warfarin and Kidney-Failure--Chronic

Optimal anticoagulation in patients with end-stage renal disease ESRD is a matter of debate since these patients are not included in randomized controlled trials (RCTs). Evolving data are in favor of apixaban compared to warfarin.. We extracted data from 2 RCTs, 5 retrospective cohort studies and 3 large data-based studies. Both dosing regimens of apixaban, standard or reduced, were accepted. In most studies characteristics of patients were balanced between arms. Patients with either atrial fibrillation (AF) or venous thromboembolism (VTE) were included. Quality of studies was graded as high and the funnel plot did not detect any publication bias. In total we analyzed the outcome of 6693 ESRD patients treated with apixaban and 19,836 treated with warfarin. Our analysis was performed by using the random effects model. We report our data as Risk Ratio (RR) and associated 95 % confidence interval values (95 %, CI).. The RR (95 % CI) of major bleeding was 0.69 (0.57-0.84) p = 0.0002 in favor of apixaban vs warfarin with heterogeneity to be statistically significant I. In our study we observed less hemorrhagic events with apixaban in ESRD patients compared to warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kidney Failure, Chronic; Pyridones; Randomized Controlled Trials as Topic; Venous Thromboembolism; Warfarin

The frequent coexistence in daily clinical practice of chronic kidney disease (CKD) and atrial fibrillation (AF), especially in the elderly, represents a conundrum for physicians, mainly related to the management of anticoagulant therapy. The reduction of estimated glomerular filtration rate (eGFR) impairs anticoagulant clearance, increasing bleeding propensity. Moreover, dysfunctional responses of endothelial cells and inflammatory systems both trigger thromboembolic status. Those mechanisms pose an increased risk of adverse events for AF patients with CKD. While several data suggested the use of direct oral anticoagulants (DOACs) over warfarin as preferred anticoagulant strategy in patients with Stage 3A to Stage 4 CKD (eGFR range of 15-49 mL/min/1.73 m2), less is known about the optimal anticoagulation management in patients with end-stage renal disease (ESRD) or on renal replacement therapy (RRT). Furthermore, a pivotal feature to be considered when choosing the anticoagulant drug in CKD patients is represented by nephroprotective capability. Indeed, anticoagulant therapy with warfarin showed detrimental effects on kidney function, whereas DOACs demonstrated a beneficial effect on renal function preservation. Mounting data showed that, when pharmacological treatment cannot be pursued due to contraindication to anticoagulation, left atrial appendage occlusion (LAAO) may represent a valid alternative. This brief review outlines the current knowledge regarding anticoagulation therapy in ESRD/RRT patients, reporting new lines of evidence on the nephroprotective effect of oral anticoagulants and on the use of LAAO as a non-pharmacological alternative to oral anticoagulation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Endothelial Cells; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Stroke; Warfarin

Up to 20% of patients with chronic kidney disease have atrial fibrillation, and 40%-50% of atrial fibrillation patients suffer from chronic kidney disease. The 2 diseases share several risk factors and frequently coincide with each other. Both entities are associ ated with a prothrombotic state, which contributes to increased thromboembolic risk. Atrial fibrillation patients with chronic kidney disease have elevated risk of stroke, major bleeding, and mortality. Clinical risk scores, including CHA2DS2-VASc score, HAS-BLED score, or ORBIT score have a limited value in adverse clinical outcome risk stratification in patients with severe chronic kidney disease. However, the inclusion of renal function in the R(2)-CHA2DS2-VASc score does not improve significantly thromboembolic risk predic tion in atrial fibrillation. There is growing evidence suggesting that biomarkers, including N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin, cystatin C, or growth differentiation factor-15, might be helpful in the assessment of thromboembolic, bleeding, and/or mortality risk in atrial fibrillation patients with chronic kidney disease. The first-choice anticoagulant therapy is based on direct oral anticoagulants in this subgroup. The highest risk of adverse events is observed in end-stage renal disease, and in Europe, in contrast to the USA, solely warfarin is recommended in such atrial fibrillation patients. Treatment of atrial fibrillation patients with chronic kidney disease should be closely moni tored with the selection of right anticoagulant agents at the appropriate dose. The current review paper summarizes available evidence and the challenges of the management of atrial fibrillation patients with chronic kidney disease with practical implications.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Warfarin

Background Non-vitamin K antagonist oral anticoagulants (NOACs) have better pharmacologic properties than warfarin and are recommended in preference to warfarin in most patients with non-valvular atrial fibrillation. Besides lower bleeding complications, other advantages of NOACs over warfarin particularly renal outcomes remain inconclusive. Methods and Results Electronic searches were conducted through Medline, Scopus, Cochrane Library databases, and ClinicalTrial.gov. Randomized controlled trials and observational cohort studies reporting incidence rates and hazard ratio (HR) of renal outcomes (including acute kidney injury, worsening renal function, doubling serum creatinine, and end-stage renal disease) were selected. The random-effects model was used to calculate pooled incidence and HR with 95% CI. Eighteen studies were included. A total of 285 201 patients were enrolled, 118 863 patients with warfarin and 166 338 patients with NOACs. The NOACs group yielded lower incidence rates of all renal outcomes when compared with the warfarin group. Patients treated with NOACs showed significantly lower HR of risk of acute kidney injury (HR, 0.70, 95% CI, 0.64-0.76;

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Biomarkers; Creatinine; Humans; Kidney; Kidney Failure, Chronic; Stroke; Warfarin

The use of warfarin in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) has been implicated with efficacy and safety concerns. Evidence on the role of direct oral anticoagulants (DOACs) in this population is limited.. Electronic databases were searched and articles comparing the safety and efficacy of warfarin with apixaban or rivaroxaban were identified. Pooled hazard ratios (HR) were computed using a random-effects model.. A total of eight articles consisting of 30,806 patients; (rivaroxaban 2196, apixaban 2745 and warfarin 25,865) were identified. The pooled HR for major bleeding events favored apixaban over warfarin (0.53, 95% confidence interval (CI) 0.33-0.84, p = 0.008). Apixaban was similar to warfarin in terms of clinically relevant non-major bleeding (HR 1.08, 95% CI 0.64-1.84, p = 0.77) and stroke events (HR 1.09, 95% CI 0.85, 1.39, p = 0.99). There was no significant difference in the risk of major bleeding events (HR 0.95, 95% CI 0.50-1.81, p = 0.88) and stroke between rivaroxaban (HR 1.39, 95% CI, 0.59-3.29, p = 0.09) and warfarin. The combined results of major bleeding in the apixaban group were not affected by the sensitivity analysis.. Apixaban may have a lower risk of major bleeding and comparable risk of stroke when compared with warfarin in AF patients with ESRD.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Warfarin

Several studies have examined the role of warfarin in preventing strokes in patients with atrial fibrillation and end-stage renal disease; however, the results remain inconclusive.. To assess recently published studies to examine the outcomes of the use of warfarin among patients with atrial fibrillation and end-stage renal disease.. A literature search was performed using the terms warfarin and atrial fibrillation and end-stage renal disease and warfarin and atrial fibrillation and dialysis in the MEDLINE, Embase, and Google Scholar databases from January 1, 2008, to February 28, 2019.. The studies included were those with patients with end-stage renal disease and atrial fibrillation who were receiving warfarin and with hazard ratios (HRs) of at least 1 primary outcome. The studies excluded were those with a lack of information on outcomes and unreliable 95% CIs of the results.. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed in selecting studies. Collected data were also scrutinized for reliable 95% CIs. Finally, studies were examined for perceived biases, their limitations, and the definitions of the outcomes.. The HRs and 95% CIs were calculated for the incidence of ischemic stroke, hemorrhagic stroke, major bleeding, and mortality among patients receiving anticoagulants and those not receiving anticoagulants.. Study selection yielded 15 studies with a total of 47 480 patients with atrial fibrillation and end-stage renal disease. Of these patients, 10 445 (22.0%) were taking warfarin. With a mean (SD) follow-up period of 2.6 (1.4) years, warfarin use was associated with no significant change for the risk of ischemic stroke (HR, 0.96; 95% CI, 0.82-1.13), with a significantly higher risk of hemorrhagic stroke (HR, 1.49; 95% CI, 1.03-1.94), with no significant difference in the risk of major bleeding (HR, 1.20; 95% CI, 0.99-1.47), and with no change in overall mortality (HR, 0.95; 95% CI, 0.83-1.09).. In the studies reviewed, warfarin use appears to have been associated with no change in the incidence of ischemic stroke in patients with atrial fibrillation and end-stage renal disease. However, from the studies reviewed, it does appear to be associated with a significantly higher risk of hemorrhagic stroke, with no significant difference in the risk of major bleeding, and with no change in mortality.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Stroke; Treatment Outcome; Warfarin

Direct oral anticoagulants (DOACs) have been shown to be superior to vitamin K antagonists (VKAs) in regards to safety and efficacy in numerous clinical trials and are now the preferred oral anticoagulant by multiple professional societies. However, patients with significant levels of organ dysfunction were excluded from all major clinical trials, leaving the clinical benefit in these subsets uncertain. Patients with chronic kidney disease (CKD) specifically often require anticoagulation for acute or long-term indications such as venous thromboembolism, atrial fibrillation, or mechanical heart valves. The efficacy and safety of anticoagulation in patients with renal failure is less certain, however, particularly with DOACs which have altered pharmacokinetics in patients with renal failure and limited observational data on their use in this population. In this review, we compile the most up to date data on the DOAC use in patients with CKD. DOAC use in patients with ESRD and advanced CKD is increasing despite the presence of a clear benefit, and with the potential for increased risk of bleeding compared to warfarin. Apixaban has the greatest amount of outcomes research supporting its use over warfarin in this patient population; however, further research on DOAC safety and efficacy in those with advanced CKD is still needed.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Europe; Hemorrhage; Humans; Kidney Failure, Chronic; Kidney Function Tests; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Severity of Illness Index; United States; Warfarin

Warfarin is the most commonly prescribed anticoagulant in hemodialysis (HD) patients with nonvalvular atrial fibrillation (NVAF). Recent trends show that Nephrologists are increasingly prescribing novel oral anticoagulants, despite the fact that no randomized clinical trials have been conducted in dialysis patients. Difficulties maintaining international normalized ratio in the therapeutic range, increased risk of intracranial hemorrhage and concerns regarding warfarin-induced vascular calcification and calciphylaxis may be responsible. Anticoagulation quality is poor in HD patients. A variety of factors contribute to this: increased antibiotic exposure; comorbid illness; decreased adherence and vitamin K deficiency. Attempts to address this with standardized protocols have been uniformly unsuccessful. In nonadherent patients, thrice weekly observed therapy improved quality. Low-dose vitamin K supplementation improves time in the therapeutic range (TTR) in those with normal kidney function and should be studied in HD patients given their high frequency of vitamin K deficiency. Vascular and valvular calcification associated with warfarin could result from reduced carboxylation of matrix Gla protein (MGP), a well-known inhibitor of vascular calcification. Multiple observational studies also link calciphylaxis to warfarin; warfarin-induced hypercoagulability and decreased carboxylation of MGP could explain this. A large observational study, two meta-analyses, and a systematic review in HD patients with NVAF showed reduced bleeding with apixaban compared to warfarin with similar efficacy in reducing stroke and systemic embolism. Given these results, apixaban is a reasonable alternative to warfarin for anticoagulation of HD patients with NVAF, especially in those with low TTR, until data from randomized clinical trials become available.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Cause of Death; Drug Substitution; Female; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Needs Assessment; Pyrazoles; Pyridones; Renal Dialysis; Risk Assessment; Stroke; Survival Rate; Treatment Outcome; Warfarin

The role of oral anticoagulants (OAC) in atrial fibrillation (AF) is well established. However, none of the randomized controlled trials included patients with end-stage renal disease (ESRD) leaving a lack of evidence in this large, challenging and unique patient group. Patients on hemodialysis (HD) with AF have additional risk factors for stroke due to vascular comorbidities, HD treatment, age, and diabetes. Conversely, they are also at increased risk of major bleeding due to uremic platelet impairment. Anticoagulants increase bleeding risk in patients with ESRD and HD up to 10-fold compared with non chronic kidney disease (CKD) patients on warfarin. There are conflicting data and recommendations regarding use of OACs in ESRD which will be reviewed in this article. We conclude by proposing a modified strategy for OAC use in ESRD based on the latest evidence.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Decision-Making; Hemorrhage; Humans; Kidney; Kidney Failure, Chronic; Patient Selection; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

At the present, apixaban is the only nonvitamin K oral anticoagulant approved by the Food and Drug Administration for use with patients with creatinine clearance <15 mL/min or end-stage renal disease (ESRD). However, the recommendations are based on pharmacokinetic and pharmacodynamic data and there was lack of clinical trial evidence. We aimed to assess safety and efficacy of apixaban in patients with advanced chronic kidney disease (CKD) or ESRD.. Databases were searched through November 2017. Studies that reported incidence or odd ratios of bleeding complications or thromboembolic events in the use of apixaban in patients with CKD stage 4-5 or ESRD on dialysis were included. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird.. Five studies were included into the analysis consisting of 43,850 patients in observational cohort studies. The majority of patients (87%) used apixaban for atrial fibrillation. The pooled estimated incidence of any bleeding complications on apixaban was 17.4% (95% confidence interval [CI]: 13.0%-23.0%). Compared to warfarin, apixaban was significantly associated with reduced risk of major bleeding (pooled odds ratio [OR], 0.42; 95% CI, 0.28-0.61). In studies in ESRD patients on dialysis, the pooled OR of major bleeding was 0.27 (95% CI, 0.07-0.95). There was no significant difference in risk of thromboembolic events in advanced CKD or ESRD patients on apixaban versus vitamin K antagonists (pooled OR, 0.56; 95% CI, 0.23-1.39).. Among patients with advanced CKD and ESRD, the use of apixaban was associated with lower risk of major bleeding compared to warfarin, and was found to be relatively effective with no excess risk of thromboembolic events.

Topics: Anticoagulants; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Thromboembolism; Thrombosis; Warfarin

Anticoagulation in patients with advanced kidney disease, defined as those with an eGFR < 25 mL/min, including patients with end-stage renal disease on hemodialysis, remains an area of controversy and debate. Due to safety concerns regarding the increased risk for bleeding in this population, these patients have been excluded from all large-scale, randomized controlled trials to date. Warfarin and apixaban are both FDA-approved for use in this population and although warfarin remains the anticoagulant of choice, apixaban use is steadily increasing. This review combines relevant literature to better understand the risk versus benefit of anticoagulation in patients with severe kidney disease as well as the safety of apixaban versus warfarin in this population. High rates of bleed were found among both anticoagulants in those with severe kidney disease, suggesting that the risk for bleed associated with anticoagulation may not outweigh the benefit of treatment. Apixaban was found to be superior in rates of major bleed in those with ESRD on HD and may be superior to warfarin in those with an eGFR < 25 mL/min. However, large-scale, randomized clinical trials are needed to validate these results. With the continued development of novel agents there may be superior alternatives to apixaban and warfarin in those with severe kidney disease in the future.

Topics: Anticoagulants; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Risk Assessment; Warfarin

Patients with end-stage kidney disease (ESKD) have an elevated incidence of atrial fibrillation (AF) and are at increased risk for thromboembolic events. However, these patients are also at increased risk for bleeding and it is unclear whether they benefit from an oral anticoagulant. Point prevalent on July 1, 2015, only ~28% of dialysis patients with AF were on oral anticoagulation. Warfarin was the most commonly used oral anticoagulant, followed by apixaban, while dabigatran and rivaroxaban were rarely used. This article reviews the current evidence regarding each oral anticoagulant especially as they relate to patients with ESKD.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridines; Pyridones; Renal Dialysis; Rivaroxaban; Thiazoles; Thromboembolism; Warfarin

Patients with atrial fibrillation who receive dialysis are at a high risk of ischemic stroke. The role of warfarin in mitigating this risk in patients with atrial fibrillation who receive dialysis is uncertain. Our objective was to examine the safety and efficacy of warfarin in patients who have atrial fibrillation and receive dialysis.. We used MedLine, Embase, and the Cochrane Library to conduct a systematic review and meta-analysis of published and unpublished observational and interventional studies related to the use of warfarin in patients with atrial fibrillation who receive dialysis, and provided data on the risk of stroke and/or bleeding outcomes relative to placebo or no anticoagulation therapy. A random effects model was used to calculate pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for these outcomes.. No randomized controlled trials met the criteria for inclusion. Fourteen observational studies (20,398 participants) were included in the analysis. The use of warfarin was not associated with ischemic stroke (14 studies; 20,398 participants; aHR, 0.77; 95% CI, 0.55-1.07), intracranial hemorrhage (hemorrhagic stroke; 4 studies; 15,726 participants; aHR, 1.93; 95% CI, 0.93-4.00), gastrointestinal bleeding (3 studies; 14,693 participants; aHR, 1.19; 95% CI, 0.8-1.76), or all-cause mortality (7 studies; 16,172 participants; aHR, 0.89; 95% CI, 0.72-1.11).. Observational studies suggest that warfarin was not associated with a clear benefit or harm among patients who have atrial fibrillation and receive dialysis. These estimates were limited by study heterogeneity including the inability to account for a number of important confounders such as the time in the therapeutic range. Because of the high prevalence of atrial fibrillation, stroke, and bleeding complications in this population, well designed clinical trials of warfarin and other anticoagulants are urgently needed.

Topics: Anticoagulants; Atrial Fibrillation; Global Health; Hemorrhage; Humans; Incidence; Kidney Failure, Chronic; Renal Dialysis; Stroke; Warfarin

The use of vitamin K antagonists (VKAs) in hemodialysis patients with atrial fibrillation (AF) is controversial. No randomized trials are available and observational studies have yielded conflicting results, engendering a large clinical practice variability and physician uncertainty. An unresolved but highly relevant question is whether AF poses a true risk of ischemic stroke in hemodialysis and whether any form of oral anticoagulation is therefore warranted.. We conducted a systematic review of studies that compared the incidence of ischemic stroke and bleeding in hemodialysis patients with AF taking VKA and those not taking VKA. When hemodialysis patients had been pooled with peritoneal dialysis, kidney transplant, or stage V chronic kidney disease patients, unpublished outcome data of the hemodialysis subgroup were obtained through personal communication. The main outcome measures were ischemic stroke/thromboembolic events, all-cause mortality, major bleeding, and hemorrhagic stroke. Combined hazard ratios (HRs) and 95% CIs were calculated using a random-effects model.. Twelve prospective or retrospective cohort studies were included in the meta-analysis, totaling 17,380 hemodialysis patients of whom 4,010 (23.1%) received VKA. In VKA-treated patients, mean CHADS. Our meta-analysis revealed a trend for a reduction of the risk of ischemic stroke in hemodialysis patients with AF treated with VKA. The true protective effect may have been underestimated, owing to inclusion of low-risk patients not expected to benefit from anticoagulation and to suboptimal anticoagulation. However, assessment of the overall effect of VKA in hemodialysis patients should also take into account the increased risk of bleeding, in particular of hemorrhagic stroke. Whether new oral anticoagulants provide a better benefit-risk ratio in hemodialysis patients should be the subject of future trials.

