not on warfarin. The main outcome was the percentage of patients who achieved warfarin reversal defined as INR ≤ 1.3 at first INR check post factor administration. We recorded baseline data including PCC dose, location of bleed, pre- and posttreatment INR, and time to INR reversal.. We included a total of 53 patients. Intracranial hemorrhage was the most common site of bleeding (26 [74.3%] in 3-PCC vs. 12 [66.7%] in 4-PCC). The mean dose of 3-PCC was 25.5 units/kg, compared to 27.9 units/kg of 4-PCC. The mean baseline INR was 2.3 in the 3-PCC group and 3 in the 4-PCC group (p = 0.03), and the first posttreatment INRs were 1.4 and 1.2, respectively (p < 0.01). Warfarin reversal was achieved in 15 (42.9%) patients who received 3-PCC and 15 (83.3%) patients who received 4-PCC (p < 0.01). Faster time to INR reversal was noted in the 4-PCC group vs. the 3-PCC group (3.7 vs. 5 h, p = 0.48).. A higher percentage of patients achieved warfarin reversal with 4-PCC compared to 3-PCC treatment. A prospective randomized control trial is necessary to confirm our results.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Retrospective Studies; Warfarin

Clinical characteristics, management, and outcomes in hemodialysis patients with atrial fibrillation (AF) remain unclear.. We studied 423 Japanese patients undergoing maintenance hemodialysis (age 65.2±12.4 years, male 70%, mean duration of hemodialysis 139±124 months). AF was present in 19% (n=82) and was independently related to increased age (odds ratio 1.070, 95% confidence interval 1.043-1.098), longer hemodialysis duration (odds ratio 1.006, 95% confidence interval 1.004-1.008), and congestive heart failure (odds ratio 2.749, 95% confidence interval 1.546-4.891). During observations lasting a mean of 36 months, the incidences of all-cause death, cardiovascular death, and major bleeding, in particular gastrointestinal bleeding, were significantly higher in the AF (n=82) than the non-AF (n=341) patients (p<0.001, p=0.004, p=0.002, p=0.027, respectively), but the incidence of ischemic stroke/systemic embolism was similar in the AF and non-AF patients. AF was independently associated with all-cause death (hazard ratio 1.728, 95% confidence interval 1.123-2.660) and major bleeding (hazard ratio 1.984, 95% confidence interval 1.010-3.896). Warfarin was prescribed in 33% of the AF patients, but the rates of all-cause death, ischemic stroke, and major bleeding during the study period were not significantly different between warfarin (n=27) and non-warfarin (n=55) groups.. In our hemodialysis patients, AF was a common comorbidity and was independently associated with all-cause death and major bleeding, but not with increased risk of ischemic stroke.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Embolism; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Proportional Hazards Models; Registries; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; Time Factors; Warfarin

Topics: Aged; Angiodysplasia; Blood Coagulation Tests; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Humans; Male; Prosthesis Design; Pyrazoles; Pyridones; Risk Factors; Thrombosis; Treatment Outcome; Ventricular Function, Left; Warfarin

Warfarin is the most commonly used oral anticoagulant and serious bleeding remains the most feared complication. Excessive warfarin anticoagulation (EWA) can be associated with adverse outcome. We aimed to identify the predictors of adverse clinical outcomes in patients admitted with EWA.. Medical records of patients admitted with EWA from March-2004 through Feb-2015 were reviewed. EWA was defined as international normalized ratio (INR)>3.5 in patients who have been receiving warfarin. Primary outcome was death within hospital and secondary outcome was major composite complications (MCC) defined as intracranial hemorrhage (ICH), a need for transfusing ≥ 4 units packed red blood cell (PRBC), a need for surgical intervention for hemostasis or death within hospital.. 267 patients (153 females and 114 male) were enrolled. 25 patients (9.4%) died during hospitalization. ICH, upper gastrointestinal bleeding and hemoptysis were more common in patients who did not survive (P-value: <0.001, 0.033 and 0.028; respectively). There was no correlation between indication for anticoagulation and death within hospital or development of MCC. In multivariate analysis, O blood group, ICH and the number of transfused PRBC and fresh frozen plasma units were identified as independent predictors of death within hospital. Lower hemoglobin concentrations and higher pulmonary pressures on admission were independent predictors of MCC, which occurred in 47 patients (17.6%).. Hospital mortality correlated with the severity of bleeding (requiring ≥ 4 units PRBC), intracranial hemorrhage and O blood group, while MCC associated with lower hemoglobin and pulmonary hypertension at the time of admission.

Topics: Anticoagulants; Aspirin; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Hospital Mortality; Humans; Incidence; Intracranial Hemorrhages; Iran; Male; Platelet Aggregation Inhibitors; Prescription Drug Overuse; Risk Factors; Survival Rate; Thromboembolism; Warfarin

Three- and four-factor prothrombin complex concentrates (PCC) are gaining popularity for acute reversal of vitamin K antagonist-associated bleeding. Although acute thrombosis after PCC administration has been described, it seems to be rare.. An 83-year-old woman on warfarin for history of deep venous thrombosis (DVT) presented to the Emergency Department with life-threatening gastrointestinal bleeding, requiring urgent PCC administration. After stabilization, she subsequently developed a new limb-threatening upper-extremity DVT. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As PCC therapy gains popularity for reversal of anticoagulant-induced bleeding in urgent bleeding scenarios, the emergency physician must be aware of the complications of PCC administration, including new limb-threatening DVT.

Topics: Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Heparin; Humans; Upper Extremity; Venous Thrombosis; Warfarin

Gastrointestinal bleeding is a well-known risk of systemic anticoagulation. However, bleeding in the setting of supratherapeutic anticoagulation may have a milder natural history than unprovoked bleeding. It is a common clinical gestalt that endoscopy is common, but bleeding source identification or intervention is uncommon, yet few data exist to inform this clinical impression. Consequently, we sought to examine our institutional experience with gastrointestinal bleeding in the setting of supratherapeutic international normalized ratio (INR) with the aim of identifying predictors of endoscopically identifiable lesions, interventions, and outcomes.. A retrospective review was conducted at a tertiary referral academic medical center to identify patients presenting with gastrointestinal bleeding in the setting of warfarin and a supratherapeutic INR (>3.5) who underwent an endoscopic procedure. Relevant clinical covariates, endoscopic findings, need for intervention, and outcomes were collected by review of the medical record. Logistic regression adjusting for potential confounders identified predictors of endoscopically significant lesions as well as intervention and outcomes.. A total of 134 patients with INR 3.5 or greater (mean 5.5, range 3.5-17.1) presented with symptoms of gastrointestinal bleeding, most commonly as melena or symptomatic anemia. Antiplatelet agents were used by 54% of patients, and 60% of patients were on concomitant acid suppression on admission. Procedures included esophagogastroduodenoscopy (upper endoscopy; EGD) (n = 128), colonoscopy (n = 73), and video capsule endoscopy (n = 32). Active bleeding at first EGD or colonoscopy was found in only 19 patients (18%), with endoscopic intervention in only 26 patients (25%). At a critical threshold of INR 7.5 at presentation, the likelihood of finding an endoscopically significant lesion fell to <20%. On multivariate logistic regression, concomitant antiplatelet therapy (odds ratio [OR] 2.59; 95% confidence interval [CI], 1.13-5.94), timing of EGD within 12 hours of presentation (OR 3.71; 95% CI, 1.05-13.08), and INR level (OR 0.79; 95% CI, 0.64-0.98) were the only significant independent predictors of identifying a source of bleeding. A risk score incorporating these covariates performed modestly in identifying risk of significant finding on EGD (area under the curve 0.68). We found no association between identification of a significant lesion at EGD and future readmission for gastrointestinal bleeding.. This study demonstrates that the relationship between INR elevation and identification of a bleeding source or endoscopic intervention at EGD are indeed antiparallel. Concomitant antiplatelet therapy increases the likelihood of bleeding source identification and intervention, as does EGD within 12 hours of presentation. However, regardless of source identification or endoscopic intervention, important clinical outcomes were unchanged, suggesting that decisions about endoscopy should be made on a case-by-case basis, particularly in patients with INR > 7.5. Future prospective studies on appropriate indications and timing of endoscopy in such patients are warranted.

Topics: Academic Medical Centers; Aged; Anemia; Anticoagulants; Capsule Endoscopy; Drug Therapy, Combination; Electronic Health Records; Endoscopy, Gastrointestinal; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Logistic Models; Male; Melena; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Warfarin

Whether dabigatran is associated with different risks of cardiovascular, bleeding events, and mortality from warfarin in Asian patients with nonvalvular atrial fibrillation remains unclear.. We used the Taiwan National Health Insurance Research Database to obtain 9940 and 9913 nonvalvular atrial fibrillation patients taking dabigatran and warfarin, respectively, from June 1, 2012, to December 31, 2013, as the dynamic cohort. Inverse probability of treatment weighting using propensity scores was used to balance covariates across 2 study groups. Patients were followed up until the first occurrence of any study outcome or end date of study.. During a median follow-up period of 0.67 years, there were 526 outcomes for dabigatran group. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.62 (0.52-0.73; P<0.0001); myocardial infarction, 0.67 (0.43-1.05; P=0.0803); intracranial hemorrhage, 0.44 (0.32-0.60; P<0.0001); major gastrointestinal bleeding, 0.99 (0.66-1.49; P=0.9658); all hospitalized major bleeding, 0.58 (0.46-0.74; P<0.0001); and all-cause mortality, 0.45 (0.38-0.53; P<0.0001). Dabigatran did not increase the risk of myocardial infarction or major gastrointestinal bleeding in all age groups when compared with warfarin. Total 8772 patients (88%) took a 110-mg dose in dabigatran group. The magnitude of effect for each outcome of 110-mg was comparable with that of 150-mg dose in the subgroup analysis.. In real-world practice, dabigatran was associated with a reduced risk of ischemic stroke, intracranial hemorrhage, all hospitalized major bleeding, and all-cause mortality compared with warfarin in Asian patients with nonvalvular atrial fibrillation. Dabigatran did not increase the risk of major gastrointestinal bleeding or myocardial infarction compared with warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Asian People; Atrial Fibrillation; Brain Ischemia; Cardiovascular Diseases; Case-Control Studies; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hospitalization; Humans; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Mortality; Myocardial Infarction; Proportional Hazards Models; Risk Factors; Stroke; Taiwan; Warfarin

Topics: Acute Disease; Anticoagulants; Gastrointestinal Hemorrhage; Humans; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Coronary Thrombosis; Female; Femoral Vein; Gastrointestinal Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Stroke; Thrombosis; Venous Thrombosis; Warfarin

Topics: Angiodysplasia; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Humans; Male; Pyrazoles; Pyridones; Ventricular Function, Left; Warfarin

To compare confounding adjustment by high-dimensional propensity scores (hdPSs) and historically developed high-dimensional disease risk scores (hdDRSs) in three comparative study examples of newly marketed medications: (1) dabigatran vs. warfarin on major hemorrhage; (2) on death; and (3) cyclooxygenase-2 inhibitors vs. nonselective nonsteroidal anti-inflammatory drugs on gastrointestinal bleeds.. In each example, we constructed a concurrent cohort of new and old drug initiators using US claims databases. In historical cohorts of old drug initiators, we developed hdDRS models including investigator-specified plus empirically identified variables and using principal component analysis and lasso regression for dimension reduction. We applied the models to the concurrent cohorts to obtain predicted outcome probabilities, which we used for confounding adjustment. We compared the resulting estimates to those from hdPS.. The crude odds ratio (OR) comparing dabigatran to warfarin was 0.52 (95% confidence interval: 0.37-0.72) for hemorrhage and 0.38 (0.26-0.55) for death. Decile stratification yielded an OR of 0.64 (0.46-0.90) for hemorrhage using hdDRS vs. 0.70 (0.49-1.02) for hdPS. ORs for death were 0.69 (0.45-1.06) and 0.73 (0.48-1.10), respectively. The relative performance of hdDRS in the cyclooxygenase-2 inhibitors example was similar.. hdDRS achieved similar or better confounding adjustment compared to conventional regression approach but worked slightly less well than hdPS.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Confounding Factors, Epidemiologic; Cyclooxygenase 2 Inhibitors; Data Interpretation, Statistical; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Propensity Score; Risk Assessment; Warfarin

Topics: Acute Disease; Anticoagulants; Gastrointestinal Hemorrhage; Humans; Warfarin

Atrial fibrillation (AF) is a common cardiac arrhythmia. Dabigatran etixalate (DE) is one of the new oral anticoagulant drugs being used in nonvalvular AF (NVAF). There is no adequate real world data in different populations about DE. The aim of this registry was to evaluate the efficacy and safety of DE Consecutive NVAF patients treated with warfarin or both DE doses were enrolled during 18 months study period. The patients were re-evaluated at regular 6-month intervals during the follow-up period. During the follow-up period outcomes were documented according to RELY methodology A total of 555 patients were analyzed. There was no significant difference in ischemic stroke rates (p = 0.73), death rates (p = 0.15) and MI rates (p = 0.56) between groups. The rate of major bleeding was significantly higher in warfarin and dabigatran 150 mg group than dabigatran 110 mg (p < 0.001). Intracranial bleeding rate and relative risk were significantly lower in dabigatran 110 mg group than warfarin group (p = 0.004). Dyspepsia was significantly higher in both DE doses than warfarin (p = 0.004) Both DE doses are as effective as warfarin in reducing stroke rates in NVAF patients, without increasing MI rates. Intracranial bleeding rates are significantly lower in warfarin than both doses of DE and gastrointestinal bleeding risk increases with increased DE doses.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Dyspepsia; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Registries; Stroke; Warfarin

Portal vein system thrombosis (PVST) is an alarming and potentially life-threatening complication of laparoscopic splenectomy and azygoportal disconnection (LSD). The objective of this study was to investigate negative and positive predictors of PVST after LSD in patients receiving anticoagulant regimens with aspirin or warfarin.. Seventy-five consecutive patients who underwent LSD from 2013 to 2014 were retrospectively reviewed. Patients received anticoagulant regimen with warfarin (n = 35) or aspirin (n = 40) according to individual preference. International normalized ratio (INR) and the incidence of PSVT were compared in patients received anticoagulant regimen with warfarin or aspirin on postoperative days (POD) 7, 30, and 90, and factors associated with PVST at these time points were determined by univariate and logistic multivariable regression analyses.. Portal vein diameter was an independent negative predictor of PVST on PODs 7, 30, and 90. Anticoagulation with warfarin was an independent positive predictor of PVST on PODs 30 and 90, and INR was an independent positive predictor of PVST on POD 90. Dynamic changes in the incidence of PVST on the day of admission and on PODs 7, 30, and 90 differed significantly between the warfarin and aspirin groups (P = 0.002). No patient experienced perioperative bleeding.. Portal vein diameter was an independent negative predictor, while anticoagulation therapy with warfarin and INR were independent positive predictors, of PVST after LSD. Early anticoagulation with warfarin is safe and effective for the prevention of PVST after LSD.

Topics: Adult; Anticoagulants; Azygos Vein; Esophageal and Gastric Varices; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Hypersplenism; Hypertension, Portal; Laparoscopy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Retrospective Studies; Splenectomy; Venous Thrombosis; Warfarin

Few large studies have evaluated the adverse events associated with therapeutic colonoscopy for colorectal neoplasia, including bleeding and bowel perforation. Our aim was to investigate factors associated with these events, using a Japanese national inpatient database.. We extracted data from the nationwide Japan Diagnosis Procedure Combination database for patients who underwent therapeutic colonoscopy for colorectal neoplasia between 2013 and 2014. Therapeutic colonoscopy included endoscopic submucosal dissection (ESD), EMR, and polypectomy. Outcomes included bleeding, perforation, cerebro-cardiovascular events, and in-hospital death. A multivariable logistic regression model was used to evaluate factors associated with bleeding and bowel perforation.. We analyzed 345,546 patients, including 16,812 (4.9%) who underwent ESD, 219,848 (63.6%) who underwent EMR, and 108,886 (31.5%) who underwent polypectomy. The rates of bleeding, bowel perforation, cardiovascular events, cerebrovascular events, and death were 32.5, 0.47, 0.05, 0.88, and 1.32 per 1000 patients, respectively. In the multivariate analysis, a higher bleeding rate was associated with being male, comorbid diseases, ESD, tumor size ≥2 cm, and use of drugs including low-dose aspirin, thienopyridines, non-aspirin antiplatelet drugs, novel oral anticoagulants, warfarin, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids. A higher bowel perforation rate was associated with being male, renal disease, ESD, tumor size ≥2 cm, and drugs including warfarin, NSAIDs, and steroids.. Although the incidence of adverse events after therapeutic colonoscopy was low, several patient-related factors were significantly associated with bleeding and bowel perforation.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cerebrovascular Disorders; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Comorbidity; Endoscopic Mucosal Resection; Female; Gastrointestinal Hemorrhage; Hospital Mortality; Humans; Incidence; Intestinal Perforation; Japan; Kidney Diseases; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Sex Factors; Steroids; Tumor Burden; Warfarin

Randomized controlled trials (RCTs) have shown that dabigatran, rivaroxaban and warfarin cause similar bleeding rates.. We performed a retrospective population-based cohort study to determine the incidence of bleeding in patients with atrial fibrillation (AF) beginning dabigatran, rivaroxaban or warfarin. Consecutive patients initiating anticoagulation for AF during a 3year period were identified using a computerized database. Patients who bled and required hospitalization underwent chart review. Bleeding incidences were calculated per 100 patient-years of treatment.. 18,249 patients were included: 9564 (52.4%) received warfarin, 5976 (32.7%) dabigatran, and 2709 (14.8%) rivaroxaban. Bleeding incidences were 3.9 (95% CI, 3.6-4.4) in warfarin-treated patients, 4.2 (95% CI, 3.7-4.7) in dabigatran patients, and 4.1 (95% CI, 3.0-5.3) in rivaroxaban patients. Intracranial hemorrhage (ICH) rates were 0.71 (95% CI, 0.56-0.90) for warfarin, 0.4 (95% CI, 0.18-0.87) for dabigatran, and 0.27 (95%CI, 0.10-0.80) for rivaroxaban. GI hemorrhage rates were 1.88 (95%CI, 1.62-2.20) for warfarin, 2.98 (95% CI, 2.4-3.5) for dabigatran and 2.39 (95%CI, 1.6-3.5) for rivaroxaban.. We demonstrate similar bleeding rates with both dabigatran 150mg and 110mg and rivaroxaban compared to warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Intracranial Hemorrhages; Israel; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

Patients who should be treated with both warfarin and a statin are frequently seen in vascular clinics. The risk for bleeding and potential drug interactions should be considered when prescribing both medications together. This study aimed to compare the risk for gastrointestinal bleeding among different statin exposures with concomitant administration of warfarin.. This is a single-hospital retrospective cohort study. We included patients who were concomitantly exposed to one of four statins (pravastatin, simvastatin, atorvastatin, and rosuvastatin) and warfarin for up to 2 years (730 days). The observation period ended when a gastrointestinal bleeding event occurred or the observation was censored. Within-class comparisons were used, and 1:1 matching using a propensity score was performed for comparisons between each statin and all of the other statins. Kaplan-Meier analyses with log-rank tests and Cox proportional hazard regression analyses were conducted to determine associations with the risk of gastrointestinal bleeding.. Data were analyzed for 1,686 patients who were concomitantly administered a statin and warfarin. Log-rank tests for the gastrointestinal bleeding-free survival rate showed that the risk for gastrointestinal bleeding was significantly lower in the pravastatin group (p = 0.0499) and higher in the rosuvastatin group (p = 0.009). In the Cox proportional hazard regression analysis, the hazard ratio of 5.394 for gastrointestinal bleeding based on statin exposure in the rosuvastatin group was significant (95% confidence interval, 1.168-24.916).. There was a relatively high risk of gastrointestinal bleeding with rosuvastatin when administered concomitantly with warfarin.

Topics: Aged; Anticoagulants; Atorvastatin; Atrial Fibrillation; Drug Interactions; Electronic Health Records; Female; Gastrointestinal Hemorrhage; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kaplan-Meier Estimate; Male; Middle Aged; Pravastatin; Proportional Hazards Models; Retrospective Studies; Risk Factors; Rosuvastatin Calcium; Simvastatin; Software; Tertiary Care Centers; Warfarin

Previous trials investigating usage of four-factor prothrombin complex concentrate (4F-PCC) excluded patients with various thrombotic risk factors. The objective of this study was to evaluate the safety and effectiveness of 4F-PCC in a real-world setting based on an institutional protocol that does not have strict exclusion criteria.. This was a retrospective study of adult patients who received 4F-PCC. The primary outcome was a confirmed thromboembolism within 14 days after 4F-PCC administration. Secondary outcomes included international normalized ratio (INR) correction to <1.5 at first draw and incidence of INR rebound for patients undergoing reversal of warfarin and hemostatic effectiveness for patients experiencing a bleed.. Ninety-three patients received 4F-PCC. Sixty-three (67.7%) were reversed for bleeding and 30 (32.3%) for surgery. Eleven patients (11.8%) developed a thromboembolism within 14 days. The median (interquartile range) time to event was 5 (2-7) days. Significant risk factors were heparin-induced thrombocytopenia (P= .01) and major surgery within 14 days (P= .02), as well as the presence of >6 thrombotic risk factors (P= .01). For patients post-warfarin reversal, 45/63 (71.4%) achieved INR correction at first draw, 55/63 (87.3%) achieved INR correction within 24 hours, and 14/55 (25.5%) experienced INR rebound. Of these 14 patients, 8 (57.1%) did not receive concomitant vitamin K.. 4F-PCC was associated with a notable thromboembolic risk. All patient-specific risk factors should be considered prior to administration. 4F-PCC remains a useful agent for warfarin reversal. Lack of concomitant vitamin K may contribute to INR rebound.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Cardiac Surgical Procedures; Dabigatran; Emergencies; Female; Gastrointestinal Hemorrhage; Heart Transplantation; Hemorrhage; Hemostatics; Heparin; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Laparotomy; Male; Middle Aged; Preoperative Care; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Surgical Procedures, Operative; Thrombocytopenia; Thromboembolism; Vitamin K; Warfarin

Although several non-vitamin K oral anticoagulants have been developed to prevent cardiogenic thrombosis, the status of hemorrhagic complications in the clinical setting among Asian populations, including Japan, remains unclear. We conducted this retrospective cohort study to clarify the current status of hemorrhagic events during antithrombotic therapy with non-vitamin K oral anticoagulants, with particular focus on gastrointestinal bleeding.. Medical charts of 475 patients prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and September 2014 were reviewed to examine whether any hemorrhagic events occurred, compared with 135 patients who received warfarin between April 2009 and March 2011.. Incidences of total and actionable hemorrhage in patient taking non-vitamin K oral anticoagulants were 13.8% per year and 4.6% per year, respectively, showing no significant differences from those in warfarin users (9.3% per year and 5.0% per year, respectively). In addition, actionable gastrointestinal hemorrhage occurred at similar rates in non-vitamin K oral anticoagulants users (2.1% per year) and warfarin users (1.5% per year). Most hemorrhages were from the lower gastrointestinal tract, and considerable events involved perianal bleeding. Multiple regression analysis showed that age, concomitant dual antiplatelet therapy, and concomitant nonsteroidal anti-inflammatory drug therapy were significant factors related to actionable gastrointestinal bleeding.. Risk of gastrointestinal hemorrhage in patients taking non-vitamin K oral anticoagulants was similar to that in patients taking warfarin. The dominant bleeding site was the lower gastrointestinal tract.
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Topics: Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Dabigatran; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Vitamin K; Warfarin

Proton pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding.. This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow-up. The study end points were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites.. Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63-0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94-1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84-1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39-0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations.. In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper gastrointestinal bleeding; the greatest reduction occurred in patients also taking antiplatelet drugs or NSAIDs.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Male; Medicaid; Medicare; Platelet Aggregation Inhibitors; Protective Factors; Proton Pump Inhibitors; Retrospective Studies; Tennessee; United States; Warfarin

Despite prescribing guidance, limited data exist to describe the use of apixaban in patients with end-stage renal disease (ESRD) requiring hemodialysis (HD). Current apixaban dosing recommendations for this patient population are based largely on a single-dose pharmacokinetic study of eight patients. We describe the clinical application and pharmacodynamic monitoring of apixaban in a 62-year-old 156-kg African-American woman with nonvalvular atrial fibrillation and ESRD requiring hemodialysis who developed calciphylaxis while receiving warfarin therapy. Based on a multidisciplinary clinical judgment decision due to concern for drug accumulation after multiple doses in patients with ESRD receiving HD, she was anticoagulated with apixaban 2.5 mg twice/day, as opposed to 5 mg twice/day as recommended by the package insert. Antifactor Xa monitoring was used, and resultant peak and trough apixaban concentrations were above the upper limit of detection for our clinical laboratory (more than 2.00 IU/ml). On day 7 of her hospitalization, the patient developed gastrointestinal bleeding, and apixaban was discontinued; no further clinical signs of bleeding occurred during her subsequent hospitalization course. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between apixaban exposure and the manifestation of gastrointestinal bleeding. The patient ultimately died 44 days after the acute bleeding event; however, coagulation concerns were not implicated in the patient's death. To our knowledge, this is the first case report that describes apixaban use and associated antifactor Xa monitoring in a patient with ESRD receiving HD, and it provides concern for current apixaban dosing recommendations in this patient population. Further pharmacokinetic and clinical data are likely necessary to better characterize apixaban use in these patients to optimize safety and efficacy.

