vitamin-k-semiquinone-radical and Gastrointestinal-Hemorrhage

Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an alternative to vitamin K antagonists (VKAs). Little is understood regarding the efficacy and safety of DOACs in AF patients with liver cirrhosis (LC).. This meta-analysis is designed to evaluate the benefits and risks of DOACs compared to VKAs in AF patients with concomitant LC.. A thorough search was conducted in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and CNKI databases up to February 2023. A total of seven clinical studies including 7551 patients were analyzed in this meta-analysis. All data analyses were performed using Review Manager software version 5.3.. Regarding efficacy outcomes, DOACs had comparable clinical benefit in reducing ischemic stroke/systemic thromboembolism (HR=0.79, 95% CI [0.59, 1.06], p = 0.12) to VKAs. The incidence of all-cause death was similar between the DOACs and VKAs group (HR 0.94, 95% CI [0.69, 1.28], p = 0.69). Regarding safety outcomes, DOACs were associated with a significantly lower risk of major bleeding (HR 0.61, 95% CI [0.50, 0.75], p < 0.00001), intracranial hemorrhage (HR 0.55, 95% CI [0.31, 0.98], p = 0.04) and major gastrointestinal bleeding (HR 0.66, 95% CI [0.51, 0.85], p = 0.001) than VKAs. Additional subgroup analysis of advanced cirrhosis revealed that DOACs were associated with a significantly lower risk of major bleeding (HR 0.59, 95% CI [0.39, 0.89], p = 0.01) than VKAs. There were no significant differences between the DOACs and VKAs group concerning the incidence of ischemic stroke/systemic thromboembolism (HR 1.38, 95% CI [0.75, 2.55], p = 0.31) and major gastrointestinal bleeding (HR 0.65, 95% CI [0.41, 1.04], p = 0.08).. DOACs are associated with more favorable safety outcomes and may be a feasible option of oral anticoagulant for individuals with atrial fibrillation and cirrhosis. Pending validation by randomized prospective studies, the findings of this study should be interpreted with caution.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Liver Cirrhosis; Prospective Studies; Stroke; Thromboembolism; Vitamin K

We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF).. A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.. Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1).. Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Network Meta-Analysis; Rivaroxaban; Stroke; Vitamin K

Although direct oral anticoagulants (DOACs) are associated with an overall favourable safety profile, the risk of gastrointestinal bleeding with DOACs compared with vitamin K antagonists (VKAs) remains controversial. Accordingly, we aimed to provide a focused overview of the risk of gastrointestinal bleeding associated with dabigatran, rivaroxaban, apixaban and edoxaban and its management.. We reviewed published studies reporting on DOACs with gastrointestinal bleeding as an outcome, including randomised controlled trials (RCTs), retrospective database studies and large-scale prospective cohort studies.. Cumulative evidence confirms no notable difference in major gastrointestinal bleeding risk between DOACs and VKAs. Moreover, gastrointestinal bleeding in DOAC-treated patients seems less severe and requires less intensive management. The main cause of upper gastrointestinal bleeding in DOAC-treated patients appears to be gastroduodenal ulcers, whereas lower gastrointestinal bleedings are mainly due to diverticula followed by angiodysplasia and haemorrhoids. The lack of head-to-head RCTs with DOACs precludes drawing conclusions on the DOAC with the lowest gastrointestinal bleeding risk. Prescribing physicians should be aware of risk factors for DOAC-related gastrointestinal bleeding (e.g. age > 65, heavy alcohol use, uncontrolled hypertension, hepatic or renal dysfunction, active cancer, anaemia) and adopt preventive measures accordingly. Management of DOAC-associated major gastrointestinal bleeding involves temporary discontinuation of the DOAC, investigation of the bleeding source and treatment of bleeding with fluid resuscitation combined with transfusion and endoscopic haemostasis.. DOACs as a class do not increase the risk of major gastrointestinal bleeding compared to VKAs, which supports their continued use for different anticoagulant indications.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Gastrointestinal Hemorrhage; Humans; Rivaroxaban; Vitamin K

The aim of the present meta-analysis was to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) vs. vitamin K antagonists (VKAs) in elderly patients with atrial fibrillation (AF) and indirectly compare NOACs in this population.. MEDLINE, Cochrane, ISI Web of Sciences, and SCOPUS were searched for randomized or adjusted observational studies comparing NOACs vs. VKAs for stroke prevention in AF patients ≥75 years. The primary efficacy and safety outcomes of this meta-analysis were the composite of stroke and systemic embolism (SSE) and major bleedings, respectively. Other secondary outcomes were also analysed. The analysis included 22 studies enrolling 440 281 AF patients ≥ 75 years. The risk of SSE was significantly lower with NOACs vs. VKAs [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.70-0.89], whereas no differences were found for major bleedings (HR 0.94; 95% CI 0.85-1.05). NOACs reduced the risk of intracranial bleeding (HR 0.46; 95% CI 0.38-0.58), haemorrhagic stroke (HR 0.61; 95% CI 0.48-0.79) and fatal bleeding (HR 0.46; 95% CI 0.30-0.72) but increased gastrointestinal (GI) bleedings (HR 1.46; 95% CI 1.30-1.65), compared to VKAs. The adjusted indirect comparison showed no significant differences in term of SSE between NOAC agents. Conversely, the risk of major bleeding was higher for rivaroxaban vs. apixaban (HR 1.69; 95% CI 1.39-2.08) and edoxaban (HR 1.37; 95% CI 1.14-1.67), and for dabigatran vs. apixaban (HR 1.47; 95% CI 1.18-1.85).. In elderly patients with AF, NOACs are associated to a lower risk of SSE, intracranial bleeding, haemorrhagic stroke and fatal bleeding than VKAs, but increase GI bleedings. In this analysis, the safety profile of individual NOAC agents was significantly different.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Vitamin K

Patients receiving anticoagulant therapies, such as vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), commonly experience gastrointestinal (GI) bleeding as a complication and may require anticoagulant reversal prior to endoscopic treatment. Anticoagulant reversal agents include prothrombin complex concentrates (PCCs; including 3 or 4 coagulation factors), plasma, vitamin K, and target-specific DOAC reversal agents (e.g., idarucizumab and andexanet alfa).. To review current US, as well as international, guidelines for anticoagulant reversal agents in patients on VKAs or DOACs presenting with GI bleeding prior to endoscopy, guideline-based management of coagulation defects, timing of endoscopy, and recommendations for resumption of anticoagulant therapy following hemostasis. Supporting clinical data were also reviewed.. This is a narrative review, based on PubMed and Internet searches reporting GI guidelines and supporting clinical data.. GI-specific guidelines state that use of reversal agents should be considered in patients with life-threatening GI bleeding. For VKA patients presenting with an international normalized ratio > 2.5, guidelines recommend PCCs (specifically 4F-PCC), as they may exhibit greater efficacy/safety compared with fresh frozen plasma in reversal of VKA-associated GI bleeding. For DOAC patients, most guidelines recommend targeted specific reversal agents in the setting of GI bleeding; however, PCCs (primarily 4F-PCC) are often listed as another option. Resumption of anticoagulant therapy following cessation of GI bleeding is also recommended to reduce risks of future thromboembolic complications.. The utility of anticoagulant reversal agents in GI bleeding is recognized in guidelines; however, such agents should be reserved for use in truly life-threatening scenarios.

Topics: Anticoagulants; Blood Coagulation Factors; Gastrointestinal Hemorrhage; Humans; Practice Guidelines as Topic; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Randomized Controlled Trials as Topic; Retrospective Studies; Vitamin K

Non-variceal upper gastrointestinal bleeding (NVUGIB) is bleeding that develops in the oesophagus, stomach or proximal duodenum. Peptic ulcers, caused by Helicobacter pylori infection or use of NSAIDs and low-dose aspirin (LDA), are the most common cause. Although the incidence and mortality associated with NVUGIB have been decreasing owing to considerable advances in the prevention and management of NVUGIB over the past 20 years, it remains a common clinical problem with an annual incidence of ∼67 per 100,000 individuals in the United States in 2012. NVUGIB is a medical emergency, and mortality is in the range ∼1-5%. After resuscitation and initial assessment, early (within 24 hours) diagnostic and therapeutic endoscopy together with intragastric pH control with proton pump inhibitors (PPIs) form the basis of treatment. With a growing ageing population treated with antiplatelet and/or anticoagulant medications, the clinical management of NVUGIB is complex as the risk between gastrointestinal bleeding events and adverse cardiovascular events needs to be balanced. The best clinical approach includes identification of risk factors and prevention of bleeding; available strategies include continuous treatment with PPIs or H. pylori eradication in those at increased risk of developing NVUGIB. Treatment with PPIs and/or use of cyclooxygenase-2-selective NSAIDs should be implemented in those patients at risk of NVUGIB who need NSAIDs and/or LDA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Duodenum; Endoscopy; Esophagus; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Prognosis; Stomach; Upper Gastrointestinal Tract; Vitamin K

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

Factor Xa (fXa)-inhibitors are as effective and safer than vitamin-K-antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim was to combine these findings in order to increase precision, assess a class effect and analyse presentation and course for different types of bleeding, i. e. intracranial, gastro-intestinal, and other. We classified the clinical presentation and course of all major bleeding events using pre-defined criteria. Both classifications comprised four categories; one being the mildest, and four the most severe. Odds ratios (OR) were calculated for all events classified as category three or four between fXa-inhibitors and VKA recipients. Also, ORs were computed for different types of bleeding. Major bleeding occurred in 111 fXa-inhibitor recipients and in 187 LMWH/VKA recipients. The clinical presentation was classified as category three or four in 35 % and 48 % of the major bleeds in fXa inhibitor and VKA recipients, respectively (OR 0.59, 95 % CI 0.36-0.97). For intracranial, gastro-intestinal and other bleeding a trend towards a less severe presentation was observed for patients treated with fXa inhibitors. Clinical course was classified as severe in 22 % of the fXa inhibitor and 25 % of the VKA associated bleeds (OR 0.83, 95 % CI 0.47-1.46). In conclusion, FXa inhibitor associated major bleeding events had a significantly less severe presentation and a similar course compared to VKA. This finding was consistent for different types of bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Transfusion; Chi-Square Distribution; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Odds Ratio; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K

Evidence on the risk of gastrointestinal (GI) bleeding associated with dabigatran etexilate (DE) is contrasting. We performed a meta-analysis of literature to address this issue.. Studies on GI bleeding risk in patients receiving DE or vitamin-K antagonists (VKA) were systematically searched. Twenty-three studies (26 datasets) showed no difference in the GI bleeding risk between the 250,871 patients treated with DE and the 460,386 receiving VKA (OR: 1.052, 95% CI: 0.815, 1.359). Similar results were obtained when pooling together adjusted ORs/HRs, obtained by means of multivariate analysis (OR: 1.06, 95% CI: 0.914, 1.222). Compared with VKA, DE use was associated with a significantly lower risk of upper GI (OR: 0.742, 95% CI: 0.569, 0.968), but not of lower GI bleedings (OR: 1.208, 95% CI: 0.902, 1.619). Furthermore, no significant difference in the GI bleeding risk was found when data on DE 110 mg and DE 150 mg twice-daily were separately compared with VKA.. No difference in GI bleeding risk was found between DE and VKA. These results were confirmed for both dosages of DE and when specifically analyzing lower GI bleeding. In contrast, the risk of upper GI bleeding was lower with DE than with VKA. KEY MESSAGES No difference in the risk of gastrointestinal (GI) bleeding can be found between dabigatran etexilate (DE) and vitamin K-antagonists (VKA). These results are confirmed for both dosages of DE. The risk of upper GI bleeding is lower with DE than with VKA.

Topics: Aged; Aged, 80 and over; Antithrombins; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Orthopedic Procedures; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Assessment; Venous Thrombosis; Vitamin K

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

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in people with liver diseases. One of them is vitamin K administration, but it is not known whether it benefits or harms people with acute or chronic liver disease and upper gastrointestinal bleeding. This is an update of this Cochrane review.. To assess the beneficial and harmful effects of vitamin K for people with acute or chronic liver disease and upper gastrointestinal bleeding.. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), and LILACS (1982 to 25 February 2015). We sought additional randomised trials from two registries of clinical trials: the World Health Organization Clinical Trials Search Portal and the metaRegister of Controlled Trials. We looked through the reference lists of the retrieved publications and review articles.. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We considered observational studies for assessment of harms only.. \\We aimed to summarise data from randomised clinical trials using Standard Cochrane methodology and assess them according to the GRADE approach.. We found no randomised trials on vitamin K for upper gastrointestinal bleeding in people with liver diseases assessing benefits and harms of the intervention. We identified no quasi-randomised studies, historically controlled studies, or observational studies assessing harms.. This updated review found no randomised clinical trials of vitamin K for upper gastrointestinal bleeding in people with liver diseases. The benefits and harms of vitamin K need to be tested in randomised clinical trials. Until randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute the use of vitamin K for upper gastrointestinal bleeding in people with liver diseases.