Topics: Anticoagulants; Atrial Fibrillation; Cause of Death; Cerebral Hemorrhage; Hemorrhage; Humans; Kidney Failure, Chronic; Mortality; Proportional Hazards Models; Renal Dialysis; Stroke; Thromboembolism; Vitamin K; Warfarin

The use of warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) can be problematic because of increased bleeding risk. We performed a systematic review and meta-analysis of observational studies that evaluated the use of warfarin in patients with AF and CKD to evaluate the risks of ischemic stroke/thromboembolism, major bleeding, and mortality.. PUBMED, EMBASE, CINAHL, ProQuest, and Google Scholar databases were electronically searched through January 12, 2015. Additionally, a manual search was performed for relevant references. Random-effects model was used to estimate the pooled hazard ratio (HR) with 95% CI. CKD was divided into non-end-stage CKD and end-stage CKD (on renal replacement therapy) and separate analyses were performed.. Thirteen publications from 11 cohorts (six retrospective and five prospective) including >48,500 total patients with >11,600 warfarin users were included in the meta-analysis. In patients with AF and non-end-stage CKD, warfarin resulted in a lower risk of ischemic stroke/thromboembolism (HR, 0.70; 95% CI, 0.54-0.89; P = .004) and mortality (HR, 0.65; 95% CI, 0.59-0.72; P < .00001), but had no effect on major bleeding (HR, 1.15; 95% CI, 0.88-1.49; P = .31). In patients with AF and end-stage CKD, warfarin had no effect on the risks of stroke (HR, 1.12; 95% CI, 0.69-1.82; P = .65) and mortality (HR, 0.96; 95% CI, 0.81-1.13; P = .60), but increased the risks of major bleeding (HR, 1.30; 95% CI, 1.08-1.56; P = .005).. Based on this meta-analysis, the use of warfarin for AF may have an unfavorable risk/benefit ratio in patients with end-stage CKD but not in those with non-end-stage CKD.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kidney Failure, Chronic; Mortality; Proportional Hazards Models; Renal Insufficiency, Chronic; Renal Replacement Therapy; Risk Assessment; Stroke; Warfarin

The purpose of this review article is to summarize the literature on diseases that are documented to have an effect on response to warfarin and other VKAs.. We searched the English literature from 1946 to September 2015 via PubMed, EMBASE, and Scopus for the effect of diseases on response vitamin K antagonists including warfarin, acenocoumarol, phenprocoumon, and fluindione.. Among many factors modifying response to VKAs, several disease states are clinically relevant. Liver disease, hyperthyroidism, and CKD are well documented to increase response to VKAs. Decompensated heart failure, fever, and diarrhea may also elevate response to VKAs, but more study is needed. Hypothyroidism is associated with decreased effect of VKAs, and obese patients will likely require higher initial doses of VKAs.. In order to minimize risks with VKAs while ensuring efficacy, clinicians must be aware of the effect of disease states when prescribing these oral anticoagulants.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Cardiovascular Diseases; Diarrhea; Fibrinolytic Agents; Heart Failure; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Diseases; Obesity; Phenindione; Phenprocoumon; Vitamin K; Warfarin

Atrial fibrillation (AF) is a frequent clinical complication in dialysis patients, and warfarin therapy represents the most common approach for reducing the risk of stroke in this population. However, current evidence based on observational studies, offer conflicting results, whereas no randomized controlled trials have been carried out so far. Additionally, many clinicians are wary of the possible role of warfarin as vascular calcification inducer and its potential to increase the high risk of bleeding among patients on dialysis. Ideally the most promising therapy would be based on direct inhibitors of factor IIa or Xa; however, at the moment, none of these drugs can be safely prescribed in dialysis patients, because of their potentially dangerous accumulation, and the lack of sufficient experience with apixaban or rivaroxaban, two drugs showing a favorable pharmacokinetic profile in end-stage renal disease. Hence, the use of vitamin K inhibitors is currently the only pharmacological option for stroke prevention in dialysis patients with atrial fibrillation, leaving the clinicians in a management conundrum.This review discusses the trade-offs implicated in warfarin use for this population, the promises of newly developed drugs, the role of dialysis as atrial fibrillation trigger, as well as potential non-pharmacological management options suitable in selected clinical situations.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Renal Dialysis; Stroke; Warfarin

Nonvitamin K-dependent oral anticoagulant agents (NOACs) are currently recommended for patients with atrial fibrillation at risk for stroke. As a group, NOACs significantly reduce stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with warfarin. All NOACs are dependent on the kidney for elimination, such that patients with creatinine clearance <25 ml/min were excluded from all the pivotal phase 3 NOAC trials. It therefore remains unclear how or if NOACs should be prescribed to patients with advanced chronic kidney disease and those on dialysis. The authors review the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <30 ml/min) and those on dialysis. The authors frame the evidence in terms of risk versus benefit to bring greater clarity to NOAC-related major bleeding and efficacy at preventing stroke specifically in patients with creatinine clearance <30 ml/min.

Topics: Anticoagulants; Atrial Fibrillation; Creatinine; Dabigatran; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Kidney Failure, Chronic; Pyrazoles; Pyridines; Pyridones; Renal Dialysis; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Thiazoles; Warfarin

Patients with end stage renal disease (ESRD), including stage 5 chronic kidney disease (CKD), hemodialysis (HD) and peritoneal dialysis (PD), are at high risk for stroke-related morbidity, mortality and bleeding. The overall risk/benefit balance of warfarin treatment among patients with ESRD and AF remains unclear.. We systematically reviewed the associations of warfarin use and stroke outcome, bleeding outcome or mortality in patients with ESRD and AF. We conducted a comprehensive literature search in Feb 2016 using key words related to ESRD, AF and warfarin in PubMed, Embase and Cochrane Library without language restriction. We searched for randomized trials and observational studies that compared the use of warfarin with no treatment, aspirin or direct oral anticoagulants (DOACs), and reported quantitative risk estimates on these outcomes. Paired reviewers screened articles, collected data and performed qualitative assessment using the Cochrane Risk of Bias Assessment Tool for Non-randomized Studies of Interventions. We conducted meta-analyses using the random-effects model with the DerSimonian - Laird estimator and the Knapp-Hartung methods as appropriate.. We identified 2709 references and included 20 observational cohort studies that examined stroke outcome, bleeding outcome and mortality associated with warfarin use in 56,146 patients with ESRD and AF. The pooled estimates from meta-analysis for the stroke outcome suggested that warfarin use was not associated with all-cause stroke (HR = 0.92, 95 % CI 0.74-1.16) or any stroke (HR = 1.01, 95 % CI 0.81-1.26), or ischemic stroke (HR = 0.80, 95 % CI 0.58-1.11) among patients with ESRD and AF. In contrast, warfarin use was associated with significantly increased risk of all-cause bleeding (HR = 1.21, 95 % CI 1.01-1.44), but not associated with major bleeding (HR = 1.18, 95 % CI 0.82-1.69) or gastrointestinal bleeding (HR = 1.19, 95 % CI 0.81-1.76) or any bleeding (HR = 1.21, 95 % CI 0.99-1.48). There was insufficient evidence to evaluate the association between warfarin use and mortality in this population (pooled risk estimate not calculated due to high heterogeneity). Results on DOACs were inconclusive due to limited relevant studies.. Given the absence of efficacy and an increased bleeding risk, these findings call into question the use of warfarin for AF treatment among patients with ESRD.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kidney Failure, Chronic; Renal Dialysis; Stroke; Warfarin

Among patients with atrial fibrillation, prophylaxis for stroke prevention with the use of anticoagulation is well established in the general population. A number of randomized controlled trials and evidence-based risk prediction tools clearly delineate the benefit and risks of therapy. Despite the high incidence of atrial fibrillation in the late stage CKD and ESRD populations, little high quality evidence exists in these populations. Is it appropriate then to extrapolate findings from the general population to those with CKD/ESRD? In our view, too much uncertainty exists regarding proof of efficacy with clear signals of harm. Routine anticoagulation for stroke prevention in atrial fibrillation is not recommended for the majority of CKD and ESRD patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Stroke; Warfarin

In routine practice, warfarin is widely used in dialysis patients with atrial fibrillation (AF) for stroke prevention though the ratio of risks to benefits remains unclear. Recent cohort studies investigating the association between warfarin use and the risks of stroke and bleeding in dialysis patients with AF present conflicting results. The objective of this study was to assess the effectiveness and safety of warfarin use in patients with AF undergoing dialysis. Three databases PubMed, EMBASE, and OVID were searched from their inception to August 2015. Observational studies which assessed the ischemic stroke or bleeding risk of warfarin use in dialysis patients with AF were included. Two reviewers independently extracted data and assessed methodological quality based on the Newcastle-Ottawa Scale score. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model and heterogeneity was assessed based on the Cochrane Q-statistic test and the I statistic. Metaregression analyses were performed to explore the source of heterogeneity. A total of 11 eligible studies with 25,407 patients were included in the analysis. Warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for ischemic stroke (HR 0.95, 95% CI 0.66-1.35). Sensitivity analyses found results to be robust. Metaregression analysis showed that demographic feature, clinical characteristics, or study-level variable had no impact of warfarin use on stroke risk. In addition, warfarin use was associated with a 27% higher risk for bleeding (95% CI 1.04-1.54). Overall, warfarin use did not have a significant association with reduced mortality (95% CI 0.96-1.11). It appears that warfarin use is not beneficial in reducing stroke risk, but with a high risk for bleeding in dialysis patients with AF. Randomized trials are needed to determine the risk-benefit ratio of warfarin in dialysis patients with AF.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Observational Studies as Topic; Renal Dialysis; Risk Assessment; Stroke; Warfarin

Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for antiphospholipid antibodies (aPLs). APS can be isolated (known as primary APS) or associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE; known as secondary APS). The kidney is a major target organ in APS and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal arteries, glomerular capillaries and renal veins); events reflect the site and size of the involved vessels. Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal prognosis is affected by the presence of aPLs in patients with lupus nephritis and can be poor. In patients with SLE and aPLs, biopsy should be performed because inflammatory and thrombotic lesions require different therapeutic approaches. Renal involvement in patients with definite APS is treated by anticoagulation with long-term warfarin. The range of renal manifestations associated with APS is broadening and, therefore, aPLs have increasing relevance in end-stage renal disease, transplantation and pregnancy.

Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Female; Humans; Infarction; Kidney; Kidney Diseases; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Lupus Nephritis; Middle Aged; Pregnancy; Renal Veins; Thrombosis; Warfarin

Incidence and prevalence of atrial fibrillation (AF) is higher in haemodialysis (HD) population than general population. AF is associated with higher morbidity and mortality than sinus rhythm in this population. The purpose of this review is to summarize all available evidence regarding use of warfarin in HD patients with AF for stroke prevention. The enormous heterogeneity of available studies does not allow pooling of the data in the form of meta-analysis or systematic review. Current evidence regarding use of warfarin for AF in terms of risk benefit ratio in this population is limited and conflicting. Randomized control trials evaluating the safety and efficacy of anticoagulation in this population by means of risk/benefit assessment tools are urgently needed. However, suitable HD patients with AF should be counselled on their likelihood of reduction of stroke risk and experiencing side-effects before initiating anticoagulant therapy. It is particularly important to incorporate the patient's preferences and willingness to trade off benefit and risk in stroke prevention. An individualized holistic approach optimizing all potential risk factors of bleeding and ischemic stroke in HD patients with AF is recommended.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kidney Failure, Chronic; Prevalence; Renal Dialysis; Risk Assessment; Stroke; Warfarin

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Azetidines; Cardiomyopathies; Ezetimibe; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Risk; Seizures; Simvastatin; Ultrasonography; Warfarin

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Electric Countershock; Factor Xa Inhibitors; Humans; Kidney Failure, Chronic; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Warfarin

The reported incidence, prevalence and outcomes of atrial fibrillation (AF) in patients with end-stage renal disease (ESRD) are variable. The risks and benefits of warfarin anticoagulation need to be defined as the risk of bleeding in ESRD patients may overwhelm the benefits of embolic stroke prevention. We undertook a systematic literature review to clarify these issues.. A literature search was undertaken using Medline and EMBASE from 1990 to September 2011. Studies that reported incidence, prevalence or selected outcomes in ESRD patients with AF were included. Cross-sectional, cohort and randomized controlled trials with >25 participants were included. The lists of authors and abstracts from the search were reviewed by two investigators to determine the manuscripts for full text review. Data were abstracted to a form designed specifically for this study. The quality of the studies was assessed using the Newcastle-Ottawa scale. Event rates were calculated using a random-effects model.. Twenty-five studies met our inclusion criteria. The prevalence of AF was 11.6% and the overall incidence was 2.7/100 patient-years. The risk of mortality and stroke was increased in ESRD patients with AF at 26.9 and 5.2/100 patient-years versus 13.4 and 1.9/100 patient-years compared with ESRD patients without AF. The majority of studies do not support a protective effect for warfarin in ESRD patients with AF.. The incidence and prevalence of AF in ESRD patients are higher than in the general population and are associated with an increased risk of stroke and mortality. An appropriately designed randomized controlled trial is required to determine whether anticoagulation is an appropriate therapeutic strategy in patients with end-stage renal disease and atrial fibrillation.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Incidence; Kidney Failure, Chronic; Prevalence; Renal Dialysis; Risk Factors; Stroke; Warfarin

Atrial fibrillation (AF) is a common cardiac arrhythmia and is associated with an increased risk for thromboembolic stroke. Anticoagulant therapy has been shown to reduce the risk for ischemic stroke in patients with AF; however, these studies have excluded patients with end-stage renal disease (ESRD). This review examines the relationships between ESRD, AF, and the use of anticoagulants to prevent ischemic stroke. Medline and Embase were used to identify relevant articles. Identified review articles and their references were searched. The prevalence of AF in patients with ESRD is higher than that in the general population; ESRD appears to be an independent risk factor for AF. The presence of AF in patients with ESRD increases the risk for stroke, although this effect is less pronounced when compared with the general population. The presence of ESRD confers an increased risk for bleeding; warfarin appears to enhance this risk. Observational data suggest that warfarin increases the rate of hemorrhagic stroke in patients with ESRD, but are unclear on its utility in reducing ischemic stroke. In addition to increasing the risk for bleeding, warfarin may also promote vascular calcification in this population. Currently, there are no oral anticoagulants other than warfarin that are approved for use in patients with ESRD. Recent guidelines suggest that warfarin only be used for secondary prevention in patients with ESRD and AF. Randomized controlled trials are needed to clarify the role of warfarin or other anticoagulants in preventing stroke in patients with ESRD and AF.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Warfarin

Children with IgA nephropathy showing diffuse (>80%) mesangial proliferation are at high risk for end-stage renal failure (ESRF). A previous controlled trial showed that combination therapy consisting of prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease reduces immunologic renal injury and prevents the progression of sclerosed glomeruli. The objective of this study was to evaluate the long-term effectiveness of combination therapy in children with IgA nephropathy showing diffuse mesangial proliferation.. A secondary analysis of a multicenter, randomized, controlled trial involving 78 children with IgA nephropathy who received either 2-year combination therapy or heparin-warfarin and dipyridamole (control) therapy was conducted.. The median duration of observation was 10 years (range, 0.5 to 18). Two of 40 patients (5%) who received combination therapy and five of 34 patients (14.7%) who received control therapy developed ESRF. A Kaplan-Meier plot of renal survival showed that the outcomes of patients in the combined therapy group were better than those in the control therapy group (log-rank P = 0.03). The 10-year renal survival probability of each group was 97.1% (95% confidence interval, 81.4 to 99.6%) and 84.8% (95% confidence interval, 55.4 to 95.5%), respectively. The Cox proportional hazards model showed that the 2-year combination therapy was significantly associated with renal survival in both univariate and multivariate analyses.. Two-year combination therapy not only ameliorated the activity of the acute phase of nephritis but also improved the long-term outcome of severe childhood IgA nephropathy.

Topics: Adolescent; Anticoagulants; Azathioprine; Cell Proliferation; Child; Dipyridamole; Disease Progression; Drug Therapy, Combination; Female; Glomerulonephritis, IGA; Heparin; Humans; Immunosuppressive Agents; Japan; Kaplan-Meier Estimate; Kidney Failure, Chronic; Kidney Glomerulus; Male; Prednisolone; Proportional Hazards Models; Prospective Studies; Proteinuria; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Warfarin

The risks and benefits of anticoagulation for stroke prevention with atrial fibrillation is clearly delineated in the general population. Little evidence exists for patients with end-stage renal disease (ESRD) about whether the extrapolation of these guidelines is appropriate. In patients with ESRD who are undergoing hemodialysis, the rates for both stroke and bleeding are 3 to 10 times higher than that for the general population. Furthermore, the proportion of hemorrhagic to ischemic strokes has increased, making the decision of whether to initiate anticoagulation problematic. In this commentary, we discuss the existing literature for stroke in atrial fibrillation, stroke type, risk reduction with anticoagulation, and bleeding risks in the hemodialysis population. We comment on validated risk stratification models of stroke prevention and bleeding and their applicability to patients undergoing hemodialysis. Finally, we recommend treatment strategies that are based on the existing state of knowledge.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Renal Dialysis; Stroke; Warfarin

Vitamin K-dependent proteins (VKDPs) require carboxylation to become biologically active. Although the coagulant factors are the most well-known VKDPs, there are many others with important physiologic roles. Matrix Gla Protein (MGP) and Growth Arrest Specific Gene 6 (Gas-6) are two particularly important VKDPs, and their roles in vascular biology are just beginning to be understood. Both function to protect the vasculature; MGP prevents vascular calcification and Gas-6 affects vascular smooth muscle cell apoptosis and movement. Unlike the coagulant factors, which undergo hepatic carboxylation, MGP and Gas-6 are carboxylated within the vasculature. This peripheral carboxylation process is distinct from hepatic carboxylation, yet both are inhibited by warfarin administration. Warfarin prevents the activation of MGP and Gas-6, and in animals, induces vascular calcification. The relationship of warfarin to vascular calcification in humans is not fully known, yet observational data suggest an association. Given the high risk of vascular calcification in those patients with chronic kidney disease, the importance of understanding warfarin's effect on VKDPs is paramount. Furthermore, recognizing the importance of VKDPs in vascular biology will stimulate new areas of research and offer potential therapeutic interventions.

Topics: Animals; Anticoagulants; Blood Vessels; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Humans; Intercellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Matrix Gla Protein; Protein Processing, Post-Translational; Risk Assessment; Risk Factors; Vascular Diseases; Vitamin K; Warfarin

Patients with renal failure have an increased risk of both thrombotic and bleeding complications. A number of antithrombotic drugs undergo renal clearance. Therefore, estimation of renal function is necessary when prescribing these drugs to patients with renal dysfunction. Pharmacokinetic and clinical data in patients with chronic renal impairment are limited for several anticoagulants, and adequate administration information is often absent. Dose adjustment of anticoagulants may be indicated when the creatinine clearance falls below 30 mL/min. Unfractionated heparin, argatroban, and vitamin K antagonists generally do not require dose adjustment with renal dysfunction. However, smaller doses of warfarin may be required to achieve a particular target international normalized ratio. Close monitoring of anticoagulation is recommended when argatroban or high doses of unfractionated heparin are administered in patients with severe chronic renal impairment. Low-molecular weight heparins, danaparoid sodium, hirudins, and bivalirudin all undergo renal clearance. Lower doses and closer anticoagulation monitoring may be advisable when these agents are used in patients with chronic renal failure. We recommend that fondaparinux sodium and ximelagatran (not yet licensed) be avoided in the presence of severe renal impairment and be used with caution in patients with moderate renal dysfunction. While acknowledging the lack of pharmacokinetic data, this review provides specific recommendations for the use of anticoagulants in patients with chronic renal impairment.

Topics: Anticoagulants; Arginine; Azetidines; Benzylamines; Fondaparinux; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Warfarin

Calciphylaxis is a relatively rare, but horribly disfiguring, skin condition that is most often associated with end-stage renal disease and long-term dialysis. Unfortunately, calciphylaxis-related morbidity and mortality are significant. The case study presented demonstrates many of the findings associated with the typical calciphylaxis patient; end-stage renal disease and an extensive, painful ulcer. The complexity of the patient s history and medical/surgical interventions, especially medication therapy with coumadin and heparin, complicated initial diagnostic processes. Close scrutiny of multiple physical assessment findings, historical factors, and test results was required for correct diagnosis. Crucial components of differential diagnosis of calciphylaxis versus coumadin-induced skin necrosis or heparin-induced thrombocytopenia necrosis include: patient history and characteristics, clinical presentation, and diagnostic test results.

Topics: Amputation, Surgical; Anticoagulants; Calciphylaxis; Diagnosis, Differential; Disease Progression; Fatal Outcome; Heparin; Humans; Kidney Failure, Chronic; Leg Ulcer; Male; Middle Aged; Necrosis; Skin Care; Thrombocytopenia; Warfarin

Topics: Apazone; Bilirubin; Binding Sites; Carrier Proteins; Diazepam; Digitoxin; Fatty Acids, Nonesterified; Half-Life; Humans; Hydrogen-Ion Concentration; Indoles; Kidney Diseases; Kidney Failure, Chronic; Kinetics; Ligands; Liver; Methods; Protein Binding; Protein Conformation; Renal Dialysis; Serum Albumin; Toxins, Biological; Uremia; Warfarin

There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF).. The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA. From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event.. There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis.. URL: https://www.. gov; Unique identifier: NCT02942407.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Kidney Failure, Chronic; Prospective Studies; Renal Dialysis; Stroke; Treatment Outcome; Warfarin

The patency of a permanent arteriovenous catheter plays a significant role in the functioning of the catheter among patients dependent on the hemodialysis. Thrombosis formation is one of the most critical reasons for the short-term efficacy of the embedded catheters. The present study aimed to evaluate the efficacy and safety of warfarin for hemodialysis catheter failure prevention.. This randomized clinical trial has been conducted on patients under hemodialysis using a permanent arteriovenous catheter. The patients were randomly allocated to the control group and the intervention group. The intervention group was treated with warfarin to achieve a target international normalized ratio (INR) of 1.5-2. The control group did not receive any treatment. The patients were followed for 12 months to assess the efficacy defined as the incidence of catheter clotting and safety defined as warfarin-related hemorrhage.. Eighty-six patients with end-stage renal disease under hemodialysis were included, among which 43 ones were allocated to the intervention group and the latter ones to the control group. The participants of both groups were similar in terms of demographic, clinical, and baseline laboratory characteristics. Four patients (9.3%) presented with warfarin-induced hematoma, among which the warfarin administration stopped for 5.33 ± 1.44 days and then restarted again. None of the patients was forced to cease warfarin therapy because of significant hemorrhages. The mean duration of catheter functioning was 8.30 ± 1.75 months in the intervention group versus 3.90 ± 1.12 months in the controls (P-value<0.001).. Based on the findings of the present study, the use of warfarin to achieve an INR level of 1.5-2 could effectively lead to a longer duration of permanent hemodialysis catheter functioning.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Catheter Obstruction; Catheterization, Central Venous; Catheters, Indwelling; Central Venous Catheters; Drug Monitoring; Female; Hemorrhage; Humans; International Normalized Ratio; Iran; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Thrombosis; Time Factors; Treatment Outcome; Warfarin

To determine whether warfarin prolongs the time to first mechanical-catheter failure.. This was a multicenter parallel-group randomized controlled trial with blinding of participants, trial staff, clinical staff, outcome assessors, and data analysts. Randomization was in a 1:1 ratio in blocks of four and was concealed by use of fax to a central pharmacy. Hemodialysis patients with newly-placed catheters received low-intensity monitored-dose warfarin, target international normalized ratio (INR) 1.5 to 1.9, or placebo, adjusted according to schedule of sham INR results. The primary outcome was time to first mechanical-catheter failure (inability to establish a circuit or blood flow less than 200 ml/min).. We randomized 174 patients: 87 to warfarin and 87 to placebo. Warfarin was associated with a hazard ratio (HR) of 0.90 (P=0.60; 95% confidence interval [CI], 0.57, 1.38) for time to first mechanical-catheter failure. Secondary analyses were: time to first guidewire exchange or catheter removal for mechanical failure (HR 0.78; 95% CI, 0.37, 1.6); time to catheter removal for mechanical failure (HR 0.67; 95% CI, 0.19, 2.37); and time to catheter removal for any cause (HR 0.89; 95% CI, 0.42, 1.81). Major bleeding occurred in 10 participants assigned to warfarin and seven on placebo (relative risk, 1.43; 95% CI, 0.57, 3.58; P=0.61).. We found no evidence for efficacy of low-intensity, monitored-dose warfarin in preventing mechanical-catheter failure.