Topics: Anticoagulants; Atrial Fibrillation; Drug Monitoring; Factor Xa Inhibitors; Fatal Outcome; Female; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Middle Aged; Pyrazoles; Pyridones; Renal Dialysis; Warfarin

It is unclear whether the non-vitamin K antagonist oral anticoagulant agents rivaroxaban and dabigatran are superior to warfarin for efficacy and safety outcomes in Asians with nonvalvular atrial fibrillation (NVAF).. The aim of this study was to compare the risk for thromboembolic events, bleeding, and mortality associated with rivaroxaban and dabigatran versus warfarin in Asians with NVAF.. A nationwide retrospective cohort study was conducted of consecutive patients with NVAF taking rivaroxaban (n = 3,916), dabigatran (n = 5,921), or warfarin (n = 5,251) using data collected from the Taiwan National Health Insurance Research Database between February 1, 2013 and December 31, 2013. The propensity score weighting method was used to balance covariates across study groups. Patients were followed until the first occurrence of any study outcome or the study end date (December 31, 2013).. A total of 3,425 (87%) and 5,301 (90%) patients were taking low-dose rivaroxaban (10 to 15 mg once daily) and dabigatran (110 mg twice daily), respectively. Compared with warfarin, both rivaroxaban and dabigatran significantly decreased the risk for ischemic stroke or systemic embolism (p = 0.0004 and p = 0.0006, respectively), intracranial hemorrhage (p = 0.0007 and p = 0.0005, respectively), and all-cause mortality (p < 0.0001 and p < 0.0001, respectively) during the short follow-up period. In comparing the 2 non-vitamin K antagonist oral anticoagulant agents with each other, no differences were found regarding risk for ischemic stroke or systemic embolism, intracranial hemorrhage, myocardial infarction, or mortality. Rivaroxaban carried a significantly higher risk for hospitalization for gastrointestinal bleeding than dabigatran (p = 0.0416), but on-treatment analysis showed that the risk for hospitalized gastrointestinal bleeding was similar between the 2 drugs (p = 0.5783).. In real-world practice among Asians with NVAF, both rivaroxaban and dabigatran were associated with reduced risk for ischemic stroke or systemic embolism, intracranial hemorrhage, and all-cause mortality without significantly increased risk for acute myocardial infarction or hospitalization for gastrointestinal bleeding compared with warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Asian People; Atrial Fibrillation; Cohort Studies; Dabigatran; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Risk Assessment; Rivaroxaban; Stroke; Thromboembolism; Warfarin

Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is among adverse effects of therapy in humans. Having in mind genetic variations in the effectiveness of WF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinal toxicity of oral warfarin in rats were examined in this study. High WF dose (3.5mg/l) led to mortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher values of prothrombin time were noted at low WF dose (0.35mg/l) in the former strain. Leukocyte infiltration in intestine noted at this dose in both strains was associated with oxidative injury and more pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cell proliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats, represent different strategies to protect vulnerable intestine from harmful immune responses.

Topics: Administration, Oral; Animals; Anticoagulants; Blood Coagulation; Cell Proliferation; Cytokines; Dose-Response Relationship, Drug; Duodenum; Gastrointestinal Hemorrhage; Jejunum; Lymph Nodes; Oxidative Stress; Prothrombin Time; Rats, Inbred Strains; Species Specificity; Warfarin

Current Japanese gastrointestinal (GI) endoscopic guidelines permit endoscopic biopsy without cessation of antiplatelet agents and warfarin in patients with a therapeutic range of prothrombin time-international normalized ratio (PT-INR) levels, although the evidence levels are low. We evaluated the safety of endoscopic biopsy in patients currently taking antithrombotics.. Consecutive patients receiving antithrombotics who underwent GI endoscopy from August 2012 to August 2013 were enrolled. Adverse events and endoscopic hemostasis after biopsy were evaluated. PT-INR level was measured in patients taking warfarin the day before endoscopy.. Among 7939 patients undergoing endoscopy, 1034 patients (13.0%, 706 men and 328 women, average age 72.8 years) were receiving antithrombotics. Antithrombotics included aspirin (44.8%), warfarin (34.7%), thienopyridine (16.1%), cilostazol (10.3%), dabigatran (4.8%) etc. PT-INR levels in patients taking warfarin were >3.0 in 13 patients (4.3%), between 2.5 and 3.0 in 18 patients (6.0%), <2.5 in 269 patients (89.7%). Two hundred and six patients received endoscopic biopsy while taking aspirin (51.2%), warfarin (22.8%), and thienopyridine (13.6%). Endoscopic hemostasis was required in three patients after endoscopic biopsy (spraying thrombin in two patients, spraying thrombin and clipping in one patient). There were no major complications. The incidence of endoscopic hemostasis after biopsy in patients without antithrombotic cessation was not significantly different than in the controls not taking antithrombotics (1.5% vs 0.98%, P = 0.51).. Endoscopic biopsy did not increase the bleeding risk despite not stopping antithrombotics prior to biopsy even among patients taking warfarin whose PT-INR was within the therapeutic range.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Biopsy; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Retrospective Studies; Risk Factors; Stomach Diseases; Thrombosis; Warfarin; Young Adult

The long-term recurrence of lower gastrointestinal bleeding (LGIB) and associated mortality have not been studied extensively. We investigated rates of recurrence of LGIB, mortality, and associated risk factors.. In a retrospective study, we analyzed data from 342 patients hospitalized for overt LGIB at the National Center for Global Health and Medicine in Japan from December 2004 through June 2013. All patients underwent colonoscopy. We assessed Charlson comorbidity index scores and the use of nonsteroidal anti-inflammatory drugs, low-dose aspirin, other antiplatelet drugs, or warfarin. Rebleeding, the total number of rebleeding episodes, and mortality were measured. The Cox proportional hazards model was used to estimate hazard ratios (HRs).. Rebleeding occurred in 84 patients, at a mean follow-up time of 19 months. The cumulative percentages of patients with rebleeding at 1 and 5 years were 19% and 46%, respectively. During the follow-up period, 29 patients (39%) had secondary rebleeding and 18 patients (62%) had subsequent rebleeding. Multivariate analysis showed age 65 years and older (HR, 1.7; P = .04) and the use of nonsteroidal anti-inflammatory drugs (HR, 2.0; P < .01) and nonaspirin antiplatelet drugs (HR, 1.8; P < .05) as independent risk factors for rebleeding. Dual therapy had a higher risk than single therapy (adjusted HR, 1.8; P < .05). During the mean follow-up period of 28 months, 21 patients died (2 from bleeding). Cumulative mortality rates at 1 and 5 years were 4.2% and 13%, respectively. Mortality was associated significantly with age ≥65 years (P < .05), Charlson comorbidity index score, and warfarin use.. Based on a retrospective analysis of patients with LGIB, 46% of all patients have rebleeding, and the overall mortality rate is 13% within 5 years after hospitalization. Besides age ≥65 years, use of antithrombotic drugs increases the risk of bleeding recurrence and mortality among patients with LGIB.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Anticoagulants; Aspirin; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Japan; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Retrospective Studies; Risk Factors; Survival Analysis; Warfarin

The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation in general practice settings has not been established.. We formed new-user cohorts of propensity score-matched elderly patients enrolled in Medicare who initiated dabigatran or warfarin for treatment of nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.80 (0.67-0.96); intracranial hemorrhage, 0.34 (0.26-0.46); major gastrointestinal bleeding, 1.28 (1.14-1.44); acute myocardial infarction, 0.92 (0.78-1.08); and death, 0.86 (0.77-0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, in which case dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150-mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis.. In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with nonvalvular atrial fibrillation. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Comorbidity; Dabigatran; Dose-Response Relationship, Drug; Follow-Up Studies; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Kidney Diseases; Medicare; Proportional Hazards Models; Retrospective Studies; Risk; Socioeconomic Factors; Stroke; Treatment Outcome; United States; Warfarin

Anticoagulants carry a significant risk of gastrointestinal bleeding (GIB). Data regarding the safety of anticoagulation continuation/cessation after GIB are limited. We sought to determine the safety and risk of continuation of anticoagulation after GIB.. We conducted a prospective observational cohort study on consecutive patients admitted to the hospital who had GIB while on systemic anticoagulation. Patients were classified into two groups at hospital discharge after GIB: those who resumed anticoagulation and those who had anticoagulation discontinued. Patients in both groups were contacted by phone 90 days after discharge to determine the following outcomes: (i) thromboembolic events, (ii) hospital readmissions related to GIB, and (iii) mortality. Univariate and multivariate Cox proportional hazards were used to determine factors associated with thrombotic events, rebleeding, and death.. We identified 197 patients who developed GIB while on systemic anticoagulation (n=145, 74% on warfarin). Following index GIB, anticoagulation was discontinued in 76 patients (39%) at discharge. In-hospital transfusion requirements, need for intensive care unit care, and etiology of GIB were similar between the two groups. During the follow-up period, 7 (4%) patients suffered a thrombotic event and 27 (14%) patients were readmitted for GIB. Anticoagulation continuation was independently associated on multivariate regression with a lower risk of major thrombotic episodes within 90 days (hazard ratio (HR)=0.121, 95% confidence interval (CI)=0.006-0.812, P=0.03). Patients with any malignancy at time of GIB had an increased risk of thromboembolism in follow-up (HR=6.1, 95% CI=1.18-28.3, P=0.03). Anticoagulation continuation at discharge was not significantly associated with an increased risk of recurrent GIB at 90 days (HR=2.17, 95% CI=0.861-6.67, P=0.10) or death within 90 days (HR=0.632, 95% CI=0.216-1.89, P=0.40).. Restarting anticoagulation at discharge after GIB was associated with fewer thromboembolic events without a significantly increased risk of recurrent GIB at 90 days. The benefits of continuing anticoagulation at discharge may outweigh the risks of recurrent GIB.

Topics: Aged; Aged, 80 and over; Anticoagulants; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Enoxaparin; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Ischemic Attack, Transient; Longitudinal Studies; Male; Middle Aged; Morpholines; Patient Readmission; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Venous Thrombosis; Warfarin; Withholding Treatment

Topics: Aged; Angiodysplasia; Anticoagulants; Blood Urea Nitrogen; Capsule Endoscopy; Cecal Diseases; Cecum; Diagnosis, Differential; Dizziness; Esophagitis; Gastrointestinal Hemorrhage; Heart-Assist Devices; Humans; Male; Myocardial Ischemia; Warfarin

We investigated the effects of proton-pump inhibitors (PPIs) on lower gastrointestinal bleeding (LGIB) and of their interactions with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, clopidogrel, and warfarin on LGIB risk.. We prospectively studied 355 patients emergently hospitalized for LGIB and 8,221 nonbleeding patients. All patients underwent colonoscopy. Smoking, alcohol drinking, drug exposure, and the Charlson comorbidity index score were assessed before colonoscopy. Adjusted odds ratios (AOR) of LGIB were estimated.. LGIB was significantly associated with older age, higher comorbidity index, and NSAID, aspirin, clopidogrel, or warfarin use. PPI use was significantly associated with older age, male sex, being a current alcohol drinker, higher comorbidity index, and NSAID, aspirin, clopidogrel, warfarin, acetaminophen, or corticosteroid use. Multivariate analysis adjusted by the confounding factors revealed LGIB was not significantly associated with PPI use (AOR 0.87; 95 % confidence interval 0.68-1.13; p = 0.311), or specifically with omeprazole (AOR 1.18; p = 0.408), esomeprazole (AOR 0.76; p = 0.432), lansoprazole (AOR 0.93; p = 0.669), or rabeprazole (AOR 0.63; p = 0.140). In the interaction model, no significant interactions were observed between PPIs and NSAIDs (AOR 1.40; p = 0.293), aspirin (AOR 1.09; p = 0.767), clopidogrel (AOR 0.99, p = 0.985), or warfarin (AOR 1.52; p = 0.398).. This large case-control study demonstrated that PPI use did not lead to an increased risk of LGIB, regardless of the type of PPI used. Further, LGIB risk was not affected by PPI use, irrespective of concomitant therapy with NSAIDs, low-dose aspirin, clopidogrel, or warfarin.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Case-Control Studies; Clopidogrel; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Proton Pump Inhibitors; Ticlopidine; Warfarin; Young Adult

This study investigated the relationship between anti-factor Xa (anti-FXa) and activated partial thromboplastin time (aPTT) for monitoring intravenous unfractionated heparin (IV-UFH) in patients with continuous-flow left ventricular assist devices (CF-LVADs).. CF-LVADs have become mainstream therapy for patients with advanced heart failure. Thromboembolic events, device thrombosis, and bleeding continue to be a challenge with this technology. Adequate anticoagulation is required to prevent these adverse events.. A prospective study of consecutive patients implanted with a CF-LVAD was conducted. Paired samples were considered concordant if aPTT values fell into expected ranges for subtherapeutic, therapeutic, and supratherapeutic anti-FXa levels. Heparin dosing was on the basis of anti-Xa levels.. A total of 340 paired values from 38 patients were evaluated. Anti-FXa and aPTT were discordant in 253 samples (74.4%), with a high degree of variability in aPTT for any given anti-FXa level (r(2) = 0.57). Results were discordant in 104 samples (63.8%) from patients undergoing bridging therapy with warfarin and in 149 samples (84.2%) from patients with device obstruction and/or hemolysis (p < 0.001). The most common pattern of discordance was a supratherapeutic aPTT value despite a therapeutic anti-FXa level (49.1% for bridging vs. 75.8% for device obstruction and/or hemolysis; p < 0.001).. Levels of aPTT were disproportionately prolonged relative to the corresponding anti-FXa levels in CF-LVAD patients, particularly those with device obstruction. Hemolysis and warfarin administration may falsely elevate aPTT, resulting in overestimation of heparin concentration and under-anticoagulation. Use of aPTT and anti-FXa to guide heparin therapy may lead to different estimates of heparin concentration in the same patient.

Topics: Anticoagulants; Drug Administration Schedule; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Hemolysis; Heparin; Humans; Infusions, Intravenous; Male; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Prosthesis Failure; Thromboembolism; Treatment Outcome; Warfarin

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Pressure; Comorbidity; Diet; Dose-Response Relationship, Drug; Endoscopy, Digestive System; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Medical History Taking; Polypharmacy; Referral and Consultation; Vitamin K; Warfarin

The risk of gastrointestinal (GI) bleeding with dabigatran when compared to warfarin has been controversial in the literature. The aim of our study was to assess this risk with the use of dabigatran.. We examined the medical records of patients who were started on dabigatran or warfarin from October 2010 to October 2012. The study was conducted in two hospitals.. A total of 417 patients were included (208 dabigatran vs. 209 warfarin). GI bleeding occurred in 10 patients (4.8%) in the dabigatran group compared to 21 patients (10.1%) in the warfarin group (p=0.0375). Multivariate analysis showed that patients who were on dabigatran for ≤ 100 days had a higher incidence of GI bleeding than those who were on it for >100 days (p=0.0007). The odds of GI bleeding in patients who were on dabigatran for ≤ 100 days was 8.2 times higher compared to those who were on the drug for >100 days. The incidence of GI bleeding in patients >65 years old was higher than in those <65 years old (p=0.0453, OR=3). History of previous GI bleeding was another risk factor for GI bleeding in the dabigatran group (p=0.036, OR=6.3). The lower GI tract was the most common site for GI bleeding in the dabigatran group (80.0% vs. 38.1%, p=0.014).. The risk of GI bleeding was lower with dabigatran. The risk factors for GI bleeding with dabigatran were the first 100 days, age >65 years, and a history of previous GI bleeding.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Retrospective Studies; Risk Factors; Warfarin

Dabigatran and warfarin are oral anticoagulant drugs widely used for the prevention of stroke in patients with atrial fibrillation. The objective of this study was to evaluate the interaction between aging and dabigatran- and warfarin-induced gastrointestinal (GI) and nervous system hemorrhage using data available in the FDA Adverse Event Reporting System (FAERS) database. We analyzed reports of hemorrhagic events in the GI and nervous system recorded in the FAERS database between 2004 and 2014 using an adjusted reporting odds ratio (ROR). We demonstrated that dabigatran-associated GI hemorrhage was significantly increased in patients over the age of 80 years. The RORs of dabigatran increased with increasing age, although aging had little effect on warfarin-associated GI hemorrhage. The ROR for anticoagulant-associated nervous system hemorrhage was not significantly affected by aging, as compared to GI hemorrhage. Our results indicate that the excretion of dabigatran may be affected by aging, as compared to warfarin, likely due to renal function decline. Our results emphasize the need for physicians to closely monitor GI bleeding in aging patients, because it is closely related to renal function deterioration.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Aged; Aged, 80 and over; Aging; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Databases, Factual; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Kidney; Male; Middle Aged; Odds Ratio; United States; United States Food and Drug Administration; Warfarin

To determine the real world risk of gastrointestinal bleeding associated with the use of the novel oral anticoagulants dabigatran and rivaroxaban compared with warfarin.. Retrospective, propensity matched cohort study.. Optum Labs Data Warehouse, a large database including administrative claims data on privately insured and Medicare Advantage enrollees.. New users of dabigatran, rivaroxaban, and warfarin from 1 November 2010 to 30 September 2013.. Incidence rates (events/100 patient years) and propensity score matched Cox proportional hazards models were used to estimate rates of total gastrointestinal bleeds, upper gastrointestinal bleeds, and lower gastrointestinal bleeds for the novel oral anticoagulants compared with warfarin in patients with and without atrial fibrillation. Heterogeneity of treatment effect related to age was examined using a marginal effects model.. The incidence of gastrointestinal bleeding associated with dabigatran was 2.29 (95% confidence interval 1.88 to 2.79) per 100 patient years and that associated with warfarin was 2.87 (2.41 to 3.41) per 100 patient years in patients with atrial fibrillation. In non-atrial fibrillation patients, the incidence of gastrointestinal bleeding was 4.10 (2.47 to 6.80) per 100 patient years with dabigatran and 3.71 (2.16 to 6.40) per 100 patient years with warfarin. With rivaroxaban, 2.84 (2.30 to 3.52) gastrointestinal bleeding events per 100 patient years occurred in atrial fibrillation patients (warfarin 3.06 (2.49 to 3.77)/100 patient years) and 1.66 (1.23 to 2.24) per 100 patient years in non-atrial fibrillation patients (warfarin 1.57 (1.25 to 1.99)/100 patient years). In propensity score matched models, the risk of gastrointestinal bleeding with novel oral anticoagulants was similar to that with warfarin in atrial fibrillation patients (dabigatran v warfarin, hazard ratio 0.79 (0.61 to 1.03); rivaroxaban v warfarin, 0.93 (0.69 to 1.25)) and in non-AF patients (dabigatran v warfarin, hazard ratio 1.14 (0.54 to 2.39); rivaroxaban v warfarin, 0.89 (0.60 to 1.32)). The risk of gastrointestinal bleeding increased after age 65, such that by age 76 the risk exceeded that with warfarin among atrial fibrillation patients taking dabigatran (hazard ratio 2.49 (1.61 to 3.83)) and patients with and without atrial fibrillation taking rivaroxaban (2.91 (1.65 to 4.81) and 4.58 (2.40 to 8.72), respectively).. The risk of gastrointestinal bleeding related to novel oral anticoagulants was similar to that for warfarin. Caution should be used when prescribing novel oral anticoagulants to older people, particularly those over 75 years of age.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Medicaid; Middle Aged; Morpholines; Patient Selection; Practice Patterns, Physicians'; Proportional Hazards Models; Retrospective Studies; Risk Factors; Rivaroxaban; Thiophenes; United States; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Gastrointestinal Hemorrhage; Humans; Male; Morpholines; Thiophenes; Warfarin

To determine the real world safety of dabigatran or rivaroxaban compared with warfarin in terms of gastrointestinal bleeding.. Retrospective cohort study.. Large administrative database of commercially insured people in United States from 1 October 2010 through 31 March 2012.. Enrollees with a prescription of warfarin, dabigatran, or rivaroxaban between 1 October 2010 and 31 March 2012, who were aged 18 years or older, had continuous enrollment and no oral anticoagulant use during the six months before the entry date, with known age and sex, and with no gastrointestinal bleeding for at least six months before the cohort entry date. The final study sample of 46,163 patients included 4907 using dabigatran, 1649 using rivaroxaban, and 39,607 using warfarin.. Time to gastrointestinal bleeding. Hazard ratios were derived from Cox proportional hazard models with propensity score weighting and robust estimates of errors.. Dabigatran users tended to be older (dabigatran v rivaroxaban v warfarin: 62.0 v 57.6 v 57.4 years) and more likely to be male (69% v 49% v 53%). The rate of gastrointestinal bleeding was highest among dabigatran users and lowest among rivaroxaban users (dabigatran v rivaroxaban v warfarin: 9.01 v 3.41 v 7.02 cases per 100 person years). After adjustment for potentially confounding covariates, there was no evidence of a statistically significant difference in the risk of gastrointestinal bleeding between dabigatran and warfarin users (adjusted hazard ratio 1.21, 95% confidence interval 0.96 to 1.53) or between rivaroxaban and warfarin users (0.98, 0.36 to 2.69).. Although rates of gastrointestinal bleeding seem to be similar in this commercially insured sample of adults in the United States, we cannot rule out as much as a 50% increase in the risk of gastrointestinal bleeding with dabigatran compared with warfarin or a more than twofold higher risk of bleeding with rivaroxaban compared with warfarin.

Topics: Administration, Oral; Adult; Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Middle Aged; Morpholines; Observational Studies as Topic; Retrospective Studies; Risk Factors; Rivaroxaban; Thiophenes; United States; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Gastrointestinal Hemorrhage; Humans; Male; Morpholines; Thiophenes; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Gastrointestinal Hemorrhage; Humans; Male; Morpholines; Thiophenes; Warfarin

Studies on unexplained gastrointestinal bleeding (GIB) are lacking. We aimed to study the clinical outcomes of patients with unexplained GIB and to determine the incidence of obscure GIB.. A population-based study on all patients undergoing endoscopy at the National University Hospital of Iceland in 2010. Indications, results of endoscopies and drug history were prospectively registered with a follow-up of 3 years. A national pharmaceutical database containing prescription data was utilized. Patients were categorized into unexplained overt and occult GIB and obscure GIB. Patients undergoing endoscopy and without GIB acted as controls.. Of 2471 patients undergoing endoscopy, 11% had unexplained GIB. Of those, 46% had unexplained overt GIB, 44% had unexplained occult GIB and 11% had obscure GIB. Multivariate analysis showed that patients with unexplained GIB and unexplained overt GIB had greater odds of NSAID use than controls, OR 1.8 (CI 1.03-3.03) and OR 2.0 (CI 1.01-3.77), respectively. Warfarin was strongly associated with all bleeder groups, OR 4-4.8. The incidence of obscure GIB was 10/100,000 inhabitants annually. Two (0.8%) patients were diagnosed with colon cancer 16 and 30 months after the index colonoscopy. Of patients with unexplained overt, unexplained occult GIB and controls, 5%, 6% and 3.5% (NS) had another overt bleeding episode, during the study period.. NSAIDs and warfarin seem to play an important role in unexplained GIB. The incidence of obscure GIB is low and missed cancers are very rare. The probability of a repeat bleeding episode is similar to that of controls.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Colonoscopy; Female; Gastrointestinal Hemorrhage; Humans; Iceland; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; Risk Factors; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Gastrointestinal Hemorrhage; Humans; Male; Morpholines; Thiophenes; Warfarin

Topics: Anticoagulants; Aortic Valve; Blood Coagulation Factors; Echocardiography; Echocardiography, Transesophageal; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Heparin; Humans; Infusions, Intravenous; Male; Middle Aged; Partial Thromboplastin Time; Splenic Infarction; Tomography, X-Ray Computed; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Gastrointestinal Hemorrhage; Humans; Male; Morpholines; Thiophenes; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Male; Rivaroxaban; Warfarin

Little is known about the major presenting features of patients with colorectal cancer (CRC) in a population-based setting, especially regarding bleeding-related symptoms.. To determine the proportion of CRC patients presenting with bleeding-related symptoms, to compare bleeders and nonbleeders and to explore the role of anticoagulants in bleeders.. This was a nationwide, population-based, retrospective study, investigating all patients diagnosed with CRC in Iceland from 2008 to 2011. Bleeding-related symptoms were defined as overt bleeding, iron deficiency anaemia or a positive faecal occult blood test. Obstructive symptoms were defined as a confirmed diagnosis of ileus or dilated intestines on imaging.. Data were available for 472/496 (95%) patients, males 51%, mean age 69 (±13) years. In all, 348 (74%) patients had bleeding-related symptoms; of these 348 patients, 61% had overt bleeding. Bleeders were less likely than nonbleeders to have metastases at diagnosis, 19% vs. 34% (P < 0.001). Overt bleeders were less likely than nonbleeders to have obstructive symptoms, 2% vs. 16% respectively (P < 0.0001). Occult bleeders were more likely to have proximal cancer (69%) than both overt (17%) and nonbleeders (44%) (P < 0.0001); however, they were less likely than nonbleeders to have metastases (22% vs. 35%, P < 0.05). Bleeders were more likely to use warfarin than nonbleeders (9% vs. 3%, P < 0.05); the use of low-dose aspirin was the same (24%).. The majority of patients with CRC present with bleeding-related symptoms. Bleeders with CRC present earlier than nonbleeders. Warfarin use may induce bleeding in some patients, resulting in an earlier diagnosis.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Anticoagulants; Aspirin; Colorectal Neoplasms; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Iceland; Male; Middle Aged; Occult Blood; Retrospective Studies; Warfarin

Data regarding the outcomes of restarting anticoagulation in patients who develop gastrointestinal bleeding (GIB) while anticoagulated are sparse. We hypothesized that restarting anticoagulation in these patients is associated with better outcomes. This is a retrospective cohort study that enrolled subjects who developed GIB while on anticoagulation from 2005 to 2010. Atrial fibrillation was defined by history and electrocardiography on presentation. GIB was defined as a decrease in hemoglobin by 2 g, visible bleeding, or positive endoscopic evaluation. Time-to-event adjusted analyses were performed to find an association of restarting warfarin and recurrent GIB, arterial thromboembolism, and mortality. Stratified analysis by duration of interruption of warfarin was also performed. Overall, 1,329 patients (mean age 76 years, women 45%) developed major GIB. Warfarin was restarted in 653 cases (49.1%). Restarting warfarin was associated with decreased thromboembolism (hazard ratio [HR] 1.18, 95% confidence interval [CI] 0.75 to 1.84, p = 0.47) [corrected] and reduced mortality (HR 0.67, 95% CI 0.56 to 0.81, p <0.0001) but not recurrent GIB (HR 1.18, 95% CI 0.94 to 1.10, p = 0.47). When the outcomes were stratified by duration of warfarin interruption, restarting warfarin after 7 days was not associated with increased risk of GIB but was associated with decreased risk of mortality and thromboembolism compared with resuming after 30 days of interruption. Decision to restart warfarin after an episode of major GIB is associated with improved survival and decreased thromboembolism without increased risk of GIB after 7 days of interruption.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Middle Aged; Retreatment; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome; United States; Warfarin

Our aim was to identify risk factors for acute gastrointestinal (GI) bleeding in patients with myocardial infarction (MI) who were prescribed clopidogrel following hospital discharge.. Data were collected retrospectively from patients treated in Veteran Affairs hospitals in Ohio, USA, from 2001 to 2008 with a primary diagnosis of MI (International Classification of Diseases, 9th Revision) and a prescription for clopidogrel filled within 48 h of discharge. Primary outcome was acute GI bleeding after discharge.. Acute GI bleeding occurred in 107 of 3218 patients. Bleeding occurred in those who were elder (66.2 vs. 62.4 years, P = 0.0002), had lower glomerular filtration rate (74 vs. 81 mL/min, P = 0.024), had filled prescription for warfarin (15.9% vs. 6.9%, P = 0.0004), diagnosed as atrial fibrillation (20.6% vs. 11.1%, P = 0.003), chronic liver (5.6% vs. 2.2%, P = 0.018) or kidney disease (29.0% vs. 19.4%, P = 0.016). A risk model and GI bleed risk score were developed and showed that patients with age >65 years, use of warfarin, the presence of chronic liver or kidney disease were at increased risk for GI bleeding.. Veterans patients of advanced age, using warfarin and with chronic liver and kidney disease may be at increased risk of GI bleeding when prescribed clopidogrel following MI. A scoring system may help to identify patients at high risk for GI bleeding.