Topics: Acute Disease; Antifibrinolytic Agents; Chronic Disease; Gastrointestinal Hemorrhage; Humans; Liver Diseases; Vitamin K

More and more patients are being treated with direct oral anticoagulants (DOAC). Under treatment with DOACs gastrointestinal bleeding appears to occur more frequently, particularly in the lower gastrointestinal tract, compared to treatment with vitamin K antagonists (e.g. warfarin).. A possible approach should now be elaborated in a joint effort by gastroenterologists and cardiologists.. A selective literatue search was carried out and own experiences were also included.. The decision to perform procoagulant therapy by slowly injecting 30-50 IU prothrombin complex concentrate (PPSB) per kg body weight intravenously depends on various factors and should be assessed critically. Specific antidotes are awaiting approval. After a bleeding episode potentially controllable and reversible triggers must be excluded (e.g. drug interactions and renal impairment). The risk of recurrent bleeding and the risk of thromboembolic events have to be weighed against each other before deciding to readminister an anticoagulant and its form. Dose reduction and changing to apixaban (in reduced dosage) are options for risk reduction and vitamin K antagonists can also be considered.. It is still unclear what role specific antidotes will play.

Topics: Administration, Oral; Anticoagulants; Critical Care; Drug Substitution; Gastrointestinal Hemorrhage; Humans; Injections, Intravenous; Prothrombin; Pyrazoles; Pyridones; Recurrence; Risk Factors; Thromboembolism; Vitamin K

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

The field of thromboembolic disease and anticoagulation has had critical advances since the Anticoagulation Forum last met (May of 2011). We summarize our "top ten list" of papers that are likely to change the care of the anticoagulated population and improve their outcomes: (1) Patient self-management of their vitamin K antagonist and self monitoring can decrease thromboembolic events; (2) restarting warfarin after gastrointestinal bleeding may decrease mortality; (3) rivaroxaban is effective in the treatment of pulmonary embolism; either (4) apixaban or (5) low-dose aspirin prevented recurrent venous thromboembolic disease after a standard course of therapy; (6) warfarin prevents thrombotic complications up to at least 90 days after bioprosthetic aortic valve replacement; (7) the relative risk reduction of apixaban compared to warfarin is similar across CHADS2 scores, but the absolute risk reduction is higher in high-risk patients; (8) adherence to a warfarin dose-adjustment algorithm improved time in the therapeutic range and thromboembolic outcomes in the RE-LY trial; (9) warfarin had little benefit (if any) over aspirin in patients with decreased ejection fraction and sinus rhythm; (10) adding clopidogrel to aspirin in patients with lacunar infarcts did not reduce the risk of recurrent stroke and increased bleeding.

Topics: Anticoagulants; Female; Gastrointestinal Hemorrhage; Humans; Male; Risk Factors; Stroke; Thromboembolism; Vitamin K

Oral anticoagulation and antiplatelet therapy are risk factors for gastrointestinal (GI) bleeding. GI bleeding-especially lower GI bleeding-seems to be associated with a poorer outcome. With the introduction of dabigatrane and rivaroxaban, difficulties in the management of bleeding complications arose. Thus, the goal of the authors was to establish a standard operating procedure (SOP) for the treatment of severe GI bleeding associated with rivaroxaban, dabigatrane, and antiplatelet therapy. Bleeding complications during phenprocoumon treatment should be treated with prothrombin complex concentrates and vitamin K1. Dabigatrane elimination is highly dependent to the renal function. The measurement of drug concentrations of dabigatrane and rivaroxaban is useful to indicate an increased risk of bleeding complications. Severe bleeding associated with dabigatrane or rivaroxaban therapy should trigger prothrombin complex therapy, whereby in cases with severe bleeding associated with antiplatelet therapy platelet transfusion should be initiated. Low-dose aspirin should be continued after 24 h.

Topics: Algorithms; Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Factors; Dabigatran; Drug Monitoring; Gastrointestinal Hemorrhage; Heart Diseases; Humans; Metabolic Clearance Rate; Morpholines; Phenprocoumon; Platelet Aggregation Inhibitors; Platelet Transfusion; Rivaroxaban; Thiophenes; Vitamin K

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in patients with liver diseases. One of them is vitamin K administration, but it is not known whether it benefits or harms patients with acute or chronic liver disease and upper gastrointestinal bleeding.. To assess the beneficial and harmful effects of vitamin K for patients with acute or chronic liver disease and upper gastrointestinal bleeding.. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (12 June 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 5 of 12, 2012), MEDLINE (Ovid SP) (1946 to 12 June 2012), EMBASE (Ovid SP) (1974 to 12 June 2012), Science Citation Index EXPANDED (1900 to 12 June 2012), and LILACS (1982 to 19 June 2012). Additional randomised trials were sought from two registries of clinical trials: the Clinical Trials Search Portal of the WHO, and the Metaregister of Controlled Trials. We looked through the reference lists of the retrieved publications and review articles.. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies were considered for assessment of harms only.. Data from randomised clinical trials were to be summarised by standard Cochrane Collaboration methodologies.. We could not find any randomised trials on vitamin K for upper gastrointestinal bleeding in patients with liver diseases in which we could assess benefits and harms. We could not identify quasi-randomised studies, historically controlled or observational studies in which we could assess harms.. This updated review found no randomised clinical trials on the benefits and harms of vitamin K for upper gastrointestinal bleeding in patients with liver diseases. The effects of vitamin K need to be tested in randomised clinical trials. Until randomised clinical trials are conducted to assess the trade off between benefits and harms, we cannot recommend nor refute vitamin K for upper gastrointestinal bleeding in patients with liver diseases.

Topics: Acute Disease; Antifibrinolytic Agents; Chronic Disease; Gastrointestinal Hemorrhage; Humans; Liver Diseases; Vitamin K

Topics: Anticoagulants; Biopsy; Colonic Polyps; Colonoscopy; Constriction, Pathologic; Dilatation; Gastrointestinal Hemorrhage; Humans; Intestinal Diseases; Intestinal Mucosa; Platelet Aggregation Inhibitors; Risk Factors; Thrombin; Vitamin K

The management of anticoagulants and antiplatelet agents in patients undergoing gastrointestinal endoscopic procedures is a common clinical problem. Although guidelines have been published, they are supported by little prospective or randomized trial data, but are primarily based on observational studies, expert opinion, and best clinical practices. As a general principle, the risks of thromboembolism need to be balanced against the risks of bleeding during the endoscopic procedure. By understanding these risks, management plans for individual cases may be made. This article reviews the current data and guidelines on the management of anticoagulants, antiplatelet agents, use of reversal agents, and the role and risks of concomitant proton pump inhibitors.

Topics: Anticoagulants; Comorbidity; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Humans; Patient Care Planning; Plasma; Platelet Aggregation Inhibitors; Postoperative Care; Practice Guidelines as Topic; Preoperative Care; Prothrombin; Proton Pump Inhibitors; Risk Assessment; Risk Factors; Thromboembolism; Vitamin K

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in patients with liver diseases. One of them is vitamin K administration, but it is unknown whether it benefits or harms patients with liver disease and upper gastrointestinal bleeding.. To assess the beneficial and harmful effects of vitamin K for patients with liver disease and upper gastrointestinal bleeding.. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2007), which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2007), MEDLINE (1950 to September 2007), EMBASE (1980 to September 2007), Science Citation Index Expanded (1945 to September 2007), and LILACS (1982 to November 2007). Additional randomised trials were sought from two registries of clinical trials, ClinicalTrials.gov and Sistema de Información Esencial en Terapéutica y Salud, the reference lists of the trials found, and reviews identified by the electronic searches.. Randomised clinical trials.. Data from randomised clinical trials were to be summarised by standard Cochrane Collaboration methodologies.. We could not find any randomised trials on vitamin K for upper gastrointestinal bleeding in patients with liver diseases.. This updated review found no randomised clinical trials on the safety and efficacy of vitamin K for upper gastrointestinal bleeding in patients with liver diseases. The effects of vitamin K need to be tested in randomised clinical trials. Unless randomised clinical trials provide evidence of a treatment effect and the trade off between potential benefits and harms are established, policy-makers, clinicians, and academics should not use vitamin K for upper gastrointestinal bleeding in patients with liver diseases.

Topics: Antifibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Liver Diseases; Vitamin K

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in patients with liver diseases. However, supplementary interventions are often used as well. One of them is vitamin K administration, but it is unknown whether it benefits or harms patients with liver disease and upper gastrointestinal bleeding.. To assess the beneficial and harmful effects of vitamin K for patients with liver disease and upper gastrointestinal bleeding.. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (February 2004), which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1, 2004), MEDLINE (1966 to March 2004), EMBASE (1988 to March 2004), and LILACS (1982 to March 2004). Additional randomised trials were sought from the reference lists of the trials found and reviews identified by the electronic searches.. We intended to include randomised clinical trials.. We intended to summarise data by standard Cochrane Collaboration methodologies.. We could not find any randomised trials on vitamin K for upper gastrointestinal bleeding in patients with liver diseases.. We were unable to identify randomised trials on the safety and efficacy of vitamin K for upper gastrointestinal bleeding in patients with liver diseases. The effects of vitamin K need to be tested in randomised clinical trials.

Topics: Antifibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Liver Diseases; Vitamin K

Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or resistance to warfarin is unlikely if the above doses of vitamin K are used. Vitamin K is less effective for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than after treatment with warfarin.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Factors; Dose-Response Relationship, Drug; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Risk Factors; Vitamin K

Topics: Blood Transfusion; Central Venous Pressure; Cimetidine; Emergencies; Esophageal and Gastric Varices; Esophagoscopy; Esophagus; Fluid Therapy; Gastrointestinal Hemorrhage; Hemostasis, Surgical; Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Prognosis; Sclerosing Solutions; Vasopressins; Vitamin K

Topics: Anti-Bacterial Agents; Blood Transfusion; Cryotherapy; Drainage; Esophageal and Gastric Varices; Esophageal Perforation; Gastrointestinal Hemorrhage; Hemostasis; Hepatic Encephalopathy; Humans; Hypertension, Portal; Intubation, Gastrointestinal; Liver Cirrhosis; Myocardial Infarction; Peptic Ulcer; Pneumonia, Aspiration; Portacaval Shunt, Surgical; Sclerosing Solutions; Therapeutic Irrigation; Ulcer; Vasopressins; Vitamin K

Topics: Bacterial Vaccines; Bicarbonates; Brain Edema; Diagnosis, Differential; Diazepam; Digoxin; Fever; Gastrointestinal Hemorrhage; Heparin; Humans; Hydrocortisone; Infant; Infant, Newborn; Isoproterenol; Mannitol; Meningitis; Meningitis, Meningococcal; Meningitis, Viral; Phenytoin; Seizures; Shock, Septic; Vitamin K

The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied.. We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding.. A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11).. In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

Topics: 4-Hydroxycoumarins; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Mortality; Phenindione; Postoperative Complications; Pyridines; Thiazoles; Thromboembolism; Transcatheter Aortic Valve Replacement; Vitamin K

Mesenteric venous thrombosis is a rare lethal disease. The main aim of the present study was to evaluate clinical efficacy and safety of direct oral anticoagulants and vitamin K antagonists in mesenteric venous thrombosis patients.. Retrospective study of 102 mesenteric venous thrombosis patients treated between 2004 and 2017 at a center with a conservative medical first approach. Median clinical follow-up was 4 years.. Computed tomography showed successful recanalization of thrombosis in 71% of patients on vitamin K antagonists and 69% of patients on direct oral anticoagulants ( p = 0.88). Overall major and esophageal variceal bleeding rate was 14.7% and 2.9%, respectively. No difference in major bleeding ( p = 0.54) was found between vitamin K antagonists and direct oral anticoagulants. No mesenteric venous thrombosis recurrence occurred during follow-up, and one venous thromboembolism occurred after cessation of anticoagulation.. Anticoagulation with direct oral anticoagulants and vitamin K antagonists was efficient in patients with mesenteric venous thrombosis. Bleeding complications was a concern during treatment in both groups.