Topics: Aged; Anticoagulants; Catheterization, Central Venous; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Placebos; Renal Dialysis; Treatment Outcome; Upper Extremity Deep Vein Thrombosis; Warfarin

Children with IgA nephropathy showing diffuse (>80%) mesangial proliferation are at high risk for end-stage renal failure (ESRF). A previous controlled trial showed that combination therapy consisting of prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease reduces immunologic renal injury and prevents the progression of sclerosed glomeruli. The objective of this study was to evaluate the long-term effectiveness of combination therapy in children with IgA nephropathy showing diffuse mesangial proliferation.. A secondary analysis of a multicenter, randomized, controlled trial involving 78 children with IgA nephropathy who received either 2-year combination therapy or heparin-warfarin and dipyridamole (control) therapy was conducted.. The median duration of observation was 10 years (range, 0.5 to 18). Two of 40 patients (5%) who received combination therapy and five of 34 patients (14.7%) who received control therapy developed ESRF. A Kaplan-Meier plot of renal survival showed that the outcomes of patients in the combined therapy group were better than those in the control therapy group (log-rank P = 0.03). The 10-year renal survival probability of each group was 97.1% (95% confidence interval, 81.4 to 99.6%) and 84.8% (95% confidence interval, 55.4 to 95.5%), respectively. The Cox proportional hazards model showed that the 2-year combination therapy was significantly associated with renal survival in both univariate and multivariate analyses.. Two-year combination therapy not only ameliorated the activity of the acute phase of nephritis but also improved the long-term outcome of severe childhood IgA nephropathy.

Topics: Adolescent; Anticoagulants; Azathioprine; Cell Proliferation; Child; Dipyridamole; Disease Progression; Drug Therapy, Combination; Female; Glomerulonephritis, IGA; Heparin; Humans; Immunosuppressive Agents; Japan; Kaplan-Meier Estimate; Kidney Failure, Chronic; Kidney Glomerulus; Male; Prednisolone; Proportional Hazards Models; Prospective Studies; Proteinuria; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Warfarin

We have studied the possibility that low-dose treatment utilizing the inhibition that may occur between two drugs at the same site of human serum albumin (HSA) improves the pharmacological effects. The purpose is to elucidate the differences in the binding capacities of sites I and II of HSA between pre-haemodialysis (HD) and post-HD in patients with end-stage renal disease.. We evaluated free fractions of site probes, (14)C-warfarin (site I) and (14)C-diazepam (site II), by ultrafiltration in serum between pre-HD and post-HD. To investigate effects on the binding capacities of HSA sites, free fractions of site probes were calculated from the radioactivities measured with a liquid scintillation counter. Endogenous uraemic toxins, 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), indoxyl sulphate (IS) and hippurate (HA), were determined by HPLC. Free fatty acid (FFA) as an endogenous substance was determined with an automatic multi-item simultaneous analyser.. The concentrations of HSA and FFA increased significantly (post-HD/pre-HD ratio: 1.18 +/- 0.10, 5.46 +/- 4.91), the concentrations of IS and HA decreased significantly (post-HD/pre-HD ratio: 0.69 +/- 0.10, 0.33 +/- 0.15) and CMPF concentrations did not alter significantly (post-HD/pre-HD ratio: 0.97 +/- 0.12, P = 0.471). The free fractions of (14)C-warfarin decreased in all 14 patients at site I at post-HD compared to pre-HD (post-HD/pre-HD ratio: 0.59 +/- 0.13). The free fractions of (14)C-diazepam at site II remarkably decreased in 10 of 14 patients (post-HD/pre-HD ratio: 0.61 +/- 0.17) and unexpectedly increased in 4 (post-HD/pre-HD ratio: 1.08 +/- 0.06) post-HD compared to pre-HD. In these four patients, when we investigated the influences of these variation factors on the reduction of the binding capacities of site II, [FFA]/[HSA] increased significantly post-HD, compared to pre-HD (post-HD/pre-HD ratio: 6.91 +/- 6.58). ([FFA]/[HSA] ratios of the 4 patients were from 1.22 to 3.55, the highest for the 14 patients post-HD, but the ratios of the other 10 were below 1.2 post-HD.). The binding capacity of site II was unexpectedly decremented by the effects of the remarkable elevation of FFA. Therefore, monitoring the binding capacity of site II in HD is important for patients with end-stage renal disease in the efficacious administration plan using the binding inhibition of HSA.

Topics: Adult; Aged; Barbiturates; Binding Sites; Carbon Radioisotopes; Diazepam; Diuretics; Fatty Acids, Nonesterified; Female; Furans; Furosemide; Hippurates; Humans; Indican; Kidney Failure, Chronic; Male; Middle Aged; Propionates; Protein Binding; Renal Dialysis; Serum Albumin; Treatment Outcome; Warfarin

Polytetrafluoroethylene (PTFE) dialysis grafts in patients with end-stage renal disease (ESRD) are prone to thrombotic failure. The objective of this multicenter, randomized, double-blind, placebo-controlled clinical trial was to determine if warfarin reduces the risk of failure of PTFE dialysis grafts. Patients with ESRD and newly placed PTFE grafts were studied at community and academic dialysis centers in Southwestern Ontario. Patients were allocated to receive warfarin or matching placebo, with the warfarin administered to achieve a target INR of 1.4 to 1.9. Time to graft failure was the main outcome measure. A total of 107 patients (56 allocated to warfarin) were randomized. The time-to-event analysis revealed no significant difference in the likelihood of graft survival between the two groups (odds ratio, 1.76 in favor of placebo; 95% confidence interval, 0.72 to 4.34). Six major bleeds occurred in five patients allocated to warfarin compared with none in the patients who received placebo (P = 0.03). In conclusion, low-dose warfarin was associated with an excess of clinically important major bleeding in patients with ESRD enrolled in this study. Furthermore, low-intensity, monitored-dose warfarin does not appear to prolong PTFE graft survival.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Vessel Prosthesis; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polytetrafluoroethylene; Renal Dialysis; Thrombosis; Treatment Outcome; Warfarin

Increased coagulation factors found in dialysis patients may explain in part the high prevalence of thrombotic cardiovascular disease. Several studies showed low-dose warfarin is effective in decreasing coagulation factors and preventing thrombosis without increasing the risk of bleeding. To evaluate the effects of fixed low-dose warfarin therapy on thrombogenesis in continuous ambulatory peritoneal dialysis (CAPD) patients, 76 CAPD patients were assigned randomly to treatment and disease control groups. The treatment group received 2 mg of warfarin daily for 12 months. International normalized ratio (INR) of the prothrombin time and plasma levels of factor VII, D-dimer, von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) were measured before and 3, 6, and 12 months after the start of medication. The same parameters were measured in 30 healthy volunteers at the beginning of the study and in the disease control group during the study period. Of 76 patients, 60 completed the study. Deaths from atherosclerotic cardiovascular disease (cerebral infarction or acute myocardial infarction) occurred in 1 patient in the treatment group (n = 29) and 3 in the disease control group (n = 31), which was not statistically significant. No major bleeding occurred during the study period. With administration of warfarin, there was a small increase in INR in the treatment group. CAPD patients at baseline had significantly higher plasma factor VII, D-dimer, vWF, and PAI-1 levels than normal controls. Warfarin therapy lowered plasma factor VII and D-dimer levels. No change was seen in vWF and PAI-1 levels. In the disease control group, these hemostatic factors showed no change during the study period. There was a negative correlation between serum albumin and INR in the treatment group during the study period. Fixed low-dose warfarin was effective in partially reversing the thrombogenic coagulation profile in CAPD patients without a big increase in the risk of bleeding.

Topics: Anticoagulants; Blood Coagulation Factors; Factor VII; Female; Fibrin Fibrinogen Degradation Products; Humans; International Normalized Ratio; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Plasminogen Activator Inhibitor 1; Serum Albumin; von Willebrand Factor; Warfarin

Antiphospholipid antibody syndrome (APAS) is characterized by the presence of anticardiolipin antibodies (ACA) in association with thrombotic disorders of arterial and/or venus systems, spontaneous abortion(s) or thrombocytopenia.. In this multicenter study, 502 end-stage renal disease (ESRD) patients awaiting renal transplants were screened to determine the frequency of APAS, the potential risk associated with APAS, and strategies for therapeutic intervention. Ninety-three patients (19%) had high titers of ACA. Twenty-three patients had documented evidence of one or more of the thrombotic disorders such as lupus, frequent abortions, frequent thrombosis of arteriovenous shunts, biopsy-proven microrenal angiopathy, or thrombocytopenia and thus were diagnosed with APAS. Of these 23 patients, 11 received kidney transplants either with (4 patients) or without (7 patients), concomitant anticoagulation therapy.. All seven of the patients with APAS not treated with anticoagulation therapy lost their allografts within 1 week as a result of renal thrombosis. In contrast, three out of four transplant patients with APAS treated with anticoagulation therapy maintained their allografts for over 2 years. The fourth patient lost his graft within a week because of thrombosis. Of the remaining 70 patients with high titers of ACA but no evidence of thrombotic disorders, 37 received kidney transplants. None lost their allografts as a result of thrombosis. Our data suggest that, although 19% of our ESRD patients exhibit high titer of ACA, only 5% of the patients have APAS.. In conclusion, our data suggest that the patients with APAS are at high risk of posttransplant renal thrombosis. Anticoagulation therapy could prevent patients from posttransplant thrombosis in patients with APAS.

Topics: Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Female; Graft Rejection; Graft Survival; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Prevalence; Risk Factors; Thrombosis; Warfarin

Topics: Calciphylaxis; Case-Control Studies; Humans; Iron; Kidney Failure, Chronic; Renal Dialysis; Retrospective Studies; Risk Factors; Sevelamer; Warfarin

Evidence suggests that an apixaban-based strategy to treat acute venous thromboembolism (VTE) in patients with End-Stage Kidney Disease (ESKD) may be safer than a warfarin-based strategy. Apixaban has an additional advantage of not requiring bridging with heparin which often necessitates long hospitalizations for patients with ESKD. We sought to determine if an apixaban-based strategy is associated with less healthcare utilization than a warfarin-based strategy.. We employed a new-user, active-comparator retrospective cohort study using inverse probability of treatment weights (IPTW) to adjust for confounding demographic and clinical variables. Patients with ESKD newly initiated on either apixaban or warfarin for an acute VTE between 2014 and 2018 in the United States Renal Data System were included. Outcomes were presence of index hospitalization, length of index hospitalization, total hospital days, total hospital days excluding index hospitalization, total emergency department (ED) visits that did not result in hospitalization, and total skilled nursing facility days.. At six months, patients who received apixaban were less likely to have an index hospitalization, had a shorter index hospitalization (median of 4.0 vs 8.0 days, p < 0.001), and had fewer total hospital days. The IPTW and index year-adjusted incidence rate ratios of total hospital days at one, three, and six months were 0.83 (95 % confidence intervals (CI) 0.79-0.86), 0.84 (95 % CI 0.81-0.88), and 0.88 (95 % CI 0.83-0.92) for apixaban compared to warfarin.. Among patients with ESKD and VTE, resource utilization for an apixaban-based strategy appears to be lower than for a warfarin-based strategy.

Topics: Anticoagulants; Humans; Kidney Failure, Chronic; Patient Acceptance of Health Care; Pyridones; Retrospective Studies; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

We present a case report highlighting a 47-year-old woman who developed warfarin-induced calciphylaxis. She initially developed bilateral leg wounds secondary to restraint straps from helicopter transportation to a higher level of care for treatment of critical aortic stenosis. She was started on warfarin following surgical implantation of a mechanical aortic valve. After her wounds failed to heal, a punch biopsy of the wounds demonstrated ulceration, altered vasculature, and soft tissue calcification. The pathology confirmed the clinical concern for calciphylaxis, which is most often diagnosed in patients with a history of end-stage renal disease on hemodialysis. However, our patient did not demonstrate evidence of renal disease prior to the onset of calciphylaxis. Her wounds began to heal after treatment with sodium thiosulfate and changing her anticoagulation from warfarin to rivaroxaban.

Topics: Biopsy; Calciphylaxis; Female; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Warfarin

A man in his 30s, with a medical history of end-stage renal disease on haemodialysis three times a week after kidney transplant rejection, anaemia of inflammatory disease, hypertension, atrial fibrillation, hyperlipidaemia, subtotal parathyroidectomy and aortic valve replacement on Coumadin treatment, presented to our institution with glans penis pain. Examination of the penis revealed a painful black eschar with ulceration on the glans penis with surrounding erythema. CT scan of the abdomen and pelvis and penile Doppler ultrasound revealed calcifications of the abdominal, pelvic and penile blood vessels. He was diagnosed with penile calciphylaxis, a very rare manifestation of calciphylaxis characterised by penile blood vessel calcification leading to occlusion, ischaemia and necrosis. Treatment with low calcium dialysate and sodium thiosulfate was initiated with haemodialysis. Five days after the treatment started, the patient's symptoms improved.

Topics: Calciphylaxis; Humans; Kidney Failure, Chronic; Male; Penile Diseases; Penis; Renal Dialysis; Warfarin

BACKGROUND Left ventricular thrombus is a serious complication of numerous cardiovascular conditions. Anticoagulation with oral vitamin K antagonists such as warfarin is a standard treatment for left ventricular thrombus and is recommended to reduce the risk of embolization. Patients with cardiac conditions share comorbidities with patients with end-stage renal disease, and patients with advanced kidney disease are predisposed to atherothrombotic and thromboembolic complications. The efficacy of direct oral anticoagulants in patients with left ventricular thrombus has not been well studied. CASE REPORT A 50-year-old man had prior myocardial infarction, heart failure with reduced ejection fraction, diabetes, hypertension, atrial fibrillation, treated hepatitis B infection, and end-stage renal disease on hemodialysis. On regular outpatient follow-up with the cardiology clinic, a transthoracic echocardiogram was requested and revealed akinesia of the mid to apical anterior wall, mid to apical septum, and left ventricular apex, and large apical thrombus measuring 20×15 mm. Apixaban 5 mg orally twice daily was started. A transthoracic echocardiogram was done after 3 months and after 6 months, and the thrombus did not resolve. The apixaban was shifted to warfarin. The international normalized range was maintained at the therapeutic range (INR 2.0-3.0). After 4 months of receiving warfarin, echocardiography showed a resolution of the left ventricular thrombus. CONCLUSIONS We report a case of left ventricular thrombus that was successfully dissolved by warfarin after treatment with apixaban failed. This case challenges the general assumption of apixaban's effectiveness in patients with end-stage renal disease on dialysis.

Topics: Anticoagulants; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Thrombosis; Vitamin K; Warfarin

There has been limited evidence reported about the outcomes of oral anticoagulants among patients with venous thromboembolism (VTE) and chronic kidney disease (CKD), especially those with stage V/end-stage renal disease (ESRD). This retrospective cohort analysis of five U.S. claims databases evaluated the risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB) for apixaban versus warfarin among VTE patients diagnosed with CKD, including ESRD. Inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Hazard ratios (HRs) were calculated for recurrent VTE, MB, and CRNMB among patients with CKD who experienced an index VTE. An interaction analysis was conducted to evaluate treatment effects across different stages of CKD. A total of 29,790 VTE patients with CKD were selected for analyses, of whom 10,669 (35.8%) initiated apixaban and 19,121 (64.2%) initiated warfarin. Among IPTW-balanced patient cohorts, the apixaban group had significantly lower risk of recurrent VTE (HR: 0.78; 95% confidence interval [CI]: 0.66-0.92), MB (HR: 0.76; 95% CI: 0.65-0.88), and CRNMB (HR: 0.86; 95% CI: 0.80-0.93) than the warfarin group. When stratified by CKD stage (stage I/II: 8.2%; stage III: 49.4%; stage IV: 12.8%; stage V/ESRD: 12.0%; stage unspecified: 17.6%), no significant interaction was observed for effects of apixaban versus warfarin on recurrent VTE or MB. In summary, apixaban was associated with a significantly lower risk of recurrent VTE and MB than warfarin among VTE patients with CKD. CKD stages did not have significant impact on treatment effects for recurrent VTE and MB.

Topics: Anticoagulants; Hemorrhage; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Retrospective Studies; Venous Thromboembolism; Warfarin

Anticoagulation is commonly used for stroke prevention among patients with atrial fibrillation (AF); however, end-stage renal disease (ESRD) patients on hemodialysis are at higher risk of bleeding and stroke, even without anticoagulation. It is unclear if patients should be continued on anticoagulation at the time of transition to ESRD. In this study, we validated risk scores for stroke and bleeding in this population and assessed risk of stroke and bleeding among warfarin users compared to nonusers.. We utilized a cohort of 28,620 pre-dialysis US veterans transitioning to hemodialysis between October 2007 and March 2015. Incident rates for the risks of stroke and bleeding were ascertained based upon CHA2DS2-VASc or HAS-BLED scores, respectively. A propensity score-based competing risk analysis was used to assess risk of stroke and bleeding.. The mean age of our cohort was 77 ± 9 years, and the median CHA2DS2-VASc and HAS-BLED scores were 7 (5, 8) and 3 (3, 4), respectively. Increasing CHA2DS2-VASc and HAS-BLED scores were predictive of increasing stroke and bleeding rates, respectively. However, warfarin use did not appear to affect the risk of stroke and bleeding (p-interaction = 0.84 for stroke and 0.24 for bleeding). Warfarin use was associated with a higher risk of stroke (adjusted SHR 1.44, 95% CI: 1.23-1.69) and a higher risk of bleeding (adjusted SHR 1.38, 95% CI: 1.25-1.52) when accounting for the competing risk of death.. There was no difference in incidence rates of stroke or bleeding among warfarin users versus nonusers. Warfarin was associated with a higher risk of stroke and bleeding after considering mortality risk.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dialysis; Hemorrhage; Humans; Kidney Failure, Chronic; Renal Dialysis; Risk Assessment; Risk Factors; Stroke; Veterans; Warfarin

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

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

This study evaluated the occurrence of major bleeding following the initiation of oral anticoagulation therapy in patients with end-stage kidney disease (ESKD) in a community teaching hospital.. This was a single-center retrospective study that enrolled patients admitted to the study hospital with ESKD and who received oral anticoagulation (warfarin or nonvitamin K oral antagonists [NOACs]). The primary endpoint was the occurrence of major bleeding at any time while taking oral anticoagulation. Key secondary endpoints included occurrence of minor bleeding, thrombotic events, and hospitalizations because of bleeding or thrombosis.. There were 36 patients who received warfarin and 32 patients who received a NOAC. A major bleeding event occurred in 15 of 36 patients (42%) in the warfarin group and in 5 of 32 patients (16%) in the NOAC group (. Warfarin increased the risk of major bleeding in patients with ESKD compared with NOACs and did not reduce the risk of thrombotic events.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kidney Failure, Chronic; Retrospective Studies; Stroke; Warfarin

Data on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in relation to the risk of cardiovascular (CV) disease and renal protection among patients with atrial fibrillation (AF), are relatively sparse. We aimed to compare the effectiveness and safety of NOACs with those of warfarin for vascular protection in a large-scale, nationwide Asian population with AF.. Patients with AF who were prescribed oral anticoagulants according to the Korean Health Insurance Review and Assessment database between 2014 and 2017 were analyzed. The warfarin and NOAC groups were balanced using propensity score weighting. Clinical outcomes included ischemic stroke, myocardial infarction, angina pectoris, peripheral artery disease, chronic kidney disease (CKD), end-stage renal disease (ESRD), CV death, and all-cause death. NOAC use was associated with a lower risk of angina pectoris (HR, 0.79 [95% CI, 0.69-0.89] p<0.001), CKD stage 4 (HR, 0.5 [95% CI, 0.28-0.89], p = 0.02), and ESRD (HR, 0.15[95% CI, 0.08-0.32], p<0.001) than warfarin use. NOACs and warfarin did not significantly differ with respect to stroke reduction (HR, 1.05 [95% CI, 0.88-1.25], p = 0.19). NOAC use was associated with a lower risk of intracranial hemorrhage (HR, 0.6 [95% CI, 0.44-0.83], p = 0.0019), CV death (HR, 0.55 [95% CI, 0.43-0.70], p<0.001), and all-cause death (HR, 0.6 [95% CI, 0.52-0.69], p<0.001) than warfarin use.. NOACs were associated with a significantly lower risk of adverse CV and renovascular outcomes than warfarin in patients with AF.