Topics: Acute Disease; Age Factors; Aged; Anticoagulants; Chronic Disease; Clopidogrel; Female; Gastrointestinal Hemorrhage; Humans; Kaplan-Meier Estimate; Kidney Diseases; Liver Diseases; Male; Middle Aged; Myocardial Infarction; Ohio; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Risk Factors; Ticlopidine; Veterans; Warfarin

Assessment of the bleeding risk of antithrombotic agents is usually performed in healthy animals with some form of vascular injury to peripheral organs to induce bleeding. However, bleeding observed in patients with currently marketed antithrombotic drugs is typically spontaneous in nature such as intracranial haemorrhage (ICH) and gastrointestinal (GI) bleeding, which happens most frequently on top of preexisting pathologies such as GI ulcerations and polyps. Apc(min/+) mice are reported to develop multiple adenomas through the entire intestinal tract and display progressive anaemia.In this study, we evaluated the potential utility of Apc(min/+) mice as a model for assessing spontaneous GI bleeding with antithrombotic agents. Apc(min/+) mice exhibited progressive blood loss starting at the age of nine weeks. Despite the increase in bleeding, Apc(min/+) mice were in a hypercoagulable state and displayed an age-dependent increase in thrombin generation and circulating fibrinogen as well as a significant decrease in clotting times. We evaluated the effect of warfarin, dabigatran etexilate, apixaban and clopidogrel in this model by administering them in diet or in the drinking water to mice for 1-4 weeks. All of these marketed drugs significantly increased GI bleeding in Apc(min/+) mice, but not in wild-type mice. Although different exposure profiles of these antithrombotic agents make it challenging to compare the bleeding risk of compounds, our results indicate that the Apc(min/+) mouse may be a sensitive preclinical model for assessing the spontaneous GI bleeding risk of novel antithrombotic agents.

Topics: Age Factors; Animals; Benzimidazoles; Clopidogrel; Dabigatran; Disease Models, Animal; Drug Evaluation, Preclinical; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Genes, APC; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Pyrazoles; Pyridines; Pyridones; Risk Factors; Ticlopidine; Warfarin

The aim of the study was to investigate the incidence and related factors of upper gastrointestinal bleeding (UGIB) in a Chinese population of peripheral arterial disease (PAD).. A total of 850 Chinese PAD patients were followed up for about 6 years. The incidence of UGIB was recorded and related factors were evaluated. A total of 749 PAD patients with complete data were included in the final statistical analysis during the median follow-up time of 69 months. The incidence of UGIB in this PAD population was 8.4% during the follow-up. Univariate analysis indicated that PAD patients with UGIB were older. A higher percentage of patients with UGIB had hypertension, CKD, history of PUD, and used aspirin or warfarin than those without UGIB. But a lower percentage of patients with UGIB used PPI. The Cox regression analysis suggested that older age (HR: 1.035, 95% CI: 1.007-1.064), comorbidities of CKD (HR: 2.410, 95% CI: 1.455-3.993), history of PUD (HR: 2.127, 95% CI: 1.102-4.100), use of aspirin (HR: 1.517, 95% CI: 1.029-2.235) or warfarin (HR: 1.576, 95% CI: 1.002-2.252) were correlated with the higher incidence of UGIB in PAD patients during follow-up. Nevertheless, PPI use (HR: 0.612, 95% CI: 0.392-0.957) was correlated with the lower incidence of UGIB.. There was a high incidence of UGIB in this Chinese population of PAD. Various factors including older age, comorbidities of CKD, history of PUD, use of aspirin or warfarin were correlated with the higher incidence of UGIB. PPI use was able to reduce the incidence of UGIB.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; China; Comorbidity; Female; Fibrinolytic Agents; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Middle Aged; Peptic Ulcer; Peripheral Arterial Disease; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Time Factors; Warfarin

Topics: Adult; Aged; Anticoagulants; Aspirin; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Thrombosis; Warfarin; Withholding Treatment

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Arteriovenous Malformations; Aspirin; Drug Therapy, Combination; Fatal Outcome; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Stents; Thiophenes; Thrombosis; Warfarin

Topics: Abdominal Wall; Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Male; Middle Aged; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Male; Warfarin

The increased risk of hemorrhage associated with anticoagulant therapy following traumatic brain injury creates a serious dilemma for medical management of older patients: Should anticoagulant therapy be resumed after traumatic brain injury, and if so, when?. To estimate the risk of thrombotic and hemorrhagic events associated with warfarin therapy resumption following traumatic brain injury.. Retrospective analysis of administrative claims data for Medicare beneficiaries aged at least 65 years hospitalized for traumatic brain injury during 2006 through 2009 who received warfarin in the month prior to injury (n = 10,782).. Warfarin use in each 30-day period following discharge after hospitalization for traumatic brain injury.. The primary outcomes were hemorrhagic and thrombotic events following discharge after hospitalization for traumatic brain injury. Hemorrhagic events were defined on inpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification codes and included hemorrhagic stroke, upper gastrointestinal bleeding, adrenal hemorrhage, and other hemorrhage. Thrombotic events included ischemic stroke, pulmonary embolism, deep venous thrombosis, and myocardial infarction. A composite of hemorrhagic or ischemic stroke was a secondary outcome.. Medicare beneficiaries with traumatic brain injury were predominantly female (64%) and white (92%), with a mean (SD) age of 81.3 (7.3) years, and 82% had atrial fibrillation. Over the 12 months following hospital discharge, 55% received warfarin during 1 or more 30-day periods. We examined the lagged effect of warfarin use on outcomes in the following period. Warfarin use in the prior period was associated with decreased risk of thrombotic events (relative risk [RR], 0.77 [95% CI, 0.67-0.88]) and increased risk of hemorrhagic events (RR, 1.51 [95% CI, 1.29-1.78]). Warfarin use in the prior period was associated with decreased risk of hemorrhagic or ischemic stroke (RR, 0.83 [95% CI, 0.72-0.96]).. Results from this study suggest that despite increased risk of hemorrhage, there is a net benefit for most patients receiving anticoagulation therapy, in terms of a reduction in risk of stroke, from warfarin therapy resumption following discharge after hospitalization for traumatic brain injury.

Topics: Adrenal Gland Diseases; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Injuries; Brain Ischemia; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Stroke; Thrombosis; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Crohn Disease; Diagnosis, Differential; Female; Gastrointestinal Hemorrhage; Hematoma; Hemoperitoneum; Humans; Ileal Diseases; Male; Middle Aged; Radiography; Warfarin

Clinical trial data suggest that dabigatran and warfarin have similar rates of major bleeding but higher rates of gastrointestinal bleeding. These findings have not been evaluated outside of a clinical trial. We evaluated the relative risks of any, gastrointestinal, intracranial, and other bleeding for Veterans Affairs patients who switched to dabigatran after at least 6 months on warfarin, compared with patients who continued on warfarin.. We used national Veterans Affairs administrative encounter and pharmacy data from fiscal years 2010-2012 to identify 85,344 patients with atrial fibrillation who had been taking warfarin for at least 180 days before June 2011, of whom 1394 (1.7%) received dabigatran (150 mg) during the next 15 months. Dates of the first occurrence of each type of bleed and dates of death from June 2011 to September 2012 were determined. Baseline and time-dependent patient characteristics were identified, including comorbid conditions, stroke and bleeding risk scores, and time in therapeutic range for international normalized ratios. Marginal structural models were used to address selection bias in the longitudinal observational data. Weighted logistic regression models were fit using generalized estimating equations and reflected baseline and time-dependent covariates and weekly indicators of anticoagulant type (warfarin or dabigatran).. Compared with patients who never used dabigatran, patients who used dabigatran at least once were younger, were more likely to be white, had lower international normalized ratio time in therapeutic range on warfarin, had lower stroke risk scores, and had similar bleeding risk scores. Overall, 10,734 patients experienced bleeding events, including 131 events after dabigatran use. The risk-adjusted rate of any bleeding was higher with dabigatran compared with warfarin, which was largely driven by a 54% higher risk of gastrointestinal bleeding with dabigatran. Rates of intracranial, other bleeding, and death were similar for dabigatran and warfarin.. Dabigatran may increase the likelihood of gastrointestinal bleeds.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Drug Substitution; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Stroke; United States; United States Department of Veterans Affairs; Warfarin

The higher incidence of gastrointestinal (GI) bleeding with the non-vitamin K oral anticoagulants (NOACs) may be related to pre-existing malignancies; diagnostic measures triggered by these bleedings could lead to early detection of these malignancies.. We retrieved the preferred terms on GI bleeding and GI cancer reported as adverse events (AEs) from phase III studies in patients with atrial fibrillation for each NOAC on ClinicalTrials.gov . We also analyzed the RE-LY trial database.. From ClinicalTrials.gov , AE-GI bleeding incidence was: dabigatran 110 mg b.i.d. (D110: 1.42% versus 1.37%), dabigatran 150 mg b.i.d. (D150: 1.93% versus 1.37%), rivaroxaban (3.52% versus 2.68%), and apixaban (1.93% versus 1.59%), compared with warfarin, respectively. The incidence of AE-GI cancer was similar between the NOACs (D110 [0.79%], D150 [0.61%], rivaroxaban [0.83%], and apixaban [0.69%]), but numerically higher compared with warfarin (0.37%; 0.73%; 0.57%, respectively). In the RE-LY database, the same pattern was seen for dabigatran, with an association between GI bleeding and GI cancer diagnosis.. Anticoagulant-related GI bleeding may represent the unmasking of pre-existing malignancies leading to increased detection of GI cancer. This may be especially in the first month of treatment and could explain the numerically higher numbers of GI malignancies observed with NOACs.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Early Detection of Cancer; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Incidence; Morpholines; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Thiophenes; Warfarin

To evaluate the risk of late rectal bleeding and its association with the timing and type of anticoagulation use in patients receiving dose-escalated radiation therapy (RT) (≥ 7,560 cGy) for prostate cancer.. Between 2003-2010, 465 patients were treated at our Institution with dose-escalated RT and included in this analysis. Patients were placed into the following categories: no anticoagulation use, aspirin during RT, clopidogrel/warfarin during RT, aspirin after completion of RT, clopidogrel/warfarin after completion of RT.. The overall bleeding rate was 7.5%. For those on aspirin during RT, the 4-year freedom from rectal bleeding (FFBS) rate was 91%, compared to 94.7% for patients who were never on anticoagulation (p=0.16). For those on warfarin/clopidogrel during RT the 4-year FFBS rate was 78.2%, compared to 94.7% in those never on anticoagulation (p<0.001). On multivariate analysis, use of warfarin/clopidogrel during radiation treatment were strongly associated with an increased risk of rectal bleeding (multivariate HR=4.84, 95% CI=1.84-12.68, p=0.001). However, initiation of anticoagulation after completion of radiation treatment did not significantly increase the risk of rectal bleeding (multivariate HR=0.78, 95% CI=0.21-2.91, p=0.71).. The use of clopidogrel or warfarin during radiation is associated with significantly increased risk of rectal bleeding. However, initiation of these medications after completion of radiation does not appear to impact such risk.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Prostatic Neoplasms; Radiation Injuries; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Rectum; Retrospective Studies; Risk; Telangiectasis; Ticlopidine; Warfarin

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration; Warfarin

Inflammatory bowel disease (IBD) patients are at increased risk of venous thromboembolism (VTE) especially during hospitalization. We assessed the safety and predictors of VTE prophylaxis in this population.. We conducted a retrospective study of 974 IBD admissions between February 2010 and May 2012. We abstracted data on clinical characteristics, VTE prophylaxis and bleeding events, and conducted multivariate analysis to determine predictors of prophylaxis.. Pharmacological VTE prophylaxis was administered to 80% of admissions; 63% were within 24h of admission. Patients on the surgical service (adjusted OR [aOR], 3.82; 95% CI: 2.00-7.29) and general medicine (aOR, 2.40; 95% CI: 1.39-4.12) were more likely to receive VTE prophylaxis compared to those on the gastroenterology service. Rectal bleeding on admission was associated with lower prophylaxis (aOR, 0.58; 95% CI: 0.35-0.97). The VTE prophylaxis rate increased from 47% to 73% (P<0.001) on non-surgical services with the introduction of a pharmacist advocate. The rates of major and minor bleeding were similar between patients who did and did not receive VTE prophylaxis (0.26 vs. 0 per 1000 person-days, P=0.7; 4.18 vs. 2.53 per 1000 person-days, P=0.4 respectively), and the major bleeding events (n=2) were post-operative. VTE prophylaxis was not associated with major postoperative bleeding (0.4% vs. 0%, P=0.96).. VTE prophylaxis was more frequent on the surgical service, where standardized protocols exist. The introduction of a pharmacist advocate greatly increased VTE prophylaxis on the non-surgical services. Prophylactic anticoagulation is safe in IBD despite the presence of rectal bleeding on admission.

Topics: Adult; Anticoagulants; Contraindications; Female; Fondaparinux; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Hospital Departments; Hospitalization; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Pharmacy Service, Hospital; Polysaccharides; Practice Patterns, Physicians'; Rectum; Retrospective Studies; Venous Thromboembolism; Warfarin; Young Adult

The aim of this study was to assess the efficacy and safety in an "everyday clinical practice" population of anticoagulant-naïve patients with atrial fibrillation (AF) treated with dabigatran etexilate after its post-approval availability in Denmark, compared with warfarin.. Concerns have been raised about an excess of bleeding events or myocardial infarction (MI) among patients treated with the new oral direct thrombin inhibitor, dabigatran etexilate.. From the Danish Registry of Medicinal Product Statistics, we identified a dabigatran-treated group and a 1:2 propensity-matched warfarin-treated group of 4,978 and 8,936, respectively. Comparisons on efficacy and safety outcomes were made on the basis of Cox-proportional hazards models stratified on propensity-matched groups.. Stroke and systemic embolism were not significantly different between warfarin- and dabigatran-treated patients. Adjusted mortality was significantly lower with both dabigatran doses (110 mg b.i.d., propensity-match group stratified hazard ratio [aHR]: 0.79, 95% confidence interval [CI]: 0.65 to 0.95; 150 mg b.i.d., aHR: 0.57, 95% CI: 0.40 to 0.80), when compared with warfarin. Pulmonary embolism was lower compared with warfarin for both doses of dabigatran. Less intracranial bleeding was seen with both dabigatran doses (110 mg b.i.d., aHR: 0.24, 95% CI: 0.08 to 0.56; 150 mg b.i.d., aHR: 0.08, 95% CI: 0.01 to 0.40). The incidence of MI was lower with both dabigatran doses (110 mg b.i.d., aHR: 0.30, 95% CI: 0.18 to 0.49; 150 mg b.i.d., aHR: 0.40, 95% CI: 0.21 to 0.70). Gastrointestinal bleeding was lower with dabigatran 110 mg b.i.d. (aHR: 0.60, 95% CI: 0.37 to 0.93) compared with warfarin but not dabigatran 150 mg b.i.d. The main findings were broadly consistent in a subgroup analysis of dabigatran users with ≥1-year follow-up (median follow-up 13.9 months [interquartile range: 12.6 to 15.3 months]).. In this "everyday clinical practice" post-approval nationwide clinical cohort, there were similar stroke/systemic embolism and major bleeding rates with dabigatran (both doses) compared with warfarin. Mortality, intracranial bleeding, pulmonary embolism, and MI were lower with dabigatran, compared with warfarin. We found no evidence of an excess of bleeding events or MI among dabigatran-treated patients in this propensity-matched comparison against warfarin, even in the subgroup with ≥1-year follow-up.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; Dabigatran; Denmark; Dose-Response Relationship, Drug; Drug Prescriptions; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Hospitalization; Humans; Incidence; Intracranial Hemorrhages; Logistic Models; Male; Myocardial Infarction; Propensity Score; Proportional Hazards Models; Prospective Studies; Pulmonary Embolism; Pyridines; Registries; Stroke; Warfarin

Postprostatectomy radiotherapy (RT) improves survival in adjuvant and salvage settings. The implantation technique and complications rate of gold markers in the prostate bed for high-precision RT were analyzed.. Patients undergoing postprostatectomy RT for prostate-specific antigen (PSA) relapse or high-risk disease were enrolled in the study. Under transrectal ultrasound guidance, three fine gold markers were implanted in the prostate bed and the technical difficulties of insertion were documented. Patients received our self-designed questionnaires concerning complications and pain. The influence of anticoagulants and coumarins on bleeding was analyzed, as was the effect of potential risk factors on pain.. In 77 consecutive patients, failure of marker implantation or marker migration was seen in six cases. Rectal bleeding was reported by 10 patients and 1 had voiding complaints. No macroscopic hematuria persisting for more than 3 days was observed. Other complications included rectal discomfort (n = 2), nausea (n = 1), abdominal discomfort (n = 1), and pain requiring analgesics (n = 4). No major complications were reported. On a 0-10 visual analogue scale (VAS), the mean pain score was 3.7. No clinically significant risk factors for complications were identified.. Transrectal implantation of gold markers in the prostate bed is feasible and safe. Alternatives like cone beam computed tomography (CBCT) should be considered, but the advantages of gold marker implantation for high-precision postprostatectomy RT would seem to outweigh the minor risks involved.

Topics: Aged; Anticoagulants; Biomarkers, Tumor; Combined Modality Therapy; Feasibility Studies; Fiducial Markers; Gastrointestinal Hemorrhage; Gold; Humans; Male; Middle Aged; Pain Measurement; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Adjuvant; Rectal Diseases; Salvage Therapy; Ultrasonography, Interventional; Warfarin

Topics: Female; Gastrointestinal Hemorrhage; Humans; Male; Thromboembolism; Warfarin; Withholding Treatment

Topics: Female; Gastrointestinal Hemorrhage; Humans; Male; Thromboembolism; Warfarin; Withholding Treatment

Artemisia absinthium, also known as wormwood, is used widely as an herbal medicine. In this report, we introduce an 82-year-old Turkish woman who was treated with warfarin for atrial fibrillation and was hospitalized for gastrointestinal bleeding as a result of extremely elevated international normalized ratio (INR) after consumption of A. absinthium. Naranjo adverse drug reaction probability scale score was 6, which indicated a probable relationship between the patient's elevated INR and her concomitant use of wormwood and warfarin. Clinicians should be vigilant about potential dangers of herbal medicines taken with conventional drugs, and patients taking drugs with a narrow therapeutic index, such as warfarin, should be educated about avoiding consumption of herbal medicines.

Topics: Aged, 80 and over; Anticoagulants; Artemisia absinthium; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Herb-Drug Interactions; Humans; Phytotherapy; Plant Preparations; Warfarin

Atrial fibrillation (AF) is emerging as a major health problem. The prevalence is as high as 32% in patients with renal disease. Gastrointestinal bleeding (GIB) is a frequent complication.. To investigate the hazards of resumption or discontinuation of anticoagulation in renal disease patients after an episode of GIB. DESIGN, SETTINGS, PARTICIPANTS AND MEASUREMENTS: This is a multicenter retrospective cohort of patients with AF on warfarin that developed an episode of GIB. Chronic kidney disease (CKD) was defined by eGFR ≤60 mL/min and end stage renal disease (ESRD) was defined by being on hemodialysis for >3 months. Outcomes were 90-day recurrent gastrointestinal bleeding (GIB), mortality, and stroke/transient ischemic attack (TIA).. Out of 11,513 AF patients, index GIB occurred in 96 ESRD and 159 CKD patients. Outcomes of CKD patients did not differ when compared with patients with normal kidney function. CKD patients who resumed warfarin had decreased stroke/TIA rates (p < 0.0001). There were no significant differences between CKD patients who resumed warfarin versus that did not resume warfarin (p > 0.05). ESRD patients also did not have significant differences in outcomes when compared to patients with normal kidney function restarted on warfarin. However, there was an increase in recurrent GIB and decrease in mortality as well as stroke/TIA when patients with ESRD that restarted warfarin were compared with ESRD patients who did not restart warfarin.. Study suggests resuming warfarin after an episode of GIB in CKD patients but recommends considering the increased risk of recurrent GIB in ESRD patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Medical Audit; Upper Gastrointestinal Tract; 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

The association between gastrointestinal (GI) bleeding and subsequent detection of GI cancer in patients using antiplatelet/anticoagulant medications is unclear. We investigated the association between the occurrence of GI bleeding and the detection of GI cancer and assessed whether this association differs in patients treated with clopidogrel or warfarin compared to non-treated patients.. A claims analysis was conducted using the Truven Health MarketScan(®) Research databases. Patients were grouped into the treatment cohort if they received a prescription for clopidogrel or warfarin or into the non-treatment cohort if they did not receive these medications. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for GI cancer diagnosed after GI bleeding.. Overall, in the treatment cohort, patients who experienced a GI bleed were 6 times (HR: 5.64, 95% CI, 5.12, 6.21) more likely to be diagnosed with GI cancer compared with those without bleeding. In the non-treatment cohort patients were 13 times (HR: 13.34, 95% CI, 12.21, 14.58) more likely to be diagnosed with GI cancer after GI bleeding. The HRs of GI cancer were higher within 6 months of the first GI bleed and decreased remarkably thereafter.. This study suggests that an episode of GI bleeding increased the rates of detection of GI cancers.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Clopidogrel; Cohort Studies; Female; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Retrospective Studies; Ticlopidine; Time Factors; Warfarin; Young Adult

There are well defined indications in which chronic anticoagulant treatment has been widely applied. However, complications of this therapy are less discussed, although these complications may lead to serious or even fatal consequences.. The aim of the authors was to analyze data of patients admitted to their multidisciplinary intensive care unit for complications of chronic anticoagulant therapy between January 1, 2006 and December 31, 2011.. Data of 73 patients admitted for serious hemorrhagic complications of chronic anticoagulant therapy were retrospectively analysed.. Of the 73 patients, 63 patients had intracranial bleeding, most of them with traumatic origin. A few patients with other hemorrhagic complications such as spinal hematoma, gastrointestinal bleeding, hemorrhagic cystitis, hemothorax and intraabdominal bleeding were also noted. The INR values were out of therapeutic range in 43 patients. The mortality of patients was very high in spite of complex intensive care; 49 of the 73 patients (75.5%) died due to hemorrhagic complications.. Due to the high proportion of traumatic origin, the large number of out-of-range INR, and the high mortality, the authors strongly believe that regular patient follow-up, transmission of detailed information, and time-to-time reevaluation of the indications and contraindications of chronic anticoagulant therapy could help to decrease the number of serious and fatal complications of chronic anticoagulant therapy.. Bevezetés: A krónikus antikoaguláns kezelést jól körülhatárolt indikációs körrel, széles körben alkalmazzák. Kevesebb szó esik azonban az általa okozott vérzéses szövődményekről, amelyek súlyosak vagy akár halálos kimenetelűek is lehetnek. Célkitűzés: A Szent János Kórház és Észak-budai Egyesített Kórházak Központi Aneszteziológiai és Intenzív Terápiás Osztályán 2006. január 1. és 2011. december 31. között krónikus antikoaguláns kezelés kapcsán kialakult vérzéses szövődményes esetek elemzése. Módszer: A szerzők multidiszciplináris intenzív osztályán a vizsgált hat év alatt összesen 73 betegnél fordult elő intenzív ellátást igénylő vérzéses szövődmény krónikus antikoagulálás kapcsán. Eredmények: Hatvanhárom esetben intracranialis vérzést észleltek, ezen belül leggyakrabban traumás eredetűt. Kisebb számban előfordult még spinalis haematoma, gastrointestinalis vérzés, haemorrhagiás cystitis, haemothorax és hasüregi vérzés. A betegek felvételi INR-értéke 43 esetben a terápiás tartományon kívül esett. A betegek mortalitása igen magas volt, a komplex intenzív kezelés ellenére 49 beteg halt meg a vérzéssel összefüggésben (75,5%). Következtetések: A gyakori traumás eredetre, a terápiás tartományon kívül eső INR-értékek nagy számára és a magas mortalitásra tekintettel a szerzők véleménye szerint rendszeres betegkövetéssel, részletes felvilágosítással, a társbetegségek alakulásával párhuzamosan revideált indikáció/kontraindikáció alapján folytatott krónikus antikoaguláns kezeléssel a vérzéses szövődmények száma csökkenthető lenne. Orv. Hetil., 2013, 154(46), 1829–1835.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Critical Care; Cystitis; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hemothorax; Humans; Hungary; Intensive Care Units; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Colonic Polyps; Colonoscopy; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Time Factors; Warfarin

Oral anticoagulants are the most common used substance for treatment and prophylaxis of warfarin venous and arterial thromboembolic disorders in the world. Therapeutic index of warfarin is narrow. CYP2C9 is a hepatic microsomal enzyme and has a primary role in metabolism of warfarin and genetic variations of CYP2C9 may cause a serious effect on the response to warfarin in patients. The aim of this study was to determine the efficiency of CYP2C9 gene polymorphisms on drug metabolism in patients who had upper gastrointestinal system bleeding while using warfarin.. There was a total of 67 patients in this study, 37 of whom had upper gastrointestinal system bleeding when INR was above 3 while using warfarin (group 1), 30 of whom had no bleeding and INR was stable under 3 (group 2).. There was no difference in terms of warfarin dose used among the groups (p>0.05). Mutant genotype, INR and aspirin usage were found significantly different in the group with bleeding (p less 0.05). When analyzed in terms of drug interaction, there was no difference between the two groups (p>0.05). Logistic regression analysis was made in order to determine the risk factors that may cause bleeding. Aspirin usage (p= 0.016) and genetic polymorphism (p= 0.024) were related to the increased risk of bleeding.. CYP2C9*2 and CYP2C9*3 polymorphisms were related to the increase of excessive anticoagulation and bleeding risk in the patients who used warfarin.