Topics: Administration, Oral; Aged; Anticoagulants; Esophageal and Gastric Varices; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Mesenteric Ischemia; Middle Aged; Retrospective Studies; Vitamin K

Treatment of splanchnic vein thrombosis (SVT) is a clinical challenge due to heterogeneity of clinical presentations, increased bleeding risk, and lack of evidences from clinical trials. We performed an international registry to describe current treatment strategies and factors associated with therapeutic decisions in a large prospective cohort of unselected SVT patients. A total of 613 patients were enrolled (mean age 53.1 years, standard deviation ± 14.8); 62.6% males; the majority (468 patients) had portal vein thrombosis. Most common risk factors included cirrhosis (27.8%), solid cancer (22.3%), and intra-abdominal inflammation/infection (11.7%); in 27.4% of patients, SVT was idiopathic. During the acute phase, 470 (76.7%) patients received anticoagulant drugs, 136 patients (22.2%) remained untreated. Incidental diagnosis, single vein thrombosis, gastrointestinal bleeding, thrombocytopenia, cancer, and cirrhosis were significantly associated with no anticoagulant treatment. Decision to start patients on vitamin K antagonists after an initial course of parenteral anticoagulation was significantly associated with younger age, symptomatic onset, multiple veins involvement, and unprovoked thrombosis. Although a nonnegligible proportion of SVT patients did not receive anticoagulant treatment, the majority received the same therapies recommended for patients with usual sites thrombosis, with some differences driven by the site of thrombosis and the pathogenesis of the disease.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Female; Fibrinolytic Agents; Fibrosis; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Registries; Retrospective Studies; Risk Factors; Splanchnic Circulation; Venous Thrombosis; Vitamin K

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

To corroborate results obtained in The Netherlands with PPSB-SD, showing a safe acute reversal of anticoagulation within 15 minutes of administration.. PPSB-SD is a concentrate prothrombin complex containing a relatively constant high level of vitamin K-dependant coagulation factors II, VII, IX and X. PPSB-SD was administered to 14 patients treated with oral anticoagulants, according the patient's weight, the initial and the target INR (< 2.0 for moderate haemorrhage and abdominal surgery, or < 1.5 for severe haemorrhage and cardio-vascular interventions). INR values were measured with the Coagucheck Pro (Roche Diagnostics) upon admission and at 15 minutes, 1, 3 and 5 hours after treatment, and confirmed by the hospitals' laboratory.. Within 15 minutes 11 patients out of 12 reached their INR target (data were missing for 2 patients). INR decreased rapidly, then remained stable for the next 5 hours. All patients had a favourable outcome: bleeding was stopped and no haemorrhage occurred during surgery. Only one adverse event was reported, but it was not related to the PPSB-SD treatment. No sign of disseminated intravascular coagulation was observed during this study. The administration of PPSB-SD along with vitamin K and dosed according to body weight and initial and target INR allowed for optimal reversal of anticoagulation, as no second infusion was necessary. The recommended dosing worked also very well for patients with high initial INR (9.2 to 22.8) who were brought down to normal values (0.9 to 1.1) within 15 minutes.. PPSB-SD can safely be used for the rapid reversal of anticoagulation as needed in emergency situations.

Topics: Abdomen; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Blood Loss, Surgical; Body Weight; Coagulants; Emergencies; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Hip Fractures; Humans; International Normalized Ratio; Male; Middle Aged; Time Factors; Treatment Outcome; Vitamin K

We report here the final analysis of a multicentre randomized, single-blind trial of propranolol for prophylaxis of first bleeding in cirrhosis. One hundred and seventy-four consecutive patients with large esophageal varices were randomly assigned to either propranolol in doses reducing the resting heart rate by 25% (85 patients) or to a placebo (vitamin K: 89 patients). Three were lost to follow-up and 26 had to be withdrawn from propranolol because of side effects (n = 23) or low compliance (n = 3). The cumulative value over 42 months of patients free of bleeding was 74% (95% confidence interval = 85%-63%) in the propranolol and 59% (95% CI = 79%-43%) in the control group and the corresponding survival figures were 51% (95% CI = 63%-39%) and 59% (95% CI = 75%-43%): neither of the differences was significant. A retrospective analysis according to the presence of ascites at randomization showed that in the subset without ascites the proportion of patients free of bleeding was significantly higher in the propranolol group than in the control group (83% vs. 61%; 95% CI = 97%-69% and 78%-44%, respectively; P = 0.028); this difference was even more evident in the ascites-free period (94% vs. 58%; 95% CI = 100%-86% and 76%-40%, respectively; P = 0.002). No differences were found in patients with ascites at randomization. Survival was not significantly affected by treatment in any subgroup, although it was shorter in the ascitic patients given propranolol than in controls (33% vs. 49%; 95% CI = 51%-15% and 71%-27%, respectively; P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Ascites; Clinical Trials as Topic; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Prognosis; Propranolol; Random Allocation; Retrospective Studies; Risk Factors; Vitamin K

The preliminary analysis of a multicentre, randomised, single-blind trial of propranolol for prophylaxis of first bleeding in cirrhosis is reported. 174 consecutively-chosen patients with large oesophageal varices were randomly assigned to either propranolol, in doses which reduced the resting heart rate by 25% (85 patients), or to vitamin K (89 patients). 25 patients had to be withdrawn from treatment with propranolol because of poor tolerance. The 30-month cumulative proportion of patients free of bleeding was 74% in the propranolol group and 63% in the vitamin K group; corresponding survival figures were 59% and 74%, respectively. These differences were not statistically significant. A retrospective analysis, according to the presence of ascites at randomisation showed that a significantly higher proportion of patients without ascites in the propranolol group were free of bleeding compared with those in the control group (87% vs 64%; p = 0.023). No significant differences were found in patients with ascites at randomisation. Length of survival was not significantly affected by treatment in any subgroup, although it was shorter in ascitic patients given propranolol than in controls (33% vs 63%; p = 0.07). If confirmed on a longer follow-up, these results suggest that propranolol could prevent primary variceal haemorrhage in patients with well-compensated cirrhosis.

Topics: Aged; Female; Gastrointestinal Hemorrhage; Hepatitis B Surface Antigens; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Propranolol; Randomized Controlled Trials as Topic; Survival Analysis; Vitamin K

In this prospective study for pharmacotherapy of non varicial upper gastrointestinal haemorrhage eight therapy groups were examined. The efficacy of the most important drugs for ulcus disease was considered. The drugs were used alone and in combination. The results indicated no favourable effect of one preparation (Cimetidine, Pirenzepine, Ranitidine). Significant benefit for the long time healing rate was noted among the combination therapies, especially with Sucralfate, which was not used alone.

Topics: Aluminum; Benzodiazepinones; Calcium; Cimetidine; Drug Therapy, Combination; Estrogens; Gastrointestinal Hemorrhage; Gelatin Sponge, Absorbable; Humans; Metoclopramide; Peptic Ulcer; Pirenzepine; Prospective Studies; Ranitidine; Sucralfate; Vitamin K

Direct oral anticoagulants (DOACs) may simplify management of Budd-Chiari syndrome (BCS). Here, we report our experience with off-label use of DOACs for anticoagulation in BCS.. The safety of DOAC vs vitamin K antagonist treatment as well as associated clinical outcomes were retrospectively assessed in 47 BCS patients treated at 6 Austrian centers.. Mean age at study inclusion was 37.9 ± 14.0 years and mean Model for End-Stage Liver Disease was 13.1 ± 5.1. Overall, 63.8% (n = 30) of patients had decompensated liver disease, and 87.2% (n = 41) showed clinical signs of portal hypertension. During a median follow-up of 82.5 (interquartile range, 43.1-121.8) months, 43 (91.5%) patients received anticoagulation alone or following interventional treatment, including 22 (46.8%) patients treated with DOACs (edoxaban: 10, apixaban: 4, rivaroxaban: 3, dabigatran: 3, more than one DOAC sequentially: 2) for a median of 24.4 (interquartile range, 5.7-35.1) months. While 72.7% (n = 16 of 22) of patients were switched from low-molecular-weight heparin (n = 12) or vitamin K antagonist (n = 4) to DOAC after disease stabilization or improvement, 27.3% (n = 6 of 22) of BCS patients were initially treated with DOAC. Complete response (European Association for the Study of the Liver criteria) was achieved or maintained in 14 (63.6%) of 22 patients, with ongoing response in 2 patients, while disease progressed in 6 patients (including 2 patients with hepatocellular carcinoma). Four major spontaneous bleedings (18.2%; incidence rate 8.8 per 100 patient-years; n = 2 upper gastrointestinal bleeding, n = 1 lower gastrointestinal bleeding, n = 1 hepatocellular carcinoma rupture), 7 minor bleedings, and 1 major procedure-related bleeding (4.5%; 2.2 per 100 patient-years) occurred during DOAC therapy. Overall transplant-free survival was 91.6% at 5 years.. DOACs seem to be effective and safe for long-term anticoagulation in patients with BCS, but confirmation by larger prospective studies is needed.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Austria; Budd-Chiari Syndrome; Carcinoma, Hepatocellular; Dabigatran; End Stage Liver Disease; Gastrointestinal Hemorrhage; Humans; Liver Neoplasms; Retrospective Studies; Severity of Illness Index; Vitamin K

Gastrointestinal bleeding (GIB) is a common adverse event related to anticoagulation therapy. However, evidence comparing the severity, etiology and outcome of GIB in patients taking direct oral anticoagulants (DOAC) vs. vitamin K antagonists (VKA) is scarce.. To evaluate the severity, etiology and outcomes of GIB in patients under DOACs compared to VKA.. Patients under oral anticoagulant therapy admitted to the emergency department with acute GIB were prospectively recruited from July 2016 to January 2018 at a tertiary referral hospital. Demographic and clinical outcome were obtained from medical records. Severity of the GIB event was classified as mild, major or severe according to clinical presentation and the type of support needed. Etiology and location of bleeding, number of packed red blood cells transfused (PRBC) and length of hospital stay were recorded until discharge or in-hospital death.. A total of 208 patients with acute GIB under oral anticoagulant treatment were recruited: 119 patients were on VKA and 89 patients on DOAC with similar characteristics. Thirty-one patients had severe GIB; 134 major and 43 mild, with no differences in severity, number of PRBC and length of hospital stay between the groups. Peptic disease was the most frequent etiology of GIB in patients on VKA (20.2 % vs. 13.6%, p=0.20). Diverticular bleeding was the most frequent adverse event in patients on DOAC (14.3% vs. 24.8%, p= 0.056).. Severity and clinical outcomes of GIB are similar between patients on DOAC and patients on VKA, regardless of etiology of GIB.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Hospital Mortality; Humans; Vitamin K

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

The incidence of early-onset vitamin K deficiency bleeding (VKDB) in at-risk neonates who did not receive vitamin K supplementation varied from 6 to 12%. This case report aims to show that VKDB can occur abruptly after birth despite vitamin K1 1 mg IM being given immediately after birth.. A term female baby was born through vaginal delivery of a 28 years old mother, G1P0A0, 39-40 weeks gestation with normal APGAR score, and birth weight was 3445 g, birth length was 52 cm. During pregnancy, the mother did not take any drugs except vitamins. There are no abnormalities on the baby's physical examination. The anus is patent. Immediately after birth, the baby received a vitamin K1 1 mg intramuscularly. Abruptly, 50 min after delivery, there was meconium with lots of fresh blood. Laboratory results showed hemoglobin, 19.6 g/dL; leukocytes, 25,010/uL; platelets, 390,000/uL, with increased PT and aPTT. A peripheral blood smear showed a normal blood morphology. When 7 h old, the baby had much hematochezia. Laboratory results showed decreased hemoglobin to 17.5 g/dL and increased PT, aPTT, and INR. No abnormalities were found on the babygram and abdominal ultrasound. The working diagnosis was gastrointestinal bleeding due to idiopathic early-onset VKDB. The baby received vitamin K1 2 mg IM, Fresh Frozen Plasma, and a Packed Red Cells transfusion. The patient returned home in good clinical condition.. Vitamin K1 1 mg IM prophylaxis should be given immediately after birth to prevent early-onset VKDB. In addition, pregnant women who receive drugs that interfere with vitamin K metabolism (anti-epileptic drugs, anti-tuberculosis drugs, vitamin K antagonist drugs) should be given prophylactic vitamin K1, 20 mg/d orally, for at least two weeks before the expected time of delivery.