Topics: Administration, Oral; Angina Pectoris; Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Pyridones; Stroke; Treatment Outcome; Warfarin

Management of antithrombotic therapy with warfarin in patients undergoing fistulograms and possible interventions is controversial and difficult because of lack of adequate outpatient bridging options. Our goal was to assess periprocedural outcomes in patients managed using different anticoagulation strategies.. A retrospective, single-institution analysis of all patients on chronic anticoagulation with warfarin undergoing fistulograms from 2011 to 2017 was performed. Anticoagulation management strategies were classified as suspended warfarin (SW), continued warfarin (CW), and a heparin bridge with suspended warfarin (HB). Periprocedural outcomes were analyzed.. There were 87 patients on chronic anticoagulation with warfarin who underwent 175 fistulograms. Median age was 63 years, and 43.4% were women. Indications for warfarin included atrial fibrillation (53%), prior pulmonary embolism/deep vein thrombosis (29%), and hypercoagulable state (14%). Distribution was SW (60%), CW (26%), and HB (14%). Approximately half (53%) were same-day procedures, 30% occurred during access-related admissions, and 14% were performed during nonaccess-related admissions. Common indications for a fistulogram included difficulty with dialysis (63.4%), access thrombosis (20.6%), and poor maturation (10.3%). Interventions included angioplasty (82.9%), thrombectomy/embolectomy (20.6%), and stenting (8.6%). Thirty-day outcomes for SW versus CW versus HB were similar for bleeding complications (5.7%, 6.5%, 8.3%; P = 0.89), systemic thrombotic complications (3.8%, 2.2%, 0%; P = 0.569), access rethrombosis (7.6%, 13%, 12.5%; P = 0.517), and tunneled dialysis catheter placement (11.4%, 13%, 12.5%; P = 0.958). After excluding procedures performed during a nonaccess-related admission, length of stay (LOS) was highest among HB (9.6 ± 7.8 days) compared with SW (2.6 ± 5.9 days) and CW (1 ± 2.8 days), (P < 0.0001).. CW therapy in patients undergoing fistulograms was not associated with increased morbidity and was associated with shorter LOS. Bridging with heparin is not associated with improved outcomes, warranting a thorough consideration of continuing warfarin is safe and may streamline preservation of dialysis accesses without significantly increasing resource utilization.

Topics: Adult; Aged; Anticoagulants; Arteriovenous Shunt, Surgical; Drug Administration Schedule; Drug Substitution; Female; Heparin; Humans; Kidney Failure, Chronic; Length of Stay; Male; Middle Aged; Perioperative Care; Postoperative Complications; Renal Dialysis; Retrospective Studies; Thrombosis; Time Factors; Treatment Outcome; Warfarin

Calciphylaxis is a rare thrombotic vasculopathy characterized by high morbidity and mortality. There is a paucity of studies examining longitudinal outcomes.. To assess mortality, days spent in the hospital, and amputations in patients with calciphylaxis.. A retrospective medical record review was conducted in 145 patients diagnosed with calciphylaxis at an urban tertiary care hospital from January 2006 to December 2018.. Six-month mortality was 37.2%, and 1-year mortality was 44.1%. Patients with nephrogenic calciphylaxis had worse survival than those with nonnephrogenic calciphylaxis (P = .007). This difference in survival disappeared when limiting mortality to deaths due to calciphylaxis. Age (P = .003) and end-stage renal disease (P = .01) were risk factors associated with 1-year mortality. Diabetes mellitus was associated with greater total hospitalization days (coefficient, 1.1; 95% confidence interval, 1.01-1.4); bedside debridement was associated with fewer hospitalization days (coefficient, 0.8; 95% confidence interval, 0.7-0.9). Amputations were not associated with any of the examined risk factors. The use of warfarin followed by a transition to nonwarfarin anticoagulation was associated with decreased hazard of death (P = .01).. Retrospective nature.. Calciphylaxis remains a complex, heterogeneous disease. Mortality is lower in patients with nonnephrogenic disease. These findings may be incorporated during discussions regarding the goals of care to facilitate informed shared decision making.

Topics: Calciphylaxis; Humans; Kidney Failure, Chronic; Retrospective Studies; Risk Factors; Warfarin

Comparing kidney disease progression among patients treated with direct oral anticoagulants (DOACs) versus warfarin has not been well studied. We hypothesized that apixaban would be associated with lower risks of progression of chronic kidney disease (CKD) and progression to incident kidney failure than warfarin in patients with atrial fibrillation (AF).. Retrospective cohort study.. Medicare recipients with stage 3, 4, or 5 CKD and incident AF who received a new prescription for apixaban or warfarin from 2013 through 2017.. Apixaban or warfarin.. Progression to incident kidney failure or, separately, to a more advanced stage of CKD.. Marginal structural cause-specific proportional hazards models with inverse probability weighting to estimate marginal hazard ratios (HRs) for each outcome. HRs compared apixaban to warfarin in intention-to-treat and censored-at-drug-switch analyses.. 12,816 individuals met inclusion criteria (50.3% received apixaban; 49.7% received warfarin). After weighting, the mean age of the cohort was 80 ± 7 years, 51% were women, and 88% were White. Approximately 84% had stage 3, 15% had stage 4, and 1% had stage 5 CKD. In the intention-to-treat analysis, apixaban, relative to warfarin, was associated with an HR of developing incident kidney failure of 0.98 (95% confidence interval [CI], 0.79-1.22) and of CKD stage progression of 0.90 (95% CI, 0.82-0.99). Corresponding HRs for censored-at-drug-switch analyses were 0.81 (95% CI, 0.56-1.17) and 0.81 (95% CI, 0.70-0.92). Results were similar for a series of subgroup and sensitivity analyses.. CKD was defined based on diagnosis codes from claims; findings may not be generalizable to non-Medicare CKD populations.. Apixaban, compared with warfarin, was associated with lower risk of CKD stage progression, but not with incident kidney failure.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Disease Progression; Factor Xa Inhibitors; Female; Humans; Ischemic Stroke; Kidney Failure, Chronic; Male; Medicare; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Retrospective Studies; Severity of Illness Index; United States; Warfarin

Haemorrhagic and thrombotic complications are common in dialysis patients on warfarin; thus, accurate international normalized ratio (INR) monitoring is critical. For expediency and patient comfort, blood sampling from the haemodialysis access or circuit is commonly performed. Point-of-care (POC) INR machines allow both peripheral vein preservation and rapid results, yet are not validated in the haemodialysis population.. A prospective cohort study in haemodialysis patients taking warfarin was undertaken. Three paired samples were drawn over a single session: peripheral blood INR, POC INR, and dialysis INR. Agreement using Bland-Altman analysis and correlation coefficients between the peripheral blood INR, haemodialysis INR, and POC INR were calculated. Inappropriate dosing decisions based on haemodialysis or POC INR were quantified.. Amongst 34 patients, agreement between the dialysis INR and peripheral blood INR was high, with the haemodialysis INR differing from the peripheral INR by <±0.2, 85.2% of the time. Correlation between the 2 methods was high (r = 0.914; p < 0.001). POC INR differed from peripheral INR values by <±0.2, 67.6% of the time, with less agreement at higher INR values. Dosing decisions were incongruent between the dialysis and peripheral INR in 6%, whilst the POC and peripheral INR disagreed in 26%.. There was good agreement and correlation between the peripheral blood, haemodialysis access/circuit, and POC INR values. POC INR was less reliable at higher values, and dosing decisions differed from the peripheral INR in a quarter of cases.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Specimen Collection; Female; Humans; International Normalized Ratio; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Warfarin

Data on the safety of apixaban compared to warfarin in hemodialysis (HD) patients are accumulating, but the impact of concomitant antiplatelet use is unknown.. Compare hemorrhagic risk and impact of antiplatelets in HD patients receiving oral anticoagulants (OAC).. Retrospective, multi-center study of HD patients started on OAC inpatient over 5 years.. 707 patients were included: 563 received warfarin, and 144 received apixaban. 197 had bleeding, most in the warfarin group (173 [30.1%] vs 24 [16.7%] in the apixaban group), P-value < .01). However, with concomitant antiplatelet use, frequencies were similar (31.4% vs 25.0%; P-value = .292). Cumulative incidence using bleeding as event of interest and death as competing risk showed higher rates of bleeding with warfarin. In a multivariate model, apixaban was associated with a lower hemorrhagic risk (hazard ratio [HR] 0.55 [95% confidence interval {CI} 0.35-0.86}). Apixaban showed lower hemorrhagic risk alone (HR 0.24, 95% CI 0.10-0.55) and similar risk when administered with antiplatelets (HR 0.93, 95% CI 0.55-1.56).. Apixaban is associated with less bleeding in HD patients compared to warfarin, but concomitant antiplatelet use may negate the safety advantage. Prospective trials are warranted to determine the impact of antiplatelets on apixaban safety.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Platelets; Factor Xa Inhibitors; Female; Health Care Surveys; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Pyrazoles; Pyridones; Renal Dialysis; Risk Assessment; Warfarin

Calciphylaxis is a rare life-threatening condition, with calcification of small and medium-sized vessels leading to skin necrosis. It has a high morbidity and mortality, and most of the patients die from wound superinfection and sepsis. A 48-year-old man with a history of end-stage renal disease on haemodialysis and Coumadin therapy for venous thromboembolism presented with pulmonary oedema after missing two haemodialysis treatment. At examination, he had bilateral lower extremity dark brown, possibly necrotic, painful ulcers. He was diagnosed with calciphylaxis and treated with sevelamer hydrochloride, low calcium dialysate and sodium thiosulfate with haemodialysis. He received daily wound care with topical collagenase. After daily wound care treatment for 4 months, the patient's ulcers completely healed. The patient had been followed for 8 months, which included 29 additional readmissions, 3 admissions related to bacteraemia and 26 admissions with the diagnosis of pulmonary oedema and hyperkalaemia requiring haemodialysis.

Topics: Calciphylaxis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Vascular Calcification; Warfarin

While direct oral anticoagulants (DOACs) are considered safe among patients without chronic kidney disease (CKD), the evidence is conflicting as to whether they are also safe in the CKD and end-stage kidney disease (ESKD) population. In this observational cohort study, we examined whether DOACs are a safe alternative to warfarin across CKD stages for a variety of anticoagulation indications.. Individuals on DOACs or warfarin were identified from OptumLabs® Data Warehouse (OLDW), a longitudinal dataset with de-identified administrative claims, from 2010 to 2017. Cox models with sensitivity analyses were used to assess the risk of cardiovascular disease and bleeding outcomes stratified by CKD stage.. Among 351,407 patients on anticoagulation, 45% were on DOACs. CKD stages 3-5 and ESKD patients comprised approximately 12% of the cohort. The most common indications for anticoagulation were atrial fibrillation (AF, 44%) and venous thromboembolism (VTE, 23%). DOACs were associated with a 22% decrease in the risk of cardiovascular outcomes (HR 0.78, 95% CI: 0.77-0.80, p < 0.001) and a 10% decrease in the risk of bleeding outcomes (HR 0.90, 95% CI: 0.88-0.92, p < 0.001) compared to warfarin after adjustment. On stratified analyses, DOACs maintained a superior safety profile across CKD stages. Patients with AF on DOACs had a consistently lower risk of cardiovascular and bleeding events than warfarin-treated patients, while among other indications (VTE, peripheral vascular disease, and arterial embolism), the risk of cardiovascular and bleeding events was the same among DOAC and warfarin users.. DOACs may be a safer alternative to warfarin even among CKD and ESKD patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Cohort Studies; Female; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Insufficiency, Chronic; Severity of Illness Index; United States; Warfarin

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

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

Topics: Administration, Oral; Antifibrinolytic Agents; Antithrombins; Atrial Fibrillation; Consensus; Delphi Technique; Diabetes Complications; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; Vascular Diseases; Warfarin

Warfarin significantly accelerates medial arterial calcification in humans. This effect is markedly augmented in end-stage renal disease.

Topics: Aged; Anticoagulants; Breast; Case-Control Studies; Disease Progression; Female; Humans; Kidney Failure, Chronic; Mammography; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Vascular Calcification; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Renal Dialysis; Warfarin

Direct oral anticoagulants (DOACs) are effective alternatives to warfarin for stroke prevention in patients with atrial fibrillation (AF) including patients with CKD III. However, data on patient outcomes with DOACs for advanced CKD are limited, while warfarin use is controversial.. A retrospective study of patients with AF using DOACs and CKD stages III-V was conducted. The primary outcomes were stroke or systemic embolism and major bleeding while on DOAC therapy among CKD IV and V patients. Rates of outcomes from the DOAC trials and from previous studies of warfarin in CKD were referenced.. Of 316 patients reviewed, 152 were included with mean CrCl of 38.8 mL/min. Stroke and systemic embolism occurred at a rate of 1.17 per 100 person-years, with no significant difference between CKD IV/V and CKD III (P = .567). Rates were comparable to DOAC use from the DOAC trials, and lower than rates in studies of warfarin in CKD IV/V patients. There was a nonstatistically significant trend toward increased major bleeding in CKD IV/V patients. Rates of major bleeding in CKD III to V subjects were comparable to published rates for warfarin users with similar levels of renal impairment.. In our study, DOACs appeared to be as efficacious and safe in CKD IV and V as in CKD III. In addition, DOACs appeared to be more effective than, and as safe as warfarin when compared with reference studies of patients with advanced CKD. Our findings support the use of DOACs for thromboembolism prevention in patients with advanced CKD and AF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

There is conflicting evidence regarding the safety and effectiveness of warfarin for atrial fibrillation (AF) treatment among older end-stage renal disease (ESRD) patients, and differences among subgroups are unclear.. Older dialysis patients who were newly diagnosed with AF (7/2007-12/2011) were identified in the United States Renal Data System. The adjusted hazard ratios (HR) of the outcomes (any stroke, ischaemic stroke, major bleeding, severe gastrointestinal bleeding, and death) by time-varying warfarin use were estimated using Cox regression accounting for the inverse probability of treatment weight.. Among 5765 older dialysis patients with incident AF, warfarin was associated with significantly increased risk of major bleeding (HR = 1.50, 95% CI 1.33-1.68), but was not statistically associated with any stroke (HR = 0.92, 95% CI 0.75-1.12), ischaemic stroke (HR = 0.88, 95%CI 0.70-1.11) or gastrointestinal bleeding (HR = 1.03, 95% CI 0.80-1.32). Warfarin use was associated with a reduced risk of mortality (HR = 0.72, 95%CI 0.65-0.80). The association between warfarin and major bleeding differed by sex (male: HR = 1.29; 95%CI 1.08-1.55; female: HR = 1.67; 95%CI 1.44-1.93; P-value for interaction = 0.03).. Older ESRD patients with AF who were treated with warfarin had a no difference in stroke risk, lower mortality risk, but increased major bleeding risk. The bleeding risk associated with warfarin was greater among women than men. The risk/benefit ratio of warfarin may be less favourable among older women.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Incidence; Kidney Failure, Chronic; Male; Renal Dialysis; Risk Assessment; Risk Factors; Sex Factors; Stroke; Time Factors; Treatment Outcome; United States; Warfarin

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

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

Little is known about how warfarin is prescribed for stroke prevention in maintenance dialysis patients with chronic atrial fibrillation (AF). We examined patterns of warfarin use, and associated factors, after AF diagnosis. This retrospective cohort analysis studied US Medicare patients receiving maintenance dialysis January 1, 2008, to June 30, 2010. Demographics, co-morbidity, and a durable medical equipment claims-based disability proxy score predicted warfarin prescription after AF diagnosis. The analysis included 8,964 patients with nonvalvular AF. Compared with nonusers, warfarin users were younger (age 65.4 ± 12.1 vs 67.0 ± 12.9 years) and more likely to be men (54.3% vs 52.8%) and of white race (64.0% vs 59.6%). After adjustment for other factors, nonwhite, versus white, race was associated with significantly less warfarin use within 30 days: odds ratios (ORs), 95% confidence intervals (CIs), were 0.80, 0.71 to 91, for black patients; 0.57, 0.43 to 0.76, for Asians; and 0.74, 0.49 to 1.12, for members of other races. Percentages of patients receiving warfarin decreased as Hypertension Abnormal renal and liver function Stroke-Bleeding Labile INR Elderly Drugs or alcohol (HAS-BLED) bleeding risk score increased (OR 0.82, 95% CI 0.73 to 0.92, HAS-BLED score 3 to 4 versus 2; 0.38, 0.26 to 0.57, score ≥ 5 vs 2). However, as CHA

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chronic Disease; Ethnicity; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Practice Patterns, Physicians'; Renal Dialysis; Retrospective Studies; Stroke; United States; Warfarin; White People; Young Adult

Topics: Atrial Appendage; Factor Xa Inhibitors; Female; Humans; Kidney Failure, Chronic; Middle Aged; Pyrazoles; Pyridones; Renal Dialysis; Thrombosis; Video Recording; Warfarin

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

Topics: Algorithms; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Renal Dialysis; Secondary Prevention; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

BACKGROUND Worldwide, the treatment of patients with chronic kidney disease (CKD) remains a challenge as warfarin treatment can be associated with severe adverse events related to bleeding. Alternative anticoagulants that can be used in CKD remain to be identified. This study aimed to compare the effects of indobufen, a new antiplatelet agent, with warfarin in a rat model of adenine-induced CKD. MATERIAL AND METHODS Forty-eight male Wistar rats were treated with intragastric adenine to create the rat model of CKD and were divided into four groups: an untreated control group (N=12), a group treated with dimethyl sulfoxide (DMSO) (N=12), a group treated with indobufen, (N=12) and a group treated with warfarin (N-12). Treatment was given for 4 weeks and 8 weeks. Kidney histology was performed, and the degree of fibrosis was quantified using Masson trichrome staining. RESULTS In the rat model of adenine-induced CKD, Masson trichrome staining showed that the degree of kidney fibrosis in the indobufen group (26%) was significantly reduced (p<0.05) when compared the DMSO group (58%) and the warfarin group (49%). Kidney fibrosis was associated with upregulation of 6-keto-PGI2/TXB2 in the rat kidney tissue. CONCLUSIONS In a rat model of adenine-induced CKD, preliminary findings showed that indobufen was associated with reduced kidney fibrosis when compared with warfarin.

Topics: Adenine; Animals; Anticoagulants; China; Disease Models, Animal; Fibrosis; Isoindoles; Kidney; Kidney Failure, Chronic; Male; Phenylbutyrates; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Renal Insufficiency, Chronic; Warfarin

Vascular calcification is highly prevalent in end-stage renal disease (ESRD) and is a significant risk factor for future cardiovascular events and death. Warfarin use results in dysfunction of matrix Gla protein, an inhibitor of vascular calcification. However, the effect of warfarin on vascular calcification in patients with ESRD is still not well characterized. Thus we investigated whether arterial calcification can be accelerated by warfarin treatment both in vitro and in vivo using a mouse remnant kidney model.. Human aortic smooth muscle cells (HASMC) were cultured in medium supplemented with warfarin and phosphate to investigate the potential role of this drug in osteoblast transdifferentiation. For in vivo study, adult male C57BL/6 mice underwent 5/6 nephrectomy were treated with active vitamin D3 plus warfarin to determine the extent of vascular calcification and parameters of cardiovascular function.. We found that the expressions of Runx2 and osteocalcin in HASMC were markedly enhanced in the culture medium containing warfarin and high phosphate concentration. Warfarin induced calcification of cultured HASMC in the presence of high phosphate levels, and this effect is inhibited by vitamin K2. Severe aortic calcification and reduced left ventricular ejection fractions were also noted in 5/6 nephrectomy mice treated with warfarin and active vitamin D3.. Warfarin treatment contributes to the accelerated vascular calcification in animal models of advanced chronic kidney disease. Clinicians should therefore be aware of the profound risk of warfarin use on vascular calcification and cardiac dysfunction in patients with ESRD and atrial fibrillation.