Topics: Administration, Oral; Aged; Anticoagulants; Biomarkers; Cytochrome P-450 CYP2C9; Drug Administration Schedule; Drug Monitoring; Female; Gastrointestinal Hemorrhage; Genotype; Humans; Male; Middle Aged; Mutation; Polymorphism, Genetic; Prospective Studies; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

The authors aimed to investigate the incidence and outcomes of acute upper gastrointestinal bleeding (AUGIB) and to examine the role of drugs potentially associated with AUGIB.. The study was prospective, population-based and consisted of all patients who underwent upper gastrointestinal endoscopy (UGE), during the year of 2010 at the National University Hospital of Iceland. Drug intake of NSAIDs, low-dose aspirin (LDA), warfarin, SSRIs and bisphosphonates prior to GIB was prospectively registered and also checked in a Pharmaceutical Database covering all prescriptions in Iceland. An age- and gender-matched control group consisted of patients who underwent UGE during the study period and were without GIB.. A total of 1731 patients underwent 2058 UGEs. Overall, 156 patients had AUGIB. The crude incidence for AUGIB was 87/100,000 inhabitants per year. The most common etiologies were duodenal (21%) and gastric ulcers (15%). Use of LDA (40% vs. 30%), NSAIDs (20% vs. 8%), warfarin (15% vs. 7%), combination of NSAIDs + LDA (8% vs. 1%) and SSRIs + LDA (8% vs. 3%) were significantly more common among bleeders than non-bleeders. Three patients (1.9%) had emergency surgery and two patients died of AUGIB. Independent predictors of clinically significant bleeding were gastric ulcer (OR 6.6, p = 0.012) and NSAIDs (OR 6.6, p = 0.004).. LDA, NSAIDs and warfarin play an important role in AUGIB etiology and particularly combinations of drugs. Gastric ulcer and NSAIDs were independent predictors of severe bleeding. Mortality and the need for surgery during hospitalization was low in this population-based setting.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Female; Gastrointestinal Hemorrhage; Hematemesis; Humans; Iceland; Incidence; Male; Melena; Middle Aged; Prospective Studies; Risk Factors; Severity of Illness Index; Upper Gastrointestinal Tract; Warfarin

The use of warfarin is growing for the prevention or treatment of cardiovascular or cerebrovascular diseases. The risk of haemorrhagic side effects is increased in patients taking warfarin.. To evaluate risks related with withholding and resuming anticoagulation in patients with upper gastrointestinal bleeding (UGIB) while on warfarin therapy and the role of the second-look endoscopic examination (SEE).. Records of 58 patients with native valvular heart diseases who presented with non-variceal UGIB during chronic anticoagulation with warfarin were retrospectively reviewed. Age- and gender-matched patients with non-variceal UGIB during aspirin therapy because of ischaemic heart disease were recruited as the control group.. Development of both recurrent bleeding and thromboembolic events were more frequent in warfarin group than in control group (7.0% vs. 0% with p = 0.03 and 16.7% vs. 2.4% with p < 0.01, respectively). One of four cases of recurrent bleeding in warfarin group was found by SEE performed in an asymptomatic patient. There were six thromboembolic events which occurred on the 21st, 27th, 28th, 31st, 58th and 75th day from the presentation out of 36 patients who ceased anticoagulation. In contrast, only one from 41 in whom aspirin was discontinued experienced myocardial infarction. There was no difference in the failure of endoscopic haemostasis necessitating angiographic embolisation or surgery, hospital stay, the need of transfusion and overall mortality.. Anticoagulation is recommended to be resumed before the 20th day from the cessation to prevent thromboembolic events. A routine SEE before resuming anticoagulation might be helpful to detect asymptomatic recurrent bleeding.

Topics: Anticoagulants; Case-Control Studies; Drug Substitution; Endoscopy, Gastrointestinal; Female; Gastrointestinal Hemorrhage; Heart Valve Diseases; Humans; Male; Middle Aged; Recurrence; Refusal to Treat; Retrospective Studies; Risk Factors; Treatment Outcome; Warfarin

This study assessed the frequency and factors associated with failure to correct international normalised ratio (INR) in patients administered fresh frozen plasma (FFP) for warfarin-related major bleeding. This retrospective database analysis used electronic health records from an integrated health system. Patients who received FFP between 01/01/2004 and 01/31/2010, and who met the following criteria were selected: major haemorrhage diagnosis the day before to the day after initial FFP administration; INR ≥2 on the day before or the day of FFP and another INR result available; warfarin prescription within 90 days. INR correction (defined as INR ≤1.3) was evaluated at the last available test up to one day following FFP. A total of 414 patients met selection criteria (mean age 75 years, 53% male, mean Charlson score 2.5). Patients presented with gastrointestinal bleeding (58%), intracranial haemorrhage (38%) and other bleed types (4%). The INR of 67% of patients remained uncorrected at the last available test up to one day following receipt of FFP. In logistic regression analysis, the INR of patients who were older, those with a Charlson score of 4 or greater, and those with non-ICH bleeds (odds ratio vs. intracranial bleeding 0.48; 95% confidence interval 0.31-0.76) were more likely to remain uncorrected within one day following FFP administration. In an alternative definition of correction, (INR ≤1.5), 39% of patients' INRs remained uncorrected. For a substantial proportion of patients, the INRs remain inadequately or uncorrected following FFP administration, with estimates varying depending on the INR threshold used.

Topics: Aged; Aged, 80 and over; Anticoagulants; Emergency Medicine; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Medical Records Systems, Computerized; Odds Ratio; Plasma; Regression Analysis; Retrospective Studies; Warfarin

We summarize data of patients with gastrointestinal bleeding (GIB) and discuss the relationship between antithrombotic drug use and age in patients with GIB.. One-hundred and twenty patients with GIB were divided into two groups according to age (=75 years old and <75 years old). The causes and clinical outcome of each group were compared.. Forty-two patients received antithrombotic therapy. The main antithrombotic drugs were low dose aspirin (38 patients), ticlopidine (5 patients) and warfarin (3 patients). Compared with younger GIB patients, elderly patients had more coexisting illness and antithrombotic drugs. In patients taking antithrombotic drugs, upper GIB is more frequent than those not taking antithrombotic drugs (p<0.05) and antithrombotic drugs were the risk for GIB from erosive lesions of the esophagus or stomach. In the lower gastrointestinal tract, there was no difference of incidence related to antithrombotic use. The initial endoscopic hemostasis was performed in 14 patients. Eight varices patients received endoscopic vanding and 6 of 43 gastroduodenal ulcer patients had mechanical clip hemostasis.. From our findings, antithrombotic drugs were considered to be a risk for GIB. It might be important to prevent or minimize GIB in elderly patients prescribed antithrombotic drugs.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Asian People; Aspirin; Chi-Square Distribution; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Hemostasis, Endoscopic; Hemostatic Techniques; Humans; Japan; Male; Middle Aged; Risk Assessment; Risk Factors; Ticlopidine; Treatment Outcome; Warfarin; Young Adult

Patients treated with continuous flow assist devices may have increased bleeding tendencies due to an induced high molecular weight von Willebrand factor (VWF) multimer deficiency. We report a patient supported with a HeartMate II (Thoratec, Pleasanton, CA) who developed severe gastrointestinal bleeding refractory to conventional therapy and needing a total of 60 transfusions. After documenting the lack of large VWF multimers, suggestive of a defective platelet function, the patient was switched from aspirin to warfarin therapy (target international normalized ratio between 1.5 and 2.0). Three days after changing the anticoagulant regimen, the patient stopped bleeding and required no further transfusion.

Topics: Anticoagulants; Gastrointestinal Hemorrhage; Heart-Assist Devices; Humans; Male; Middle Aged; Severity of Illness Index; von Willebrand Diseases; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Colonoscopy; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Rectal Diseases; Warfarin

Spontaneous hematomas are rare and most occur secondary to hematologic disorders or during anticoagulant therapy. Most spontaneous hematomas occur above the sigmoid colon, and rarely in the rectum. Herein we present the case of a patient with a spontaneous perforating hematoma of the rectum who presented with severe abdominal pain after a bloody stool. The hemoglobin level decreased by 33 g/L within 20 h. An abdominal sonogram showed a hydrops in the lower abdomen with a maximum depth of 7.0 cm. A hematoma, 8 cm × 6 cm × 5 cm in size, was noted intra-operatively in the rectosigmoid junction, with a 1.5-cm perforation in the hematoma and active hemorrhage. Thus, a partial rectectomy and sigmoidostomy were performed. Three months later, a second operative procedure to re-establish intestinal continuity was performed. The patient is in good condition 12 mo after the last surgery. In addition to this case, the causes of spontaneous perforating hematomas and the treatment are discussed.

Topics: Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Male; Middle Aged; Rectal Diseases; Warfarin

Topics: Acute Disease; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Blood Component Transfusion; Clopidogrel; Contraindications; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Lypressin; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors; Resuscitation; Risk Assessment; Secondary Prevention; Terlipressin; Ticlopidine; United Kingdom; Vasoconstrictor Agents; Warfarin

Patients who not only survive a warfarin-associated gastrointestinal tract bleeding (GIB) event but also have an ongoing risk for thromboembolism present 2 clinical dilemmas: whether and when to resume anticoagulation. The objective of this study was to determine the incidence of thrombosis, recurrent GIB, and death, as well as the time to resumption of anticoagulant therapy, during the 90 days following a GIB event.. In this retrospective, cohort study using administrative and clinical databases, patients experiencing GIB during warfarin therapy were categorized according to whether they resumed warfarin therapy after GIB and followed up for 90 days. Variables describing the management and severity of the index GIB were also collected. Kaplan-Meier curves were constructed to estimate the survival function of thrombosis, recurrent GIB, and death between the "resumed warfarin therapy" and "did not resume warfarin therapy" groups, with Cox proportional hazards modeling to adjust for potentially confounding factors.. There were 442 patients with warfarin-associated index GIB included in the analyses. Following the index GIB, 260 patients (58.8%) resumed warfarin therapy. Warfarin therapy resumption after the index GIB was associated with a lower adjusted risk for thrombosis (hazard ratio [HR], 0.05; 95% CI, 0.01-0.58) and death (HR, 0.31; 95% CI, 0.15-0.62), without significantly increasing the risk for recurrent GIB (HR, 1.32; 95% CI, 0.50-3.57).. The decision to not resume warfarin therapy in the 90 days following a GIB event is associated with increased risk for thrombosis and death. For many patients who have experienced warfarin-associated GIB, the benefits of resuming anticoagulant therapy will outweigh the risks.

Topics: Aged; Anticoagulants; Cause of Death; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Recurrence; Retrospective Studies; Risk Factors; Survival Rate; Thromboembolism; United States; Warfarin; Withholding Treatment

Topics: Female; Gastrointestinal Hemorrhage; Humans; Male; Thromboembolism; Warfarin; Withholding Treatment

Venous complications in patients with acute pancreatitis typically occur as a form of splenic, portal, or superior mesenteric vein thrombosis and have been detected more frequently in recent reports. Although a well-organized protocol for the treatment of venous thrombosis has not been established, anticoagulation therapy is commonly recommended. A 73-year-old man was diagnosed with acute progressive portal vein thrombosis associated with acute pancreatitis. After one month of anticoagulation therapy, the patient developed severe hematemesis. With endoscopy and an abdominal computed tomography scan, hemorrhages in the pancreatic pseudocyst, which was ruptured into the duodenal bulb, were confirmed. After conservative treatment, the patient was stabilized. While the rupture of a pseudocyst into the surrounding viscera is a well-known phenomenon, spontaneous rupture into the duodenum is rare. Moreover, no reports of upper gastrointestinal bleeding caused by pseudocyst rupture in patients under anticoagulation therapy for venous thrombosis associated with acute pancreatitis have been published. Herein, we report a unique case of massive upper gastrointestinal bleeding due to pancreatic pseudocyst rupture into the duodenum, which developed during anticoagulation therapy for portal vein thrombosis associated with acute pancreatitis.

Topics: Acute Disease; Aged; Anticoagulants; Duodenal Diseases; Gastrointestinal Hemorrhage; Hematemesis; Humans; Intestinal Fistula; Male; Pancreatic Pseudocyst; Pancreatitis, Alcoholic; Portal Vein; Risk Factors; Rupture, Spontaneous; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

An extrahepatic arterioportal fistula (APF) involving the gastroduodenal artery and superior mesenteric vein is rare and mostly results from iatrogenic injuries. The clinical symptoms associated with APFs may include abdominal pain, gastrointestinal bleeding, ascites, nausea, vomiting, diarrhea, or even congestive heart failure. We present the case of a 70-year-old man who presented with chronic abdominal pain and gastrointestinal bleeding secondary to APF and portal vein thrombosis. The endovascular embolization of APF was accomplished successfully, and symptoms of portal hypertension resolved immediately after intervention. Unfortunately, the patient did not respond well to anticoagulation therapy with warfarin. Therefore, the patient underwent implantation of a transjugular intrahepatic portosystemic shunt, and the complications of portal hypertension resolved. In conclusion, the embolization of APF is technically feasible and effective and can be considered the first-choice therapy in selected patients.

Topics: Abdominal Pain; Aged; Aneurysm; Anticoagulants; Arteriovenous Fistula; Duodenum; Embolization, Therapeutic; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Male; Mesenteric Veins; Phlebography; Portal Vein; Portasystemic Shunt, Surgical; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Antioxidants; Beverages; Food-Drug Interactions; Gastrointestinal Hemorrhage; Health Knowledge, Attitudes, Practice; Humans; Vaccinium macrocarpon; Warfarin

Antithrombotics is increasingly being used for cardiovascular prevention. In more recent studies, small bowel injury and enteropathy associated with low-dose aspirin are increasingly being recognized. Aim of this study was to evaluate small bowel injury using video capsule endoscopy (VCE) in obscure gastrointestinal bleeding (OGIB) patients taking low-dose aspirin including other antithrombotics.. This is a retrospective review of chronic users of antithrombotics who underwent VCE for suspected small bowel bleeding. Small bowel mucosal injury was evaluated using VCE findings.. Fifty-four OGIB patients (36 men and 18 women, mean age 72.4 years) underwent VCE from January 2007 to May 2009. Twenty-two patients were taking 100 mg of enteric-coated aspirin (aspirin group), 8 taking thienopyridine, (ticlopidine or clopidogrel, thienopyridine group), 13 taking aspirin combined with thienopyridine (combined group), and 11 taking warfarin (warfarin group). The mucosal injury, especially ulcers were most frequently detected in the combined group (46.2%, p = 0.01) among the four groups. The median number of redness lesions in the combined group was the highest among the four groups and was significantly higher than that in the warfarin group. The lesions of redness or small erosions in the aspirin and the combined groups tended to exist in the proximal part of small bowel.. Combination of low-dose aspirin therapy and thienopyridine may exacerbate small bowel injury, and the preventive strategies should be established.

Topics: Aged; Aged, 80 and over; Aspirin; Capsule Endoscopy; Clopidogrel; Drug Therapy, Combination; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Intestinal Mucosa; Intestine, Small; Male; Middle Aged; Pyridines; Retrospective Studies; Ticlopidine; Ulcer; Warfarin

The management of vitamin K antagonists (VKAs) associated coagulopathy is a cornerstone of pre-endoscopic assessment of anticoagulated patients presenting with acute gastrointestinal bleeding.. To evaluate physician attitudes in the management of VKAs-associated coagulopathy in patients presenting with gastrointestinal bleeding and to assess their compliance to current practice guidelines.. Cross sectional physician web-based survey amongst regional members of three Italian Gastroenterological Societies (AIGO, SIED, SIGE) practicing in academic medical centres or community hospitals. Physicians were asked to provide management preferences in four hypothetical case-scenarios describing patients with warfarin-associated coagulopathy presenting with gastrointestinal bleeding of varying severity.. A total of 105 out of 238 (48%) members responded; mean age±SD: 46.3±9.8 years, 68% male. The adherence to practice guidelines for the reversal of warfarin-induced anticoagulation ranged from 24% to 86% and it was not dependent on age, years and type of specialisation, hospital setting and active performance of "on call" emergency endoscopy or not.. There is a considerable variability amongst physicians in the management of gastrointestinal bleeding patients with VKAs-associated coagulopathy and a poor compliance to practice guidelines. These data indicate that better education is needed in this area.

Topics: Adult; Aged; Anticoagulants; Attitude of Health Personnel; Cross-Sectional Studies; Female; Gastrointestinal Hemorrhage; Guideline Adherence; Humans; International Normalized Ratio; Italy; Male; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Vitamin K; Warfarin

An increasing number of patients are treated with anticoagulation for many medical conditions. Our practice is to suspend warfarin 5-7 days, aspirin 3 days, and clopidogrel (Plavix) 7 days prior to colonoscopy that may require polypectomy. Generally, we accept an INR of ≤1.5 as safe. However, there are no published case series documenting when it is safe to resume these medications after polypectomy. Therefore, the management of anticoagulation after polypectomy varies. We sought to evaluate the safety of our practice with regard to anticoagulation and polypectomy.. We conducted a retrospective review of all patients over the age of 18 who underwent colonoscopy with polypectomy while on anticoagulation for various medical comorbidities at our institution over a 15-month period (July 2007 to September 2008). All morbidity and mortality that occurred for the first 3 weeks post-polypectomy was recorded. The Mann-Whitney test was performed using SPSS 15.5.. From July 2007 to September 2008, we performed 579 colonoscopies with polypectomy on patients who were on anticoagulation therapy during the study period. Seven (1.2%) patients presented to the Emergency Room or were hospitalized within 3 weeks after polypectomy for lower gastrointestinal bleeding. Distribution of anticoagulants was listed: 2 (28.6%) patients on warfarin, 4 (57.1%) on aspirin, and 1 (14.3%) on clopidogrel. Warfarin was held for, on average, 4 days pre-polypectomy and 1 day post-polypectomy. Aspirin was held, on average, 3 days both pre- and post-polypectomy. Clopidogrel was held, on average 6.5 days pre-polypectomy but restarted immediately post-polypectomy. No statistically significant difference was found between the number of days that anticoagulation was held pre- or post-polypectomy in individuals who did and did not bleed.. We found that our practice of resuming anticoagulation or antiplatelet agents (warfarin, aspirin, and clopidogrel) post-polypectomy was safe and did not prove to significantly affect the post-polypectomy rate of hemorrhage.

Topics: Anticoagulants; Aspirin; Clopidogrel; Colonic Polyps; Colonoscopy; Female; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Postoperative Period; Retrospective Studies; Ticlopidine; Warfarin

Topics: Aged; Anticoagulants; Gastrointestinal Hemorrhage; Humans; Hyperplasia; Male; Polyps; Stomach Diseases; Warfarin

Bleeding is the most common and worrisome adverse effect of warfarin therapy. One of the factors that might increase bleeding risk is initiation of interacting drugs that potentiate warfarin. We sought to evaluate whether initiation of an antidepressant increases the risk of hospitalization for gastrointestinal bleeding in warfarin users.. Medicaid claims data (1999-2005) were used to perform an observational case-control study nested within person-time exposed to warfarin in those ≥18 years. In total, 430,455 warfarin users contributed 407,370 person-years of warfarin use. The incidence rate of hospitalization for GI bleeding among warfarin users was 4.48 per 100 person-years (95% CI, 4.42-4.55). Each gastrointestinal bleeding cases was matched to 50 controls based on index date and state. Warfarin users had an increased odds ratio of gastrointestinal bleeding upon initiation of citalopram (OR = 1.73 [95% CI, 1.25-2.38]), fluoxetine (OR = 1.63 [95% CI, 1.11-2.38]), paroxetine (OR = 1.64 [95% CI, 1.27-2.12]), amitriptyline (OR = 1.47 [95% CI, 1.02-2.11]). Also mirtazapine, which is not believed to interact with warfarin, increased the risk of GI bleeding (OR = 1.75 [95% CI, 1.30-2.35]).. Warfarin users who initiated citalopram, fluoxetine, paroxetine, amitriptyline, or mirtazapine had an increased risk of hospitalization for gastrointestinal bleeding. However, the elevated risk with mirtazapine suggests that a drug-drug interaction may not have been responsible for all of the observed increased risk.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents; Case-Control Studies; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Odds Ratio; Risk Factors; Warfarin; Young Adult

Topics: Adult; Anticoagulants; Duodenal Diseases; Duodenoscopy; Duodenum; Endosonography; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Portal Vein; Varicose Veins; Venous Thrombosis; Warfarin

A 60-year-old man with liver cirrhosis caused by hepatitis C, who was receiving warfarin anticoagulation following acute myocardial infarction, was diagnosed with advanced hepatocellular carcinoma and multiple lung metastases, and began treatment with sorafenib 200 mg daily. From the treatment's start to 14 and 63 days later, sorafenib was increased to 400 mg and 600 mg, respectively. After increasing the quantity to 600 mg, he had an increase in PT-INR values and experienced a lower-extremity hemorrhage. For the patient with liver cirrhosis, who is receiving warfarin, PT-INR values might be elevated during the early period of sorafenib treatment dosage as for the increase in quantity. Therefore, when increasing dosage, a frequent measurement of PT-INR and a careful follow-up for PT-INR is necessary.

Topics: Anticoagulants; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Humans; Liver Neoplasms; Male; Middle Aged; Niacinamide; Phenylurea Compounds; Pyridines; Sorafenib; Tomography, X-Ray Computed; Warfarin

Bleeding in the upper gastrointestinal tract is a common medical problem, with an incidence of 48 to 160 cases per 1000 adults per year and a mortality rate of 5% to 14%. The risk of gastrointestinal bleeding is increased with the use of antiplatelet medications including aspirin and clopidogrel, as well as warfarin or a combination of these medications. The recurrence rate for bleeding in patients who continue to take aspirin after an episode of peptic ulcer disease-related bleeding can reach up to 300 cases per 1000 person-years and varies by age, sex, and the use of nonsteroidal anti-inflammatory medications. Using the case of Ms S, an 86-year-old woman who presented to the emergency department with an episode of nonvariceal upper gastrointestinal tract bleeding, we address the management of patients who are receiving antiplatelet or anticoagulation therapy who present with gastrointestinal bleeding, including when to restart antiplatelet or anticoagulation therapy, interventions to reduce the risk of bleeding recurrence, and the potential for drug interactions between clopidogrel and proton pump inhibitors.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Peptic Ulcer; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Ticlopidine; Warfarin

Topics: Aged; Anticoagulants; Endoscopy, Gastrointestinal; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Ultrasonography; Warfarin

This study aimed to assess surgical workload and risk factors for gastrointestinal bleeding in patients on warfarin admitted to a hospital.. Data was collected for all warfarinised patients admitted between April 2005 and October 2007 with gastrointestinal bleeding.. A total of 30 patients (average 80 years) were recorded. Indications for warfarin therapy were atrial fibrillation (80%), mechanical heart valve (6.67%) and embolic disease (13.33%). Fifty percent were admitted with an INR above therapeutic range and of these patients, 83% were on one or more medications known to potentiate the anti-coagulation effect of warfarin. Nine patients were also taking anti-platelet medication. Five of these nine had an admission INR within the intended therapeutic range. Thirteen patients received blood transfusions and had a significantly higher (p<0.05) INR (average 9) than the 17 patients not requiring transfusion (average 2.8). The average cost of transfusion per patient was pound470. None of the patients required acute surgical intervention. The average length of stay was 7 days, at a total cost of pound1444 per patient. Investigations found the cause of bleeding to be diverticulosis in 9 patients and neoplastic disease in 4 patients. Almost half of the patients received no investigation due to risks from co-morbidity.. Uncontrolled anti-coagulation, polypharmacy and age were overwhelming risk factors for major gastrointestinal bleeding. Our results show that adding anti-platelet therapy has to be clearly justified against the increased risk of bleeding. Cost to the surgical department was high and no patients required surgical or radiological intervention. WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Warfarin is an important drug, but the complications of its use are difficult and expensive to deal with. Warfarin use is a risk factor for haemorrhage, and this commonly involves the gastrointestinal tract. The use of warfarin is set to increase as the population ages and atrial fibrillation and other cardiovascular risk factors become more prevalent. Consequently, one can expect a rise in warfarin-related gastrointestinal haemorrhage. WHAT DOES THIS ARTICLE ADD?: Our study aimed to assess the burden of gastrointestinal haemorrhage secondary to warfarin on our surgical department (which was high), and also to assess what the risk factors for haemorrhage for patients on warfarin. One of the risk factors we uncovered was polypharmacy, particularly involving anti-platelets e.g. aspirin. We highlight the need for further guidance with regards to managing patients on warfarin, and suggest possible solutions to the problems uncovered.