Topics: Adult; Female; Gastrointestinal Hemorrhage; Humans; Infant; Infant, Newborn; Pregnancy; Vitamin K; Vitamin K 1; Vitamin K Deficiency Bleeding; Vitamins

Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures.. We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment.. The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively).. In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.

Topics: Administration, Oral; Anticoagulants; Colonic Polyps; Colonoscopy; Gastrointestinal Hemorrhage; Humans; Prospective Studies; Vitamin K

Gastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.. This is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012-2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case-control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent.. 98 376 patients on NOACs (median age: 75 years (IQR: 68-82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36).. Concomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Glucocorticoids; Humans; Male; Risk Factors; Stroke; Vitamin K

The increased risk of upper gastrointestinal bleeding (UGIB) related to direct oral anticoagulants (DOACs) as compared to vitamin K antagonists (VKA) remains debated.. To describe the epidemiology and outcomes of UGIB in patients treated with oral anticoagulants.. A prospective, multicentre study in French general hospitals enrolled all consecutive patients with UGIB during one year. Patients treated with oral anticoagulants were retrieved from the cohort. Main outcomes were mortality and rebleeding during the first 6 weeks and need for non-endoscopic treatment (surgery or interventional radiology).. Among the 2498 patients included, 475 (19%) had an oral anticoagulant, mostly with VKA (267 patients [56.2%]). Baseline characteristics were similar between the groups except for renal failure and cirrhosis that were more prevalent in the VKA group. Gastroscopy was normal in 73 patients (15.3%); peptic lesions were the main cause of UGIB (n = 233, 49%). Endoscopic treatment was performed in 128 patients (26.9%), leading to bleeding resolution in 74% (n = 95). Mortality rate at 6 weeks was 12.4% (59 patients), and was higher in the VKA group compared to DOACs (16.1% vs 7.8%, P < 0.01). By multivariate analysis, only the Charlson index ≥ 5 and UGIB occurrring in in-patients were independently associated with mortality. Rebleeding (56 patients [11.8%]) and need for non-endoscopic treatment (18 patients [3.8%]) were not associated with the type of anticoagulant.. DOACs do not alter outcomes of UGIB as compared to VKA. Comorbidities and associated treatment are the most important factors worsening the prognosis of UGIB.

Topics: Administration, Oral; Anticoagulants; Cohort Studies; Gastrointestinal Hemorrhage; Humans; Prospective Studies; Vitamin K

Topics: Anticoagulants; Gastrointestinal Hemorrhage; Humans; Vitamin K

Direct oral anticoagulants (DOACs) were developed to avoid the limitations of vitamin K antagonists (VKAs). DOACs are associated with a greater incidence of gastrointestinal bleeding and a smaller number of intracranial haemorrhages than VKAs. Therefore, it is important to deepen our knowledge of their safety profiles. The aim of this study was thus to analyse adverse drug reaction (ADR) reports on DOACs and VKAs using the Sicilian Spontaneous Reporting System (SRS) database.. All ADR reports with DOACs and VKAs as suspected drugs that were entered into the Sicilian SRS database during the period 2001-2019 were selected. In detail, all reports with the following single active substances were included: dabigatran etexilate, rivaroxaban, apixaban and edoxaban; acenocoumarol and warfarin were included as a comparator group. Descriptive statistical methodology was used to evaluate characteristics of the reported cases with a case-by-case assessment.. Out of 521 reports related to anticoagulants, 444 (85.2%) and 77 (14.8%) involved DOACs and VKAs, respectively. DOAC-related reports were mainly of gastrointestinal disorders. In contrast, VKAs were mostly associated with blood and lymphatic system disorders, injury, investigations and vascular disorders. Many more cases of ADRs in the form of gastrointestinal disorders concerned dabigatran etexilate (n = 179, 73.7%) than the other DOACs, while ADRs in the form of blood disorders were mainly associated with acenocoumarol (n = 27, 57.4%). The most commonly reported Preferred Terms for DOACs were dyspepsia (n = 89, 17.1%), upper abdominal pain (n = 41, 9.2%) and pruritus (n = 26, 5.8%), whereas for VKAs, they were anaemia (n = 21, 27.3%) and hypocoagulable state (n = 18, 3.5%). Potentially interacting concomitant medications particularly included antithrombotic agents (n = 19, 4.3%) for DOACs and proton-pump inhibitors (PPIs) (n = 37, 48.1%) and antithrombotic agents (n = 13, 16.9%) for VKAs.. The ADRs most commonly associated with DOACs, especially dabigatran, were gastrointestinal disorders, particularly gastrointestinal bleeding. Our study also highlights the potential role of drug-drug interactions in the ADRs. The cases of gastrointestinal bleeding highlight the need for careful prescribing of DOACs and use of potentially interacting concomitant drugs.

Topics: Adverse Drug Reaction Reporting Systems; Anticoagulants; Drug Interactions; Factor Xa Inhibitors; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Italy; Vitamin K

Administrative data were used to investigate changes in hospitalizations for atrial fibrillation (AF), AF-related stroke, and treatment patterns between 2012 and 2016.. From the 'Ricerca e Salute' database, a population- and patient-based repository involving >12 million inhabitants and linking demographics, prescriptions, and hospital discharge records, all patients discharged alive with a diagnosis of AF between 2012 and 2015 were followed for 1 year.. A total of 194,030 AF patients were included. The number of AF cases increased ~10% over time, from 4.0 per 1,000 inhabitants in 2012 to 4.4 per 1,000 in 2015. At 1 year, hospitalizations for ischemic stroke decreased from 21.3 per 1,000 patients with AF in 2012-2013 to 14.7 per 1,000 in 2015-2016 (-31%, 95% CI -18 to -41). Over the same period, oral anticoagulant (OAC) use increased from 56.7% to 64.4% (+14%, 95% CI +8 to +26), vitamin K antagonist use decreased (from 55.9 to 36.7%; -34%, 95% CI -21 to -44), whereas direct OACs (DOACs) increased (from <1% in 2012 to 27.7% in 2015). Antiplatelet prescriptions fell from 42.6% in 2012 to 28.1% in 2015. Hospitalizations for major bleeds, mainly gastrointestinal, increased from 1.5‰ in 2012-2013 to 2.3‰ in 2015-2016, whereas hemorrhagic stroke admissions decreased from 6.5‰ to 4.1‰.. There was a slight increase in the prevalence of AF between 2012 and 2015, whereas the overall use of antiplatelet agents decreased and that of OAC, particularly DOACs, increased. Over the same period, 1-year hospitalizations for ischemic stroke declined substantially, with a declining rate of hemorrhagic strokes.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Catchment Area, Health; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Health Expenditures; Hemorrhage; Hospitalization; Humans; Italy; Male; Platelet Aggregation Inhibitors; Retrospective Studies; Stroke; Time Factors; Vitamin K

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

Clinical trials have indicated that the direct-acting oral anticoagulants dabigatran and rivaroxaban have better risk/benefit profiles than do vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (NVAF).. Our objective was to compare the 1-year real-life risk of major clinical events with dabigatran or rivaroxaban versus VKAs for NVAF.. This was a high-dimensional propensity score (hdPS)-matched cohort study of new users of dabigatran, rivaroxaban or VKAs for NVAF in the French national healthcare systems database in 2013 followed-up for 1 year [22]. Hazard ratios (HRs) with 95% confidence intervals (CIs) for clinical events and death were determined during exposure.. In 2013, a total of 103,101 new anticoagulant users had definite NVAF: 44,653 VKA, 27,060 dabigatran, and 31,388 rivaroxaban. In matched populations, HRs were as follows for dabigatran versus VKAs (20,489 per group): stroke and systemic embolism (SSE) 0.75 (95% CI 0.63-0.88), clinically relevant bleeding (CRB) 0.58 (95% CI 0.51-0.66), hemorrhagic stroke (HS) 0.22 (95% CI 0.14-0.36), gastrointestinal bleeding (GIB) 0.98 (95% CI 0.80-1.19), acute coronary syndrome (ACS) 0.79 (95% CI 0.65-0.95), death 0.74 (95% CI 0.67-0.82), composite (any of the above) 0.71 (95% CI 0.66-0.76). For matched rivaroxaban versus VKA (23,053 per group) HRs were as follows: SSE 0.98 (95% CI 0.85-1.14), CRB 0.83 (95% CI 0.75-0.92), HS 0.65 (95% CI 0.49-0.87), GIB 1.08 (95% CI 0.90-1.30), ACS 0.84 (95% CI 0.71-1.00), death 0.77 (95% CI 0.71-0.84), composite 0.84 (95% CI 0.79-0.89). Numbers needed to treat to observe one fewer death were 49 ± 0.05 with dabigatran or rivaroxaban versus VKAs.. Consistent with results from clinical trials and other observational studies, dabigatran and rivaroxaban were at least as effective and safer than VKAs for the prevention of thromboembolic events in NVAF over 1 year in the French population.. European Medicines Agency EUPAS 13017 (www.encepp.eu) Clinicaltrials.gov id NCT02785354.

Topics: Administration, Oral; Aged; Aged, 80 and over; Atrial Fibrillation; Cohort Studies; Dabigatran; Data Systems; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Male; Propensity Score; Rivaroxaban; Vitamin K

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

Vitamin K antagonists (VKA) continue to be the standard of long-term anticoagulation. Direct oral anticoagulants(DOAC) are increasingly used. In many trials DOAC were at least as effective as VKA. In this study we evaluate the bleeding profiles, frequencies and etiologies of patients receiving DOAC versus VKA in a real-life setting. All patients presenting with suspected gastrointestinal bleeding (GIB) in the emergency department of the University Hospital Erlangen in one year were enrolled in this study. They were looked up for the intake of either DOAC (dabigatran, rivaroxaban and apixaban) or VKA. The results showed that 406 patients with suspected GIB were admitted to the emergency unit of the University Hospital Erlangen. In 228 of those patients GIB could be verified (56.2%). Fifty four of those patients (23.7%) were administered either VKA or DOAC. In 35 of those 54 patients (64.8%) GIB was classified as 'major bleeding'. In 27 patients with administration of VKA upper GIB was recorded and lower GIB was detected four times. In 16 patients with administration of DOAC upper GIB was found and lower GIB was found in 7 patients. The presented data do not show higher GIB rates for DOAC (mainly dabigatran and rivaroxaban), but do also not indicate a significantly higher safety of DOAC concerning GIB than VKA. This finding represents a clear contrast to the reduced bleeding rates of DOAC for intracerebral bleeding and other non-GIB events. According to our study, the absolute number of DOAC-associated GIB events is lower than in the VKA group.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Vitamin K; Young Adult

Topics: 4-Hydroxycoumarins; Acute Disease; Aged; Duodenal Diseases; Duodenum; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Indenes; Male; Middle Aged; Pancreatitis; Vitamin K

Whether bleeding should be considered a sufficient sign to justify thorough cancer surveillance in atrial fibrillation (AF) patients receiving nonvitamin K antagonist oral anticoagulants (NOACs) remains unclear. We investigated the relationships between bleeding events and new-onset cancers in AF patients receiving NOACs in a prospective cohort (n = 395, mean follow-up duration of 2.8 years). There were 18 patients who were diagnosed with new-onset cancers 584 ± 372 days after the initiation of NOACs. The patients with new-onset cancers had higher HAS-BLED scores (no, preexisting and new-onset cancer: 1.51 ± 0.81, 1.69 ± 0.87, and 2.11 ± 0.96, respectively; p = 0.006) and a higher incidence of bleeding events (22%, 33%, 67%, respectively; p<0.001) than did patients without new-onset cancers. Bleeding events that preceded the diagnosis of new-onset cancers were independently correlated with new-onset cancers (odds ratio: 7.89, p = 0.001) in the multivariate logistic regression. More than half of the patients (61%) with new-onset cancers had either a significant period of drug interruption for at least 2 months or discontinued NOACs. In conclusions, bleeding in AF patients receiving NOACs could be an alerting sign of new-onset cancers and should prompt the initiation of thorough surveillance to detect early cancers.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Neoplasms; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Taiwan; Time Factors; Vitamin K