Topics: Animals; Anticoagulants; Cells, Cultured; Heart Diseases; Humans; Kidney Failure, Chronic; Male; Mice; Mice, Inbred C57BL; Myocytes, Smooth Muscle; Nephrectomy; Vascular Calcification; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Renal Dialysis; Stroke; Warfarin

Topics: Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Warfarin

Current guidelines make no specific recommendations on the selection of direct oral anticoagulants for the prevention and treatment of venous thromboembolism in patients with end-stage renal disease (ESRD) receiving hemodialysis. Based on these guidelines, warfarin remains the anticoagulant of choice in these patients.. To compare bleeding rates in patients receiving apixaban or warfarin with ESRD undergoing chronic hemodialysis.. This was a single-center, retrospective, institutional review board-approved cohort analysis. Patients with ESRD undergoing chronic hemodialysis and receiving anticoagulation therapy with either apixaban or warfarin were included in this study. All data were collected from paper charts and electronic medical records and included documentation of bleeding events and related interventions. The primary outcome of this study was clinically relevant major bleeding events. Secondary outcomes included clinically relevant nonmajor bleeding events and minor bleeding events.. A total of 160 patients were included in this study (warfarin group, n = 120; apixaban group, n = 40). There were 7 major bleeding events in the warfarin group compared with zero in the apixaban group ( P = 0.34). There were similar rates of clinically relevant nonmajor bleeding events (12.5% vs 5.8%, P = 0.17) and minor bleeding (2.5% vs 2.5%, P = 0.74) events in patients receiving apixaban and warfarin.. There were no observed differences in bleeding rates in patients receiving apixaban compared with those receiving warfarin. Apixaban may be a cautious consideration in hemodialysis patients until there is further insight into the effect of subsequent, multiple doses on drug accumulation and clinical outcomes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Humans; Kidney Failure, Chronic; Patient Safety; Pyrazoles; Pyridones; Warfarin

The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry.. Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models.. Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Databases, Factual; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Kidney Failure, Chronic; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Renal Dialysis; Republic of Korea; Stroke; Thromboembolism; Warfarin

Controversy exists regarding the benefits and risks of warfarin therapy in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In this study, we assessed mortality and cardiovascular outcomes associated with warfarin treatment in patients with stages 3-5 CKD and ESRD admitted to the University of California-Irvine Medical Center.. In a retrospective matched cohort study, we identified 59 adult patients with stages 3-6 CKD initiated on warfarin during the period 2011-2013, and 144 patients with stages 3-6 CKD who had indications for anticoagulation therapy but were not initiated on warfarin. All-cause mortality risk associated with warfarin treatment was estimated using Cox proportional hazard regression analysis, and the risk of significant bleeding and major adverse cardiovascular events were analyzed with Poisson regression analysis. Adjustment models were used to account for age, gender, diabetes mellitus, use of antiplatelet agents, and preexisting cardiovascular disease, and stratified by pre-dialysis CKD stages 3-5 vs. ESRD.. During 5.8 years of follow-up, unadjusted mortality risk was higher in CKD patients on warfarin therapy (hazard ratio [HR] 2.34 with 95% CI 1.25-4.39; p < 0.01). After multivariate adjustment and stratification by CKD stage, the mortality risk remained significant in ESRD patients receiving warfarin (HR 6.62 with 95% CI 2.56-17.16; p < 0.001). Furthermore, adjusted rates of significant bleeding (incident rate ratio, IRR 3.57 with 95% CI 1.51-8.45; p < 0.01) and myocardial infarction (IRR 4.20 with 95% CI 1.78-9.91; p < 0.01) were higher among warfarin users. No differences in rates of ischemic or hemorrhagic strokes were found between the 2 groups.. Warfarin use was associated with several-fold higher risk of death, bleeding, and myocardial infarction in dialysis patients. If additional studies suggest similar associations, the use of warfarin in dialysis patients warrants immediate reconsideration.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Hemorrhage; Hospitalization; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Pulmonary Embolism; Renal Dialysis; Retrospective Studies; Risk Assessment; Stroke; Thrombosis; Treatment Outcome; Warfarin

Stroke risk may be more than 3-fold higher among patients with chronic kidney disease stage 5D (CKD-5D) compared to the general population, with the highest stroke rates noted among those 85 years and older. Atrial fibrillation (AF), a strong risk factor for stroke, is the most common arrhythmia and affects >7% of the population with CKD-5D. Warfarin use is widely acknowledged as an important intervention for stroke prevention with nonvalvular AF in the general population. However, use of oral anticoagulants for stroke prevention in patients with CKD-5D and nonvalvular AF continues to be debated by the nephrology community. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) controversies report, we discuss the existing observational studies that examine warfarin use and associated stroke and bleeding risks in adults with CKD-5D and AF. Non-vitamin K-dependent oral anticoagulants and their potential use for stroke prevention in patients with CKD-5D and nonvalvular AF are also discussed. Data from randomized clinical trials are urgently needed to determine the benefits and risks of oral anticoagulant use for stroke prevention in the setting of AF among patients with CKD-5D.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Renal Dialysis; Rivaroxaban; Stroke; Thiazoles; Warfarin

Calcific uremic arteriolopathy (CUA) is an often-fatal condition in dialysis patients. The clinical descriptions and treatments of CUA patients have been confined mostly to case reports. We report a comprehensive characterization of CUA and its associated diagnosis, treatment patterns, and outcome.. An internet-based registry collected information about CUA in dialysis patients. Univariate analysis using Cox proportional hazards models estimated hazard ratios of the association between clinical characteristics, laboratory values, and treatments with all-cause mortality.. A total of 117 CUA patients had adequate information for analysis. The majority of patients (56.7%) were diagnosed clinically, with only 32.5% biopsied. Debridement was undertaken in 42.6% of cases. Intravenous sodium thiosulfate (STS) was initiated in 54.7% of patients; most received ≥ 12.5 g of STS (98.3%) for < 3 months (79.7%). Mean parathyroid hormone (PTH) and phosphorus (P) were 459 ± 492 pg/mL and 6.3 ± 2.1 mg/dL, respectively. A total of 24 patients (21.6%, of 111 with information) died, with a median survival time of 2.9 months. In univariate analysis, higher mortality was observed in patients with cardiovascular disease (CVD; HR = 10.47; 95% CI 1.40-78.38), those taking warfarin at time of diagnosis (HR = 2.74; 95% CI 1.16-6.51), and those who had both diabetes (DM) and CVD and who were taking warfarin (HR = 13.41; 95% CI 1.66-109.29).. In real-world clinical practice, there is substantial variability in the diagnosis and treatment of CUA. There is usually only modest derangement of bone and mineral parameters at the time of diagnosis. Death is common. The presence of CVD and use of warfarin may influence clinical outcome after diagnosis of CUA.

Topics: Aged; Anticoagulants; Arterioles; Calciphylaxis; Cardiovascular Diseases; Chelating Agents; Debridement; Diabetes Mellitus; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Registries; Renal Dialysis; Risk Factors; Survival Rate; Thiosulfates; Warfarin

The aim of this study was to evaluate, in a cohort of haemodialysis patients with atrial fibrillation (AF), the relationship between oral anticoagulant therapy (OAT) and mortality, thromboembolic events and haemorrhage.. Two hundred and ninety patients with AF were prospectively followed for 4 years. Warfarin and antiplatelet intake, age, dialytic age, comorbidities, CHA. At recruitment, 134/290 patients were taking warfarin. During follow-up there were 170 deaths, 28 thromboembolic events and 95 bleedings. After balancing for treatment propensity, intention-to-treat analysis on OAT intake at recruitment did not show differences in total mortality, thromboembolic events and bleedings, while the as-treated analysis, accounting for treatment switch, showed that patients taking OAT at recruitment had a significantly lower mortality than those not taking it [hazard ratio, HR 0.53 (95% confidence interval 0.28-0.90), p = 0.04], with a decrease of thromboembolic events [HR 0.36 (0.13-1.05), p = 0.06], and an increase of bleedings [HR 1.79 (0.72-4.39), p = 0.20], both non-significant. Among patients taking OAT at recruitment, those continuing to take warfarin had a significant reduction in the risk of total [HR 0.28 (0.14-0.53), p < 0.001] and cardiovascular [HR 0.21 (0.11-0.40), p < 0.001] mortality compared to patients stopping OAT.. In haemodialysis patients with AF, continuously taking warfarin is associated with a reduction of the risk of total and cardiovascular mortality.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Female; Hemorrhage; Humans; Intention to Treat Analysis; Italy; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Protective Factors; Renal Dialysis; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

There is increasing evidence questioning the use of warfarin for atrial fibrillation (AF) among older adults with end stage renal disease (ESRD). We assessed the patterns and determinants of warfarin utilization among these patients in the US.. We assembled a cohort of older adults (age ≥65) undergoing dialysis with incident AF from July 2007 to November 2011 from the US Renal Data System (USRDS). We used descriptive statistics to characterize warfarin utilization within 30 days of AF discharge, and logistic regression to quantify patient characteristics associated with warfarin initiation.. Among 5730 older adults undergoing dialysis with incident AF, 15.5% initiated warfarin. Among 2906 patients with high risk of bleeding, 12.7% initiated warfarin; whereas 14.9% initiated warfarin among 4824 patients with high risk of stroke. After adjustment for patient characteristics, warfarin initiation was lower among patients who were older [odds ratio (OR) = 0.74 per 10-year increase, 95% confidence interval (CI) 0.66-0.83] and those with a history of diabetes (OR = 0.75, 95% CI 0.63-0.90), myocardial infarction (OR = 0.64, 95% CI 0.50-0.80), or bleeding (OR = 0.63, 95% CI 0.50-0.80). There was no association between sex, race, or dialysis modality and warfarin initiation. Among patients who initiated warfarin, 46.8% discontinued warfarin use after a median treatment length of 8.6 months.. Despite the unclear benefit and increased bleeding risk of warfarin treatment in patients with ESRD, 1 in 8 older adults undergoing dialysis with incident AF in the US who had high risk of bleeding used warfarin. Changes to warfarin therapy due to discontinuation were common after initiation.

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

The optimal management of stroke prophylaxis in hemodialysis patients with atrial fibrillation is controversial.. The purpose of this study was to determine the risk of mortality, stroke, and bleeding associated with the use of warfarin in hemodialysis patients with atrial fibrillation.. This was a retrospective, population-based study of hemodialysis patients with atrial fibrillation between January 1, 2006, and September 30, 2015. Association of warfarin use with mortality, stroke, and bleeding was determined by propensity score-matched, Cox proportional hazard models.. Among the 4286 patients with atrial fibrillation on hemodialysis, 989 (23%) were prescribed warfarin. Propensity score matching was used to identify 888 matched pairs with similar baseline characteristics. Warfarin use was associated with lower risk of all-cause death (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.69-0.84) and lower risk of ischemic stroke (HR 0.68, 95% CI 0.52-0.91). Warfarin use was not associated with a higher risk of hemorrhagic stroke (HR 1.2, 95% CI 0.6-2.2) or gastrointestinal bleeding (HR 0.97, 95% CI 0.77-1.2). The treatment effect was largest in the group with the best international normalized ratio control as measured by time in therapeutic range. Subgroup analyses showed warfarin use was associated with survival benefit in most subgroups. The 2 subgroups that did not benefit were patients with a history of hemorrhagic stroke and patients with concurrent aspirin use.. Warfarin use is associated with lower all-cause mortality and ischemic stroke, without significantly increasing the risk of bleeding in hemodialysis patients with atrial fibrillation.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kidney Failure, Chronic; Propensity Score; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Warfarin

Atrial fibrillation (AF) is one of the major risk factor for ischemic stroke, and oral anticoagulation is generally indicated for prevention of stroke. However, the utility of oral anticoagulation for AF in dialysis patients remains controversial. In this single-center, retrospective, observational study, data from 1120 patients on maintenance hemodialysis were analyzed. Baseline medical data were collected from dialysis records including age, gender, the cause of end-stage renal disease, dialysis vintage, and comorbidities. We evaluated outcomes including stroke, major hemorrhage, and death. A total of 106 (11.4 %) patients had AF. After exclusion criteria were applied, 84 patients had analyzable data. Warfarin was prescribed in 30 (35.7 %) of these patients. The remaining 54 patients were classified as the non-warfarin group. CHADS2 score was not significantly different between the warfarin and non-warfarin group. During the mean 47 months of follow up, 7 strokes occurred. However, warfarin use was not associated with the risk for stroke [hazard ratio (HR) 1.07; 95 % confidence interval (CI) 0.20-5.74]. Kaplan-Meier analysis showed no statistically significant difference in the overall survival, stroke-free survival or bleeding-free survival between the warfarin and non-warfarin group. AF is common in Japanese dialysis patients. Despite a certain prevalence of oral anticoagulation, the present study demonstrated neither beneficial nor detrimental effects. A large randomized controlled trial should be considered.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Incidence; Japan; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Risk Factors; Stroke; Warfarin

Stroke prevention in dialysis-dependent patients with atrial fibrillation (AF) is an unresolved clinical dilemma. Indeed, no randomized controlled trial evaluating the efficacy and safety of oral anticoagulants in this population, has been conducted so far. Observational research on the use of warfarin in patients on dialysis has shown conflicting results. This uncertainty is mirrored by the wide variations in warfarin prescription patterns across centers. We sought to evaluate the association between the use of vitamin K antagonists (VKAs) and mortality among hemodialysis patient with AF and to assess potential factors affecting the risk-benefit profile of warfarin in this population.. A total of 91,987 patients registered in the European Clinical Dialysis Database® system from January 2004 to January 2015. Of which, 9,238 patients were identified with a diagnosis of AF. After excluding ineligible patients, a 1:1 propensity score matched cohort of 1,324 warfarin users and non-users were assembled.. VKA use was associated with both increased 90-day survival (hazard ratio, HR 0.47, p < 0.01) and 6-year survival (HR 0.76, p < 0.01); however, a trend indicated a stronger early benefit (p for time-interaction <0.01). Moderation analysis showed that patients' age and clinical history of stroke strongly influenced warfarin-related benefits on survival.. VKA may provide an early survival benefit; however, this is partially offset later during the follow-up. In addition, heterogeneous risk-benefit profiles were observed among subgroups of dialysis-dependent patients with AF, further emphasizing the complexities of tailoring stroke prevention strategies in this population.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Europe; Humans; Kidney Failure, Chronic; Middle Aged; Mortality; Propensity Score; Registries; Renal Dialysis; Risk Assessment; Stroke; Survival Rate; Time Factors; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Renal Dialysis; Stroke; Thromboembolism; Warfarin

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

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

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Stroke; Warfarin

Warfarin has had a thin margin of benefit over risk for the prevention of stroke and systemic embolism in patients with ESRD because of higher bleeding risks and complications of therapy. The successful use of warfarin has been dependent on the selection of patients with nonvalvular atrial fibrillation at relatively high risk of stroke and systemic embolism and lower risks of bleeding over the course of therapy. Without such selection strategies, broad use of warfarin has not proven to be beneficial to the broad population of patients with ESRD and nonvalvular atrial fibrillation. In a recent meta-analysis of use of warfarin in patients with nonvalvular atrial fibrillation and ESRD, warfarin had no effect on the risks of stroke (hazard ratio, 1.12; 95% confidence interval, 0.69 to 1.82; P=0.65) or mortality (hazard ratio, 0.96; 95% confidence interval, 0.81 to 1.13; P=0.60) but was associated with increased risk of major bleeding (hazard ratio, 1.30; 95% confidence interval, 1.08 to 1.56; P<0.01). In pivotal trials, novel oral anticoagulants were generally at least equal to warfarin for efficacy and safety in nonvalvular atrial fibrillation and mild to moderate renal impairment. Clinical data for ESRD are limited, because pivotal trials excluded such patients. Given the very high risk of stroke and systemic embolism and the early evidence of acceptable safety profiles of novel oral anticoagulants, we think that patients with ESRD should be considered for treatment with chronic anticoagulation provided that there is an acceptable bleeding profile. Apixaban is currently indicated in ESRD for this application and may be preferable to warfarin given the body of evidence for warfarin and its difficulty of use and attendant adverse events.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Kidney Failure, Chronic; Patient Selection; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Warfarin

Antiphospholipid syndrome (APS), autoantibodies directed against phospholipid-binding proteins are associated with cause vascular thrombosis. Patients with APS requiring renal transplantation are at risk of early graft loss due to arterial or venous thrombosis, or thrombotic microangiopathy (TMA). Here, we report 3 cases of successful renal transplantation in patients with APS.. A 53-year-old man with end-stage renal disease (ESRD) had experienced bilateral deep venous thrombosis (DVT) in the lower extremities 16 years ago and was administered warfarin. However, he frequently experienced recurrent DVT despite of anticoagulation therapy. Before the surgery, APS was confirmed based on positive results lupus anticoagulant in serological tests. A 40-year-old man with polycystic kidney disease and a history recurrent DVT tested positive for lupus anticoagulant and anticardiolipin antibodies. Lastly, a 42-year-old woman with ESRD was diagnosed with APS 7 years ago. She also developed DVT and tested positive for lupus anticoagulant and anti-B2-glycoprotein 1.. Warfarin was stopped 5 days before living donor renal transplantation and intravenous heparin therapy was started. During surgery, bolus heparin injections (3000 U) were administered to prevent arterial or venous thrombosis. Heparin was substituted with warfarin on postoperative day 4. The third patient (42/F) developed clinical rejection indicated by increased serum creatinine levels and donor-specific antibodies (DSA) and received steroid pulse therapy, plasmapheresis, and rituximab. This treatment restored graft function to within the normal range. The latest graft function in all patients was maintained at normal levels in the outpatient clinic.. Living donor renal transplantation may be successful in patients with APS following perioperative anticoagulation therapy. However, because of the high risk of TMA or vascular thrombosis in the early postoperative period, close monitoring for hypercoagulability and continuous anticoagulation is essential for maintaining graft function.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Drug Substitution; Female; Graft Rejection; Heparin; Humans; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Male; Middle Aged; Plasmapheresis; Recurrence; Treatment Outcome; Venous Thrombosis; Warfarin

Dabigatran and rivaroxaban are new oral anticoagulants that are eliminated through the kidneys. Their use in dialysis patients is discouraged because these drugs can bioaccumulate to precipitate inadvertent bleeding. We wanted to determine whether prescription of dabigatran or rivaroxaban was occurring in the dialysis population and whether these practices were safe.. Prevalence plots were used to describe the point prevalence (monthly) of dabigatran and rivaroxaban use among 29977 hemodialysis patients with atrial fibrillation. Poisson regression compared the rate of bleeding, stroke, and arterial embolism in patients who started dabigatran, rivaroxaban, or warfarin. The first record of dabigatran prescription among hemodialysis patients occurred 45 days after the drug became available in the United States. Since then, dabigatran and rivaroxaban use in the atrial fibrillation-end-stage renal disease population has steadily risen where 5.9% of anticoagulated dialysis patients are started on dabigatrian or rivaroxaban. In covariate adjusted Poisson regression, dabigatran (rate ratio, 1.48; 95% confidence interval, 1.21-1.81; P=0.0001) and rivaroxaban (rate ratio, 1.38; 95% confidence interval, 1.03-1.83; P=0.04) associated with a higher risk of hospitalization or death from bleeding when compared with warfarin. The risk of hemorrhagic death was even larger with dabigatran (rate ratio, 1.78; 95% confidence interval, 1.18-2.68; P=0.006) and rivaroxaban (rate ratio, 1.71; 95% confidence interval, 0.94-3.12; P=0.07) relative to warfarin. There were too few events in the study to detect meaningful differences in stroke and arterial embolism between the drug groups.. More dialysis patients are being started on dabigatran and rivaroxaban, even when their use is contraindicated and there are no studies to support that the benefits outweigh the risks of these drugs in end-stage renal disease.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Databases, Factual; Dose-Response Relationship, Drug; Drug Utilization; Female; Hemorrhage; Hospitalization; Humans; Kidney; Kidney Failure, Chronic; Male; Matched-Pair Analysis; Middle Aged; Morpholines; Poisson Distribution; Practice Patterns, Physicians'; Renal Dialysis; Retrospective Studies; Risk; Rivaroxaban; Stroke; Thiophenes; Warfarin

Caseous mitral annulus calcification involving aortomitral curtain is a rare occurrence. We report a case of a 64-year-old woman with end-stage renal failure and a candidate for renal transplant who presented with late ST-elevation myocardial infarction. Intracoronary imaging, computed tomography cardiac imaging, and histopathology confirmed coronary embolus into the left main stem artery from an extensive caseous mitral annulus calcification.