Topics: Age Factors; Aged, 80 and over; Anticoagulants; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Length of Stay; Male; Platelet Aggregation Inhibitors; Polypharmacy; Postoperative Complications; Risk Factors; Statistics, Nonparametric; Warfarin; Workload

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Risk Factors; Warfarin

Antithrombotic drugs such as warfarin cause a general increase in bleeding tendency and therefore could influence fecal occult blood test results.. A population-based retrospective cohort study was conducted to investigate the performance of the fecal occult blood test for colorectal cancer screening in patients taking warfarin. The study population included 1356 tests performed in warfarin-treated patients and 64,088 tests in those not taking antithrombotics. Data on lower gastrointestinal evaluation were collected on 425 cases with a positive fecal occult blood test: all positives on warfarin and positive cases of a subsample of those tests in the group without antithrombotic treatment.. The positivity rate of the fecal occult blood test in the warfarin group was found to be doubled (7.7% (95%CI, 6.3%-9.2%)) compared with those not taking antithrombotics (3.6% (95%CI, 3.4%-3.7%)) (P <.0001). No significant difference in the positive predictive value for carcinoma and significant adenomas was found comparing the warfarin group to the no-antithrombotic group. The detection rates of both clinically significant adenomas and findings not indicative of significant neoplasia were increased in the warfarin group (8.9/1000 and 32.5/1000 respectively) compared with the no-antithrombotic group (4.0/1000 and 11.3/1000) (P = .02 and P <.0001 respectively), whereas that of carcinoma was not found to be different (3.7/1000 in the warfarin group vs 3.3/1000, P = .85).. Fecal occult blood test screening in warfarin users results in a higher, yet reasonable, positivity load and in a higher detection of premalignant lesions than in the general population. We consider fecal occult blood test screening appropriate for the warfarin-taking population.

Topics: Aged; Anticoagulants; Colorectal Neoplasms; Diagnosis, Differential; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Israel; Male; Mass Screening; Middle Aged; Occult Blood; Retrospective Studies; Thrombosis; Warfarin

To evaluate whether initiation of a fibrate or statin increases the risk of hospitalization for gastrointestinal bleeding in warfarin users.. We used Medicaid claims data (1999-2003) to perform an observational case-control study nested within person-time exposed to warfarin in those > or =18 years (n=353,489). Gastrointestinal bleeding cases were matched to 50 controls based on index date and state.. Chronic warfarin users had an increased odds ratio of gastrointestinal bleeding upon initiation of gemfibrozil (1.88; 95% confidence interval [CI], 1.00-3.54] for the first prescription; 1.75; 95% CI, 0.77-3.95 for the second prescription); simvastatin (1.46; 95% CI, 1.03-2.07 for the first prescription; 1.60; 95% CI, 1.07-2.39 for the second prescription); or atorvastatin (1.39; 95% CI, 1.07-1.81 for the first prescription; 1.05; 95% CI, 0.73-1.52 for the second prescription). In contrast, no increased risk was found with pravastatin initiation (0.75; 95% CI, 0.39-1.46 for the first prescription; 0.90; 95% CI, 0.43-1.91 for the second prescription).. Initiation of a fibrate or statin that inhibits CYP3A4 enzymes, including atorvastatin, was associated with an increased risk of hospitalization for gastrointestinal bleeding. Initiation of pravastatin, which is mainly excreted unchanged, was not associated with an increased risk.

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Anticoagulants; Case-Control Studies; Clofibric Acid; Cohort Studies; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Risk Factors; United States; Warfarin

To determine the effect of anticoagulants and antiplatelet medications on the positive-predictive-value of fecal occult blood test (FOBT).. All patients who underwent a colonoscopy at our institution from 1995 to 2006 for a positive FOBT were identified. Medical records were searched, and patients were stratified into five groups selected a priori: low-dose aspirin, NSAIDs, warfarin, clopidogrel, or controls. The positive-predictive-value of FOBT for advanced colonic neoplasia was computed for each group.. During the study period, 1,126 patients underwent colonoscopy for a positive FOBT and met entry criteria. The average age of study participants was 69 years and most were men. The positive-predictive-value of FOBT for advanced colon neoplasia was significantly higher in the control group (30.5%) when compared to those on low-dose aspirin (20.5%; p = 0.003), NSAIDs (19.7%; p = 0.003), clopidogrel (7.3%; p = 0.002), or warfarin (20%; p = 0.05). The positive-predictive-value of FOBT was significantly lower for those on clopidogrel than those on low-dose aspirin (p = 0.04) and NSAIDs (p = 0.05), but not warfarin (p = 0.08). The positive-predictive-value for FOBT was similar for those on aspirin, NSAIDs, and warfarin. There was a linear trend between the number of number of positive FOBT cards and prevalence of advanced colon neoplasia (p = 0.01).. Anticoagulants and antiplatelet medications lower the positive-predictive-value of FOBT for advance colonic neoplasia and should be stopped if clinically feasible prior to stool collection.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Clopidogrel; Colonic Neoplasms; Colonoscopy; Female; Gastrointestinal Hemorrhage; Humans; Logistic Models; Male; Mass Screening; Middle Aged; Occult Blood; Odds Ratio; Platelet Aggregation Inhibitors; Predictive Value of Tests; Retrospective Studies; Ticlopidine; Unnecessary Procedures; Warfarin

The HeartMate II (HMII) Left Ventricular Assist System (Thoratec Corporation, Pleasanton, CA, USA), an axial continuous-flow left ventricular assist device (LVAD), has been approved for use in bridge-to-transplant patients and is under investigation for destination therapy. To avoid device-related thromboembolic complications, antiplatelet, and anticoagulation therapy are routinely administered. A worrisome frequency of gastrointestinal (GI) bleeding events has been observed.. A retrospective review of all 33 patients undergoing long-term LVAD implantation between June 1, 2006 and July 31, 2008 at our institution for any indication was conducted. Anticoagulation consisted of heparin (intravenous or subcutaneous) followed by transition to Coumadin therapy to a target INR of two to three. Antiplatelet therapy consisted of low-dose aspirin and dipyridamole.. Twenty patients received the HMII and 13 patients received other devices. Eight (40%) HMII recipients suffered at least one episode of GI bleeding while no GI bleeding occurred in recipients of other devices (p = 0.012). Of 17 total bleeding episodes, no definitive source could be identified in 11 instances (65%).. Although definitive source identification remains elusive, we believe that the majority of bleeding arises in the small bowel, possibly due to angiodysplasias, similar to the pathophysiology encountered in patients with aortic stenosis and GI bleeding. As we move toward wider use of the HMII and other axial continuous-flow devices in both bridge-to-transplant patients and for destination therapy, more studies will be necessary to understand the mechanisms of this obscure GI bleeding and develop treatment strategies to minimize its development.

Topics: Anticoagulants; Aspirin; Dipyridamole; Female; Gastrointestinal Hemorrhage; Heart Ventricles; Heart-Assist Devices; Heparin; Humans; Incidence; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Warfarin

Some antibiotic agents, including cotrimoxazole, inhibit the metabolism of warfarin sodium and possibly increase the risk of hemorrhage. We examined the risk of upper gastrointestinal (UGI) tract hemorrhage in older patients receiving warfarin in combination with antibiotics commonly used to treat urinary tract infection, with a focus on cotrimoxazole.. This population-based, nested case-control study using health care databases in Ontario, Canada, between April 1, 1997, and March 31, 2007, identified residents 66 years or older who were continuously treated with warfarin. Cases were hospitalized with UGI tract hemorrhage. For each case, we selected up to 10 age- and sex-matched control subjects. We calculated adjusted odds ratios (aORs) for exposure to cotrimoxazole, amoxicillin trihydrate, ampicillin trihydrate, ciprofloxacin hydrochloride, nitrofurantoin, and norfloxacin within 14 days before the UGI tract hemorrhage.. We identified 134 637 patients receiving warfarin, of whom 2151 cases were hospitalized for UGI tract hemorrhage. Cases were almost 4 times more likely than controls to have recently received cotrimoxazole (aOR, 3.84; 95% confidence interval [CI], 2.33-6.33). Treatment with ciprofloxacin was also associated with increased risk (aOR, 1.94; 95% CI, 1.28-2.95), but no significant association was observed with amoxicillin or ampicillin (1.37; 0.92-2.05), nitrofurantoin (1.40; 0.71-2.75), or norfloxacin (0.38; 0.12-1.26). Compared with amoxicillin or ampicillin, cotrimoxazole prescription was associated with an almost 3-fold risk (ratio of ORs, 2.80; 95% CI, 1.48-5.32).. Among older patients receiving warfarin, cotrimoxazole is associated with a significantly higher risk of UGI tract hemorrhage than other commonly used antibiotics. Whenever possible, clinicians should prescribe alternative antibiotics in patients receiving warfarin.

Topics: Aged; Aged, 80 and over; Amoxicillin; Ampicillin; Anti-Infective Agents, Urinary; Anticoagulants; Case-Control Studies; Databases, Factual; Drug Interactions; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Humans; Male; Multivariate Analysis; Odds Ratio; Ontario; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Female; Gastrointestinal Hemorrhage; Hematoma; Hemoperitoneum; Humans; Intestine, Small; Medication Adherence; Warfarin

Warfarin is a widely used drug for the prevention of thromboembolic events. Knowledge of its adverse effects is necessary for patient follow-up. Although the development of blood dyscrasias is a potential complication in these patients, retroperitoneal bleeding is rare. This article reports the case of a patient who developed iliopsoas muscle hematoma during treatment with warfarin after implantation of a metallic prosthetic aortic valve. The clinical manifestations involved important differential diagnoses.

Topics: Aged; Anticoagulants; Diagnosis, Differential; Femoral Nerve; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Hematoma; Humans; Male; Nerve Compression Syndromes; Postoperative Complications; Psoas Muscles; Warfarin

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Clopidogrel; Colonic Neoplasms; Colonoscopy; Gastrointestinal Hemorrhage; Humans; Mass Screening; Occult Blood; Platelet Aggregation Inhibitors; Predictive Value of Tests; Ticlopidine; Unnecessary Procedures; Warfarin

To assess the impact of increased use of low-dose aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), warfarin, corticosteroids and selective serotonin re-uptake inhibitors (SSRIs) on the site and outcome of non-variceal gastrointestinal (GI) bleeds.. Retrospective review of 731 patients with peptic ulcer bleeds (PUBs), non-ulcer, non-variceal upper (NUUPGIBs) and lower GI bleeds (LGIBs) in 1984, 1994 and 2004 at Lund University Hospital, Sweden. Incidence and mortality rates, risk factors for fatal outcome and associations with different sites of GI bleeds were evaluated.. Between 1984 and 2004, incidence of PUBs decreased from 62.0 to 32.1 per 100,000 inhabitants (p<0.001). Incidence of NUUPGIBs (29.0-30.4 per 100,000) and LGIBs (45.5-43.2 per 100,000) was stable. The case-fatality rate ranged from 4-6% (p=0.65) for upper GI bleed to 1-8% (p=0.033) for LGIB. No drug impacted on fatal outcome. Aspirin, warfarin and SSRI users tended to suffer more severe GI bleeds than non-users of these drugs. When comparing non-ulcer GI bleeds with PUBs, aspirin (OR 0.56, 95% CI 0.38-0.82) was more strongly associated with PUBs, whereas SSRIs (OR 3.71, 95% CI 1.39-12.9) and corticosteroids (OR 2.8, 95% CI 1.28-6.82) were more associated with non-ulcer GI bleeds after adjusting for age, gender and co-morbidity.. Increased use of drugs that promote bleeding has not impacted on incidence and fatal outcome of non-variceal GI bleeds, although the severity of bleeding has increased. Aspirin is more strongly associated with PUBs, while corticosteroids and SSRIs are associated with non-ulcer, non-variceal GI bleeds.

Topics: Adrenal Cortex Hormones; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Selective Serotonin Reuptake Inhibitors; Warfarin

Topics: Aged; Anticoagulants; Atherosclerosis; Cystitis; Diagnosis, Differential; Embolism, Cholesterol; Female; Foreign-Body Reaction; Gastrointestinal Hemorrhage; Granuloma; Hematuria; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Ischemic Attack, Transient; Risk Factors; Syndrome; Tuberculosis, Urogenital; Urinary Bladder Neoplasms; Warfarin

Long-term use of warfarin can provide benefits in the treatment of many diseases, but adverse bleeding events are unpreventable because of a narrow therapeutic range.. The aim of this retrospective chart review with data abstraction was to investigate the clinical presentations of intestinal intramural hemorrhage in emergency department (ED) patients.. We reviewed the cases of 17 patients with acute abdominal pain in our ED. Medical records including demographic data and results of abdominal computed tomography were retrospectively reviewed and analyzed.. The mean ± SD age of the reviewed patients was 77.7 ± 8.5 years (range, 60-93 years). The mean ± SD duration from onset of symptoms to ED visit was 2.5 ± 1.3 days (range, 1-5 days). All patients had abdominal pain, and 64.7% had nausea/vomiting. A total of 64.7% of patients had peritoneal signs. The jejunum was most commonly involved (88.2% of all cases). The maximal mean ± SD wall thickening of the bowel was 14.1 ± 4.4 mm (range, 7.4-26.7 mm), and the estimated mean ± SD length was 35.6 ± 24.4 cm (range, 9-105 cm). The mean ± SD prothrombin time and activated partial thromboplastin time were prolonged to 86.5 ± 26.9 and 116.2 ± 43.1 seconds, respectively. All patients received medical treatment and survived. At the last follow-up (mean, 27.4 months), none of the patients had recurrence of intestinal intramural hemorrhage or intestinal obstruction.. Prolonged prothrombin time and drug history can indicate the possibility of intramural intestinal hemorrhage, and abdominal computed tomography may help to exclude surgical diseases and prevent unnecessary surgery.

Topics: Abdominal Pain; Aged; Aged, 80 and over; Anticoagulants; Emergency Service, Hospital; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Retrospective Studies; Statistics, Nonparametric; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

In the study of the association of transient drug exposures with acute outcomes, the case-crossover design is an efficient alternative to the case-control approach. This design based exclusively on the case series uses within-subject comparisons of drug exposures over time to estimate the rate ratio of the outcome associated with the drug under study. This design inherently removes the biasing effects of unmeasured, time-invariant confounding factors from the estimated rate ratio, but is sensitive to several assumptions. We illustrated the case-crossover design and explored its sensitivity using data from 4028 cases of gastrointestinal bleeding from the General Practice Research Database in assessing the effects of the drug warfarin. We compared the use of different time window lengths to assess exposure and considered the use of a case-time-control design to account for exposure time trends. The case-crossover approach found no excess risk of bleeding with warfarin exposure [rate ratio 0.98; 95% confidence interval (CI): 0.74-1.28] using a 1-month time window. When we restricted the analysis to subjects with truly transient drug exposure, defined by 1 to 3 prescriptions in the previous year, the rate ratio was 2.59 (95% CI: 1.42-4.74). To consider the longer 1-year exposure time window, the case-time-control approach was used and resulted in a rate ratio of 1.72 (95% CI: 1.08-2.43). In conclusion, the case-crossover design is potentially a powerful approach to assess the risk of drugs. This design is, however, highly sensitive to assumptions about intermittency of drug use and the length of the exposure time window, as demonstrated with the example of bleeding associated with warfarin use.

Topics: Anticoagulants; Cross-Over Studies; Gastrointestinal Hemorrhage; Humans; Models, Statistical; Pharmacoepidemiology; Warfarin

We reported 3 cases of the uncommon type of persistent gastrointestinal bleeding during anticoagulation therapy due to cardiovascular disorders or collagen disease. Endoscopic observation showed non pulsatile active bleeding from apparently normal mucosa, without any ulcer or obvious vascularectasia. The outflow of bleeding was string-like and continuous. Based on previous reports, we considered the possibly of these cases unique bleeding angiodysplasia and angiodysplasia during anticoagulation therapy. The frequency of this type of bleeding may increase, as anticoagulation therapy has become more common. We should pay attention to such lesions when we treat gastrointestinal bleeding.

Topics: Aged; Angiodysplasia; Anticoagulants; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Intestinal Mucosa; Middle Aged; Warfarin

To report a probable interaction between warfarin and marijuana smoking, resulting in increased international normalized ratio (INR) values and bleeding complications.. A 56-year-old white male had been receiving chronic warfarin therapy for 11 years after mechanical heart valve replacement. He was admitted to the hospital with a diagnosis of upper gastrointestinal bleeding. Upon admission, his INR value was supratherapeutic at 10.41, and his hemoglobin level was 6.6 g/dL. He received 4 units of fresh frozen plasma and one 10-mg dose of oral vitamin K; his INR was 1.8 the next day. He was discharged 7 days after admission. Fifteen days after hospital discharge, he was readmitted with a constant nosebleed and increased bruising. His INR value was 11.55. After treatment, he was discharged with an INR value of 1.14. The patient smoked marijuana more frequently throughout the period of these 2 hospitalizations due to his depression. He was counseled by the pharmacist on the potential interaction of warfarin and marijuana. The patient decided to stop smoking marijuana after the third counseling session. During the 9 months that he did not smoke marijuana, his INR values ranged from 1.08 to 4.40 with no significant bleeding complications.. Marijuana may increase warfarin anticoagulant effect by inhibiting its metabolism, and to a lesser extent, displacing warfarin from protein-binding sites. Other causes (eg, nonadherence) of the patient's increased INR were ruled out. Using the Horn Drug Interaction Probability Scale, our patient's warfarinmarijuana interaction appeared to be probable.. To our knowledge, there have been no other reported cases of warfarin-marijuana interaction. While more clinical reports would be useful to confirm this interaction, clinicians should be aware of its probability so as to manage patients appropriately.

Topics: Anticoagulants; Drug Interactions; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Male; Marijuana Smoking; Middle Aged; Protein Binding; Warfarin

Topics: Anticoagulants; Colonoscopy; Dalteparin; Enoxaparin; Gastrointestinal Hemorrhage; Humans; Preoperative Care; Time Factors; Warfarin

Topics: Aged; Anti-Infective Agents; Anticoagulants; Drug Interactions; Gastrointestinal Hemorrhage; Humans; Ischemia; Leg; Male; Nalidixic Acid; Postoperative Hemorrhage; Thromboembolism; Urethritis; Warfarin

The interaction between warfarin and nonsteroidal antiinflammatory drugs (NSAIDs) is well known. However, warfarin and NSAIDs are still commonly prescribed together. Selective cyclooxygenase-2 (COX-2) inhibitors, a newer class of NSAID, offer potential advantages over the nonselective NSAIDs in patients treated with warfarin.. To study the rates of hospitalization for gastrointestinal (GI) bleeding events in 3 groups of patients: those taking warfarin only, those taking warfarin plus a nonselective NSAID, and those taking warfarin plus a selective COX-2 inhibitor.. This was a retrospective cohort analysis in a large nonprofit health maintenance organization. All warfarin users from January 1, 2000, to December 31, 2005, were eligible for inclusion in the study. Eligible patients were grouped by their exposure time to warfarin only, warfarin plus nonselective NSAIDs, or warfarin plus selective COX-2 inhibitor. The study endpoint was hospitalization for a GI bleed. Patients were matched using a propensity scoring methodology. A multivariate Cox proportional hazards model was used to estimate the hazard ratio for GI bleeding between patient cohorts, controlling for age, sex, baseline medical conditions, prior history of GI bleeding, and prescription drug use.. The eligible population consisted of 35,548 patients undergoing 46,214 courses of warfarin therapy. The adjusted hazard ratio for hospital-associated GI bleeding in the warfarin plus nonselective NSAID group versus warfarin alone was 3.58 (95% CI 2.31 to 5.55; p < 0.01) and for warfarin plus selective COX-2 inhibitor versus warfarin alone was 1.71 (95% CI 0.60 to 4.84; p = 0.31). For nonselective NSAIDs plus warfarin versus selective COX-2 inhibitor plus warfarin, the adjusted hazard ratio was 3.69 (95% CI 1.42 to 9.60; p = 0.01).. In general, nonselective NSAIDs and selective COX-2 inhibitors should be avoided in patients taking warfarin. In situations where patients require NSAIDs and cannot be managed using other therapies, our results suggest that selective COX-2 inhibitors are associated with fewer hospitalizations for GI bleeding.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Drug Interactions; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Warfarin

Topics: Aged, 80 and over; Angiodysplasia; Anticoagulants; Aortic Valve Stenosis; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Heart Valve Prosthesis Implantation; Humans; Syndrome; 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

Topics: Aged; Anticoagulants; Female; Gastrointestinal Hemorrhage; Humans; Intestinal Volvulus; Jejunal Diseases; Tomography, X-Ray Computed; Warfarin

Endoscopic band ligation is an effective technique for primary and secondary prevention of gastro-esophageal variceal bleeding (GEVB), but can also result in rebleeding from postbanding ulcers. Its use in primary and secondary prevention of GEVB in anticoagulated patients has not been systematically studied. The aim of the study was to evaluate the feasibility of band ligation in primary and secondary prevention of GEVB in anticoagulated patients. Five patients (age 60.2+/-7.3 SD years: 3 males, 2 females) with esophageal varices on anticoagulation were studied using a retrospective chart review in a tertiary hospital setting. Patients were on mandatory anticoagulation with warfarin (international normalized ratio >2), on nonselective beta-blocker therapy if tolerated and were not transvenous intrahepatic porto-systemic shunting candidates. One patient had polycythemia vera (noncirrhotic), the rest were cirrhotics Child class B/C (1 cardiogenic, 1 primary sclerosing cholangitis, 1 Budd-Chiari, and 1 cryptogenic cirrhosis). Two patients had experienced prior acute GEVB; band ligation performed during acute bleeding was not included in the study. All patients had at least grade III-IV esophageal varices on outpatient follow-up for band ligation. Three bands were placed/patient and study patients underwent 3 banding sessions on an average. None of the patients developed GEVB after band ligation. In 3 patients banding resulted in complete variceal eradication, the remaining 2 are still being followed-up for outpatient band ligation. In conclusion, this case series suggests that endoscopic band ligation can potentially be used in anticoagulated patients without alternatives for prevention of acute GEVB.

Topics: Aged; Anticoagulants; Esophageal and Gastric Varices; Esophagoscopy; Female; Gastrointestinal Hemorrhage; Humans; Ligation; Male; Middle Aged; Treatment Outcome; Warfarin

The aim of this study was to determine whether a potential pharmacokinetic interaction between warfarin and orally administered anti-infectives increases the risk of hospitalization for gastrointestinal (GI) bleeding in warfarin users. We conducted a nested case-control and case-crossover study using US Medicaid data. Logistic regression was used to determine the association between GI bleeding and prior use of ciprofloxacin, levofloxacin, gatifloxacin, co-trimoxazole, or fluconazole vs. no exposure and also vs. use of cephalexin, which would not be expected to interact with warfarin. All of the anti-infectives examined were associated with elevated odds ratios (ORs) when compared to no exposure to these drugs. With cephalexin data as the reference, the ORs for co-trimoxazole (OR: 1.68 (95% confidence interval (CI): 1.21-2.33) in the prior 6-10 days) and fluconazole (OR: 2.09 (95% CI: 1.34-3.26) in the prior 11-15 days) were significantly elevated. Warfarin users who had received an anti-infective agent showed a substantially increased risk of GI bleeding. However, a drug-drug interaction with warfarin was evident only for co-trimoxazole and fluconazole.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Anticoagulants; Antifungal Agents; Azoles; Case-Control Studies; Cross-Over Studies; Drug Interactions; Female; Fluoroquinolones; Gastrointestinal Hemorrhage; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Risk; Sulfonamides; Warfarin

Bleeding is the most common complication of anticoagulant therapy. Despite the frequency of its occurrence, little evidence is available to guide the care of anticoagulated patients with, or at high risk of, bleeding. This article attempts, using a case based format, to describe common clinical scenarios encountered by clinicians who manage anticoagulated patients and who are bleeding. The paper is "case based" and narrative since there is little evidence to guide practice in this area.

Topics: Aged; Aged, 80 and over; Angiodysplasia; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Duodenal Ulcer; Female; Gastrointestinal Hemorrhage; Gastrointestinal Tract; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Mitral Valve; Warfarin; Young Adult

We report a case of fatal internal haemorrhage in an elderly man who consumed only cranberry juice for two weeks while maintaining his usual dosage of warfarin. We propose that naturally occurring compounds such as flavonoids, which are present in fruit juices, may increase the potency of warfarin by competing for the enzymes that normally inactivate warfarin. While traditionally regarded as foodstuffs, consumption of fruit juices should be considered when patients develop adverse drug reactions.