Although dabigatran has a favorable risk-benefit profile compared with vitamin K antagonist therapy for venous thromboembolism and nonvalvular atrial fibrillation, major bleeding events, including gastrointestinal (GI) bleeding, may occur. Therefore, our aim was to provide insights into the efficacy and safety of idarucizumab for urgent dabigatran reversal in patients with major GI bleeding.. Patients with uncontrollable GI bleeding requiring reversal were enrolled from June 2014 through July 2016 in the RE-VERSE AD study (Reversal of Dabigatran Anticoagulant Effect With Idarucizumab), a prospective, multicenter, open-label study of idarucizumab, and were followed up for 90 days for primary and secondary outcomes. Patients were to receive a 5-g dose of intravenous idarucizumab, administered as 2 bolus infusions of 2.5 g no more than 15 minutes apart. The primary end point was the maximum reversal of dabigatran anticoagulation within 4 hours after administration of idarucizumab as measured by the dabigatran-specific assays diluted thrombin time and ecarin clotting time. Further end points included investigator-reported bleeding cessation within the first 24 hours and incidence of rebleeding, thromboembolic events, or mortality.. GI bleeding occurred in 137 patients enrolled in RE-VERSE AD, of which 84% was adjudicated as major or life-threatening, 48 (35.0%) was upper GI tract in origin, 43 (31.4%) was lower GI in origin, and 46 (33.6%) was either both or unknown. Complete reversal of dabigatran was observed in 118 of 121 patients (97.5%) with an elevated diluted thrombin time at presentation and 95 of 131 patients (72.5%) with an elevated ecarin clotting time and was similar for upper and lower GI bleeding. Bleeding cessation within 24 hours was reported in 92 of 134 evaluable patients (68.7%) after a median duration of 2.4 hours (interquartile range, 2.0-3.9 hours). During the 90-day follow-up, 6 patients (4.4%) had a postreversal thromboembolic event, and 20 patients (14.6%) died.. Idarucizumab showed a rapid and complete reversal of dabigatran activity in nearly all patients presenting with GI bleeding, facilitating emergency patient care without the additional presence of anticoagulation.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT02104947.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Anticoagulants; Dabigatran; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Risk Assessment; United States; Venous Thromboembolism; Vitamin K

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Asian People; Atrial Fibrillation; Brain Ischemia; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Kidney Function Tests; Male; Republic of Korea; Retrospective Studies; Risk Factors; Stroke; Vitamin K

To evaluate the effectiveness and safety of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) among patients with non-valvular atrial fibrillation (NVAF), particularly those with chronic kidney disease (CKD).. Population-based matched cohort study.. Over 670 primary care practices in the UK, contributing to the Clinical Practice Research Datalink.. Up to 6818 adult patients newly treated with NOACs between 2011 and 2016, matched 1:1 to new users of VKAs on age, sex and high-dimensional propensity score.. Current exposure to NOACs compared with current exposure to VKAs.. HRs of ischaemic stroke and systemic embolism (SE), major bleeding, gastrointestinal (GI) bleeding, intracranial bleeding, myocardial infarction and all-cause mortality.. In as-treated analyses, the rates of ischaemic stroke/SE were similar between NOACs and VKAs (HR 0.94; 95% CI 0.62 to 1.42), as were the rates of major bleeding (HR 0.86; 95% CI 0.56 to 1.33). NOACs also significantly increased the risk of GI bleeding (HR 1.78; 95% CI 1.27 to 2.48). In patients with NVAF and CKD, NOACs and VKAs remained comparable with respect to the risk of ischaemic stroke/SE (HR 0.79; 95% CI 0.40 to 1.58) and major bleeding (HR 0.88; 95% CI 0.47 to 1.62), with no difference in the risk of GI bleeding (HR 0.99; 95% CI 0.63 to 1.55). Similar results were obtained in on-treatment analyses using a time-dependent exposure definition.. Our results suggest that in the UK primary care, NOACs are overall effective and safe alternatives to VKAs, among patients with NVAF altogether, as well as in patients with NVAF and CKD.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Primary Health Care; Regression Analysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; United Kingdom; Vitamin K; Young Adult

To determine the preventability of serious adverse drug reactions (ADRs) related to the use of direct oral anticoagulants (DOACs), and to explore contributing factors to preventable ADRs. Results were compared with vitamin K antagonists (VKAs).. We conducted a prospective observational study in the emergency departments of two teaching hospitals from July 2015 to January 2016. Patients admitted with a thrombotic or bleeding event while under DOAC or VKA were included. Four independent reviewers assessed causality, seriousness and preventability of ADRs using pilot-tested scales. For cases of serious and potentially preventable ADRs, we performed semi-structured interviews with general practitioners to identify contributing factors to ADRs. The primary outcome was the proportion of serious ADRs that were potentially preventable.. The analysis included 46 DOAC and 43 VKA patients (median age 79 years). Gastrointestinal (n = 34) and intracranial (n = 16) bleedings were the most frequent ADRs. Results were that 53% of DOAC- and 61% of VKA-related serious ADRs were deemed potentially preventable. Prescribing issues and inadequate monitoring were frequent for DOAC and VKA respectively. We identified many causes of preventable ADRs that applied to all oral anticoagulants, such as pharmacodynamic drug interactions and lack of communication.. More than half of serious ADRs were potentially preventable for both DOACs and VKAs. Interventions focusing on prescribing, patient education and continuity of care should help improve the use of DOACs in practice.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Continuity of Patient Care; Emergency Service, Hospital; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Intracranial Hemorrhages; Male; Patient Education as Topic; Prospective Studies; Stroke; Thromboembolism; Vitamin K

This study aimed to evaluate the profile of patients hospitalized for anticoagulant-induced hemorrhage. We conducted a retrospective, descriptive study within the Department of Cardiology at the Yalgado Ouedraogo Teaching Hospital, in Ouagadougou, over a period of 2 years from 1 January 2007 to 31 December 2008. All hospitalized patients with anticoagulant-induced hemorrhage were included in the study. The average age of patients was 49,31 ± 17,68 years, the sex-ratio was 2,17. Myocardial infarction was the first indication for anticoagulant treatment, with a rate of 21.05%. Anti vitamin K (AVK) was associated with hemorrhage in 63,16% (n=12) of patients versus 36,84% (n=7) of patients treated with low molecular weight heparins (LMWH); 10 patients had major hemorrhage while nine patients had minor hemorrhage. The average duration of Anti vitamin K (AVK) treatment was 16 ± 58 weeks. Hemorrhage in the digestive tract was the most frequent symptom (31,58%) and, in 89,47% of patients, treatment was associated with platelet aggregation. Treatment of hemorrhagic accident was based on definitive cessation of anticoagulant therapy in 73,68% of patients. Four patients (21.05%) died. The inaccessibility to antidotes such as protamine sulphate and PPSD (Prothrombin, Proconvertine, Stuart factor, and anti-haemophilia B factor) constitutes a real obstacle to adequate treatment for complications; a better education of patients receiving these drugs would be the most important preventive measure, because more than 50% of these accidents are preventable.

Topics: Adult; Aged; Anticoagulants; Antidotes; Burkina Faso; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin, Low-Molecular-Weight; Hospitalization; Hospitals, Teaching; Humans; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Vitamin K; Young Adult

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

Direct-acting oral anticoagulants (DOACs) are used in patients with splanchnic vein thrombosis (SVT) and cirrhosis, but evidence for safety and efficacy in this setting is limited. Our aim was to identify indications and reasons for starting or switching to DOACs and to report adverse effects, complications and short-term outcome.. Data collection including demographic information, laboratory values, treatment and complications through the Vascular Liver Disease Interest Group Consortium.. Forty-five centres (90%) of the consortium completed the initial eCRF. We report here a series of 94 patients from 17 centres. Thirty-six patients (38%) had cirrhosis. Child-Pugh score was 6 (range 5-8), and MELD score 10.2 (range 6-19). Indications for anticoagulation were splanchnic vein thrombosis (75%), deep vein thrombosis (5%), atrial fibrillation (14%) and others (6%). DOACs used were rivaroxaban (83%), dabigatran (11%) and apixaban (6%). Patients were followed up for a median duration of 15 months (cirrhotic) and 26.5 months (non-cirrhotic). Adverse events occurred in 17% of patients and included one case of recurrent portal vein thrombosis and five cases of bleeding. Treatment with DOACs was stopped in three cases. The major reasons for choosing DOACs were no need for monitoring or inadequacy of INR to guide anticoagulation in cirrhotic patients. Renal and liver function did not change during treatment.. A consistent number of patients with SVT and/or cirrhosis are currently treated with DOACs, which seem to be effective and safe. These data provide a basis for performing randomized clinical trials of DOACs vs. low molecular weight heparin or vitamin K antagonists.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Europe; Female; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Splanchnic Circulation; Venous Thrombosis; Vitamin K; Young Adult

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Consensus; Coronary Artery Disease; Drug Substitution; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; Stents; Thrombosis; Vitamin K

The aim of this study was to assess effectiveness and safety of antithrombotics for stroke prevention in non-valvular atrial fibrillation in real-use conditions.. We used a population-based retrospective cohort study. Information emerges from SIDIAP, a database containing anonymized information from electronic health records from 274 primary healthcare centres of the Catalan Health Institute, Catalonia (Spain), with a reference population of 5 835 000 people. Population includes all adults with a new diagnosis of non-valvular atrial fibrillation registered in SIDIAP from 2007 to 2012. The main outcome of antithrombotics' effectiveness was stroke. The main outcomes of safety were cerebral and gastrointestinal haemorrhages. We also estimated all-cause mortality. We used multivariable Cox proportional hazard models to examine association between antithrombotic treatment and main outcomes.. We included 22 205 subjects with non-valvular atrial fibrillation; 40.8% initiated on vitamin K antagonists (VKA), 33.4% on antiplatelets and 25.8% untreated. We found stroke-risk reduction with VKA, hazard ratio (HR) 0.72 (95% confidence interval (CI), 0.58-0.91), also seen in patients with CHADS. This study found a stroke-risk reduction associated with VKA and an increased risk of gastrointestinal bleeding associated with platelet-aggregation inhibitors in comparison with untreated patients. Both antithrombotic groups showed a reduction in all-cause mortality. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Cohort Studies; Databases, Factual; Electronic Health Records; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Primary Health Care; Proportional Hazards Models; Retrospective Studies; Spain; Stroke; Treatment Outcome; Vitamin K

The optimal timing of vitamin K antagonists (VKAs) resumption after an upper gastrointestinal (GI) bleeding, in patients with continued indication for oral anticoagulation, is uncertain. We included consecutive cases of VKA-associated upper GI bleeding from three hospitals retrospectively. Data on the bleeding location, timing of VKA resumption, recurrent GI bleeding and thromboembolic events were collected. A model was constructed to evaluate the 'total risk', based on the sum of the cumulative rates of recurrent GI bleeding and thromboembolic events, depending on the timing of VKA resumption. A total of 121 (58 %) of 207 patients with VKA-associated upper GI bleeding were restarted on anticoagulation after a median (interquartile range) of one (0.2-3.4) week after the index bleeding. Restarting VKAs was associated with a reduced risk of thromboembolism (HR 0.19; 95 % CI, 0.07-0.55) and death (HR 0.61; 95 % CI, 0.39-0.94), but with an increased risk of recurrent GI bleeding (HR 2.5; 95 % CI, 1.4-4.5). The composite risk obtained from the combined statistical model of recurrent GI bleeding, and thromboembolism decreased if VKAs were resumed after three weeks and reached a nadir at six weeks after the index GI bleeding. On this background we will discuss how the disutility of the outcomes may influence the decision regarding timing of resumption. In conclusion, the optimal timing of VKA resumption after VKA-associated upper GI bleeding appears to be between 3-6 weeks after the index bleeding event but has to take into account the degree of thromboembolic risk, patient values and preferences.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Clinical Decision-Making; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Ontario; Proportional Hazards Models; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Sweden; Thromboembolism; Time Factors; Vitamin K