Topics: Anticoagulants; Coronary Angiography; Coronary Vessels; Embolism; Female; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Middle Aged; Mitral Valve; Multimodal Imaging; Myocardial Infarction; Predictive Value of Tests; Risk Assessment; Sensitivity and Specificity; Tomography, Spiral Computed; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Interventional; Vascular Calcification; Warfarin

Topics: Anticoagulants; Hematoma; Humans; Kidney Failure, Chronic; Kidney Transplantation; Postoperative Complications; Prognosis; Retrospective Studies; Risk Factors; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers.

Topics: Aged; Antidotes; Antithrombins; Atrial Fibrillation; Blood Coagulation Factors; Blood Transfusion; Clinical Protocols; Clinical Trials, Phase III as Topic; Disease Management; Drug Design; Factor Xa Inhibitors; Hemorrhage; Hemostatic Techniques; Humans; Intracranial Hemorrhages; Kidney Failure, Chronic; Meta-Analysis as Topic; Neoplasms; Perioperative Care; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Assessment; Thrombophilia; Vulnerable Populations; Warfarin

Although warfarin is indicated to prevent ischemic strokes in most patients with atrial fibrillation (AF), evidence supporting its use in hemodialysis patients is limited. Our aim was to examine outcomes after warfarin therapy initiation, relative to no warfarin use, following incident AF in a large cohort of hemodialysis patients who had comprehensive prescription drug coverage through Medicare Part D.. Retrospective observational cohort study.. Patients in the US Renal Data System undergoing maintenance hemodialysis who had AF newly diagnosed in 2007 to 2011, with Medicare Part D coverage, who had no recorded history of warfarin use.. Warfarin therapy initiation, identified by a filled prescription within 30 days of the AF event.. Death, ischemic stroke, hemorrhagic stroke, severe gastrointestinal bleeding, and composite outcomes.. HRs estimated by applying Cox regression to an inverse probability of treatment and censoring-weighted cohort.. Of 12,284 patients with newly diagnosed AF, 1,838 (15%) initiated warfarin therapy within 30 days; however, ∼70% discontinued its use within 1 year. In intention-to-treat analyses, warfarin use was marginally associated with a reduced risk of ischemic stroke (HR, 0.68; 95% CI, 0.47-0.99), but not with the other outcomes. In as-treated analyses, warfarin use was associated with reduced mortality (HR, 0.84; 95% CI, 0.73-0.97).. Short observation period, limited number of nonfatal events, limited generalizability of results to more affluent patients.. In hemodialysis patients with incident AF, warfarin use was marginally associated with reduced risk of ischemic stroke, and there was a signal toward reduced mortality in as-treated analyses. These results support clinical equipoise regarding the use of warfarin in hemodialysis patients and underscore the need for randomized trials to fill this evidence gap.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Cohort Studies; Databases, Factual; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Risk Assessment; Stroke; Survival Rate; Treatment Outcome; Warfarin

The functional expression of several hepatic drug metabolizing enzymes and transporters are altered in patients with end-stage renal disease (ESRD). We aimed to assess the effect of ESRD on the expression and function of hepatic reductases. Cytosolic and microsomal fractions were isolated from liver tissue from deceased ESRD (n=10) and deceased control patients (n=11). Gene and protein expression, and metabolic activity of reductases were assessed by conducting qRT-PCR, Western blotting and enzyme kinetics, respectively. A 65% decrease in carbonyl reductase 1 protein expression (p<0.05), and a trend toward decreased reductase mRNA expression and activity was observed in ESRD livers versus controls. These results demonstrate a trend toward decreased functional expression of selective hepatic reductases in ESRD livers, which may partially explain altered pharmacokinetics of CBR1 drug substrates in ESRD. Future studies with larger sample size are warranted to confirm these findings.

Topics: Aged; Alcohol Oxidoreductases; Case-Control Studies; Down-Regulation; Female; Gene Expression Regulation, Enzymologic; Humans; Kidney Failure, Chronic; Kinetics; Liver; Male; Middle Aged; Oxidation-Reduction; RNA, Messenger; Substrate Specificity; Warfarin

Although generally recommended for atrial fibrillation (AF) in the general population, the efficacy and safety of warfarin in hemodialysis patients remains controversial. Warfarin use in hemodialysis patients may confer an additional risk of bleeding that is not appreciated in patients without renal failure because hemodialysis patients have platelet defects and receive anticoagulation agents during dialysis. The incidence of major bleeding was reported to be higher in Japanese AF patients on warfarin therapy compared to patients in other countries, suggesting that racial differences may influence bleeding tendency. Thus, examining risks and benefits of warfarin therapy in Japanese hemodialysis patients with AF is important.. In order to determine associations between warfarin use and new ischemic stroke events, major bleeding, and all-cause mortality, a prospective cohort study of 60 Japanese hemodialysis patients with chronic sustained AF was conducted using Cox proportional modeling and propensity score matching.. The mean patient age was 68.1 years. During 110 person-years of follow-up, 13 ischemic strokes occurred. After adjusting for CHADS2 score, warfarin use was not associated with a significant reduction in ischemic stroke events [hazard ratio (HR) 3.36; 95 % confidence interval (CI) 0.94-11.23]. Similar results were obtained after propensity score matching (HR 3.36; 95 % CI 0.67-16.66). Warfarin use was not associated with significant increases in major bleeding or all-cause mortality.. These results suggest that warfarin may not prevent ischemic stroke in Japanese hemodialysis patients with chronic sustained AF. Adequately powered studies are needed to determine the risks and benefits of anticoagulation therapy in these patients.

Topics: Aged; Anticoagulants; Asian People; Atrial Fibrillation; Brain Ischemia; Chronic Disease; Female; Hemorrhage; Humans; Incidence; Japan; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Risk Factors; Stroke; Time Factors; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Calciphylaxis; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Renal Dialysis; Stroke; Warfarin

The effect of chronic kidney disease (CKD) on warfarin has gained attention because of an increased risk of thromboembolism and an increased risk of bleeding associated with warfarin treatment in these patients. Data suggest that patients with reduced kidney function require lower warfarin doses; however, relatively few patients with end-stage renal disease (ESRD) were included in previous studies. The goal of this study was to evaluate warfarin dosing requirements and time to reach therapeutic international normalized ratio (INR) in patients with CKD stages 3-5 and ESRD compared with patients with normal kidney function (NKF).. A historical cohort was identified to evaluate warfarin response in 210 hospitalized adults with varying degrees of kidney function initiated or maintained on warfarin for 4 or more consecutive days including 49 patients with NKF (glomerular filtration rate [GFR] higher than 60 ml/min/1.73 m(2) ), 44 with CKD stage 3, 27 with CKD stage 4/5, and 90 with ESRD. The average daily dose (ADD), time to achieve a therapeutic INR, and adverse effects were compared.. The ADD to maintain a therapeutic INR was 5.6 ± 1.7 mg in the NKF group, 4.3 ± 1.6 mg in CKD stage 3, 4.6 ± 1.9 mg in CKD stage 4/5, and 4.8 ± 1.9 mg in ESRD. The ADD was lower in CKD/ESRD patients compared with NKF patients (p=0.001), especially among whites. The time to reach a therapeutic INR in patients newly initiated on warfarin was significantly lower in the CKD/ESRD group when compared with the NKF group (p=0.02). No differences in bleeding episodes were observed during hospitalization or within 30 days of discharge in patients with CKD stage 3 or higher compared with patients with NKF.. Our findings suggest that CKD and ESRD patients require ~20% lower warfarin doses to maintain a therapeutic INR and may require less time to achieve a therapeutic INR compared with patients with NKF.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Dose-Response Relationship, Drug; Drug Evaluation; Female; Hospitalization; Humans; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Warfarin

Accelerated progression of aortic stiffness in patients with advanced chronic kidney disease is not well explained by the traditional cardiovascular risk factors. We hypothesized that vitamin K deficiency may result in an accelerated progression of aortic stiffness in the pro-calcifying uremic milieu.. Eighteen hemodialysis (HD) patients on warfarin were matched to 54 HD patients without warfarin (control). Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. In the control group, spontaneous vitamin K deficiency was defined as proteins induced by vitamin K deficiency/absence-II >median.. At baseline, clinical characteristics and cf-PWV were similar. Adjusted cf-PWV increased by 0.86 ± 1.87 m/s in control and by 2.24 ± 2.68 m/s in warfarin group (P = 0.024). After adjustments for confounders, warfarin therapy was independently associated with progression of aortic stiffness (P = 0.016). The rate of progression of aortic stiffness showed a linear trend in response to vitamin K status and warfarin therapy, suggesting that at least part of the effects are mediated through reduced availability of vitamin K. The unadjusted and adjusted hazard ratio (HR) of warfarin therapy on mortality were, respectively, 2.40 (P = 0.006) and 2.53 (P = 0.006). In a forward conditional Cox regression analysis, age, albumin, augmentation index (AIx) and a cf-PWV > 13.8 m/s at the time of follow-up (HR: 2.11, P = 0.05) were independent determinants of mortality, whereas warfarin use was not retained as an independent factor. Finally, control patients with poor vitamin K status had an intermediate survival as compared with controls with better vitamin K status and patients with warfarin (P = 0.01).. This is the first study to show a temporal association between warfarin, functional vitamin K deficiency and progression of aortic stiffness in HD patients. These findings suggest that the net cardiovascular benefit of long-term warfarin therapy may need to be reevaluated in this population.

Topics: Aged; Anticoagulants; Aorta, Thoracic; Cardiovascular Diseases; Disease Progression; Female; Follow-Up Studies; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Pulse Wave Analysis; Quebec; Renal Dialysis; Risk Factors; Survival Rate; Time Factors; Vascular Stiffness; Warfarin

Early graft thrombosis and bleeding complications remain important causes of early graft loss following kidney transplantation in patients with antiphospholipid syndrome. Anti-β2-glycoprotein I IgG is a disease-specific antibody in patients with antiphospholipid syndrome. Although plasmapheresis is partially effective for antibody removal, the optimal treatment allowing successful transplantation in patients with antiphospholipid syndrome has not been established. This is the first report of a patient with antiphospholipid syndrome who successfully underwent living-donor kidney transplantation following prophylactic plasmapheresis for removal of anti-β2-glycoprotein I IgG.. A 37-year-old Japanese female was scheduled to undergo a living-donor kidney transplant from her mother. At age 25 years, she experienced renal vein thrombosis, was diagnosed with antiphospholipid syndrome secondary to systemic lupus erythematosus, and was subsequently treated with prednisolone and warfarin. At age 37 years, she was diagnosed with end stage kidney disease, requiring maintenance hemodialysis because of recurrent renal vein thrombosis despite taking anticoagulation therapy. The pretreatment protocol consisted of prophylactic plasmapheresis plus full anticoagulation therapy to counteract the risks of early graft thrombosis. Anticardiolipin and anti-β2-glycoprotein I IgGs were successfully removed by both double filtration plasmapheresis and plasma exchange. The allograft kidney began to function soon after transplantation. No obvious thrombotic complications were observed after transplantation, although anti-β2-glycoprotein I IgG increased to the level observed before plasmapheresis. One year after transplantation, the patient's kidney function remains stable while receiving anticoagulation therapy as well as a maintenance immunosuppressive regimen.. Prophylactic plasmapheresis plus full anticoagulation therapy may be an effective strategy in patients with antiphospholipid syndrome undergoing living-donor kidney transplantation.

Topics: Adrenal Cortex Hormones; Adult; Anticoagulants; Antiphospholipid Syndrome; Autoantigens; beta 2-Glycoprotein I; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Lupus Erythematosus, Systemic; Plasma Exchange; Plasmapheresis; Preoperative Care; Renal Dialysis; Thrombophilia; Thrombosis; Warfarin

Vascular access is often considered the Achilles heel the of hemodialysis because of its impact on morbidity, all cause mortality and finally costs of these patients. The most common complication of permanent hemodialysis (HD) vascular access is thrombosis, with some cases being related to hypercoagulability states. Antiphospholipid antibody syndrome (APAS) is a cause of increased thrombotic tendency, and this may complicate the management of such patients on HD.. We describe a 41-year-old woman with end stage renal disease (ESRD) from Adult Polycystic Kidney Disease who was referred to our tertiary care center for treatment and selection of renal replacement therapy form. It was thought to initiate with peritoneal dialysis considering her actual conditions. She was putted on hemodialysis for several sessions, and a subclavian cathether was her first vascular access. The surgeon created an arterio-venous fistula which did not mature. After the implantation of the peritoneal cathether she started peritoneal dialysis and continued living with that for 2 years. She felt exhausted and because of a grave peritonitis episode accompanied with procedure failure and a long hospitalization she was transferred to hemodialysis. Renal transplantation was not possible because she didn't have a kidney donation. She was maintained on regular HD, but her dialysis care was complicated by recurrent vascular access failures. She had multiple interventions for arterio-venous fistulas and grafts but almost all of them failed due to thrombosis to the extent that only one access site was available for her routine renal replacement treatment. A thorough thrombophilia screen confirmed the presence of antiphospholipid antibodies. A diagnosis of APAS was made and she was anticoagulated with warfarin. The AVG made in this last available site is still working from 18 months. If it fails we have no answers and solutions for her.. The presence of APAS can complicate HD management by causing recurrent vascular access thrombosis and failure, and nephrologist must remain alert to this possibility. Checking and treating as soon as possible it's our future challenge.

Topics: Adult; Anticoagulants; Catheters, Indwelling; Female; Humans; Kidney Failure, Chronic; Renal Dialysis; Thrombosis; Treatment Outcome; Warfarin

Warfarin-related nephropathy (WRN) is a recently described disease entity, in which excessive warfarinization (international normalized ratio (INR) >3.0) causes acute kidney injury. Previous reports regarding WRN included few Asian patients who might have differed from the western WRN patients in terms of genetic and environmental factors.. During the period of March 2003 to December 2011, the data about a total of 1297 patients who had serum creatinine (sCr) level measured within 1 week after INR >3.0 and within 6 months before INR >3.0 was analyzed through the retrospective review of electronic medical records of a single tertiary hospital in Korea.. WRN developed in 19.3% of patients having excessive warfarinization. The incidence was higher in the chronic kidney disease (CKD) group than the non-CKD group. The risk of WRN increased as the basal serum albumin level decreased and was strongly associated with highest quartile serum AST level at post INR elevation and the presence of congestive heart failure. But the presence of atrial fibrillation was protective against the development of WRN. Neither the presence of CKD nor basal estimated glomerular filtration rate (eGFR) was an independent risk factor for WRN. Despite no difference in the basal sCr level, the sCr level was higher in patients with WRN than those without WRN after follow-up. The mortality rates were also higher in patients with WRN.. WRN developed in 19.3% of patients having excessive warfarinization. A lower basal serum albumin, highest quartile serum AST level at post INR elevation, and congestive heart failure were associated with the occurrence of WRN. The development of WRN adversely affected renal and patient outcomes.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Asian People; Creatinine; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Risk Factors; Serum Albumin; Survival Analysis; Warfarin

The purpose of this study was to examine whether long-term use of anticoagulants in elderly patients with atrial fibrillation (AF) and chronic kidney disease (CKD) influences renal function.. In this retrospective observational study, we reviewed the records of 2023 patients who attended our institution for treatment of CKD between January 2001 and September 2012. Inclusion criteria were having been under review for three months or more, age older than 60 years, permanent AF, a CHADS2 score > 2, and National Kidney Foundation Kidney Disease Outcomes Quality Initiative CKD stage 3-5. Sixty-one patients fulfilled these criteria, and were divided into those receiving antiplatelet anticoagulation (group A) and those receiving warfarin (group B). The results of laboratory investigations and estimated glomerular filtration rate (GFR) were recorded at months 3, 6, 12, and 18 from treatment initiation. We also recorded the occurrence of serious cardiovascular and neurological events, significant bleeding, and survival beyond 12 years.. Of the 61 patients enrolled, 35 were in group A and 26 were in group B. The mean international normalized ratio (INR) was 1.95 ± 1.01 (goal < 3.0). After adjustment for potential confounding variables, we found that patients in group B had a higher estimated GFR (6.06 ± 2.36 mL per minute, P = 0.01). Over a 12-year observation period, group B patients had significantly (P = 0.013) better survival than group A, with an adjusted hazard ratio for mortality of 0.318 (P = 0.022).. Warfarin therapy may delay deterioration in renal function and improve survival of elderly patients with CKD and AF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Data Interpretation, Statistical; Disease Progression; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Calcinosis; Female; Hip; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Radiography; Renal Dialysis; Vascular Diseases; Warfarin

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

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

Calciphylaxis or calciphic uremic arteriolopathy (CUA) is a rare syndrome characterized by the deposition of calcium within the walls of small and medium size vessels in the dermis and in the subcutaneous tissue. The disease mainly affects patients with end-stage renal disease. We report here our experience with 4 cases of calciphylaxis in dialysis patients. The main predisposing factor observed in our 4 patients was warfarin use (2 patients, 50%), while local traumas and diabetes were respectively present in only one patient. None of our patients was obese. Lower legs were the most frequently involved site of CUA (3/4 patients, 75%). In our experience biopsy was crucial to achieve a correct diagnosis and did not cause aggravation of the ulcers. Therapeutic approach was multimodal: mainly hyperbaric oxygen therapy, cinacalcet and sodium thiosulphate. Although many recent case reports have shown exceptional results and healing with the use of sodium thiosulphate, we did not experience any change in the poor prognosis of our patients with the use of this drug, at a dosage of 5 g thrice weekly endovenously.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Biopsy; Calciphylaxis; Cinacalcet; Combined Modality Therapy; Fatal Outcome; Female; Hemodialysis Solutions; Heparin; Humans; Hyperbaric Oxygenation; Kidney Failure, Chronic; Leg Ulcer; Male; Middle Aged; Naphthalenes; Prognosis; Renal Dialysis; Skin Ulcer; Thiosulfates; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Contraindications; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Humans; Kidney Failure, Chronic; Polysaccharides; Renal Dialysis; Thromboembolism; Vascular Calcification; Vitamin K; Warfarin

Calciphylaxis, also called calcific uremic arteriolopathy, is a rare and often fatal complication of end-stage renal disease and is characterized by painful skin ulceration, necrosis, medial calcification and intimal proliferation of small arteries. Studies in western countries have reported incidences ranging from 1 to 4% in chronic hemodialysis patients. Since no systematic studies of calciphylaxis have ever been performed in Japan, we conducted a nationwide survey and a case-control study to identify the characteristics of calciphylaxis in the Japanese dialysis population.. Firstly, we sent a questionnaire to 3760 hemodialysis centers in Japan, asking whether calciphylaxis cases had been encountered in the past, and detailed clinical data regarding each case were then collected from the centers. In addition, two control dialysis patients matched for age and duration of hemodialysis to each calciphylaxis case were identified at the participating centers, and their data were analyzed to identify risk factors for calciphylaxis.. Responses to the questionnaire were obtained from 1838 centers (48.3%), and 151 centers reported that a total of 249 cases had been encountered. Sixty-four centers agreed to participate in the case-control study, and detailed clinical data in regard to 67 cases were obtained. In 28 of the 67 cases, a definite diagnosis of calciphylaxis was made by our study group based on the clinical characteristics and skin biopsy findings. A univariate logistic regression model comparing them with 56-matched controls identified warfarin therapy [odds ratio (OR) 11.4, 95% confidence interval (CI)] 2.7-48.1, P=0.0009], each 1 g/dL decline in serum albumin level (OR 19.8, 95% CI 4.4-89.5, P=0.0001), each 100 mg/dL increment in plasma glucose level (OR 3.74, 95% CI 1.08-12.9, P=0.037) and each 1 mg/dL increment in adjusted serum calcium level (OR 3.2, 95% CI 1.63-6.30, P=0.0008) at the time of diagnosis as significantly associated with calciphylaxis, but no significant associations were found with female gender, vitamin D analog therapy, serum phosphate level, adjusted calcium-phosphate products or serum alkaline-phosphatase level. Warfarin therapy and lower serum albumin levels were still significant risk factors after a multivariate logistic regression model analysis.. The results of this study showed that warfarin therapy and lower serum albumin levels are significant and strong risk factors for the development of calciphylaxis in chronic hemodialysis patients in Japan.

Topics: Adult; Aged; Anticoagulants; Calciphylaxis; Case-Control Studies; Female; Humans; Japan; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Prognosis; Renal Dialysis; Risk Factors; Serum Albumin; Warfarin; Young Adult

Calciphylaxis is still an incompletely understood rare disease, which most often affects people on haemodialysis. For the majority of patients, calciphylaxis means a massive reduction in quality of life and is associated with high morbidity and mortality. We still know little about the concert of local and systemic risk factors and underlying causes that finally lead to the development of calciphylaxis. Recent work from Asia points towards persistent uncertainties in the diagnosis and management of the disease which the nephrology community has to address by establishing standards in both diagnosis as well as treatment strategies. Hayashi et al. have published results from a Japanese survey in which the authors collected data from calciphylaxis patients and compared clinical and laboratory data with those of control subjects. This innovative approach allowed the authors to calculate relative risks for various parameters in terms of calciphylaxis development. While uncontrolled hyperparathyroidism seemingly plays a secondary role, vitamin K antagonist usage proved to be of particular importance. Survey as well as registry data may help to close the gap in our knowledge about calciphylaxis which may ultimately result in improved prevention, patient care and outcome.