Topics: Aged; Anticoagulants; Beverages; Fatal Outcome; Flavonoids; Food-Drug Interactions; Gastrointestinal Hemorrhage; Humans; Male; Pericardial Effusion; Phytotherapy; Vaccinium macrocarpon; Warfarin

Topics: Administration, Oral; Anticoagulants; Aspirin; Blood Coagulation; Clopidogrel; Coumarins; Dipyridamole; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Hemorrhage; Hospitalization; Humans; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Risk Factors; Ticlopidine; Warfarin

Topics: Drug Interactions; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Warfarin

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Clopidogrel; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Colonic Neoplasms; Diagnosis, Differential; Gastrointestinal Hemorrhage; Hematoma; Humans; Male; Neoplasm Recurrence, Local; Warfarin

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Case-Control Studies; Confounding Factors, Epidemiologic; Drug-Related Side Effects and Adverse Reactions; Gastrointestinal Hemorrhage; Humans; Pharmacoepidemiology; Risk Factors; United Kingdom; Warfarin

Topics: Anticoagulants; Antifibrinolytic Agents; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Middle Aged; Senna Extract; Vitamin K; Warfarin

(i) To determine the effects of selective serotonin reuptake inhibitors (SSRI) and other classes of antidepressants on upper gastro-intestinal (GI) haemorrhage and (ii) to assess the drug-drug interaction effects of antidepressants and warfarin or clopidogrel on the risk of GI haemorrhage.. This was a population-based case control study in the General Practice Research Database (GPRD). Cases with a first episode of upper GI haemorrhage between 2000 and 2005 were matched with up to 10 controls. Exposure to the study drugs was defined by a prescription issued in the 90 days before the index date. Rate ratios were estimated using conditional logistic regression.. Four thousand and twenty-eight cases of GI haemorrhage and 40 171 controls were identified. The excess risk of GI haemorrhage with SSRI use was small (Rate Ratio [RR]: 1.3; 95% confidence interval [CI]: 1.1, 1.6) and null with exposure to tricyclic antidepressants (TCAs) (RR 1.0; 95% CI: 0.8, 1.3). The risk of GI haemorrhage was highest with venlafaxine use (RR: 1.9; 95% CI: 1.3, 2.6). There was no drug-drug interaction between warfarin anticoagulation and antidepressant use.. This study supports a small increased risk of upper GI haemorrhage with the use of SSRI antidepressants compared with the older TCA drugs, but to a lesser extent than previously reported due to confounding by alcohol use. The small elevation in risk of GI haemorrhage with SSRI and venlafaxine should be weighed against the therapeutic benefit of their use.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antidepressive Agents; Case-Control Studies; Clopidogrel; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Selective Serotonin Reuptake Inhibitors; Ticlopidine; Warfarin

The natural history of chronic portomesenteric (PM) and portosplenomesenteric (PSM) venous thrombosis is defined poorly. Therapeutic options are limited, and are directed at the prevention of variceal bleeding and the control of abdominal pain related to gastrointestinal hyperemia.. Patients with extensive PM and PSM thrombosis were reviewed retrospectively to evaluate the efficacy of medical therapy and to determine which clinical variables had prognostic significance regarding long-term survival.. Sixty patients, with a median age at diagnosis of 44 years (range, 18-68 y), were assessed. The median follow-up period was 3.5 years (range, 0.2-32.0 y). The overall survival rate was 73.3%, with 1- and 5-year survival rates of 81.6%, and 78.3%, respectively. One- and 5-year survival rates, excluding patients who died from malignancy-related causes, were 85.7% and 82.1%, respectively. Factors associated with improved survival included treatment with beta-blockers (P = .02; odds ratio [OR], .09; 95% confidence interval [CI], 0.01-0.70) and anticoagulation (P = .005; OR, 0.01; 95% CI, <0.01 to 0.26). Eighteen patients in total were anticoagulated, including 8 patients who had variceal bleeding, all of whom underwent endoscopic band ligation of esophageal varices before anticoagulation. By using Cox regression analysis, variables associated with reduced survival were the presence of ascites (P = .001; OR, 42.6; 95% CI, 5.03-360), and hyperbilirubinemia (P = .01; OR, 13.8; 95% CI, 1.9-100) at presentation. Six patients died of variceal hemorrhage.. Patients with chronic PM and PSM venous thrombosis without underlying malignancy have an acceptable long-term survival. Treatment with beta-blockers and anticoagulation appears to improve outcome.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Anticoagulants; Ascites; Chronic Disease; Esophageal and Gastric Varices; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Hyperbilirubinemia; Ligation; London; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Multivariate Analysis; Serum Albumin; Survival Rate; Venous Thrombosis; Warfarin

Anticoagulated patients who need to undergo endoscopy present unique challenges to the gastroenterologist. The continuation of anticoagulant therapy increases the risk of haemorrhagic complications of gastrointestinal endoscopy. Reversing the anticoagulation increases the risk of thromboembolism. In our experience in various endoscopy units, there are variable policies on the management of anticoagulated patients undergoing gastrointestinal endoscopy.. To study the current practice, survey questionnaires were sent to 2320 doctors, working in 231 hospitals across the United Kingdom.. Responses were obtained from 219 hospitals (94.8%), but only from 434 doctors (18.7%). The results show 40.8% endoscopists continued the patients on warfarin when performing a planned upper gastrointestinal endoscopy, whereas 26% stopped it; 33.2% gave varying reports, that is, they used their own judgement according to the disease for which the anticoagulant was being given. For planned lower gastrointestinal endoscopy, 48.7% doctors preferred to stop warfarin; 53.3% of the endoscopists stated that they have a policy in place at their hospital for both upper and lower gastrointestinal endoscopy in anticoagulated patients; 5.5% had a policy for upper gastrointestinal endoscopy only and 6.2% for lower gastrointestinal endoscopy only. Thirty-five per cent doctors reported that they did not have any standard policy. We compared the responses from within a hospital to see whether the doctors were uniformly aware of an existing policy in their hospital. For upper gastrointestinal endoscopy, the responses were the same (either yes or no) by 51% of the doctors, whereas they were different by 49%. For lower gastrointestinal endoscopies, the same response was given by 49% of the doctors, whereas 51% gave different answers. The poor response rate from the doctors, however, makes firm interpretation of the data difficult.. A wide variation in practice is seen across the country. A robust national guideline to streamline the endoscopy practice in anticoagulated patients is needed.

Topics: Anticoagulants; Biopsy; Drug Administration Schedule; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Guideline Adherence; Health Care Surveys; Humans; International Normalized Ratio; Practice Guidelines as Topic; Professional Practice; Warfarin

Topics: Adrenal Cortex Hormones; Aging; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cardiovascular Diseases; Cyclooxygenase 2 Inhibitors; Drug Administration Schedule; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Factors; Ulcer; Warfarin

Anticoagulants and antiplatelet drugs (e.g., warfarin, clopidogrel and acetylsalicylic acid) are key therapeutic agents in the treatment of cardiovascular diseases. However, drug-drug interactions may lead to a greatly increased risk of gastrointestinal bleeding when these drugs are combined. We assessed whether antithrombotic drug combinations increased the risk of such bleeding in a general practice population.. We conducted a population-based, retrospective case-control study using records in the United Kingdom General Practice Research Database from 2000 through 2005. Cases were identified as patients over 18 years of age with a first-ever diagnosis of gastrointestinal bleeding. They were matched with controls by physician practice, patient age and index date (date of diagnosis of bleeding). All eligible patients had to have at least 3 years of follow-up data in the database. Drug exposure was considered to be any prescription issued in the 90 days before the index date.. There were 4028 cases with a diagnosis of gastrointestinal bleeding and 40 171 matched controls. The prescribing of acetylsalicylic acid with either clopidogrel (adjusted rate ratio [RR] 3.90, 95% confidence interval [CI] 2.78-5.47) or warfarin (adjusted RR 6.48, 95% CI 4.25-9.87) was associated with a greater risk of gastrointestinal bleeding than that observed with each drug alone. The same was true when a nonsteroidal anti-inflammatory drug was combined with either clopidogrel (adjusted RR 2.93, 95% CI 1.74-4.93) or warfarin (RR 4.60, 95% CI 2.77-7.64).. Drug combinations involving antiplatelets and anticoagulants are associated with a high risk of gastrointestinal bleeding beyond that associated with each drug used alone. Physicians should be aware of these risks to better assess their patients' therapeutic risk-benefit profiles.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Clopidogrel; Drug Interactions; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

Topics: Drug Interactions; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Warfarin

Topics: Anticoagulants; Compartment Syndromes; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Middle Aged; Retroperitoneal Space; 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

The extent and complications of the interaction between capecitabine and warfarin are not fully known.. A retrospective study of 77 patients who received capecitabine was performed to analyze coagulation abnormalities with or without warfarin.. Twenty-one patients received warfarin with capecitabine. Twelve were on an average warfarin dosage of 19.4 mg per week (range, 7-35 mg) before capecitabine treatment, with a stable international normalized ratio (INR; range, 0.9-3.3). The dose of capecitabine ranged from 1.6 g/m2 to 2 g/m2 per day. Thirteen patients (11 on warfarin) had an INR > 3 (range, 3.23-11.5), resulting in a probability of an INR > 3 of 32% in the warfarin group versus 4% for those not on warfarin (P = 5.1 x 10(-14)) at 130 days. Six patients required a warfarin dose reduction (1-2.5 mg decrease). There were 7 episodes of bleeding (all gastrointestinal; 5 with warfarin). Seven patients who experienced bleeding had INRs ranging from 1.06 to 8 (average, 3.31) at the time bleeding occurred. Of the 7 bleeding episodes, 5 patients required transfusions, averaging 3.25 units of red blood cells and 2.4 units of fresh frozen plasma. The incidence of bleeding at 130 days of treatment with capecitabine was 18% with warfarin versus 2% without (P = 4 x 10(-13)). Bleeding episodes were not significantly different between patients with or without liver involvement (4 of 40 episodes vs. 3 of 37 episodes, respectively; P = 0.12). Patients with an INR > 3 were evenly distributed between those with or without liver involvement (6 of 40 patients vs. 7 of 37 patients, respectively). No INR increases persisted after discontinuation of capecitabine.. This study confirms a clinically significant interaction between warfarin and capecitabine-based chemotherapy akin to that already known for 5-fluorouracil. In addition to altered coagulation parameters, bleeding can be a complication. These events occurred in patients with and without liver metastases. We recommend weekly monitoring of coagulation parameters for all patients receiving concomitant warfarin and capecitabine, with an appropriate adjustment of warfarin dose. The nature and extent of this interaction requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antimetabolites, Antineoplastic; Blood Coagulation Disorders; Capecitabine; Deoxycytidine; Drug Interactions; Female; Fluorouracil; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Polypharmacy; Retrospective Studies; Warfarin

Selective serotonin reuptake inhibitors (SSRIs) can adversely affect platelet function and impair haemostasis. Various bleeding complications have been reported in persons taking SSRIs including an increased risk of gastrointestinal haemorrhage (GIH).. To evaluate SSRI use in patients hospitalized with GIH compared with controls.. A retrospective, multicentre case-control study determined use of SSRIs, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, clopidogrel, coumadin and enoxaparin in patients admitted with GIH and age- and sex-matched controls. Exclusion criteria included liver disease, portal hypertension or bleeding diathesis.. A total of 579 cases were matched with 1000 controls. SSRI use was 19.2% in cases and 13.6% in controls [OR (95% CI) = 1.5 (1.2-2.0); P = 0.003]. NSAIDs were used by 7.3% of cases and 3.8% of controls [OR = 2.0 (1.3-3.1); P = 0.003]. SSRI use was more strongly associated with lower [1.8 (1.2-2.8)] rather than upper [1.3 (0.83-1.9)] GIH. Significant interactions existed for SSRI use with NSAIDs and aspirin.. Patients admitted with GIH gastrointestinal bleeding were more likely to be taking SSRIs than controls. This association exists for lower as well as upper GIH. Physicians should be aware of this risk particularly in patients already using medications that increase GIH risk.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Black or African American; Blood Coagulation; Case-Control Studies; Clopidogrel; Drug Interactions; Enoxaparin; Female; Gastrointestinal Hemorrhage; Hispanic or Latino; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Selective Serotonin Reuptake Inhibitors; Ticlopidine; Warfarin; White People

A 73-year-old woman presented with a history of persistent atrial fibrillation, which had lasted more than five years. She also had a remote history of transient ischemic attack and had received warfarin therapy. The international normalized ratio had been carefully maintained at slightly subtherapeutic levels because of recurrent gastrointestinal bleeding, which was severe enough to require frequent blood transfusions. With colonoscopy, the source of bleeding was localized to multiple arterial-venous malformations. The patient underwent catheter ablation of the atrioventricular junction and received a single chamber pacemaker. Two years later, she received a dual chamber pacemaker followed by cardioversion to restore a sinus rhythm. Following brief cardioversion, her symptoms of atrial fibrillation returned after two days.. Transesophageal echocardiography, pacemaker interrogation.. Persistent atrial fibrillation, gastrointestinal bleeding requiring transfusion.. Percutaneous left atrial appendage occlusion, antiplatelet therapy.

Topics: Aged; Anticoagulants; Arteries; Arteriovenous Fistula; Atrial Appendage; Atrial Fibrillation; Catheter Ablation; Colon; Colonic Diseases; Electric Countershock; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Pacemaker, Artificial; Recurrence; Reoperation; Veins; Warfarin

The long-term effects of axial-flow mechanical circulatory support in humans are unclear. We report 3 cases of chronic gastrointestinal bleeding after implantation of a Jarvik 2000 axial-flow left ventricular assist device. The bleeding was refractory to aggressive management and in 2 cases resolved only after orthotopic cardiac transplantation.

Topics: Aged; Anticoagulants; Arteriovenous Malformations; Cardiomyopathies; Female; Gastrointestinal Hemorrhage; Heart-Assist Devices; Humans; Intestine, Small; Male; Middle Aged; Myocardial Ischemia; Warfarin

Little is known about the risk of upper gastrointestinal (GI) hemorrhage during the concomitant use of warfarin and selective cyclooxygenase (COX)-2 inhibitors. We examined the association between the concomitant use of warfarin and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitors in older adults hospitalized for upper GI hemorrhage.. This nested case-control analysis of multiple linked health care databases conducted over 1 year identified a cohort of patients in Ontario, Canada, who were older than 66 years and continuously prescribed warfarin. Case patients were those admitted to the hospital with upper GI hemorrhage while taking warfarin. We compared their prescription records prior to hospitalization with those of age- and sex-matched controls who were also receiving warfarin (the control-case ratio was 4:1). Odds ratios (ORs) for the risk of hospitalization for upper GI hemorrhage while concomitantly using warfarin and celecoxib, rofecoxib, or nonselective NSAIDs were determined.. During the study period, we identified 98 821 elderly patients continuously receiving warfarin. Of those, 361 (0.3%) were admitted to the hospital with upper GI hemorrhage. After adjusting for other potential confounders, case patients were significantly more likely to be also taking nonselective NSAIDs (OR, 1.9; 95% confidence interval [CI], 1.4-3.7), celecoxib (OR, 1.7; 95% CI, 1.2-3.6), or rofecoxib (OR, 2.4; 95% CI, 1.7-3.6) prior to hospitalization relative to controls.. Patients taking warfarin concomitantly with selective COX-2 inhibitors have an increased risk of hospitalization for upper GI hemorrhage. The risk appears similar to that of patients simultaneously taking warfarin and nonselective NSAIDs.

Topics: Age Distribution; Aged; Aged, 80 and over; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Cohort Studies; Cyclooxygenase Inhibitors; Drug Interactions; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Logistic Models; Male; Multivariate Analysis; Ontario; Prognosis; Registries; Risk Assessment; Sex Distribution; Warfarin

Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients.. From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin.. The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P < 0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P = 0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy.. Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Endoscopy, Digestive System; Female; Gastrointestinal Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Peptic Ulcer; Prognosis; Retrospective Studies; Treatment Outcome; Warfarin

To determine the relation between warfarin use and the frequency of bleeding complications after biopsy of the prostate guided by transrectal ultrasound (TRUS).. Overall, 1022 consecutive patients with suspected prostatic disease were followed after biopsy. Warfarin and aspirin use was determined on the day of the procedure. A TRUS-guided biopsy was performed and patients were offered a questionnaire to complete 10 days after the procedure, to determine any immediate or delayed bleeding complications. Follow-up telephone calls were made to those who had not replied within the stipulated period.. Of the 1000 patients who replied, 49 were receiving warfarin, 220 were receiving aspirin and 731 were not receiving any anticoagulant drugs. Of the 49 subjects reporting current use of warfarin, 18 (36.7%) experienced haematuria, compared with 440 (60.2%) of the patients receiving no anti-coagulant drugs who reported haematuria. This was statistically significant (p = 0.001). Of the group receiving warfarin, 4 (8.2%) experienced haematospermia whereas 153 (21%) of the group receiving no anticoagulant medication reported haematospermia. This difference also was statistically significant (p = 0.030). Rectal bleeding was experienced by 7 (14.3%) of the group receiving warfarin compared with 95 (13%) in the group without anticoagulant medication, but this was not statistically significant (p = 0.80). We also demonstrated that there was no statistically significant association between the severity of the bleeding complications and medication with warfarin.. None of the group receiving warfarin experienced clinically important bleeding complications. Our results suggest that the frequency and severity of bleeding complications were no worse in the warfarin group than in the control group and that discontinuing anticoagulation medication before prostate biopsy may be unnecessary.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Biopsy; Blood; Fibrinolytic Agents; Follow-Up Studies; Gastrointestinal Hemorrhage; Hematuria; Humans; Male; Middle Aged; Postoperative Hemorrhage; Prostate; Prostatic Neoplasms; Rectum; Semen; Severity of Illness Index; Ultrasonography, Interventional; Warfarin

We present a rare case of small bowel obstruction in a patient on long-term anticoagulation. A 53-year woman presented with abdominal pain and vomiting. She was on warfarin following aortic and mitral valve surgery. A small bowel follow through revealed jejunal narrowing consistent with a stricture. This probably was the result of submucosal bleeding because of over warfarinazation. The warfarin was stopped and she started on heparin with complete resolution of symptoms. This rare complication of anticoagulation should be considered in patients on warfarin. Early diagnosis is crucial as most patients are treated conservatively with very few patients requiring surgery.

Topics: Female; Gastrointestinal Hemorrhage; Heparin; Humans; Intestinal Obstruction; Intestine, Small; Middle Aged; Treatment Outcome; Warfarin

Case reports suggest that some selective serotonin reuptake inhibitors can interact with warfarin to increase the likelihood of bleeding. We speculated that, among patients receiving warfarin, initiation of selective serotonin reuptake inhibitor treatment would be associated with an increased risk of hospitalization for upper gastrointestinal tract bleeding (UGIB).. We conducted a population-based, nested, case-control study involving Ontario residents 66 years or older continuously treated with warfarin for at least 1 year. Cases admitted with UGIB were compared with matched controls (1:10) to explore the odds ratio for initiation of various antidepressants within 42, 90, and 180 days before the index admission.. From January 1994 to December 2002, we identified 98,784 elderly patients continuously receiving warfarin for at least 1 year; of whom 1538 (0.6%) were admitted to hospital for UGIB. The adjusted odds ratio for fluoxetine/fluvoxamine exposure in 90 days before UGIB hospitalization is 1.2 (95% confidence interval, 0.8-1.7), and the adjusted odds ratio for other selective serotonin reuptake inhibitors in the same period was 1.1 (95% confidence interval, 0.9-1.4). The odds ratios for exposure to antidepressants in 180 days before UGIB hospitalization were similar.. The initiation of selective serotonin reuptake inhibitor treatment in patients receiving warfarin was not associated with a significant increase in the risk of hospitalization for UGIB.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antidepressive Agents, Tricyclic; Case-Control Studies; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Male; Ontario; Polypharmacy; Risk Assessment; Selective Serotonin Reuptake Inhibitors; Warfarin

Warfarin and aspirin are commonly used to prevent cardiovascular diseases. Aspirin was recently found to have chemopreventive effects on colon cancer and polyps by inhibiting cyclooxygenase-2. Therefore, we evaluated whether the symptoms of bleeding related with aspirin or warfarin could be a clue in early detection of colon cancer. We also assessed the effect of aspirin on the development of synchronous polyps.. A total of forty-one and 16 patients diagnosed as colon cancer, taking aspirin or warfarin respectively were enrolled. In addition, 171 patients with colon cancers were age and gender matched as a control group. We investigated the difference of clinical features and laboratory findings among three groups.. The incidence of bleeding was 81.3% (warfarin), 53.7% (aspirin), 40.4% (control). Among three groups, location and size of cancer, number of lymph nodes involvement and stages were not different, but the number of patients in Duke stage D in warfarin group (n=1, 6.3%) were less than that of the control (n=44, 25.7%) (p=0.049). The extent of circumferential involvement by cancer was lower in aspirin group (67%) than in the control group (80%) (p=0.035). The percentage of patients with synchronous polyps and mean number of synchronous polyps in aspirin group (34.1%, 0.68, respectively) was lower than that of control group (53.6%, 1.69, respectively) (p=0.029, 0.008, respectively).. Bleeding related with aspirin or warfarin usage had no effect on the early diagnosis of colon cancer. However, lower incidence of Duke stage D in warfarin group might be related to anti-metastatic effect of warfarin. In addition, aspirin may have a role in suppressing the development of synchronous polyps.

Topics: Aged; Anticoagulants; Aspirin; Cardiovascular Diseases; Colonic Neoplasms; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Warfarin

Our goal was to establish whether psychosocial risk factors for nonadherence, previously identified as negative predictors of warfarin prescribing, are predictors of adverse events for patients with nonvalvular atrial fibrillation receiving warfarin.. Retrospective cohort analysis.. Ohio Medicaid administrative database.. We studied Ohio Medicaid recipients with nonvalvular atrial fibrillation receiving warfarin to determine whether a history of substance abuse, psychiatric illness, or social factors (identified as conditions perceived to be barriers to adherence) are predictors of adverse events, including stroke, intracranial hemorrhage, and gastrointestinal bleeding. Multivariable risk ratios were calculated for each risk factor using Cox proportional hazards models.. 9,345 patients were identified as having nonvalvular atrial fibrillation and receiving 2 or more warfarin prescriptions between 1997 and 2002. The event rates for the sample as a whole were 1.5 strokes, 0.7 intracranial hemorrhages, and 4.3 gastrointestinal bleeds per 100 person-years of follow-up. Subjects with substance abuse had the highest adjusted risk ratio, 2.4 (95% confidence interval [CI]: 1.4, 4.0) for an intracranial hemorrhage while receiving warfarin, followed by subjects with psychiatric illness, adjusted risk ratio of 1.5 (95% CI: 1.04, 2.1). Subjects with psychiatric illness also had an adjusted risk ratio of 1.4 (95% CI: 1.1, 1.7) for stroke. Patients in all 3 identified risk groups were at a significantly increased risk of gastrointestinal bleeding.. Patients with nonvalvular atrial fibrillation treated with warfarin who have psychosocial risk factors for nonadherence have an increased risk of adverse events.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Mental Disorders; Middle Aged; Retrospective Studies; Risk Factors; Socioeconomic Factors; Stroke; Substance-Related Disorders; Treatment Outcome; Treatment Refusal; Warfarin

Anticoagulants and antiplatelet agents commonly are used to treat patients with cardiovascular and cerebrovascular diseases. Data on the safety of the use of these drugs before colonoscopic polypectomy are scanty.. An audit was conducted for a 2-year period of consecutive patients undergoing colonoscopy and polypectomy. Patient demographics, site and size of polyps, and the use of anticoagulants and antiplatelet agents were documented from a hospital on-line database. Bleeding episodes were classified as immediate or delayed and were graded as mild, moderate, or severe. Risk factors associated with postendoscopy bleeding were analyzed by multivariate logistic regression analysis.. A total of 5593 cases were reviewed. Polypectomy was performed in 1657 patients. There were 37 cases of polypectomy-associated bleeding (2.2%); bleeding was immediate in 32 and delayed in 5. Multivariate analysis showed that warfarin use, after adjustment for the effects of each of the other factors, was an independent risk factor for bleeding, with an odds ratio 13.37: 95% CI[4.10, 43.65]. Age; the location and size of polyp; and the use of aspirin, non-steroidal anti-inflammatory drugs, and other antiplatelet agents were not associated with a higher risk of polypectomy-associated bleeding.. The use of antiplatelet agents during polypectomy was not associated with an increase in post-polypectomy bleeding. In contrast, treatment with warfarin should be discontinued, because this was associated with a significant increase in post-polypectomy bleeding.

Topics: Aged; Anticoagulants; Clopidogrel; Colonic Polyps; Colonoscopy; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; 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

The Framingham Heart Study records of participants with atrial fibrillation (AF) during 1980 and 1994 were retrospectively reviewed to determine the prevalence of warfarin and aspirin use in AF. Anticoagulant use increased significantly in the 393 men and women (mean ages 72.5 and 79.0 years, respectively) who developed AF over the observation period: aspirin use increased from 14% to 39% in men and from 19% to 33% in women, and warfarin use increased from 10% to 39% in men and from 17% to 38% in women. There were no significant gender differences in anticoagulant use (p = 0.61), but participants using warfarin were younger. A total of 65 participants (17%) had major bleeding complications

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Heart Failure; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prevalence; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome; Warfarin

The study investigated clinical, radiological findings and treatment methods used in patients who developed intraabdominal hemorrhage due to chronic warfarin use.. Eight patients receiving warfarin for cardiac valve replacement, pulmonary thromboemboli, and atrial fibrillation were admitted to our hospital. The patients had abdominal pain, nausea, and vomiting although there was no hematemesis and melena.. Abdominal ultrasonography and computerized tomography identified the individuals' problems as intraabdominal hemorrhage (n=2), intestinal intramural and intraabdominal hemorrhage (n=2), bleeding into the sheath of the rectus abdominus muscle (n=1), subcapsular splenic hemorrhage (n=1), and bleeding due to ruptured ovarian cyst (n=2).. Clinicians must be alert for intraabdominal bleeding in patients who are prescribed warfarin treatment. Abdominal ultrasonography and computerized tomography should be used to investigate all such cases of suspected hemorrhage. Blood and plasma replacements are first line of supportive treatment and surgery should be avoided if possible.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Heart Valve Prosthesis Implantation; Hematoma; Humans; Male; Middle Aged; Pulmonary Embolism; Thromboembolism; Tomography, X-Ray Computed; Turkey; Ultrasonography; Warfarin

Intramural hematoma of the intestine is a rare complication of anticoagulant therapy. We evaluated 7 nontrauma patients with intramural hematoma of the intestine diagnosed at our institution between May 1998 and June 2001. All of the patients were receiving long-term anticoagulant therapy for previous diseases. All 7 patients had abdominal pain, 6 had additional symptoms of nausea and vomiting, and 4 had melanotic stools at admission. Six of the patients had abnormal coagulation parameters. Both abdominal ultrasonography (US) and computerized tomography (CT) showed the exact pathology in all patients. Five of the 7 patients were treated, nonoperatively, and the other patients underwent surgery. All of the patients were followed with abdominal US and CT (mean 12 = months), with complete resolution of their intramural hematomas. Abdominal US and CT evaluation performed together will help the accuracy of diagnosis of intramural hematoma, but nonoperative therapy is the treatment of choice, with surgery indicated if generalized peritonitis or intestinal obstruction develops.

Topics: Abdomen; Abdomen, Acute; Abdominal Pain; Adult; Aged; Anticoagulants; Diagnosis, Differential; Drug Overdose; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Hematoma; Humans; Male; Middle Aged; Radiography, Abdominal; Treatment Outcome; Ultrasonography; Warfarin

Warfarin is involved in the majority of fatal adverse drug events in Norway. The aim of this study is to identify risk factors behind the haemorrhagic complications.. We analysed all adverse event reports involving bleeding related to warfarin that were received by the Norwegian Medicines Agency from 1990 to 2000.. 713 reports were included; 71% of the patients were above 70 years of age. The most frequent diagnosis was atrial fibrillation (39%). Cerebral bleedings were reported in 57% of the cases, 73% of which were fatal, as were 39 % of gastrointestinal bleedings and 14% of other bleedings. International normalised ratio values (INR values) at the time of bleeding were reported in 83% of the cases; mean INR value was 4.4 (range 1.2 - > 8.0). INR values above recommended limits at the time of bleeding were found in 74% of the patients. In 63%, bleedings occurred during the first month; in 30% during the first five days. Median duration of treatment was shorter in fatal (16 days) than in non-fatal cases (24 days).. Our results show that haemorrhagic complications are associated with high INR values and initiation of treatment. Simple strategies for reducing bleedings include better monitoring of patients, careful dose adjustment, and INR values in the lower end of the recommended ranges.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Anticoagulants; Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Risk Factors; Warfarin

We present a patient receiving chronic anticoagulant treatment with recurrent and intractable gastrointestinal bleeding due to diffuse angiodysplasia. Following failure of previous medical and surgical treatment, and in light of the patient's need for chronic anticoagulation due to mechanical heart valve, she was treated with somatostatin analogue, octreotide s.c. 100 microg on alternate days for 28 months. Treatment significantly decreased the occurrence of bleeding episodes, the need for hospitalization and blood transfusion requirements despite continued anticoagulant therapy. Octreotide treatment should be considered in patients with refractory gastrointestinal bleeding due to angiodysplasia in particular in those who need anticoagulant treatment.