Nonvitamin K antagonist oral anticoagulants (NOACs) are now available for the prevention of stroke in patients with atrial fibrillation (AF) as an alternative to vitamin K antagonists (VKA) and aspirin. The comparative effectiveness and safety in daily practice of these different drug classes is still unclear. The objective of this study was to evaluate the risk of major bleeding and stroke in AF patients using NOACs, VKAs or aspirin.. A retrospective cohort study was conducted among AF patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). New users of VKAs, NOACs and low dose aspirin were followed from the date of first prescription of an antithrombotic drug until the occurrence of stroke or major bleeding. Analyses were adjusted for a history of comorbidities and drug use with Cox regression analysis.. A total of 31 497 patients were eligible for the study. The hazard ratio (HR) of major bleeding was 2.07 [95% confidence interval (CI) 1.27-3.38] for NOACs compared with VKAs, which was mainly attributed by the increased risk of gastrointestinal bleeding (HR 2.63, 95% CI 1.50-4.62). This increased bleeding risk was restricted to women (HR 3.14, 95% CI 1.76-5.60). Aspirin showed a similar bleeding risk as VKAs. NOACs showed equal effectiveness as VKA in preventing ischaemic stroke (HR 1.22, 95% CI 0.67-2.19). VKAs were more effective than aspirin (HR 2.18, 95% CI 1.83-2.59).. NOACs were associated with a higher risk on gastrointestinal bleeding, particularly in women. The use of NOACs in patients who are vulnerable for this type of bleeding should be carefully considered. NOACs and VKAs are equally effective in preventing stroke. Aspirin was not effective in the prevention of stroke in AF.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Young Adult

Topics: Gastrointestinal Hemorrhage; Humans; Intestinal Obstruction; Male; Middle Aged; Tomography, X-Ray Computed; Treatment Outcome; Vitamin K

To examine the long-term persistence and safety of the non-vitamin-K-antagonist oral anticoagulants (NOACs) dabigatran (D), rivaroxaban (R) and apixaban (A) in patients with non-valvular atrial fibrillation (AF) treated in the framework of a well structured, nurse-based AF unit for initiation and follow-up of NOAC.. Retrospective clinical data were collected for 766 consequent patients from a single cardiology outpatient clinic incorporating the AF unit.. The follow-up time, median (q1-q3), was 367 days (183-493) for D patients (n = 233), 432 days (255-546) for R patients (n = 282) and 348 days (267-419) for A patients (n = 251). No significant differences were found between the three groups with regard to age, sex, renal function, or CHA2DS2-VASc score. For all bleeding events the incidence rates per 100 patient-years of follow-up (95% confidence interval [CI], p-value) were reported more often for treatment with R (17.2, 12.7-22.8) than for D (7.0, 4.0-11.3, p = 0.001) and A (8.7, 5.2-13.6, p = 0.013). The differences remained significant after adjustment for clinically relevant variables. Discontinuation rates (n = 167) were lower for A (11.5, 7.5-16.8) than for D (30, 23.4-37.9, p < 0.001) and R (23.9, 18.6-30.1, p = 0.001), and were mainly attributed to drug-specific side effects and bleedings. The majority of discontinued patients (n = 142, 85%) proceeded with other types of oral anticoagulants.. The main limitation of the study is the small patient population with a short follow-up time.. In a retrospective study at a single AF clinic, NOACs showed significantly different bleeding rates and varied discontinuation rates when compared to each other, related mainly to agent-specific side effects and bleedings. The majority of patients that discontinued proceeded with other types of oral anticoagulant.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Dabigatran; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Patient Safety; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Time Factors; Vitamin K

Pathophysiological mechanisms of the vitamin K impact, including those in the gut with ulcerative affection, are studied still insufficiently. Investigations of pharmacogenomics of the vitamin K gives a new approach to therapy in patients, suffering gastro-intestinal hemorrhage. Possibilities of titration of the vitamin K3 (menadione) doses, depending on level of estrogenemia and genetic constitution, concerning genes-candidates ESR1 (rs2234693) and VKORC1 (rs9923231), were studied. There were examined 36 patients, who were treated for the ulcer hemorrhage. The blood serum concentration of estradiol was investigated in accordance to method of solid phase enzyme immunoassay, the genotyping procedure was performed in accordance to indices of polymerase chain reaction with analysis of the restrictional fragments length. The initial daily dose of menadione have constituted 20 mg. After a genotype determination made (first-second day after admittance to hospital) in patients with normoestrogenemia in genotypes CC/GG, CC/GA, CT/GG, CT/GA a vitaminotherapy was prolonged in daily dose of 20 mg, and in a conditionally-pathological variant of genotype the dose of vitamin K was enhanced up to 30 mg. Determination of hormones and the patients' genetic constitution makes possible to apply a personified approach for the vitamin K3 application in the ulcerative hemorrhage.

Topics: Adult; Anticoagulants; Drug Dosage Calculations; Duodenal Ulcer; Estradiol; Estrogen Receptor alpha; Female; Gastrointestinal Hemorrhage; Gene Expression; Genotype; Humans; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Precision Medicine; Stomach Ulcer; Vitamin K; Vitamin K Epoxide Reductases

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

Gastrointestinal bleeding during treatment with non -vitamin K antagonist oral anticoagulants (NOACs) may be caused by malignant lesions Gastrointestinal bleeding due to underlying malignancy may not be uncommon in real life patients on non vitamin K antagonist oral anticoagulants (NOACs) like dabigatran, rivaroxaban or apixaban. We performed a small pilot study in patients referred to endoscopy due to suspected gastrointestinal bleeding. In twenty NOAC-treated patients, we found four cases of manifest malignant colon tumors, one premalignant colon adenoma, and one gastric B-cell lymphoma. All lesions were previously unknown and non-symptomatic apart from suspected gastrointestinal bleeding. Endoscopy should be performed in patients on NOACs with signs or suspicions of gastrointestinal bleeding. Whether a fecal occult blood test should be incorporated in the follow-up of patients on NOAC treatment deserves to be investigated in future studies.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Colonoscopy; Dabigatran; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Male; Pilot Projects; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Vitamin K

Infants may present to the emergency department (ED) with vague complaints worrisome to parents and may initially appear well, despite serious underlying pathology. Whereas sepsis and nonaccidental trauma are high on most providers' diagnostic considerations, we report a case representative of a worrisome trend secondary to the refusal of parenteral vitamin K at birth leading to significant neurologic sequelae.. A 10-week-old boy presented to the ED with gradual increase in fussiness for 2 weeks and new onset of blood flecks in the stool on the day of presentation. Careful physical examination revealed a pale-appearing infant, leading to diagnostic evaluation demonstrating profound anemia and intracranial bleeding. The patient was diagnosed with late-onset vitamin K-deficient bleeding (VKDB) secondary to parental refusal of the vitamin K shot at birth. Why Should Emergency Physicians be Aware of This? Emergency Medicine providers need to add this serious treatable disease into their diagnostic consideration for fussy infants, infants with unexplained bruising or bleeding, or infants with new-onset seizures. Rapid identification of VKDB can lead to prompt treatment and halt the rapid progression of symptoms. Emergency Medicine providers should ask all parents if their infant received parenteral vitamin K in the newborn period, especially if they are exclusively breastfed or born out of the hospital.

Topics: Anemia; Breast Feeding; Gastrointestinal Hemorrhage; Hematoma, Subdural; Humans; Infant; Injections, Intramuscular; Male; Treatment Refusal; Vitamin K; Vitamin K Deficiency Bleeding

The treatment of splanchnic vein thrombosis (SVT) is challenging, due to the increased risk of bleeding and potentially life-threatening complications. Current recommendations are based on evidence from the treatment of venous thrombosis in usual sites, but small observational studies in SVT population suggest that the bleeding risk may offset the benefit of anticoagulant treatment in this setting. The aim of this study was to evaluate the safety of vitamin K antagonists (VKAs) in SVT patients.. We retrospectively included SVT patients treated with VKAs followed by 37 Italian anticoagulation clinics, until June 2013. The primary outcome was the incidence of major bleeding (MB), according to the ISTH definition, during VKA treatment. Vascular events, including both arterial and venous thrombosis, and mortality were also documented.. Three hundred and seventy-five patients were included (median age 53 years; 54.7% males). During a median VKA treatment duration of 1.98 years, 15 MB events occurred, corresponding to an incidence rate of 1.24 (95% confidence interval [CI], 0.75-2.06) per 100 patient-years. Gastrointestinal bleeding represented 40% of all MB events. At multivariate analysis, the presence of esophageal varices emerged as independent predictor of MB (hazard ratio 5.4; 95% CI, 1.4-21.1). The incidence rate of vascular events on treatment was 1.37 (95% CI, 0.84-2.23) per 100 patient-years and the mortality rate was 0.83 (95% CI, 0.44-1.54) per 100 patient-years.. Selected SVT patients followed by anticoagulation clinics for the management of VKA treatment show a low rate of major bleeding and vascular events.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Chi-Square Distribution; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Patient Safety; Proportional Hazards Models; Retrospective Studies; Risk Factors; Splanchnic Circulation; Time Factors; Treatment Outcome; Venous Thrombosis; Vitamin K; Young Adult

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

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antifibrinolytic Agents; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Hemostasis, Endoscopic; Humans; Liver Cirrhosis; Middle Aged; Octreotide; Plasma; Proton Pump Inhibitors; Vitamin K

Upper gastrointestinal bleeding (UGIB) is a potentially life threatening medical emergency requiring an appropriate diagnostic and therapeutic approach. Therefore, the primary focus in a child with UGIB is resuscitation and stabilization followed by a diagnostic evaluation. The differential diagnosis of UGIB in children is determined by age and severity of bleed. In infants and toddlers mucosal bleed (gastritis and stress ulcers) is a common cause. In children above 2 y variceal bleeding due to Extra-Hepatic Portal Venous Obstruction (EHPVO) is the commonest cause of significant UGIB in developing countries as against peptic ulcer in the developed countries. Upper gastrointestinal endoscopy is the most accurate and useful diagnostic tool to evaluate UGIB in children. Parenteral vitamin K (infants, 1-2 mg/dose; children, 5-10 mg) and parenteral Proton Pump Inhibitors (PPI's), should be administered empirically in case of a major UGIB. Octreotide infusion is useful in control of significant UGIB due to variceal hemorrhage. A temporarily placed, Sengstaken-Blakemore tube can be life saving if pharmacologic/ endoscopic methods fail to control variceal bleeding. Therapy in patients having mucosal bleed is directed at neutralization and/or prevention of gastric acid release; High dose Proton Pump Inhibitors (PPIs, Pantoprazole) are more efficacious than H2 receptor antagonists for this purpose.

Topics: Balloon Occlusion; Child; Developing Countries; Diagnosis, Differential; Drug Therapy, Combination; Emergencies; Esophagoscopy; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Hypertension, Portal; India; Interdisciplinary Communication; Oxygen Inhalation Therapy; Proton Pump Inhibitors; Risk Assessment; Severity of Illness Index; Treatment Outcome; Upper Gastrointestinal Tract; Vitamin K; Vitamins

Ileocolic anastomosis is performed using a stapled or manual technique, but with either there is a risk of bleeding from the suture line. The aim of this study was to analyse, retrospectively, bleeding after different anastomotic techniques.. Patients having elective right colectomy were divided, according to the type of ileocolic anastomosis, into Group 1 (circular, double-stapled, end-to-side), Group 2 (linear-stapled, side-to-side) and Group 3 (handsewn, side-to-side). Postoperative lower gastrointestinal bleeding (LGIB) was studied in the three groups. Uni- and multivariate analysis was performed to study risk factors for LGIB and the need for postoperative allogeneic blood transfusion.. Three-hundred and fifty patients were included: 174 in Group 1, 59 in Group 2 and 117 in Group 3. The postoperative LGIB rate was 4.9% and occurred exclusively in Group 1. Five patients had severe anastomotic bleeding. Postoperative blood transfusion was indicated in Groups 1, 2 and 3 in 19.0%, 5.1% and 13.7% of patients. In the five patients with severe bleeding, four attempts of colonoscopic arrest were made, achieving bleeding control in one. Angiographic embolization was successful in one patient. There were no procedure-specific complications.. End-to-side, circular, double-stapling ileocolic anastomosis seems to be related to an increased incidence of anastomotic bleeding and of postoperative blood transfusion compared with patients having other techniques of ileocolic anastomosis.