Topics: Anticoagulants; Calciphylaxis; Female; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Serum Albumin; Warfarin

Topics: Anticoagulants; Calciphylaxis; Female; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Serum Albumin; Warfarin

Topics: Adult; Anticoagulants; Echocardiography, Stress; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Kidney Failure, Chronic; Kidney Transplantation; Lupus Nephritis; Mitral Valve; Mitral Valve Annuloplasty; Monitoring, Physiologic; Preoperative Care; Risk Adjustment; Stroke; Treatment Outcome; Warfarin

Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions.. Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease.. Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both.. Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).

Topics: Aged; Aspirin; Atrial Fibrillation; Female; Hematologic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Myocardial Infarction; Proportional Hazards Models; Renal Insufficiency, Chronic; Renal Replacement Therapy; Risk; Stroke; Thromboembolism; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebral Infarction; Comorbidity; Fibrinolytic Agents; Humans; Kidney Failure, Chronic; Proportional Hazards Models; Risk Factors; Thromboembolism; Warfarin

Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) suffer from a number of metabolic derangements. Ectopic deposition of calcium in the skin, soft tissues, blood vessels, and viscera is a potentially devastating consequence of disorders of calcium and phosphorus homeostasis. We report the case of a patient with ESRD and secondary hyperparathyroidism receiving HD who developed metastatic pulmonary calcification and calciphylaxis following initiation of warfarin therapy after mechanical valve replacement. Because not all patients with ESRD receiving HD develop ectopic calcification, there appears to be a complex cascade of metabolic interactions that predispose patients to this process. Warfarin is a vitamin K antagonist with inhibitory effects not only on proteins of the coagulation cascade, but also on other important protein systems. Its role in ectopic calcium deposition has been the subject of theories and has been reported in the literature, but no link with metastatic pulmonary calcification has been made. Patients receiving HD have an increased incidence of conditions that require chronic anticoagulation with warfarin, such as VTE, atrial fibrillation, and valvular heart disease requiring valve replacement surgery. Bioprosthetic valves should be considered in these patients because of the potential risk of metastatic calcification when warfarin is used in the setting of mechanical valve replacement.

Topics: Adult; Anticoagulants; Calciphylaxis; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Male; Warfarin

There is growing evidence that kidney disease affects hepatically cleared drugs. Accordingly, we hypothesized that chronic kidney disease (CKD) would disrupt anticoagulation of warfarin-treated patients and thereby increase the amount of management required to maintain appropriate anticoagulation. Specifically, we anticipated that more dose manipulations (both dose changes and transient dose adjustments) and shorter times between scheduled clinic visits would be required for anticoagulation patients with CKD.. To determine how CKD affected warfarin maintenance dose, anticoagulation stability, the proportion of clinic visits that necessitated a dose manipulation (either a change in the prescribed weekly dose or a transient dose adjustment), and the length of time between scheduled visits in 2 pharmacist-managed anticoagulation clinics.. Our retrospective, cohort chart review investigated warfarin response in anticoagulation clinic patients. From the clinic database of patients with an international normalized ratio (INR) target range of 2.0-3.0, we matched 20 of 24 patients with CKD (estimated creatinine clearance less than 60 mL per minute) to 20 comparison group patients (estimated creatinine clearance greater than 60 mL per minute) based on parameters demonstrated to affect warfarin dose: ethnicity, gender, age, body surface area, and simvastatin use. We calculated the average weekly dose used to maintain target INR (assessment period range=116-1,408 days). To evaluate anticoagulation stability and patient management, we quantified several parameters, including the percentage of total time in therapeutic range, the proportion of clinic visits that required a dose change, and the time between scheduled visits. We compared group means using t-tests, and categorical data were compared using Fisher's exact test.. Our population was predominantly female (75%) and of African ancestry (95%); average age 60 years. Patients with CKD required a 24% lower dose than the comparison group (mean [SD]=35.9 [10.7] vs. 47.0 [11.2] mg per week, P=0.003) and spent less time in therapeutic range required increased clinic management versus the comparison group, as indicated by a significantly higher proportion of clinic visits at which dose changes occurred (22% vs. 12%, P<0.001) and a decreased time between scheduled visits (mean [SD] of 16.0 [3.2] days vs. 19.7 [3.4] days, respectively, P=0.001).. CKD was associated with both decreased warfarin maintenance dose and decreased anticoagulation stability which, in turn, required more frequent and intensive anticoagulation clinic management.

Topics: Adult; Aged; Ambulatory Care Facilities; Anticoagulants; Cohort Studies; Creatinine; Databases, Factual; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; International Normalized Ratio; Kidney Failure, Chronic; Male; Middle Aged; Pharmacists; Renal Insufficiency, Chronic; Retrospective Studies; Warfarin; Young Adult

Warfarin nomograms to guide dosing have been shown to improve control of the international normalized ratio (INR) in the general outpatient setting. However, the effectiveness of these nomograms in hemodialysis patients is unknown. We evaluated the effectiveness of anticoagulation using an electronic warfarin nomogram administered by nurses in outpatient hemodialysis patients, compared to physician directed therapy.. Hemodialysis patients at any of the six outpatient clinics in Calgary, Alberta, treated with warfarin anticoagulation were included. Two five-month time periods were compared: prior to and post implementation of the nomogram. The primary endpoint was adequacy of anticoagulation (proportion of INR measurements within range ± 0.5 units).. Overall, 67 patients were included in the pre- and 55 in the post-period (with 40 patients in both periods). Using generalized linear mixed models, the adequacy of INR control was similar in both periods for all range INR levels: in detail, range INR 1.5 to 2.5 (pre 93.6% (95% CI: 88.6% - 96.5%); post 95.6% (95% CI: 89.4% - 98.3%); p = 0.95); INR 2.0 to 3.0 (pre 82.2% (95% CI: 77.9% - 85.8%); post 77.4% (95% CI: 72.0% - 82.0%); p = 0.20); and, INR 2.5 to 3.5 (pre 84.3% (95% CI: 59.4% - 95.1%); post 66.8% (95% CI: 39.9% - 86.0%); p = 0.29). The mean number of INR measurements per patient decreased significantly between the pre- (30.5, 95% CI: 27.0 - 34.0) and post- (22.3, 95% CI: 18.4 - 26.1) (p = 0.003) period. There were 3 bleeding events in each of the periods.. An electronic warfarin anticoagulation nomogram administered by nurses achieved INR control similar to that of physician directed therapy among hemodialysis patients in an outpatient setting, with a significant reduction in frequency of testing. Future controlled trials are required to confirm the efficacy of this nomogram.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; Drug Administration Schedule; Electronic Health Records; Female; Humans; International Normalized Ratio; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Specialties, Nursing; Thrombosis; Warfarin

Although generally recommended in atrial fibrillation (AF) patients, the effectiveness and safety of oral anticoagulation in dialysis patients with AF is unknown.. We assembled a cohort of older hemodialysis patients who initiated dialysis without prior record of AF and who had prescription drug benefits through three state-administered programs. The index event was a first hospitalization with diagnosed AF; patients with any recorded prior warfarin use were excluded. Eligible patients survived ≥30 days from discharge, and new warfarin use was recorded from prescription records during that 30-day window. Propensity-matched warfarin users and nonusers were compared using Cox regression. Outcomes included ischemic stroke, hemorrhagic stroke, and mortality.. Among 2313 patients with new AF who survived 30 days from discharge, 249 (10.8%) filled a prescription for warfarin. Comparing 237 warfarin users and 948 propensity-matched nonusers over 2287 person-years of follow-up, the occurrence of ischemic stroke was similar (HR = 0.92; 95% CI, 0.61 to 1.37), whereas warfarin users experienced twice the risk of hemorrhagic stroke (HR = 2.38; 95% CI, 1.15 to 4.96). The risks of stroke, gastrointestinal hemorrhage, and mortality did not differ between groups. As-treated analyses yielded similar findings, as did analyses restricted to patients with CHADS(2) scores ≥2.. Although we confirmed association between warfarin use and hemorrhagic stroke in dialysis patients with AF, we found no association between warfarin use and ischemic stroke. Adequately powered randomized trials are required to conclusively determine the risks and benefits of the studied warfarin indication in hemodialysis patients.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Case-Control Studies; Drug Prescriptions; Female; Hospitalization; Humans; Intracranial Hemorrhages; Kidney Failure, Chronic; Logistic Models; Male; Medicare; Middle Aged; Proportional Hazards Models; Renal Dialysis; Risk Assessment; Risk Factors; Stroke; Survival Rate; Time Factors; Treatment Outcome; United States; Warfarin

Necrotic skin lesions are unfortunately common in patients with end stage renal disease undergoing dialysis therapy. We present a case of a necrotic skin lesion in a peritoneal dialysis patient shortly after the initiation of warfarin therapy for atrial fibrillation. We discuss and contrast distinguishing features of two diagnostic possibilities: warfarin skin necrosis (WSN) and calcific uremic arteriopathy (CUA) in terms of clinical presentation, risk factors and pathology. Lastly, we outline the importance of establishing a diagnosis as treatment regimens differ substantially.

Topics: Anticoagulants; Calciphylaxis; Diabetic Nephropathies; Diagnosis, Differential; Humans; Kidney Failure, Chronic; Male; Middle Aged; Necrosis; Skin Diseases; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Risk Factors; Stroke; Warfarin

The case of a superior vena cava syndrome due to a central venous catheter thrombosis occurring in a second renal transplant patient is described. Imaging revealed thrombosis of the right internal jugular vein with extension along the confluence of the brachiocephalic veins and partial obstruction of the superior vena cava. Anticoagulant therapy with subcutaneous low-molecular-weight heparin was followed by warfarin administration. Despite adequate treatment, the symptomatology worsened because of thrombus organization. A workup revealed a complex prothrombotic underlying condition. Cardiothoracic surgeons were consulted, and an operative reconstruction of the superior vena cava using spiral vein bypass grafting was performed. In this report we describe the clinical presentation, diagnosis, and treatment of this case, with an emphasis on the role of thrombophilia.

Topics: Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Jugular Veins; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Postoperative Complications; Reoperation; Superior Vena Cava Syndrome; Thromboembolism; Warfarin

To report 3 cases of venous thromboembolism (VTE) in patients with end-stage renal disease (ESRD) treated with subcutaneous unfractionated heparin (UFH) bridged with warfarin.. Three patients with ESRD were successfully treated for VTE with unmonitored, fixed-dose subcutaneous UFH every 12 hours and dose-adjusted warfarin. The first patient was initiated on continuous infusion UFH for deep-vein thrombosis, but due to poor vascular access, nurses were unable to consistently measure anti-Xa levels. Therefore, subcutaneous UFH 17,500 units (∼245 units/kg/dose) every 12 hours was initiated. Oral warfarin 5 mg/day was started the following day. The patient received 4 days of inpatient subcutaneous UFH and then was discharged to complete the bridge as an outpatient. The second patient received subcutaneous UFH 10,000 units (∼244 units/kg/dose) every 12 hours and oral warfarin 2.5 mg/day to treat a nonocclusive thrombus along her right femoral vein hemodialysis catheter. The patient received 1 day of inpatient subcutaneous UFH treatment prior to discharge and continued bridge therapy with warfarin as an outpatient. The third patient was initiated on subcutaneous UFH 20,000 units (∼223 units/kg/dose) every 12 hours and oral warfarin 7.5 mg/day due to a subtherapeutic INR (1.50) 5 days after receiving fresh frozen plasma to reduce her therapeutic INR for a procedure. The patient received 2 doses of subcutaneous UFH as an inpatient before treatment was discontinued because her INR was therapeutic at 2.3.. Subcutaneous UFH has been used to treat VTE since the early 1980s; however, with the advent of low-molecular-weight heparin (LMWH), subcutaneous UFH use diminished. Several studies comparing the use of subcutaneous UFH to both continuous infusion UFH and LMWH concluded that subcutaneous UFH is a safe and efficacious alternative. The 2008 Chest Guidelines for Antithrombotic Therapy for Venous Thromboembolic Disease support the use of subcutaneous UFH for the treatment of VTE with a Grade 1A recommendation and provide a Grade 2C recommendation for use of UFH over LMWH for patients with VTE and severe renal failure.. Safe and convenient treatment options for VTE in patients with ESRD are limited. Fixed-dose, unmonitored subcutaneous UFH as a bridge to warfarin therapy is an effective option in patients with ESRD and those with financial restrictions. The pharmacist plays a key role in identifying patients for whom subcutaneous UFH treatment may be a viable alternative, recommending an appropriate dosing regimen, and educating health-care professionals and patients about safe use.

Topics: Adult; Anticoagulants; Drug Therapy, Combination; Female; Heparin; Humans; Infusions, Subcutaneous; Kidney Failure, Chronic; Venous Thromboembolism; Warfarin

Although management of warfarin is challenging for patients with chronic kidney disease (CKD), no prospective studies have compared response to warfarin among patients with minimal, moderate, and severe CKD. This secondary analysis of a prospective cohort of 578 patients evaluated the influence of kidney function on warfarin dosage, anticoagulation control, and risk for hemorrhagic complications. We adjusted all multivariable regression and proportional hazard analyses for clinical and genetic factors. Patients with severe CKD (estimated GFR <30 ml/min per 1.73 kg/m2) required significantly lower warfarin dosages (P = 0.0002), spent less time with their international normalized ratio within the target range (P = 0.049), and were at a higher risk for overanticoagulation (international normalized ratio >4; P = 0.052), compared with patients with no, mild, or moderate CKD. Patients with severe CKD had a risk for major hemorrhage more than double that of patients with lesser degrees of renal dysfunction (hazard ratio 2.4, 95% confidence interval 1.1 to 5.3). In conclusion, patients with reduced kidney function require lower dosages of warfarin, have poorer control of anticoagulation, and are at a higher risk for major hemorrhage. These observations suggest that warfarin may need to be initiated at a lower dosage and monitored more closely in patients with moderate or severe CKD compared with the general population. Diminished renal function may have implications for a larger proportion of warfarin users than previously estimated.

Topics: Adult; Aged; Anticoagulants; Blood Urea Nitrogen; Cohort Studies; Creatinine; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney Failure, Chronic; Kidney Function Tests; Middle Aged; Patient Selection; Proportional Hazards Models; Regression Analysis; Risk Factors; Severity of Illness Index; Warfarin

Many prescribe anticoagulants and antiplatelet medications to prevent thromboembolic events and access thrombosis in dialysis patients despite limited evidence of their efficacy in this population. This retrospective cohort study examined whether use of warfarin, clopidogrel, and/or aspirin affected survival in 41,425 incident hemodialysis patients during 5 yr of follow-up. The prescription frequencies for warfarin, clopidogrel, and aspirin were 8.3, 10.0, and 30.4%, respectively, during the first 90 d of initiating chronic hemodialysis. Compared with the 24,740 patients receiving none of these medications, Cox proportional hazards analysis suggested that exposure to these medications was associated with increased risk for mortality (warfarin hazard ratio [HR] 1.27 [95% confidence interval (CI) 1.18 to 1.37]; clopidogrel HR 1.24 [95% CI 1.13 to 1.35]; and aspirin HR 1.06 [95% CI 1.01 to 1.11]). The increased mortality associated with warfarin or clopidogrel use remained in stratified analyses. A covariate- and propensity-adjusted time-varying analysis, which accounted for longitudinal changes in prescription, produced similar results. In addition, matching for treatment facility and attending physician revealed similar associations between prescription and mortality. We conclude that warfarin, aspirin, or clopidogrel prescription is associated with higher mortality among hemodialysis patients. Given the possibility of confounding by indication, randomized trials are needed to determine definitively the risk and benefit of these medications.

Topics: Aged; Anticoagulants; Clopidogrel; Cohort Studies; Confidence Intervals; Female; Humans; International Normalized Ratio; Kidney Failure, Chronic; Longitudinal Studies; Male; Platelet Aggregation Inhibitors; Proportional Hazards Models; Racial Groups; Renal Dialysis; Retrospective Studies; Risk Assessment; Ticlopidine; Warfarin

Calciphylaxis is a rare complication that occurs in 1% of patients with end-stage renal disease (ESRD) each year. Extensive microvascular calcification and occlusion/thrombosis lead to violaceous skin lesions, which progress to nonhealing ulcers with secondary infection, often leading to sepsis and death. The lower extremities are predominantly involved (roughly 90% of patients). Although most calciphylaxis patients have abnormalities of the calcium-phosphate axis or elevated levels of parathyroid hormone, these abnormalities do not appear to be fundamental to the pathophysiology of the disorder. We report on a case of histologically proven calciphylaxis in a 54-year-old woman with normal renal function and normal calcium-parathyroid homeostasis. She had a history of alcoholic cardiomyopathy, and was treated with warfarin anticoagulation. She has been successfully treated with antibiotics, i.v. biophosphonates and intensive local wound care. We recorded a complete wound healing in contrast to what is reported in other series.

Topics: Alcoholism; Anti-Bacterial Agents; Anticoagulants; Calciphylaxis; Clindamycin; Diphosphonates; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Meropenem; Middle Aged; Risk Factors; Thienamycins; Vancomycin; Warfarin

Many hemodialysis patients receive antiplatelet therapy or warfarin; however, little is known about the effect of this on iron requirements. Given the association of antiplatelet therapy with bleeding we hypothesized that there should be a greater need for iron in such patients, which we tested in this study.. Retrospective 1-year cohort study of 205 chronic hemodialysis patients. The primary outcome variable was total iron dose, which was analyzed according to antiplatelet/warfarin use. Data were also collected on potential confounders, allowing for both unadjusted and adjusted (multiple regression) analysis.. 97/205 patients received antiplatelet/warfarin therapy. This group was older, with a higher incidence of macrovascular disease and diabetes and a higher median C-reactive protein (6.0 vs. 3.75 mg/l). Overall, median iron requirement was 1,300 mg/year. In a multiple regression analysis, antiplatelet/warfarin use was associated with an additional iron requirement of 703 mg (95% confidence interval 188-1,220 mg), with the strongest effect observed in patients with normal inflammatory markers.. We found a high requirement for iron in patients receiving antiplatelet agents/warfarin. We argue that the most likely mechanism for this association is chronic, low-grade blood loss, although further study is required before causality can be established.

Topics: Age Factors; Aged; Anemia, Iron-Deficiency; C-Reactive Protein; Comorbidity; Diabetic Nephropathies; Female; Ferric Compounds; Ferritins; Hemorrhage; Humans; Inflammation; Iron; Iron Deficiencies; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Requirements; Platelet Aggregation Inhibitors; Renal Dialysis; Retrospective Studies; Thrombophilia; Transferrin; Vascular Diseases; Warfarin

Use of warfarin, clopidogrel, or aspirin associates with mortality among patients with ESRD, but the risk-benefit ratio may depend on underlying comorbidities. Here, we investigated the association between these medications and new stroke, mortality, and hospitalization in a retrospective cohort analysis of 1671 incident hemodialysis patients with preexisting atrial fibrillation. We followed patient outcomes from the time of initiation of dialysis for an average of 1.6 yr. Compared with nonuse, warfarin use associated with a significantly increased risk for new stroke (hazard ratio 1.93; 95% confidence interval 1.29 to 2.90); clopidogrel or aspirin use did not associate with increased risk for new stroke. Analysis using international normalized ratio (INR) suggested a dose-response relationship between the degree of anticoagulation and new stroke in patients on warfarin (P = 0.02 for trend). Warfarin users who received no INR monitoring in the first 90 d of dialysis had the highest risk for stroke compared with nonusers (hazard ratio 2.79; 95% confidence interval 1.65 to 4.70). Warfarin use did not associate with statistically significant increases in all-cause mortality or hospitalization. In conclusion, warfarin use among patients with both ESRD and atrial fibrillation associates with an increased risk for stroke. The risk is greatest in warfarin users who do not receive in-facility INR monitoring.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Hospitalization; Humans; International Normalized Ratio; Kidney Failure, Chronic; Male; Regression Analysis; Renal Dialysis; Retrospective Studies; Risk; Stroke; Warfarin

Argatroban is a direct thrombin inhibitor approved for the treatment of heparin-induced thrombocytopenia (HIT) type II. Argatroban is predominantly metabolized in the liver. It is widely believed that no dosage adjustment is required in patients with renal insufficiency, making it a preferred agent in patients on renal replacement therapy (Reddy and Grossman, Ann Pharm 2005;39:1601-1605). The elimination half-life of argatroban is approximately 50 min. Lupus anticoagulants can cause baseline elevation of the PTT and hence it is difficult to monitor the effects of anticoagulants such as heparin, lepirudin, or argatroban in patients with antiphospholipid antibody syndrome. Heparin levels may be used as an alternative for heparin monitoring but plasma levels of argatroban are not commercially available. A chromogenic antifactor IIa assay could be useful for monitoring argatroban in the presence of a lupus anticoagulant, but it is not widely available at present. We report a patient with end-stage renal disease, maintained on peritoneal dialysis with HIT, who demonstrated a markedly prolonged half-life when treated with argatroban despite the discontinuation of therapy. This case also demonstrates the lack of guidelines for the monitoring of argatroban therapy in the presence of an underlying lupus anticoagulant.