Topics: Aged; Angiodysplasia; Anticoagulants; Chronic Disease; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Hemostatics; Humans; Octreotide; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Antimetabolites, Antineoplastic; Capecitabine; Deoxycytidine; Fluorouracil; Gastrointestinal Hemorrhage; Humans; Male; Warfarin

Acute GI bleeding is a life-threatening complication of warfarin therapy. Acute GI bleeding in patients with an international normalized ratio of 4.0 or greater (supratherapeutic) is often attributed to trivial mucosal lesions. The aim of the study was to determine the frequency of potentially significant lesions that would warrant endoscopy in this setting.. A retrospective review was conducted of patients treated with warfarin who were admitted to a single Veterans Affairs hospital from 1996 to 2000 with acute GI bleeding. Endoscopic findings, clinical management, and outcomes are reviewed for patients with a supratherapeutic international normalized ratio (>or=4.0) and compared with patients with an international normalized ratio in the therapeutic range (2.0-3.9).. Fifty-five patients with an international normalized ratio of 4.0 or greater (mean 8.4 [3.9]) and 43 patients with an international normalized ratio between 2.0 and 3.9 (mean 2.9 [0.6]) were hospitalized with acute GI bleeding. Thirty-seven patients (67%) with a supratherapeutic international normalized ratio and GI bleeding underwent upper endoscopy. Of these, 81.1% had positive findings, 18.9% had peptic ulcer disease, and 7.2% required endoscopic treatment. Thirty-eight percent of the patients with a supratherapeutic international normalized ratio underwent lower endoscopy; of these, 57.1% had abnormal findings and 9.5% required endoscopic treatment. Four patients (7.3%) in the supratherapeutic international normalized ratio group died during the index hospitalization. When patients with GI bleeding and a therapeutic international normalized ratio were compared with those with a supratherapeutic international normalized ratio, there were no significant differences between the two groups with regard to days of hospitalization, units of blood transfused, frequency of recurrent bleeding, need for surgery, or in-hospital deaths.. The high frequency of clinically significant lesions in patients taking warfarin with an international normalized ratio in the supratherapeutic range and acute GI bleeding supports a role for endoscopic evaluation.

Topics: Acute Disease; Aged; Anticoagulants; Case-Control Studies; Endoscopy, Gastrointestinal; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Length of Stay; Male; Retrospective Studies; Treatment Outcome; Warfarin

Topics: Aged; Anticoagulants; Beverages; Fatal Outcome; Food-Drug Interactions; Gastrointestinal Hemorrhage; Heart Diseases; Hemorrhage; Humans; International Normalized Ratio; Male; Pericardium; Vaccinium macrocarpon; Warfarin

Topics: Aged; Anticoagulants; Drug Prescriptions; Fatal Outcome; Gastrointestinal Hemorrhage; Humans; Male; Medication Errors; Warfarin

Topics: Anticoagulants; Gastrointestinal Hemorrhage; Humans; Medication Errors; Warfarin

A 90-year-old woman was hospitalized for gastrointestinal bleeding. Although she had been receiving only warfarin 5 mg/day, her international normalized ratio (INR) was 66. Warfarin was discontinued, and her INR fell to 3.7 after transfusion of fresh-frozen plasma. However, it rose again spontaneously to 7.5. Eleven days after the last dose of warfarin had been administered, it was still detectable in the patient's plasma, indicating that impaired warfarin clearance may have caused an enhanced anticoagulation effect. Genetic analysis of the cytochrome P450 (CYP) isoenzyme 2C9, which mediates the major deactivating pathway of S-warfarin, revealed that the patient was a compound heterozygote carrying two variant alleles: CYP2C9*2 and CYP2C9*3. The patient's enhanced sensitivity to warfarin 5 mg/day can be ascribed to decreased clearance of S-warfarin secondary to genetic alteration of the gene encoding CYP2C9, resulting in a life-threatening complication.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Female; Gastrointestinal Hemorrhage; Genetic Predisposition to Disease; Half-Life; Humans; International Normalized Ratio; Polymorphism, Genetic; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Warfarin

To determine how factors that increase the risk of major upper gastrointestinal (GI) tract hemorrhage (recent upper GI tract bleeding or concurrent use of nonsteroidal anti-inflammatory drugs) influence the choice of antithrombotic therapy in older patients (those > or = 65 years) with atrial fibrillation.. For older patients with atrial fibrillation and no other contraindications to antithrombotic therapy, a Markov decision-analytic model was used to determine the preferred treatment strategy (no antithrombotic therapy, long-term aspirin use, or long-term warfarin sodium use) based on their risk of major upper GI tract hemorrhage. Input data were obtained by a systematic review of MEDLINE. Outcomes were expressed as quality-adjusted life-years (QALYs).. For 65-year-old patients with average risks of stroke and upper GI tract bleeding, warfarin therapy was associated with 12.1 QALYs per patient; aspirin therapy, 10.8 QALYs; and no antithrombotic therapy, 10.1 QALYs. For persons with significantly higher risks of upper GI tract bleeding and/or lower risks of stroke, warfarin was no longer clearly the optimal antithrombotic therapy (eg, for 80-year-old persons with a baseline risk of stroke of 4.3% per year who were concurrently taking a conventional nonsteroidal anti-inflammatory drug: warfarin, 7.44 QALYs; aspirin, 7.39 QALYs; and no treatment, 7.21 QALYs).. For older patients with atrial fibrillation and factors that place them at a higher than average risk of upper GI tract bleeding, the optimal choice of antithrombotic therapy to prevent stroke can vary according to the magnitude of this risk. Based on the risks of stroke and upper GI tract bleeding, clinicians can use the treatment recommendations of this study to provide rational stroke prevention therapy for older patients with atrial fibrillation.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Atrial Fibrillation; Decision Support Techniques; Gastrointestinal Hemorrhage; Humans; Middle Aged; Quality-Adjusted Life Years; Risk Assessment; Stroke; Warfarin

To identify the risk of thromboembolism after withholding or reversing the effect of warfarin therapy following a major hemorrhage.. Retrospective medical record review.. Tertiary-care hospital.. Twenty-eight patients with prosthetic heart valves receiving warfarin were hospitalized for major hemorrhage from 1990 to 1997. The mean +/- SD age was 61 +/- 11 years (15 men and 13 women). Twenty patients had St. Jude valves, 4 patients had Carpentier-Edwards bioprosthetic valves, 2 patients had Starr Edwards valves, and 2 patients had Bjork-Shiley valves. Valves were in the mitral position in 12 patients, the aortic position in 12 patients, and both mitral and aortic positions in 4 patients. The average interval from valve surgery to index bleeding was 7 years. Twenty-five patients had GI or retroperitoneal hemorrhage, 2 patients had an intracranial hemorrhage, and 1 patient had a subdural hematoma.. Vitamin K was administered to five patients and fresh frozen plasma was given to seven patients to reverse anticoagulation. The mean duration of anticoagulation withholding was 15 +/- 4 days.. None of the patients had thromboembolic complications. There were four in-hospital deaths. Twenty-two of the 24 hospital survivors resumed warfarin therapy at hospital discharge. At 6-month follow-up, 10 of 19 patients remaining on warfarin therapy had recurrent GI bleeding.. Thromboembolic risk is low in prosthetic heart valve patients hospitalized with major hemorrhage when their warfarin therapy is reversed or withheld. Recurrent bleeding within 6 months of the resumption of anticoagulation is common, and aggressive treatment of the bleeding source and the risk-benefit ratio of continued anticoagulation need to be considered.

Topics: Aged; Anticoagulants; Female; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Recurrence; Retrospective Studies; Thromboembolism; Warfarin

We sought to describe the development and outcomes of a hospital-based program designed to provide safe and effective outpatient treatment to a diverse group of patients with acute deep venous thrombosis.. Patients enrolled in the program were usually discharged on the day of or the day after presentation. Low- molecular-weight heparin was administered for a minimum of 5 days and warfarin was given for a minimum of 3 months. The hospital provided low-molecular-weight heparin free of charge to patients. Patients received daily home nursing visits to monitor the prothrombin time, assess compliance, and detect complications. The inpatient and outpatient records of the first 89 consecutive patients enrolled in the program were reviewed. Patients were observed for a 3-month period after enrollment.. The median length of stay was 1 day. Low-molecular-weight heparin was administered for a mean (+/- standard deviation [SD]) of 4.7 +/- 2.4 days at home. Recurrent thromboembolism was noted in 1 patient (1%), major bleeding in 2 patients (2%), and minor bleeding in 2 patients (2%). No patients died or developed thrombocytopenia. Assuming that patients would have been hospitalized for the duration of treatment with low-molecular-weight heparin, the program eliminated a mean of 4.7 days of hospitalization, with an estimated reduction of $1,645 in total health care costs per patient.. This hospital-based program to provide outpatient treatment of deep venous thrombosis to a diverse group of inner-city patients achieved a low incidence of adverse events and substantial health care cost savings. Specific strategies, including providing low-molecular-weight heparin free of charge and daily home nursing visits, can be utilized to facilitate access to outpatient treatment and ensure high-quality care.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; Comorbidity; Costs and Cost Analysis; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Insurance, Health; Length of Stay; Male; Middle Aged; Urban Population; Venous Thrombosis; Warfarin

The aim of this study was to assess perioperative warfarin management and complications in patients requiring colonoscopy.. We retrospectively reviewed 109 cases of colonoscopies performed on 94 patients requiring anticoagulation with warfarin. Patients stopped their warfarin three days before colonoscopy. Coagulation profiles obtained just before the colonoscopy showed a median prothrombin time of 13.4 seconds with a range of 11.1 to 29.1 (normal range, 10.9-13) and a median international normalized ratio of 1.2 with a range of 0.9 to 2.6. Patients restarted warfarin the day after the examination.. During the 109 colonoscopies, 47 percent of the patients underwent either hot biopsy or snare polypectomy. One examination that included several biopsies was associated with a hemorrhagic complication (0.92 percent) requiring hospitalization and transfusion. Subset analysis of the therapeutic (biopsy and snare polypectomy) group indicated a slightly higher complication rate (1.96 percent) with a median international normalized ratio of 1.3 (range, 1-2.3) and a median prothrombin time of 13.7 (range, 11.6-25.9).. Patients taking warfarin for anticoagulation may safely undergo colonoscopy. The risk of hemorrhagic complications increases slightly with hot biopsy or snare procedures. Further studies are needed to refine guidelines for colonoscopy in the patient requiring anticoagulation.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Chi-Square Distribution; Colonoscopy; Female; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prothrombin Time; Retrospective Studies; Risk Factors; Safety; Treatment Outcome; Warfarin

Gastrointestinal side effects from nonsteroidal anti-inflammatory drugs (NSAIDs) result mainly from inhibition of the enzyme cyclooxygenase (COX)-1; it is responsible for the synthesis of prostaglandin E2, which leads to increased mucosal blood flow, increased bicarbonate secretion, and mucus production, thus protecting the gastrointestinal mucosa. In inflammation, COX-2 is induced, causing synthesis of the prostaglandins in conditions such as osteoarthritis and rheumatoid arthritis. Two NSAIDs (celecoxib and rofecoxib) with very high specificity for COX-2 and virtually no activity against COX-1 at therapeutic doses have been approved for clinical use. In trials of celecoxib and rofecoxib, only 0.02% of patients had clinically significant gastrointestinal bleeding, compared to a 1% to 2% yearly incidence of severe gastrointestinal side effects with NSAIDs. Our patient had arthritis of the hips and chronic atrial fibrillation and was on warfarin therapy for stroke prevention; less than a week after starting celecoxib therapy, gastrointestinal bleeding and hypoprothrombinemia occurred.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arthritis; Atrial Fibrillation; Bicarbonates; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Gastric Mucosa; Gastrointestinal Hemorrhage; Hip Joint; Humans; Hypoprothrombinemias; Incidence; Intestinal Mucosa; Isoenzymes; Lactones; Male; Membrane Proteins; Mucus; Peroxidases; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Sulfonamides; Sulfones; Warfarin

Complication rates of medical therapy for secondary stroke prevention derived from clinical trials may or may not be applicable to patients with cerebrovascular disease in the general population.. To determine complication rates for aspirin, warfarin, and intravenous heparin administered for secondary stroke prevention after first episodes of ischemic stroke, transient ischemic attack, or amaurosis fugax in a community.. Population-based historical cohort study.. Rochester, Minnesota.. All residents of Rochester who, between 1985 and 1989, received aspirin (n = 339) or warfarin (n = 145) within 2 years after first ischemic stroke, transient ischemic attack, or amaurosis fugax or received intravenous heparin (n = 201) within 2 weeks after first ischemic stroke, transient ischemic attack, or amaurosis fugax.. Occurrence of major complications caused by therapy.. Twenty aspirin-associated complications (1 fatal) occurred during an average 1.7 years of treatment, 8 warfarin-associated complications occurred during an average 0.7 years of treatment, and 3 heparin-associated complications (1 fatal) occurred during an average 5.1 days of treatment. Complication rates were 3.5 per 100 person-years (95% CI, 2.1 to 5.4) for aspirin, 7.9 per 100 person-years (CI, 3.4 to 15.6) for warfarin, and 0.30 (CI, 0.06 to 0.86) per 100 person-days for heparin. Rates of fatal complications were 0.2 per 100 person-years (CI, 0 to 1.0) for aspirin, 0 per 100 person-years (CI, 0 to 3.6) for warfarin, and 0.10 per 100 person-days (0 to 0.55) for heparin.. Complication rates for warfarin and intravenous heparin given as therapy for secondary stroke prevention in Rochester, Minnesota, were lower than rates reported from earlier trials and observational studies. However, complication rates for warfarin were higher than in more recent referral-based studies and multicenter randomized trials. After adjustment for duration of therapy, complication rates for heparin were higher than those for aspirin or warfarin. These rates can be used to judge the applicability of complication rates derived from ongoing clinical trials.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cerebral Hemorrhage; Cerebrovascular Disorders; Cohort Studies; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Infusions, Intravenous; Male; Warfarin

To determine the incidence of major hemorrhage among outpatients started on warfarin therapy after the recommendation in 1986 for reduced-intensity anticoagulation therapy was made, and to identify baseline patient characteristics that predict those patients who will have a major hemorrhage.. Retrospective cohort study.. A university-affiliated Veterans Affairs Medical Center.. Five hundred seventy-nine patients who were discharged from the hospital after being started on warfarin therapy.. The primary outcome variable was major hemorrhage. In our cohort of 579 patients, there were 40 first-time major hemorrhages with only one fatal bleed. The cumulative incidence was 7% at 1 year. The average monthly incidence of major hemorrhage was 0.82% during the first 3 months of treatment and decreased to 0.36% thereafter. Three independent predictors of major hemorrhage were identified: a history of alcohol abuse, chronic renal insufficiency, and a previous gastrointestinal bleed. Age, comorbidities, medications known to influence prothrombin levels, and baseline laboratory values were not associated with major hemorrhage.. The incidence of major hemorrhage in this population of outpatients treated with warfarin was lower than previous estimates of major hemorrhage measured before the recommendation for reduced-intensity anticoagulation therapy was made, but still higher than estimates reported from clinical trials. Alcohol abuse, chronic renal insufficiency, and a previous gastrointestinal bleed were associated with increased risk of major hemorrhage.

Topics: Aged; Alcoholism; Ambulatory Care; Anticoagulants; Cohort Studies; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Incidence; Kidney Failure, Chronic; Male; Retrospective Studies; Risk Factors; Warfarin

Haemorrhagic infarction of the small bowel is a rare complication of warfarin therapy. We take this opportunity to report a case that needed a resection of the small bowel.

Topics: Anticoagulants; Female; Gastrointestinal Hemorrhage; Humans; Infarction; Intestine, Small; Middle Aged; Warfarin

Topics: Aged; Anticoagulants; Antifungal Agents; Drug Interactions; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Ileum; Miconazole; Peritoneal Diseases; Psoas Muscles; Warfarin

Colonic angiodysplasia is one of the most frequent causes of recurrent lower gastrointestinal tract bleeding, mainly in the elderly. In 50% of patients multiple angiodysplastic lesions were reported when they were the cause of rectal bleeding. Bleeding from angiodysplasia is more severe and less responsive to treatment in those with coagulation disorders. A 74-year-old woman with an artificial mitral valve who was treated with coumadine is reported. A few years after operation she began to develop severe recurrent rectal bleeding because of multiple angiodysplastic lesions along the right colon, proven by colonoscopy. She was frequently hospitalized for blood transfusions; endoscopic treatment was not feasible and the surgical risk of colectomy was very high. Treatment with estrogen and progesterone significantly decreased recurrent episodes of bleeding.

Topics: Aged; Angiodysplasia; Anticoagulants; Blood Transfusion; Colonic Diseases; Ethinyl Estradiol; Female; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Humans; Norgestrel; Warfarin

By 1992, several prospective trials established the efficacy of anticoagulation (AC) and to some extent antiplatelet (AP) agents in the prevention of stroke in the setting of atrial fibrillation (AF). The objective of this study was to determine whether practice patterns in AF stroke prophylaxis reflect the findings of clinical trials and whether stroke prophylaxis in AF differs between community hospitals and tertiary teaching hospitals.. Retrospectively, 1250 hospital charts were reviewed. After patients who had undergone recent surgery, received treatment for malignancy, or were not in chronic AF on discharge were eliminated, 651 remaining records were analyzed for the presence of 26 clinical factors influencing the selection of thromboembolism prophylaxis. Descriptive statistics and logistic regression were used to analyze the association between clinical and demographic factors and the decision to treat with AC, AP, or no specific antiembolic therapy.. Of the 651 patients in AF, 273 (42%) received noemboli prophylaxis while 219 (34%) were treated with AC (warfarin), 146 (22%) were treated with AP, and 13 (2%) received both agents. Patients discharged in AF from community hospitals were significantly less likely to be treated with either AC or AP agents than patients discharged from tertiary centers. A strong bias against thromboembolism prophylaxis with either AC or AP agents in AF existed with age over 45 years. Multivariate logistic regression indicated that the decision to treat was associated only with the presence of prosthetic valve, history of prior stroke, mitral disease, and absence of a recent gastrointestinal bleed or occult blood in stool. Even after adjustment for these factors, a significant bias against treatment with either AC or AP agents with advancing age and discharge from community hospitals remained.. Thromboembolism prophylaxis with either AC or AP agents is underutilized in the setting of AF. Furthermore, factors known to increase the risk of embolization in AF such as age, hypertension, diabetes, and heart disease were not associated with decisions to treat with either AP or AC agents. This study suggests that the use of clinical guidelines suggested by trials of thromboembolism prophylaxis in AF could reduce the incidence of stroke.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Hospitals, Community; Hospitals, Teaching; Humans; Intracranial Embolism and Thrombosis; Medical Records; Middle Aged; Mitral Valve Stenosis; Multivariate Analysis; New York; Occult Blood; Platelet Aggregation Inhibitors; Regression Analysis; Retrospective Studies; Warfarin

Multiple studies link the use of nonsteroidal antiinflammatory drugs (NSAIDs) with severe upper gastrointestinal bleeding (UGIB); the incidence of such bleeding is 2-4%. One common regimen to assure patency after intracoronary stent placement requires an anticoagulant (warfarin) combined with aspirin as an antiplatelet agent. However, a 13-fold increase in the risk of UGIB occurs with long-term use of oral anticoagulants and NSAIDs. We retrospectively assessed the rate of UGIB in 138 patients who had received coronary stents (group I, receiving heparin followed by warfarin in combination with aspirin) and 109 angioplasty patients without stents (group II, receiving aspirin alone) between 1990 and 1994. UGIB was identified by hematemesis or melena, which led to gastrointestinal consultation. Patients were analyzed for multiple risk factors. UGIB occurred in 28 of 138 group I patients (20%; 95% CI 13.3-26.7%) and 0 of 109 group II patients (P < 0.0001). Esophagogastroduodenoscopy (EGD) findings on the 28 patients with UGIB included 13 patients with esophagitis or gastritis, 7 patients with gastric or duodenal ulcers, and 8 patients with no identifiable source of bleeding. UGIB occurred within a mean of 2.5 days of initiation of combination therapy. Of patients with UGIB, 10 required blood transfusion (mean number of units = 5.3). Previous history of peptic ulcer disease, smoking, and use of antiulcer medication did not significantly differ between the two groups. The concurrent use of anticoagulant and aspirin in patients with coronary stents creates a significant potential for UGIB and should be used only with extreme caution.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Heparin; Humans; Middle Aged; Retrospective Studies; Risk Factors; Stents; Thrombosis; Warfarin

Warfarin is commonly used in the prophylaxis or treatment of thromboembolic disease. Haemorrhage is a recognised complication which may be life-threatening. This paper describes eight cases in which lower gastrointestinal bleeding while on warfarin therapy resulted in the discovery of previously unrecognised large bowel malignancy. Diagnosis of an otherwise asymptomatic carcinoma in this way enabled surgery to be carried out at an earlier stage and so may have resulted in a better prognosis for these patients. Bleeding while on anticoagulant therapy is caused by a specific organic lesion in 30% to 50% of cases. This may be the case even when the prothrombin time is very prolonged. It is important, therefore, that such cases are fully investigated, especially in the elderly.

Topics: Aged; Anticoagulants; Cecal Neoplasms; Colonic Neoplasms; Gastrointestinal Hemorrhage; Humans; Warfarin

We sought evidence for thromboembolic sequelae after the transient withdrawal of chronic anti-coagulation because of acute GI bleeding.. Our Gastrointestinal Bleeding Team endoscopic database was reviewed over a 5-yr period to identify patients who underwent a transient withdrawal from chronic anticoagulation as a result of acute GI bleeding. Long term follow-up records were available for all study patients and were carefully scrutinized for any symptomatic thromboembolic events.. Twenty-seven patients were included in the study, of which 17 (63%) were on chronic anticoagulation for prosthetic heart valves. Chronic anticoagulation was withheld for a median period of 3 days (range = 2-7 days) for patients with prosthetic heart valves and 7 days (range = 2-15 days) for patients on chronic anticoagulation for other indications. Over a median follow-up period of 8 months (range = 1-54 months), one patient developed documented lower extremity thromboembolism.. We conclude that symptomatic thromboembolism can occur after the transient withdrawal of chronic anticoagulation for acute GI bleeding but that it does not occur frequently.

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Chronic Disease; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Male; Middle Aged; Risk Factors; Substance Withdrawal Syndrome; Thromboembolism; Time Factors; Warfarin

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Drug Interactions; Fatal Outcome; Female; Gastrointestinal Hemorrhage; Humans; Ibuprofen; Warfarin

To determine whether low-dose aspirin or warfarin induces fecal occult blood loss.. A prospective, cross-over study, of 100 participants over 40 years of age in 1 of 3 groups, taking: (1) no aspirin or warfarin, (2) daily aspirin (either 81 or 325 mg), or (3) warfarin, but no aspirin. Stool samples were collected and analyzed for the presence of occult blood using HemoQuant and Hemoccult II. After collection of baseline samples, patients initially taking no aspirin (group 1) were asked to take regular aspirin (325 mg daily) for 2 months. Patients initially taking aspirin 81 mg daily (group 2) were switched to 325 mg daily for 2 months, and vice versa.. Patients taking no aspirin had mean fecal blood of 0.68 +/- 0.05 mg hemoglobin/g stool, which increased to 1.41 +/- 0.36 mg/g after taking 325 mg of aspirin daily (P = 0.02). In contrast, patients in group 2, taking 81 mg and 325 mg of aspirin, had mean fecal blood of 0.82 +/- 0.08 mg/g (P = 0.57) and 1.04 +/- 0.23 mg/g (P = 0.13), respectively (comparisons with patients taking no aspirin). The mean blood loss in patients taking warfarin was 0.51 +/- 0.04 mg/g (P = 0.55), and fecal blood was not related to the degree of anticoagulation. There was no increase over normal in the rate of Hemoccult II-positive stool tests with aspirin or warfarin therapy.. Aspirin, but not warfarin, caused a small but clinically insignificant increase in occult fecal blood. The small blood loss in patients taking aspirin or warfarin is unlikely to interfere with fecal occult blood test. Therefore, positive fecal occult blood tests, in patients taking either low-dose aspirin or warfarin, should be managed in the same fashion as patients not taking these medications.

Topics: Analysis of Variance; Anticoagulants; Aspirin; Cardiovascular Diseases; Chronic Disease; Cross-Over Studies; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Occult Blood; Platelet Aggregation Inhibitors; Prospective Studies; Specimen Handling; Warfarin

Topics: Aged; Anticoagulants; Cardiac Output, Low; Female; Gastrointestinal Hemorrhage; Hematoma; Hip Prosthesis; Humans; Malpractice; Postoperative Complications; Retroperitoneal Space; Risk Management; Warfarin

The underlying diagnosis and clinical course of 52 patients who presented with severe acute gastrointestinal haemorrhage while taking the anticoagulant warfarin is reviewed. A bleeding site was identified in 83% of cases, only slightly fewer than the 92% found in a control of group of 710 patients not taking warfarin who presented in the same four year period. The degree or duration of anticoagulation was unrelated to the frequency of establishing a diagnosis. The commonest diagnosis was peptic ulcer (25 cases) and endoscopic treatment by injection or heater probe was attempted in 23 of these. The outcome in this subgroup was compared with that in 50 closely matched control subjects who had similar risk factors for rebleeding from peptic ulcer. Permanent haemostasis was achieved in (91%) of the anticoagulated and in 92% of the control patients. There were no complications related to endoscopy. Patients who present with acute gastrointestinal haemorrhage while taking warfarin usually bleed from mucosal disease. They should be endoscoped after resuscitation and those with major bleeding from a peptic ulcer should be offered endoscopic treatment.