Topics: Aged; Aged, 80 and over; Anastomosis, Surgical; Anticoagulants; Blood Transfusion; Colectomy; Colon; Colonoscopy; Embolization, Therapeutic; Female; Gastrointestinal Hemorrhage; Humans; Ileum; Male; Middle Aged; Postoperative Hemorrhage; Retrospective Studies; Suture Techniques; Vitamin K

Topics: Aged; Anticoagulants; Colonoscopy; Diagnosis, Differential; Female; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Sigmoid Neoplasms; Venous Thrombosis; Vitamin K

Topics: Aged; Aged, 80 and over; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Palliative Care; Pilot Projects; Treatment Outcome; Vitamin K; Vitamin K Deficiency

Several drug classes are known to be associated with serious upper gastrointestinal bleeding (UGIB), among others NSAID, low-dose acetylsalicylic acid (ASA), vitamin K antagonists (VKA), clopidogrel and selective serotonin reuptake inhibitors (SSRIs). There are few data on how and to what extent these drugs are reintroduced in patients who have been discharged after a bleeding episode related to any of them.. To assess if physicians re-prescribed potential causative drugs after an episode of UGIB and to explore whether drugs with antihaemostatic action (DAHA) are re-prescribed without a gastro-protective agent.. By use of the Kaplan-Meyer method, we estimated the time from UGIB to re-prescribing for 3652 cases who were all admitted to hospital with a diagnosis of serious upper gastrointestinal bleeding from 1995 to 2006. Data on drug exposure were retrieved from a Danish prescription database, a recent study on drug-related UGIB, and The National Board of Health in Denmark.. One-year rates of re-prescribing after UGIB were; 82%, 25%, 43%, 68%, 55%, 71% for SSRIs, NSAID, low-dose ASA, VKA, clopidogrel and dipyridamol, respectively. However, re-prescribing rates without proton pump inhibitors (PPIs) were markedly lower 25%, 3%, 5%, 1%, 17% and 6%, respectively. Non-users of DAHA had a prevalence of PPI use of about 30% a few months after an UGIB.. Drugs with antihaemostatic action are re-prescribed to a large extent after an episode of upper gastrointestinal bleeding, but usually covered by PPIs. This use of PPI is specific for users of drugs with antihaemostatic action.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Drug Prescriptions; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Gastrointestinal Hemorrhage; Hematologic Agents; Humans; Middle Aged; Patient Discharge; Practice Patterns, Physicians'; Proton Pump Inhibitors; Risk Factors; Selective Serotonin Reuptake Inhibitors; Time Factors; Vitamin K

Antiphospholipid syndrome associate thromboembolic events (arterial or venous), and presence of antiphospholipid antibodies, and require anticoagulation. A catastrophic variant may develop, resulting in multiorgan failure, with high mortality rate. This article presented a patient with antiphospholipid syndrome presenting a catastrophic antiphospholipide syndrome after anticoagulation suspending for gastrointestinal bleeding. Multidisciplinary management in intensive care unit and aggressive therapies (corticosteroids, anticoagulation, plasma exchange) were essential to rescue the patient.

Topics: Anemia; Anticoagulants; Antiphospholipid Syndrome; Biopsy; Catastrophic Illness; Gastrointestinal Hemorrhage; Hemoglobins; Hemostatics; Heparin; Humans; Male; Middle Aged; Platelet Count; Respiratory Insufficiency; Vitamin K

Superwarfarins (brodifacoum, difenacoum, bromodialone and chlorphacinone) are anticoagulant rodenticides that were developed in 1970s to overcome resistance to warfarin in rats. A 26-year-old previously healthy man was admitted to the emergency department with epigastric pain, severe upper and lower gastrointestinal haemorrhage, gingival bleeding and melena. The patient stated that he had been healthy with no prior hospital admissions and no personal or family history of bleeding diathesis. The patient, who later admitted attempted suicide, stated that he had taken 400 g rodenticide including brodifacoum orally for five days prior to admission to hospital. He had oral mucosal bleeding, numerous bruises over the arms, legs and abdomen, and an abdominal tenderness, together with melena. Laboratory tests revealed a haemoglobin level of 12.3 g/dl, leucocyte count of 9.1 × 10(9) /l, haematocrit of 28% and platelet count of 280 × 10(9) /l. The prothrombin time (PT) was > 200 s (normal range 10.5-15.2 s) and the activated partial thromboplastin time (aPTT) was 91 s (normal range 20-45 s). The INR (International normalised ratio) was reported to be > 17 (normal range 0.8-1.2). The thrombin time and plasma fibrinogen levels were in the normal range. The results showed the presence of brodifacoum at a concentration of 61 ng/ml, detected by reversed-phase liquid chromatography.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; 4-Hydroxycoumarins; Adult; Animals; Anti-Ulcer Agents; Anticoagulants; Blood Coagulation Disorders; Emergency Service, Hospital; Gastrointestinal Hemorrhage; Humans; Male; Pantoprazole; Partial Thromboplastin Time; Poisoning; Prothrombin; Rats; Rodenticides; Suicide, Attempted; Treatment Outcome; Vitamin K

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

Treatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. In order to elucidate the bleeding risk of users of antiplatelet drugs among users of coumarins, we assessed the odds ratio of major bleeding associated with use of antiplatelet drugs in users of the coumarins acenocoumarol and phenprocoumon. We used data from a Dutch record linkage system, including pharmacy and linked hospitalization records for approximately two million subjects, to conduct a nested case control study in a cohort of new users of coumarins. Cases were patients who were hospitalized with a primary diagnosis of major bleeding while taking coumarin and were matched with up to four control subjects. Conditional logistic regression analysis was used to determine ORs and 95% confidence intervals (CI). We identified 1848 case patients who were matched to 5818 controls. Users of clopidogrel or aspirin showed a significantly increased risk of hospitalization because of major bleeding (OR 2.9, 95% CI 1.2-6.9 and OR 1.6, 95% CI 1.3-1.9, respectively), whereas users of dipyridamole and combinations of antiplatelet drugs showed a strong trend (OR 1.5, 95% CI 1.0-2.3 and OR 1.8, 95 % CI 1.0-3.3, respectively). In all cases, the risks were greater for upper gastrointestinal bleedings than for other bleedings. In conclusion, the use of any antiplatelet drug increases the risk of hospitalization for major bleeding among users of coumarins. Concurrent use of clopidogrel or dipyridamole and coumarins is probably not safer than concurrent use of aspirin and coumarins.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Blood Coagulation; Case-Control Studies; Clopidogrel; Coumarins; Dipyridamole; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hospitalization; Humans; Logistic Models; Male; Medical Records Systems, Computerized; Middle Aged; Netherlands; Odds Ratio; Phenprocoumon; Platelet Aggregation Inhibitors; Risk Assessment; Ticlopidine; Vitamin K

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

The authors report the case of a boy with PFIC type 2 or BRIC type 2 who suffered from liver dysfunction at 2 months after birth.. A liver biopsy specimen revealed mild liver cirrhosis, and the findings resembled those observed in Byler disease. Genetic examination revealed a normal familial intrahepatic cholestasis-1 gene, but a heterozygous mutation for the ABCB11, C1620A (F540L), was observed. Therefore, the patient was initially diagnosed with PFIC type 2. For 3 years after the diagnosis, he had severe pruritus, an increased serum bile acid, and normal serum values of gamma-glutamyl transaminase. At the age of 2, treatment with administration of ursodeoxycholic acid was started; subsequently, a gradual improvement in his liver function was observed. At the age of 3, he suffered from massive intestinal and pulmonary hemorrhage, which improved immediately after the administration of vitamin K. He was then admitted to our hospital for liver transplantation. At 1 month after the admission, his liver dysfunction showed further improvement, except for a mild increase in the serum bile acid level. This condition did not show any change during the 5-year follow-up period. In addition, the patient showed severe growth failure and was diagnosed with growth hormone deficiency. Hence, he receives growth hormone administration.. The patient could be genetically diagnosed with bile salt export pump disease of PFIC type 2 or BRIC type 2. Various clinical features are observed in PFIC or BRIC patients with ABCB11 mutation.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Bile Acids and Salts; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Follow-Up Studies; Gastrointestinal Hemorrhage; Growth Hormone; Humans; Infant; Liver; Male; Mutation, Missense; Phenotype; Polymorphism, Restriction Fragment Length; Ursodeoxycholic Acid; Vitamin K

Topics: Androstanols; Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Antifibrinolytic Agents; Blood Transfusion; Chemical and Drug Induced Liver Injury; Desflurane; Diagnosis, Differential; Fentanyl; Fundoplication; Gastrointestinal Hemorrhage; Humans; Infant; Isoflurane; Liver; Liver Function Tests; Male; Mobius Syndrome; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Remifentanil; Rocuronium; Vitamin K

Topics: Anticoagulants; Celiac Disease; Diagnosis, Differential; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Thromboplastin; Thrombosis; Vitamin K

Topics: Adult; Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Male; Phenprocoumon; Rectal Diseases; Tomography, X-Ray Computed; Vitamin K

Topics: Cholestasis, Intrahepatic; Gastrointestinal Hemorrhage; Humans; Infant; Infant, Newborn; Medical Audit; Retrospective Studies; Vitamin K

Topics: Algorithms; Antithrombin III; Biopsy; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Gastrointestinal Hemorrhage; Humans; Hypersplenism; Hypertension, Portal; Liver; Liver Diseases; Liver Transplantation; Thrombocytopenia; Vitamin K

A review of 127 infants with haemorrhagic disease of the newborn (HDN) is presented. The case definition of HDN used in the selection of patients was bleeding during the 1st week of life in a newborn with normal platelet count, normal peripheral blood smear and complete clinical response to parenteral vitamin K. Equivocal cases with respect to cause of bleeding were excluded. The eligible cases consisted of 0.9% of all admissions to the unit and the male:female ratio was 1.8:1. Most were from families of low economic status and poor educational background. Omission of vitamin K prophylaxis and exclusive breastfeeding were the commonest antecedents. The mean (SE) gestation and admission weight were 39.3 (0.2) weeks and 2981 (78) g, respectively. One hundred and two (80.3%) had classical HDN with a mean (SE) age at onset of 63 (4.4) hours. Gastro-intestinal bleeding was the commonest observation. Thirty-three infants (26%) died, most of them from exsanguination. There is a need for well designed work to determine the magnitude of the problem, including that of late-onset HDN, the antecedent risk factors, the preferred route for administering prophylactic vitamin K and a clear policy guideline on prevention of the disease.

Topics: Body Weight; Breast Feeding; Educational Status; Ethiopia; Female; Gastrointestinal Hemorrhage; Humans; Infant, Newborn; Male; Socioeconomic Factors; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Administration, Oral; Age Factors; Biliary Tract Diseases; Cerebral Hemorrhage; Ecchymosis; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hemothorax; Humans; Infant; Infant, Newborn; Liver Diseases; Male; Sweden; Time Factors; Vitamin K; Vitamin K Deficiency

Topics: Gastrointestinal Hemorrhage; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Milk, Human; Quinones; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

The paper describes 8 cases of delayed haemorrhagic disease caused by vitamin K deficiency, occurring from 16 days to 3 months after birth and observed in 1982-87. All these infants were breast fed and had received no vitamin K prophylaxis. On the basis of these findings, the preventive role of vitamin K in breast fed infants is emphasised.

Topics: Age Factors; Breast Feeding; Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Infant; Infant, Newborn; Male; Vitamin K; Vitamin K Deficiency

The role of Vit. K prophylaxis in preventing haemorrhagic disease of newborn has been well established for many years. Although the opinions differ on a general prophylaxis and selective prophylaxis i.e. prophylaxis only for newborn at risk. In our hospital only the selective Vit. K prophylaxis was administered to newborns during the last 20 years. We observed a marked reduction in the incidence of haemorrhagic disease of newborn, particularly after the availability of neonatal intensive care unit. This could be attributed to the effectiveness of Vit. K prophylaxis and better neonatal care and observation. Hence, the present study, reinforced by the experience of the past emphasise the efficacy and safety of Vit. K prophylaxis in the prevention of haemorrhagic disease of newborn.

Topics: Blood Coagulation Factors; Gastrointestinal Hemorrhage; Humans; Infant, Newborn; Infant, Premature, Diseases; Retrospective Studies; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Blood Coagulation Tests; Blood Transfusion; Gastrointestinal Hemorrhage; Humans; Infant; Lymphangiectasis, Intestinal; Malabsorption Syndromes; Male; Protein-Losing Enteropathies; Shock, Hemorrhagic; Vitamin K; Vitamin K Deficiency

The alcohol withdrawal syndromes are generally self-limited processes from which spontaneous recovery can be anticipated. To achieve this outcome, the various types of withdrawal must be managed in such a way as to prevent the occurrence of life-threatening situations. This begins with a good initial evaluation, followed by the appropriate pharmacologic and behavioral steps to control the severity of withdrawal symptoms and to manage complications. Once the withdrawal process is completed, the patient can then be entered into a long-term treatment program.

Topics: Acute Disease; Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Chloral Hydrate; Ethanol; Folic Acid; Gastrointestinal Hemorrhage; Hallucinations; Humans; Nutrition Disorders; Seizures; Social Support; Substance Withdrawal Syndrome; Thiamine; Vitamin K; Water-Electrolyte Imbalance

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestine, Small; Male; Middle Aged; Prothrombin; Vitamin K

Topics: Cerebral Hemorrhage; Gastrointestinal Hemorrhage; Humans; Infant, Newborn; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Bacteria; Cefamandole; Cephalosporins; Depression, Chemical; Gastrointestinal Hemorrhage; Humans; Intestines; Vitamin K; Vitamin K Deficiency

Topics: Breast Feeding; Gastrointestinal Hemorrhage; Humans; Infant, Newborn; Male; Time Factors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

A bleeding syndrome due to severe prothrombin complex deficiency is reported in 93 infants. Most were breast fed (98 per cent), aged 2 weeks to 1 year and there were no serious preceding or associated diseases. Hemorrhagic diathesis, pallor and mild hepatomegaly were the major manifestations. The incidence of intracr anial bleeding was strikingly high (63 per cent) particularly with subdural and subarachnoid hemorrhage. Acute onset, short course and rapid clinical and laboratory improvement after vitamin K therapy were observed. Mortality rate was 35 per cent but has been reduced to 17 per cent since 1969. The location of bleeding, prompt diagnosis and early treatment are the major factors affecting prognosis. Severe prothrombin complex deficiency due to vitamin K deficiency accounted for the pathogenesis of bleeding. Possible causes of vitamin K deficiency were discussed but definite conclusions could not be drawn.

Topics: Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Male; Subarachnoid Hemorrhage; Syndrome; Vitamin K; Vitamin K Deficiency

Topics: Celiac Disease; Female; Gastrointestinal Hemorrhage; Humans; Intestine, Small; Malabsorption Syndromes; Middle Aged; Vitamin K

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Chronic Disease; Diarrhea, Infantile; Female; Gastrointestinal Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Malabsorption Syndromes; Male; Maternal-Fetal Exchange; Pregnancy; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Topics: Anti-Bacterial Agents; Blood Transfusion; Emergencies; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Microcirculation; Portacaval Shunt, Surgical; Prognosis; Therapeutic Irrigation; Time Factors; Vitamin K

Topics: Aminocaproates; Calcium; Emergencies; Gastrointestinal Hemorrhage; Gluconates; Humans; Peptic Ulcer Hemorrhage; Shock, Hemorrhagic; Transportation of Patients; Vitamin K

A total of 240 cases of a bleeding syndrome in infants due to prothrombin complex deficiency of unknown aetiology were reviewed. The majority of patients were breast fed, aged 1-2 months and the syndrome was more prevalent in males. Clinical manifestations consisted of bleeding, pallor and mild hepatomegaly in the majority of cases. Mild fever, diarrhoea, jaundice, and upper respiratory tract infection were associated in a few patients. Acute onset, short course and a high rate of intracranial bleeding (65%), particularly subdural and subarachnoid, were observed. The haemostatic defects appeared to be a marked reduction in factor II, VII, IX, and X. Complete blood counts remained relatively normal, with the exception of some changes (anaemia, leukocytosis), in response to the acute bleeding. Liver chemistry was normal or slightly impaired. No specific pathological changes were noted at autopsy, there were mild changes of liver cells, such as rare focal necrosis of liver cells, the proliferation of Kupffer cells, extramedullary haemopoeisis and mild cholestasis. Clinical improvement and correction of hemostatic defects were noted after vitamin K therapy alone or with fresh blood transfusion. Mortality rates were high in infants with intracranial bleeding (40-55%), while the overall mortality rate was 25%. The pathogenesis and the possibility of prevention of the syndrome were discussed.

Topics: Blood Coagulation; Blood Coagulation Factors; Breast Feeding; Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Liver; Male; Purpura; Thailand; Vitamin K

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: Adenosine Diphosphate; Blood Coagulation Disorders; Epinephrine; Female; Gastrointestinal Hemorrhage; Humans; Infant, Newborn; Maternal-Fetal Exchange; Platelet Adhesiveness; Pregnancy; Salicylates; Vitamin K

Topics: Adult; Aged; Blood Coagulation Disorders; Coumarins; Diagnosis, Differential; Female; Gastrointestinal Hemorrhage; Hematoma; Hemophilia A; Humans; Intestinal Diseases; Intestine, Small; Jejunum; Male; Middle Aged; Radiography; Vitamin K

Topics: Abdominal Muscles; Anticoagulants; Aspirin; Drug Synergism; Gastrointestinal Hemorrhage; Hematoma; Humans; Peritoneum; Vitamin K

Topics: Anti-Inflammatory Agents; Anticoagulants; Aspirin; Drug-Related Side Effects and Adverse Reactions; Gastrointestinal Hemorrhage; Heparin; Humans; Vitamin K

Topics: Aged; Colonic Diseases; Coumarins; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestinal Obstruction; Intestine, Small; Male; Middle Aged; Radiography; Vitamin K

Topics: Adolescent; Adult; Aged; Antacids; Blood Transfusion; Cardiac Surgical Procedures; Duodenal Ulcer; Female; Gastrectomy; Gastric Lavage; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Peptic Ulcer; Peptic Ulcer Perforation; Stomach Ulcer; Stress, Physiological; Stress, Psychological; Tranquilizing Agents; Vagotomy; Vitamin K

Topics: Adenocarcinoma; Aged; Atrial Fibrillation; Blood Transfusion; Cephalothin; Digoxin; Disseminated Intravascular Coagulation; Gangrene; Gastrointestinal Hemorrhage; Gentamicins; Heparin; Humans; Hydronephrosis; Hypothermia; Lymphatic Metastasis; Male; Prostatic Neoplasms; Pyelonephritis; Stomach Neoplasms; Vitamin K

Topics: Catalysis; Feces; Gastrointestinal Hemorrhage; Hemoglobins; Humans; Infant, Newborn; Meconium; Melena; Oxygen; Polarography; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Adult; Aged; Anti-Bacterial Agents; Anticoagulants; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestinal Diseases; Intestinal Obstruction; Intestine, Small; Male; Middle Aged; Radiography; Vitamin K

Topics: Gastrointestinal Hemorrhage; Humans; Infant, Newborn; Isotonic Solutions; Methods; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Aged; Anticoagulants; Colonic Diseases; Gastrointestinal Hemorrhage; Hematoma; Humans; Male; Prognosis; Prothrombin Time; Time Factors; Vitamin K

Topics: Aminocaproates; Animals; Blood Coagulation; Blood Coagulation Tests; Carbon Tetrachloride Poisoning; Cellulose; Collagen; Gastrointestinal Hemorrhage; Hemorrhage; Hemostatics; Injections, Intravenous; Liver; Powders; Rats; Tissue Extracts; Vitamin K

Topics: Blood Coagulation Disorders; Blood Transfusion; Exchange Transfusion, Whole Blood; Female; Gastrointestinal Hemorrhage; Hemoperitoneum; Humans; Infant, Newborn; Infant, Newborn, Diseases; Laparotomy; Liver; Prothrombin Time; Rupture; Vitamin K

Topics: Aminocaproates; Blood Coagulation Disorders; Blood Transfusion; Duodenal Ulcer; Esophageal and Gastric Varices; Esophagitis; Fibrinogen; Fibrinolysis; Gastritis; Gastrointestinal Hemorrhage; Heparin; Humans; Liver Diseases; Phosphorus Isotopes; Portacaval Shunt, Surgical; Stomach Ulcer; Therapeutic Irrigation; Vasopressins; Vitamin K

Topics: Acute Disease; Ascorbic Acid; Blood Transfusion; Diet; Diet Therapy; Duodenal Ulcer; Endoscopy; Esophageal and Gastric Varices; Gastritis; Gastrointestinal Hemorrhage; Hematemesis; Hernia, Diaphragmatic; Humans; Melena; Myocardial Infarction; Peptic Ulcer Hemorrhage; Radiography; Stomach Neoplasms; Vagotomy; Vitamin K

Topics: Adolescent; Adult; Aged; Anticoagulants; Blood Pressure; Blood Transfusion; Coumarins; Female; Follow-Up Studies; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Heart Diseases; Heparin; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Prothrombin; Thromboembolism; Vitamin K

Topics: Abdomen, Acute; Anticoagulants; Gastrointestinal Hemorrhage; Humans; Vitamin K

Topics: Anti-Bacterial Agents; Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Child; Cystic Fibrosis; Fibrinolysis; Gastrointestinal Hemorrhage; Hemoptysis; Hepatomegaly; Humans; Liver; Liver Function Tests; Lung; Prospective Studies; Prothrombin Time; Splenomegaly; Thrombocytopenia; Thromboplastin; Vitamin K

Topics: Anemia; Angiography; Animals; Cats; Cerebral Hemorrhage; Dogs; Ecchymosis; Embolism; Fever; Gastrointestinal Hemorrhage; Hematoma; Hematuria; Hemorrhage; Hemothorax; Heparin; Humans; Hypotension; Ischemia; Leukocytosis; Shivering; Streptokinase; Thrombosis; Vitamin K

Topics: Aged; Anti-Bacterial Agents; Chloramphenicol; Female; Gastrointestinal Hemorrhage; Humans; Hypoprothrombinemias; Male; Middle Aged; Penicillin G Procaine; Tetracycline; Vitamin K

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: Adult; Afibrinogenemia; Aminocaproates; Ascorbic Acid; Blood Coagulation Tests; Duodenal Ulcer; Fibrinogen; Fibrinolysis; Gastrectomy; Gastrointestinal Hemorrhage; Humans; Male; Rutin; Vitamin K

Topics: Adult; Biopsy; Blood Transfusion; Female; Gastritis; Gastrointestinal Hemorrhage; Humans; Hypothermia, Induced; Shock, Hemorrhagic; Stomach; Stomach Diseases; Vitamin K

Topics: Blood Transfusion; Drug Therapy; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Vitamin K

Topics: Blood Coagulation Factors; Blood Transfusion; Drug Therapy; Gastrointestinal Hemorrhage; Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Melena; Prednisone; Thrombin; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Antacids; Anti-Bacterial Agents; Antibiotics, Antitubercular; Cathartics; Diet; Diet Therapy; Gastric Lavage; Gastrointestinal Hemorrhage; Hemorrhage; Hepatic Encephalopathy; Humans; Parasympatholytics; Pituitary Hormones; Pituitary Hormones, Posterior; Rest; Serum Albumin; Shock; Shock, Hemorrhagic; Statistics as Topic; Tranquilizing Agents; Vitamin K; Vitamin K 1; Water-Electrolyte Balance

Topics: Ammonia; Anti-Bacterial Agents; Antibiotics, Antitubercular; Blood; Diuretics; Gastrointestinal Hemorrhage; Hemorrhage; Hepatic Encephalopathy; Humans; Infections; Physiology; Shock, Hemorrhagic; Vitamin K; Vitamins

Topics: Alcoholism; Anemia; Anemia, Hypochromic; Avitaminosis; Cholestyramine Resin; Common Bile Duct; Diet; Diet Therapy; Diuretics; Folic Acid; Folic Acid Deficiency; Gastrointestinal Hemorrhage; Humans; Hydrochlorothiazide; Ion Exchange Resins; Jaundice; Liver Cirrhosis; Liver Cirrhosis, Biliary; Postoperative Complications; Prothrombin Time; Vitamin B 12; Vitamin B Complex; Vitamin K

Topics: Appendicitis; Blood Transfusion; Gastrointestinal Hemorrhage; Humans; Intestinal Perforation; Paratyphoid Fever; Peptic Ulcer; Peritonitis; Surgical Procedures, Operative; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vitamin K

Topics: Aspirin; Gastrointestinal Hemorrhage; Gastrointestinal Tract; Hemorrhage; Humans; Vitamin K