Topics: Acute Disease; Aged; Aged, 80 and over; Electrocoagulation; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Prospective Studies; Sclerotherapy; Stomach Diseases; Treatment Outcome; Warfarin

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Drug Combinations; Female; Gastrointestinal Hemorrhage; Hip Fractures; Humans; Ketorolac Tromethamine; Tolmetin; Tromethamine; Warfarin

Described is an elderly woman who developed gastrointestinal bleeding probably potentiated by the interaction of fluconazole with warfarin. Because varied clinical uses are being found for fluconazole, clinicians should be aware of this potential interaction.

Topics: Aged; Drug Synergism; Female; Fluconazole; Gastrointestinal Hemorrhage; Humans; Warfarin

Topics: Aged; Angiodysplasia; Aortic Valve Stenosis; Calcinosis; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Humans; Male; Recurrence; Syndrome; Warfarin

A case of warfarin-induced intramural hematoma and hemorrhagic infarction of the small intestine is described, and the literature on this adverse effect is reviewed. A 32-year-old white woman who had been receiving warfarin and carbamazepine came to a clinic complaining of lower back and stomach pain. She had a history of iliofemoral deep venous thromboses and seizures. A pelvic sonogram showed a large quantity of fluid present. Her prothrombin time (PT) was 29.2 sec. Her hemoglobin concentration and hematocrit were within the normal ranges. The patient was admitted to the hospital when her back pain increased and she vomited. The warfarin was discontinued. On day 5 the patient was still having abdominal pain and nausea. Her hemoglobin concentration and hematocrit had fallen to 6.6 g/dL and 20%, although her PT had decreased to 12.5 sec. On the same day, the patient underwent an exploratory laparotomy, and an indurated and ischemic area of jejunum was found and resected. The pathology report indicated the presence of hemorrhage and infarction consistent with an anticoagulant-related disorder. About 100 cases of intramural hematoma of the small intestine induced by anticoagulant therapy have been reported. Most patients are white males about 60 years of age. The sites most frequently involved are the duodenum and proximal jejunum. Symptoms include constipation, nausea, vomiting, and abdominal pain. Laboratory test and radiological findings are fairly nonspecific, but when found together in a patient receiving an anticoagulant, the diagnosis can be made with some confidence. Management may be complicated by the bleeding disorder, the intestinal obstruction if present, and the original indication for warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestine, Small; Warfarin

We describe a patient with a 3-year history of recurrent deep vein thromboses (DVT) of the lower limbs, who developed adrenal insufficiency following withdrawal of warfarin therapy. Multiple splinter haemorrhages of the nail beds were evident, simultaneous with the development of adrenal infarction in the absence of infective endocarditis. CT scans of the adrenal glands were consistent with bilateral adrenal infarctions. The patient had persistently high titres of IgG anticardiolipin antibodies (aCL) over the previous 4 years in the absence of antinuclear antibodies (ANA), antibodies to double stranded deoxyribonucleic acid (dsDNA) or extractable nuclear antigens (ENA). Thrombocytopenia and an intermittently positive Coombs' test had been noted. Previous episodes of DVT were associated with inadequate warfarin control and a period of warfarin resistance. He conforms to a diagnosis of a 'primary' antiphospholipid syndrome.

Topics: Adrenal Gland Diseases; Adult; Antiphospholipid Syndrome; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Infarction; Male; Nail Diseases; Rectum; Thrombophlebitis; Tomography, X-Ray Computed; Warfarin

Topics: Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestinal Obstruction; Jejunal Diseases; Male; Middle Aged; Warfarin

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

Two patients who developed hypoprothrombinemia and bleeding due to lovastatin-warfarin drug interaction are described. Because of the wider use of lovastatin and warfarin, heightened clinical awareness of this potentially serious interaction must be publicized. Therefore, prothrombin time should be monitored diligently when warfarin is prescribed to patients receiving lovastatin.

Topics: Atrial Fibrillation; Drug Interactions; Epistaxis; Gastrointestinal Hemorrhage; Hematuria; Humans; Hypercholesterolemia; Hypoprothrombinemias; Intracranial Embolism and Thrombosis; Lovastatin; Male; Middle Aged; Warfarin

A 31-year-old man had recurrent gastrointestinal hemorrhage after aortic valve replacement and initiation of anticoagulation therapy with coumadin. Radionuclide bleeding scan and subsequent contrast angiogram demonstrated a site of hemorrhage in the distal ileum, and at surgery a 1.8-cm spherical duplication was found. On histologic examination, the duplication was lined with normal ileal mucosa, and near the mouth of the duplication an inflammatory ulceration proved to be the site of hemorrhage. In a young patient with anticoagulation-associated gastrointestinal hemorrhage, alimentary tract duplication should be considered.

Topics: Adult; Aortic Valve; Gastrointestinal Hemorrhage; Humans; Ileum; Male; Radiography; Warfarin

The adverse effect of topical methylsalicylate ointment on warfarin anticoagulation is studied in 11 patients. All patients had an abnormally elevated international normalized ratio after significant usage of topical methylsalicylate ointment as obvious from both the clinical history and a positive blood level of salicylate. Out of the 11 patients, 3 had bleeding manifestation; 2 with bruises and 1 with gastrointestinal bleeding. It is concluded that topical methylsalicylate ointment should be prescribed with care to patients on warfarin and excessive usage is to be avoided since potentially dangerous drug interaction could occur.

Topics: Administration, Topical; Adult; Aged; Blood Coagulation; Drug Synergism; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Ointments; Salicylates; Warfarin

Twenty-three patients with malignant glial neoplasms were treated with anticoagulant therapy for thromboembolic complications. Fifteen patients had deep vein thrombosis alone, and 8 patients had both deep vein thrombosis and pulmonary embolism. Serum prothrombin times were maintained at 1.25 times control for an average of 5.8 months per patient, for a total patient exposure to warfarin therapy of 132 patient-months (11 patient-years). Only 1 patient suffered a recurrent pulmonary embolism, and this occurred during an episode of gastrointestinal bleeding, when anticoagulant therapy had to be discontinued prematurely. All patients were followed with serial computed tomographic or magnetic resonance imaging scans, and no patient showed radiographic evidence of intratumoral hemorrhage either during or after warfarin therapy. One patient, who died from a large recurrent glioblastoma, was found at autopsy to have scattered foci of intratumoral hemorrhage. This series, together with a review of the available literature, suggests that oral anticoagulant therapy is both a safe and effective means of treating thromboembolic complications in patients with residual malignant glial tumors.

Topics: Adult; Aged; Anticoagulants; Brain Neoplasms; Female; Gastrointestinal Hemorrhage; Glioma; Heparin; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Pulmonary Embolism; Warfarin

The experiment of a self-injury by permanent intoxication with the coumarin derivative Warfarin is described. Various isolated haemostatic defects as differential-diagnostically demarcated causes for the leading symptom decrease of the value of the thromboplastin time which concern the effect of coumarin are mentioned. It is referred to the coagulation-analytic and chemical-toxic methods of proof of coumarins.

Topics: Adult; Blood Coagulation Tests; Diagnosis, Differential; Female; Gastrointestinal Hemorrhage; Hematoma; Hemorrhage; Humans; Self Mutilation; Urologic Diseases; Warfarin

Acute gastrointestinal hemorrhage is one of the most feared complications of anticoagulation therapy. We prospectively evaluated 18 episodes of acute gastrointestinal bleeding in 17 patients anticoagulated with coumadin or heparin. Endoscopic examination revealed significant lesions irrespective of age, duration of anticoagulation, level of anticoagulation or symptoms. The high frequency of objective findings (e.g., 44% ulcers) suggests that diagnostic endoscopy should be performed in patients with acute gastrointestinal bleeding associated with anticoagulant therapy.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Gastrointestinal Hemorrhage; Heparin; Humans; Middle Aged; Prospective Studies; Warfarin

Between 1970 and 1987, 3000 total hip replacements were performed at the University of California at Los Angeles, and all patients were given warfarin prophylactically, in conjunction with early postoperative elevation of the lower limb in balanced suspension and the application of elastic hose. Since 1973, the first dose of warfarin has been given on the night of the operation, and the prothrombin time has been maintained between sixteen and eighteen seconds. A pulmonary embolism occurred after fourteen (0.5 per cent) of the 3000 operations. It was never fatal. Bleeding occurred after forty-four operations (1.5 per cent). The effectiveness of the protocol of the University of California at Los Angeles was demonstrated in a large number of patients over a seventeen-year period. Since 1974, the protocol has included closer monitoring of the prothrombin time. After 2595 hip replacements that were done between 1974 and 1987, the rate of pulmonary embolism was 0.2 per cent and the rate of bleeding complications was 1.0 per cent. However, recently a higher incidence of bleeding complications (2.3 per cent) has been noted after non-cemented total hip (stem-type) replacement.

Topics: Drug Evaluation; Gastrointestinal Hemorrhage; Hip Prosthesis; Humans; Los Angeles; Postoperative Care; Postoperative Complications; Prospective Studies; Prothrombin Time; Pulmonary Embolism; Warfarin

To determine the incidence of major bleeding in outpatients treated with warfarin and to identify predictive factors known at the start of therapy.. The records of 565 patients starting outpatient therapy with warfarin upon discharge from a university hospital were reviewed. Follow-up information was obtained for 562 patients (99.5%). Bleeding was classified as major or minor using explicit criteria. The cumulative incidence of bleeding was estimated by means of survival analysis. Independent risk factors for major bleeding were identified using Cox regression analysis in 375 randomly chosen patients; they were tested in the remaining 187 patients.. Major bleeding occurred in 65 patients (12%) and was fatal in 10 patients (2%). The cumulative incidences of major bleeding at one, 12, and 48 months were 3%, 11%, and 22%, respectively. The monthly risk of major bleeding decreased over time, from 3% during the first month of outpatient therapy to 0.3% per month after the first year of therapy. Five independent risk factors for major bleeding--age 65 years or greater, history of stroke, history of gastrointestinal bleeding, a serious comorbid condition (recent myocardial infarction, renal insufficiency, or severe anemia), atrial fibrillation--predicted major bleeding in the testing group; the cumulative incidence of major bleeding at 48 months was 2% in 57 low-risk patients, 17% in 110 middle-risk patients, and 63% in 20 high-risk patients.. These findings provide a quantitative basis for evaluating the risk of major bleeding in individual patients at the start of outpatient therapy with warfarin. Whether the risk of bleeding can be reduced in high-risk patients without reducing the benefit of therapy remains to be determined.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care; Cerebral Hemorrhage; Cohort Studies; Follow-Up Studies; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Middle Aged; Risk Factors; Warfarin

Topics: Dextrans; Gastrointestinal Hemorrhage; Graft Rejection; Humans; Kidney Tubular Necrosis, Acute; Pancreas Transplantation; Postoperative Complications; Thrombosis; Warfarin

Topics: Drug Interactions; Gastrointestinal Hemorrhage; Humans; Ketoprofen; Male; Middle Aged; Phenylpropionates; Prothrombin Time; Warfarin

Topics: Drug Therapy, Combination; Gastrointestinal Hemorrhage; Humans; Ketoprofen; Phenylpropionates; Warfarin

When gastrointestinal (Gl) bleeding occurs in patients receiving anticoagulation, an underlying pathologic lesion is usually suspected and a thorough diagnostic evaluation is undertaken. Over a 15-year period, 50 patients were identified as having Gl bleeding while receiving warfarin. Approximately half of all bleeding episodes occurred from the upper Gl tract, with a lesion identified 81 percent of the time, usually peptic ulcer disease. Lower Gl bleeding occurred in one-third of bleeding episodes, with a diagnosis made in only 52 percent. Only three neoplasms were found and all were diagnosed by barium studies. No diagnosis was established in 47 percent of all bleeding episodes despite appropriate evaluation; in these patients, a mean follow-up of 39.6 months disclosed no premalignant or malignant lesions. Mortality associated with bleeding was less than 2 percent. These data suggest that a diagnosis is usually established in patients receiving anticoagulation who experience upper Gl bleeding, whereas the cause of lower Gl bleeding may remain occult even after a thorough evaluation; however, the absence of a definitive diagnosis carries a good prognosis.

Topics: Adult; Aged; Aged, 80 and over; Barium Sulfate; Endoscopy; Female; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Prothrombin Time; Radiography; Recurrence; Retrospective Studies; Warfarin

Among 617 hospitalized patients who started long-term anticoagulant therapy, major bleeding developed before discharge in 28 (5 percent) and minor bleeding in another 38 (6 percent), with daily incidence rates of 0.4 and 0.5 percent, respectively. The most common site of bleeding was gastrointestinal, and one patient died from bleeding. Four independent risk factors for major in-hospital bleeding were identified and weighted using multivariate discriminant analysis in a randomly chosen group of 411 patients: co-morbid conditions other than the indication for anticoagulant therapy (specific signs of heart, liver, or kidney dysfunction, cancer, and severe anemia); the use of heparin to begin therapy in patients age 60 years or older; the intensity of therapy (measured by the maximal prothrombin time or partial thromboplastin time); and liver dysfunction that worsened during treatment. These findings were validated in an independent testing group of 206 patients; the risk factors identified 151 patients at low (1 percent) risk of major bleeding, 33 at moderate (6 percent) risk, and 22 at high (23 percent) risk. The accuracy and clinical impact of this prediction rule should be evaluated further in other hospitals.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Hospitalization; Humans; Male; Middle Aged; Risk; Warfarin

Topics: Aged; Colonic Neoplasms; Female; Gastrointestinal Hemorrhage; Humans; Middle Aged; Rectum; Warfarin

Intramural hematomas of the small bowel, an uncommon complication of anticoagulant therapy, usually present with nausea, vomiting, crampy abdominal pain, and often gastrointestinal bleeding of some degree. The diagnosis can be suggested by history and by a plain abdominal x-ray film, but an upper GI series is the most reliable means of confirming the diagnosis. Treatment is nonoperative, with emphasis on correction of clotting abnormalities, and blood loss, continuous nasogastric decompression, parenteral alimentation, and hydration.

Topics: Aged; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestine, Small; Radiography; Warfarin

The purpose of this investigation was to analyze the thromboembolic and/or major bleeding complications of 124 consecutive but nonrandomized patients who had only mitral valve replacement with the Hancock porcine xenograft between September, 1974 and June, 1979. These patients were treated either with or without anticoagulants. Four basic study groups were created: Group 1, warfarin; Group 2, aspirin; Group 3, no anticoagulants; and Group 4, warfarin and aspirin. Group 5 combined Groups 1 and 4 (warfarin and warfarin plus aspirin) and Group 6 combined Groups 2 and 3 (aspirin and no anticoagulants). The cardiac rhythm, history of embolism, and intraoperative findings of a thrombus in the left atrium were examined as risk factors for later thromboembolism . Follow-up time was 3.03 years (range 2.0 to 4.2 years). The embolic rate was not significantly different in any group (n = NS). In Groups 5 and 6 the embolic rate was 2.97 and 3.25 embolisms per 100 patient-years, respectively. Warfarin therapy resulted in significant major bleeding episodes, including two deaths (p less than 0.05). The number of patients with a history of a previous embolism, the finding of an intraoperative left atrial thrombus, or abnormal cardiac rhythm was insufficient to test embolic risk in the four treatment groups. We conclude that long-term warfarin therapy increases the risk of bleeding complications but may not significantly influence the incidence of thromboembolism arising from the Hancock porcine xenograft mitral valve. Other and larger studies are needed to confirm this last point.

Topics: Adult; Aged; Aspirin; Bioprosthesis; Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Risk; Thromboembolism; Warfarin

The records of 32 cancer patients who were treated with heparin sodium and warfarin sodium for thromboembolic disease were reviewed. Standard techniques for anticoagulation were neither safe nor effective. Sixteen patients experienced 21 different hemorrhagic complications. Eight patients had major hemorrhages that led to cessation of therapy or death. Six of 32 patients had pulmonary embolisms while receiving anticoagulants. It is suggested that venous interruption may be a safer and more effective method of prophylaxis against pulmonary embolism in cancer patients.

Topics: Adolescent; Adult; Aged; Anticoagulants; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Humans; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Thromboembolism; Warfarin

Rates of drug-induced gastrointestinal bleeding were estimated from data on 16 646 consecutively monitored medical inpatients who had no known predisposing illness. Heparin, warfarin, ethacrynic acid, steroids, and aspirin-containing drugs were associated with gastrointestinal bleeding and were estimated to account for about two-thirds of such bleeds. Major gastrointestinal bleeding, defined as bleeding severe enough to require transfusion, occurred in only 57 patients (0.3%).

Topics: Anticoagulants; Aspirin; Chlordiazepoxide; Drug Therapy, Combination; Ethacrynic Acid; Gastrointestinal Hemorrhage; Glucocorticoids; Heparin; Humans; Nitrofurantoin; Warfarin

In 66 months, a general hospital's outpatient Anticoagulation Service (ACS) monitored 263 patients who received 280 courses of warfarin sodium totalling 254 patient treatment years. Major hemorrhagic morbidity was 4% of courses and there was no mortality attributable to warfarin therapy. Major hemorrhage occurred in patients with increased anatomic risk of bleeding (diverticulosis, hemorrhoids, cystitis), and was not a function of patient age, sex, anticoagulation control, or medications administered concurrently with warfarin. Control of anticoagulation was not correlated with age or other medications, but was worsened significantly by the presence of congestive heart failure. We attribute a favorable experience with outpatient ACS to careful patient selection, patient education and monitoring, attention to duration of anticoagulation, and continuing communication with primary physicians who retained responsibility for medical care. An ACS offers safety, consistency, efficiency, and a unified approach to outpatient anticoagulation in the general hospital setting.

Topics: Aged; Blood Coagulation Disorders; Female; Gastrointestinal Hemorrhage; Health Education; Heart Failure; Hematuria; Humans; Male; Maryland; Middle Aged; Outpatient Clinics, Hospital; Prothrombin Time; Thromboembolism; Time Factors; Warfarin

Topics: Cecum; Colon; Diagnosis, Differential; Embolism; Gastrointestinal Hemorrhage; Hematoma; Humans; Ileum; Intestinal Mucosa; Intestinal Obstruction; Intestine, Small; Male; Mesentery; Middle Aged; Warfarin

Topics: Aged; Aspirin; Binding Sites; Binding, Competitive; Depression, Chemical; Drug Interactions; Drug Synergism; Drug Therapy; Gastrointestinal Hemorrhage; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Kidney; Kinetics; Liver; Male; Pharmaceutical Preparations; Phenylbutazone; Protein Binding; Receptors, Drug; Stimulation, Chemical; Warfarin

From March 1971 through April 1975, one hundred twenty patients underwent mitral valve replacement with a Hancock "stabilized glutaraldehyde process" porcine aortic xenograft. A simultaneous canine experimental series was also carried out. In the clinical series, the early mortality was 8.3%. Actuarial analyses of all patients predicts survival at two years of 81.0% and at four years of 70.0%. The predicted survival for patients without coronary disease or prior prosthetic valve replacement is 87.5% at two years and 77.5% at four years. There were four thromboembolic episodes, a rate of 2.4% per patient-year. None were fatal. No valve failure were noted. Histologic examination and shrink temperature analysis of recovered valves show excellent tissue preservation at 40 months. The data indicate that the Hancock valve is durable, enjoys a low incidence of thromboembolism, and may be the valve of choice for mitral valve replacement.

Topics: Adult; Aged; Aldehydes; Animals; Aortic Valve; Brain Diseases; Cardiac Surgical Procedures; Coronary Disease; Dogs; Endocarditis, Bacterial; Evaluation Studies as Topic; Female; Gastrointestinal Hemorrhage; Glutaral; Hematoma; Humans; Male; Methods; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Mitral Valve Stenosis; Postoperative Complications; Swine; Thromboembolism; Thrombophlebitis; Transplantation, Heterologous; Warfarin

Topics: Aged; Female; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Hematoma; Humans; Intestinal Obstruction; Postoperative Complications; Thrombosis; Warfarin

Topics: Gastrointestinal Hemorrhage; Hematoma; Humans; Jejunum; Male; Middle Aged; Warfarin

Topics: Abdominal Muscles; Aged; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestinal Obstruction; Male; Middle Aged; Myocardial Infarction; Radiography; Retroperitoneal Space; Warfarin

Topics: Aged; Arrhythmias, Cardiac; Blood Transfusion; Coronary Disease; Diverticulum, Colon; Gastrointestinal Hemorrhage; Hematocrit; Humans; Hypertension; Intracranial Embolism and Thrombosis; Middle Aged; Prothrombin Time; Pulmonary Embolism; Thrombophlebitis; Vitamin K; Warfarin

Topics: Adult; Aged; Anesthesia, Inhalation; Blood Pressure; Blood Transfusion; Female; Gastrointestinal Hemorrhage; Halothane; Heart Arrest; Hip; Humans; Hypotension, Controlled; Joint Prosthesis; Male; Methylmethacrylates; Middle Aged; Myocardial Infarction; Osteotomy; Pentolinium Tartrate; Postoperative Complications; Pulmonary Embolism; Respiratory Insufficiency; Sodium; Thromboembolism; Thrombophlebitis; Warfarin

Topics: Animals; Blood Coagulation; Blood Platelets; Depression, Chemical; Disseminated Intravascular Coagulation; Ethanol; Factor V; Female; Fibrinogen; Gastrointestinal Hemorrhage; Hematocrit; Infusions, Parenteral; Male; Rabbits; Thromboplastin; Time Factors; Warfarin

Topics: Adult; Age Factors; Cholecystitis; Chromium Alloys; Follow-Up Studies; Gastrointestinal Hemorrhage; Hepatitis; Hip; Hip Dislocation; Hip Joint; Humans; Joint Prosthesis; Middle Aged; Molecular Weight; Peripheral Nervous System Diseases; Polyethylenes; Postoperative Complications; Prosthesis Design; Surgical Wound Infection; Thromboembolism; Urinary Tract Infections; Warfarin

Topics: Acute Disease; Adult; Aged; Emergencies; Gastrointestinal Hemorrhage; Hematoma; Humans; Hypoprothrombinemias; Intestinal Obstruction; Male; Middle Aged; Phenindione; Radiography; Warfarin

Topics: Aged; Dextrans; Female; Femoral Neck Fractures; Gastrointestinal Hemorrhage; Humans; Male; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis; Warfarin

Topics: Anti-Bacterial Agents; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestine, Small; Middle Aged; Shock, Septic; Warfarin

Topics: Aged; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestinal Obstruction; Intestine, Small; Laparotomy; Male; Necrosis; Postoperative Complications; Warfarin

Topics: Agranulocytosis; Anus Diseases; Anus Neoplasms; Blood Coagulation Disorders; Blood Platelet Disorders; Blood Platelets; Blood Transfusion; Colitis, Ulcerative; Colonic Diseases; Colonic Neoplasms; Factor V Deficiency; Factor VII Deficiency; Gastrointestinal Hemorrhage; Hemophilia A; Humans; Hypoprothrombinemias; Liver Diseases; Lymphoma; Rectal Diseases; Warfarin

Topics: Adult; Age Factors; Aged; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiac Surgical Procedures; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Peptic Ulcer Hemorrhage; Postoperative Complications; Sex Factors; Warfarin

Topics: Aged; Alcoholism; Allopurinol; Arrhythmias, Cardiac; Chloral Hydrate; Colchicine; Digoxin; Drug Synergism; Gastrointestinal Hemorrhage; Gout; Hospitals, Teaching; Humans; Liver Diseases; Male; Middle Aged; Nitroglycerin; Patient Care Team; Pharmacists; Pharmacy Service, Hospital; Quinidine; Warfarin; Washington

Topics: Adult; Aged; Cecum; Colectomy; Colon, Sigmoid; Diet Therapy; Diverticulitis, Colonic; Diverticulum, Colon; Female; Gastrointestinal Hemorrhage; Humans; Hypnotics and Sedatives; Ileostomy; Male; Middle Aged; Rest; Warfarin

Topics: Adult; Autopsy; Coronary Disease; Female; Gastrointestinal Hemorrhage; Humans; Intestinal Mucosa; Intestinal Obstruction; Intestine, Small; Jejunum; Radiography; Warfarin

Topics: Aged; Anticoagulants; Gastrointestinal Hemorrhage; Humans; Jejunum; Male; Prothrombin Time; Pulmonary Embolism; Radiography; Warfarin

Topics: Adenocarcinoma, Papillary; Blood Coagulation Tests; Blood Platelet Disorders; Blood Transfusion; Chromium Isotopes; Colectomy; Colonic Neoplasms; Gastrointestinal Hemorrhage; Hematoma; Humans; Male; Middle Aged; Postoperative Complications; Staphylococcus; Thrombocytopenia; Thrombophlebitis; Warfarin

Topics: Aged; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Infarction; Male; Preoperative Care; Substance Withdrawal Syndrome; Thromboembolism; Warfarin

Topics: Diverticulum; Gastrointestinal Hemorrhage; Gastrostomy; Humans; Jejunum; Male; Middle Aged; Vascular Diseases; Vitamin K; Warfarin

Topics: Aged; Duodenal Obstruction; Female; Gastrointestinal Hemorrhage; Humans; Hypoprothrombinemias; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Phenindione; Radiography; Vitamin K; Warfarin

Topics: Dicumarol; Duodenal Diseases; Gastrointestinal Hemorrhage; Geriatrics; Hematuria; Hemorrhage; Hypoprothrombinemias; Ileum; Intestinal Obstruction; Intestine, Small; Jejunum; Pathology; Radiography; Surgical Procedures, Operative; Toxicology; Warfarin

Topics: Atrial Fibrillation; Embolectomy; Embolism; Gastrointestinal Hemorrhage; Heparin; Humans; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Postoperative Care; Postoperative Complications; Preoperative Care; Radiography; Rheumatic Heart Disease; Vascular Surgical Procedures; Warfarin

Topics: Coagulants; Gastrointestinal Hemorrhage; Hematoma; Hemorrhage; Humans; Jejunum; Warfarin