Topics: Anticoagulants; Antiphospholipid Syndrome; Arginine; Cholangiopancreatography, Endoscopic Retrograde; Female; Half-Life; Heparin; Humans; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Middle Aged; Peritoneal Dialysis; Pipecolic Acids; Sulfonamides; Thrombocytopenia; Treatment Outcome; Warfarin

Few studies have examined risk factors for hemorrhage in hemodialysis patients. The contribution of warfarin and antiplatelet agent exposure to the incidence of first major bleeding episodes in hemodialysis patients was determined.. Retrospective chart review was performed in eligible hemodialysis patients. Incidence rates were determined as the number of first major bleeding events divided by the total exposure time on each treatment combination. Time-dependent covariates and Cox proportional hazard models were used to determine the hazard rate of having a first major bleeding event.. A total of 1028 person-years of exposure were observed from 255 patients with a median follow-up time of 3.6 yr. The incidence rate of major bleeding episodes was 2.5% per person-year. The incidence of major bleeding episodes was 3.1% per person-year of warfarin exposure, 4.4% per person-year of aspirin exposure, and 6.3% per person-year of exposure to the combination of warfarin and aspirin. Compared with patients who were not prescribed warfarin or aspirin, the multivariable hazard ratio for time to first major bleeding event was 3.59 for warfarin, 5.24 for aspirin, and 6.19 for the combination of aspirin and warfarin.. The risk for major bleeding episodes in hemodialysis patients increases significantly while on aspirin and/or warfarin, although warfarin alone did not reach statistical significance. Future studies should evaluate the efficacy of these agents in the secondary prevention of cardiovascular events in this high-risk population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Renal Dialysis; Risk Factors; Thrombosis; Warfarin

Infective endocarditis is an infection of the endocardium that usually involves the valves and adjacent structures. The classical fever of unknown origin presentation represents a minority of infective endocarditis. The presented case was a 21-yearold young lady presenting with acute renal failure and fever to the emergency room. Cardiac auscultation revealed a soft S1 and 4/6 apical holosystolic murmur extended to axilla. Echocardiography showed mobile fresh vegetation under the mitral posterior leaflet. She was diagnosed as having infective endocarditis. Hemodialysis was started with antimicrobial therapy. However, because of the presence of severe mitral regurgitation with left ventricle dilatation and large mobile vegetation, mitral prosthetic mechanical valve replacement was performed. Although treated with antibiotics combined with surgery, renal functions were deteriorated and progressed to chronic renal failure.

Topics: Acute Disease; Acute Kidney Injury; Adult; Anti-Infective Agents; Anticoagulants; Disease Progression; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Kidney Failure, Chronic; Renal Dialysis; Staphylococcal Infections; Staphylococcus aureus; Warfarin

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

Topics: Adult; Antibody Specificity; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cross Reactions; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Heparin; Hirudins; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Mitral Valve Insufficiency; Peptide Fragments; Platelet Count; Platelet Factor 4; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Thrombophilia; Warfarin

Normal prothrombin time (PT) and partial thromboplastin time (PTT) are recommended for administration of recombinant tissue-plasminogen activator (rt-PA) in stroke, but waiting for results can delay use. We examined the charts of 365 stroke patients to assess predetermined risk factors associated with elevated PT/PTT. Elevated PT/PTT can be predicted in patients taking warfarin or heparin/heparinoid or on hemodialysis, according to emergency department triage, with 100% sensitivity and 94.7% specificity. These results could be applied to rt-PA candidates and reduce potential delays.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antiphospholipid Syndrome; Brain Ischemia; Coagulation Protein Disorders; Female; Heparin; Humans; Kidney Failure, Chronic; Liver Failure; Male; Middle Aged; Partial Thromboplastin Time; Predictive Value of Tests; Prothrombin Time; Recombinant Proteins; Renal Dialysis; Stroke; Time Factors; Tissue Plasminogen Activator; Triage; Warfarin

Hemodialysis catheters (HC) were developed as a vascular access, intended to be a bridging device until a permanent access is placed. Although many reports exist of indwelling catheter-related thrombosis, optimal diagnostic study and therapeutic options are yet to be established. We are presenting a case with HC thrombosis diagnosed by TEE managed conservatively with excellent long-term outcome.

Topics: Adult; Anticoagulants; Catheterization, Central Venous; Catheters, Indwelling; Echocardiography, Transesophageal; Heparin; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Thrombosis; Vena Cava, Superior; Warfarin

Causes of gross hematuria in a patient with end-stage renal disease are limited compared with those in patients with normal renal function. Given the increased likelihood of patients with end-stage renal disease developing renal cell carcinoma, the workup focuses on a careful evaluation of the collecting system. The workup for gross hematuria in a renal transplant recipient is similar; however, the focus shifts toward a more thorough evaluation of the transplanted kidney and bladder because immunosuppression increases the overall risk for malignancy. An immunosuppressed patient also is at risk for infectious processes in the transplanted kidney manifesting as gross hematuria. Concerns for chronic rejection also should be investigated, although microscopic hematuria is more common in this scenario. If this is unrevealing, then close scrutiny of the native kidneys for possible sources of bleeding is warranted. We present an interesting and unusual cause of painless gross hematuria in a patient with end-stage renal disease and transplant nephrectomy 3 months before the onset of bleeding.

Topics: BK Virus; Diagnosis, Differential; Embolization, Therapeutic; Fistula; Graft Rejection; Hematuria; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nephrectomy; Nephritis; Polyomavirus Infections; Postoperative Complications; Renal Artery; Renal Dialysis; Suture Techniques; Thrombosis; Tumor Virus Infections; Urinary Fistula; Urologic Neoplasms; Valsalva Maneuver; Vascular Diseases; Warfarin; Weight Lifting

The antiphospholipid syndrome is an antibody-mediated hypercoagulable state characterized by recurrent venous and arterial thromboembolic events. Several studies have determined that the frequency of antiphospholipid syndrome in patients presenting with a venous thromboembolic event is between 4% and 14%. Because of the high risk for recurrent thromboembolism in these patients, current recommendations suggest a longer, potentially lifelong, course of antithrombotic therapy following an initial event. Although most authorities agree on an extended course of therapy, considerable controversy surrounds the optimal target therapeutic INR for patients with antiphospholipid syndrome. For an initial venous thromboembolic event, a target INR of 2.0 to 3.0 is supported by two prospective, randomized clinical trials. In contrast, relatively limited data exist for an initial arterial thromboembolic event in patients who have the antiphospholipid syndrome, and therapeutic recommendations range from aspirin to warfarin with a high target INR. Recurrent thromboembolic events can be extremely difficult to treat, and some patients may benefit from the addition of immunosuppressive therapies. Importantly, as many as 50% of the initial thromboembolic events sustained by patients with antiphospholipid antibodies occur in the setting of additional, coincident prothrombotic risk factors, indicating the importance of addressing any additional risk factors, such as hypercholesterolemia, in these patients. Prospective studies are needed to address the role of thromboprophylactic strategies in asymptomatic individuals with antiphospholipid antibodies in the absence of additional risk factors.

Topics: Animals; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cardiolipins; Disease Models, Animal; Humans; Incidence; International Normalized Ratio; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Renal Dialysis; Venous Thromboembolism; Warfarin

The life expectancy of patients with chronic renal failure who are dependent on dialysis is very poor. This study was undertaken to determine time-related outcomes in dialysis patients requiring cardiac valve replacement.. From 1994 to 2001, 29 end-stage renal disease (ESRD) patients on hemodialysis (HD) program underwent 30 valve replacement operations: 29 received mechanical valves (97%), and one received bioprosthetic valves. The sites of valve replacement were 11 aortic (36.7%), 18 mitral (60%), and one both aortic and mitral (3.3%). Mean age was 42.46 +/- 14.26 years (range 17-75 years). Follow-up was completed in 28 patients (96.5%).. Early postoperative mortality (in the first 30 days) was 3.4% (n = 1). The overall estimated Kaplan-Meier survival was 56.7% at 36 months, 46.7% at 60 months, and 43.3% at 96 months. HD program was discontinued for two patients after renal transplantation in the follow-up period. All patients, except the one with bioprosthesis, used warfarin sodium for anticoagulation and none of them had bleeding. One of the patients had a major cerebrovascular accident (CVA) and another one had a minor CVA at the follow-up (6.7%).. Life quality is better and life expectancy is longer after valve replacement in ESRD patients who have valvular disease. Also, longer life expectancy increases the probability for finding donors for kidney transplantation.

Topics: Adolescent; Adult; Aged; Anticoagulants; Aortic Valve; Bioprosthesis; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Kidney Failure, Chronic; Kidney Transplantation; Life Expectancy; Male; Middle Aged; Mitral Valve; Renal Dialysis; Treatment Outcome; Warfarin

To identify factors that may influence the function, outcome, and complications associated with tunneled hemodialysis catheters.. Radiology reports and hemodialysis, medical, and Clinical Information System (computerized patient medical record system) records were retrospectively reviewed in 221 consecutive patients who underwent tunneled hemodialysis catheter placement by interventional radiologists between January 11, 1996 and January 13, 2000 at Dartmouth-Hitchcock Medical Center. Various patient characteristics (diabetes, smoking, hypertension, age, sex, atherosclerotic cardiovascular disease, history of cardiac catheterization, coumadin use, functional status, and obesity) were assessed for their relationship to the outcome of hemodialysis catheters. Catheter outcome was examined by calculating infection rate, thrombosis rate, fibrin formation rate, mechanical malfunction rate, and total complication rate. With these patient characteristics and outcome variables, multiple regression analysis was performed with STATA (College Station, TX) statistical analysis software.. Of the 221 patients reviewed, 39 patients were lost to follow-up. Among the remaining 182 patients, 427 catheters were placed for a total number of 36994 catheter-days. For overall complication rate, multiple regression analysis revealed a statistically significant positive correlation only for hypertension (P =.032). Total complication rate was 0.76 events per 100 catheter-days (95% CI: 0.53-1.00) for patients with a documented history of hypertension and 0.27 events per 100 catheter-days (95% CI: 0.08-0.45) for patients without (P =.024, paired student t test). For patients with diabetes versus patients without, the infection rates were 0.34 episodes per 100 catheter-days (95% CI: 0.15-0.53) and 0.12 episodes per 100 catheter-days (95% CI: 0.06-0.18), respectively, (P =.011, paired student t test). Thrombosis rate for patients on coumadin was 0.13 events per 100 catheter-days (95% CI: -0.14-0.40), while thrombosis rate for patients not taking coumadin was 0.03 events per 100 catheter-days (95% CI: 0-0.05) (P =.036, paired student t test).. Hypertension is a risk factor for poor outcome of tunneled hemodialysis catheters as measured by total complication rate requiring catheter removal or exchange. In this retrospective study, no other specific risk factors predicted an increased need for removal or exchange of tunneled hemodialysis catheters.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiac Catheterization; Catheterization; Catheters, Indwelling; Diabetes Complications; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Obesity; Predictive Value of Tests; Regression Analysis; Renal Dialysis; Retrospective Studies; Risk Factors; Sex Factors; Smoking; Treatment Outcome; Vascular Diseases; Warfarin

Plasma proteins in hemodialysis patients display a significant increase in deamidated/isomerized Asx (asparagine and aspartic acid) content, a marker of protein fatigue damage. This has been linked to the toxic effects of hyperhomocysteinemia in uremic erythrocytes; however, treatment aimed at abating homocysteine levels did not lead to significant reductions in plasma protein damage. The hypothesis that lack of reduction in protein damage could be due to protein increased intrinsic instability, as result of interference with the uremic milieu rather than to hyperhomocysteinemia, was put forward. The deamidated/isomerized Asx content of normal plasma incubated with several uremic toxins for 24 h, 72 h, and 7 d was measured, identifying a group of toxins that were able to elicit this kind of damage. Uremic toxins were also incubated with purified human albumin, and dose-response experiments with the two most toxic agents in terms of protein damage (guanidine and guanidinopropionic acid) were carried out. The effect of the hemodialysis procedure on protein damage was evaluated. For investigating also the consequences of these alterations, human albumin was treated in vitro to produce an increase in deamidated/isomerized Asx residues, and the effects of albumin deamidation on protein binding were evaluated. Among the uremic toxins that are able to elicit protein damage, guanidine produced a dose-dependent increase in protein damage. No difference was found after a hemodialysis session. Deamidated albumin shows normal binding capacity to warfarin, salicylic acid, or diazepam but reduced binding to homocysteine. In conclusion, uremic toxins, especially guanidine, display an ability to induce significant protein damage, which can in turn have functional consequences.

Topics: Asparagine; Aspartic Acid; Biomarkers; Blood Chemical Analysis; Blood Proteins; Diazepam; Female; Humans; In Vitro Techniques; Kidney Failure, Chronic; Male; Prognosis; Protein Binding; Renal Dialysis; Risk Assessment; Salicylates; Sampling Studies; Sensitivity and Specificity; Warfarin

Topics: Adult; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Down-Regulation; Female; Genotype; Humans; Kidney Failure, Chronic; Male; Middle Aged; Warfarin

Tunneled hemodialysis catheters (caths) often fail as a result of luminal obstructive thrombus or formation of a fibrin sheath at the tip. Anecdotal and non-randomized studies have indicated that aspirin (A) and/or warfarin (W) can prolong cath patency. We examined the effect of chronic usage of either A or W on primary cath patency.. A prospective cross-sectional monitoring of cath patency was conducted over a 3-year period. Patients were grouped according to their long-term usage of either A (325 mg daily) or W. Patients on neither medication served as a control (C). The end point of the study occurred at cannulation of the patients' arteriovenous fistulae, when there was development of cath-related bacteremia or when there was inability to maintain a blood flow of 250 ml/min.. Sixty-three patients with a mean age of 57 +/- 15 years completed the study. There were 21 patients in the A group, 11 in the W group and 31 in the C group. Cath survival was 91%, 73% and 29% at 120 days for the A, W and C groups, respectively (A vs C, p < 0.0001; W vs C, p < 0.0001; A vs W, p = NS). The mean durations of cath patency were 114 +/- 18, 111 +/- 17 and 68 +/- 37 days for the A, W and C groups, respectively (A vs C, p < 0.0001; W vs C, p < 0.0001; A vs W, p = NS). Gastrointestinal (GI) bleeding complication rates were 24%, 18% and 0% for the A, W and C groups, respectively (A vs C, p = 0.02; W vs C, p = 0.02; A vs W, p = NS). The relative risk of GI bleeding associated with aspirin was 0.71 [95% confidence interval (CI) 0.11-4.4, p = 0.7] but among elderly aspirin users it was 1.14 (CI 1.0-1.3, p = 0.008).. Both aspirin and warfarin are equally effective at prolonging cath patency but their routine use for failing caths cannot be unequivocally recommended because of the increased risk of GI bleeding. Further prospective and randomized studies are called for.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Catheters, Indwelling; Equipment Failure; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Renal Dialysis; Thrombosis; Treatment Outcome; Warfarin

Vascular access site thrombosis is a major cause of morbidity in patients receiving hemodialysis. The role of hypercoagulable states in recurrent vascular access site thrombosis remains poorly understood. Data are limited regarding systemic anticoagulation to improve access graft patency, because of concern about hemorrhagic complications. We determined the prevalence of hypercoagulable states and clinical outcome (thrombotic and hemorrhagic) after initiation of antithrombotic therapy in a series of patients with recurrent vascular access site thrombosis. We evaluated 31 patients who had sustained 119 thrombotic events that resulted in vascular access graft failure during the year before evaluation. Sixty-eight percent of patients tested had elevated concentrations of antibody to anticardiolipin or topical bovine thrombin, and 18% of patients tested had heparin-induced antibodies. More than 90% of patients had elevated factor VIII concentration, 62% had elevated fibrinogen concentrations, and 42% had elevated C-reactive protein concentrations. Twenty-nine patients were given antithrombotic therapy: 13 with warfarin sodium, 12 with unfractionated heparin (UFH), and 11 with low molecular weight heparin (LMWH). Seven patients received more than one antithrombotic agent, sequentially. Nineteen patients have had no thrombotic events since beginning antithrombotic therapy (10 with warfarin, 3 with UFH, 6 with LMWH). Mean follow-up was 8.6 months (median, 7 months). Eight patients sustained 10 bleeding complications (5 with warfarin, 3 with UFH, and 2 with LMWH). In conclusion, hypercoagulable states are common in patients with recurrent vascular access site thrombosis. Antithrombotic therapy may increase vascular access graft patency, but is associated with significant risk for hemorrhage. Prospective studies are needed to evaluate the role and safety of antithrombotic agents in improving vascular access graft patency.

Topics: Adult; Aged; Antibodies, Anticardiolipin; Arteriovenous Shunt, Surgical; Biomarkers; C-Reactive Protein; Catheters, Indwelling; Factor VIII; Female; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prognosis; Recurrence; Renal Dialysis; Risk Assessment; Thrombosis; Treatment Outcome; Warfarin

We report a patient with diabetic endstage renal disease with an initial platelet count of 17.6 x 10(4)/mm3 who developed type-II heparin-induced thrombocytopenia (HIT) during the induction period of hemodialysis (HD) when unfractionated heparin was used. Because the recognition of the condition and the treatment of this patient with HIT was unsatisfactory, she developed deep venous thrombosis, myocardial infarction, and occlusion of vascular access, at times of platelet counts of 4.1 x 10(4), 7.7 x 10(4), and 6.4 x 10(4)/mm3, respectively, with antibodies to heparin/platelet factor 4 complex. Unfortunately, we misjudged in our belief that the thromboembolic events might be associated with an underlying procoagulant state in diabetic nephrotic syndrome, rather than being associated with the clinical picture of HIT. This case report suggests that the clinician must consider HIT in the differential diagnosis for thromboembolic complications during the induction period of HD, because unfractionated heparin is the major anticoagulant used in HD.

Topics: Anticoagulants; Catheters, Indwelling; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Fibrinolytic Agents; Heparin; Humans; Kidney Failure, Chronic; Middle Aged; Myocardial Infarction; Phlebography; Renal Dialysis; Thrombocytopenia; Ticlopidine; Venous Thrombosis; Warfarin

Several drugs have been proposed to improve vascular access patency based on favorable anticoagulant, antiplatelet, or vascular-remodeling properties. However, there is little evidence to guide drug strategies.. The association between vascular access patency and the use of specific drugs was studied in a large sample of US hemodialysis patients enrolled in the Dialysis Outcomes and Practice Patterns Study, an international, prospective, observational study. In general, it was assumed that the drugs were prescribed for indications unrelated to vascular access preservation. Primary (unassisted survival) and secondary vascular access patency (assisted survival) were modeled using Cox regression (time to failure) adjusted for age, sex, race, body mass index, incidence to end-stage renal disease, diabetes mellitus, hypertension, valvular disease, chronic obstructive pulmonary disease, aortic aneurysm, deep-vein thrombosis, number of previous permanent accesses, and facility-clustering effects. Fistulae (n = 900) and grafts (n = 1,944) were evaluated separately. Technical failures within the first 30 days of surgical placement were excluded from the analysis.. Treatment with calcium channel blockers was associated with improved primary graft patency (relative risk [RR] for failure, 0.86; P = 0.034). Aspirin therapy was associated with better secondary graft patency (RR, 0.70; P < 0.001). Treatment with angiotensin-converting enzyme inhibitors was associated with significantly better secondary fistula patency (RR, 0.56; P = 0.010). Patients administered warfarin showed worse primary graft patency (RR, 1.33; P = 0.037).. These findings should help guide clinical trial priorities toward vascular access preservation using one or more of the agents that show significant risk reduction for access failure in this study.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arteriovenous Shunt, Surgical; Aspirin; Drug Evaluation; Graft Occlusion, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Failure, Chronic; Longitudinal Studies; Prospective Studies; Regression Analysis; Renal Dialysis; Risk Factors; Treatment Failure; Treatment Outcome; Vascular Patency; Vasodilator Agents; Warfarin

Treatment of critically ill patients who have heparin-induced thrombocytopenia and thrombosis (HITT) and also renal failure is a challenge. Recombinant hirudin (Refludan, Hoechst Marion Roussel) is a direct thrombin inhibitor indicated for anticoagulation in HITT and approved by the United States Food and Drug Administration. Because this drug is renally cleared, a single dose of hirudin may induce prolonged (up to one week) unpredictable anticoagulation in patients with renal insufficiency. There are a few case reports of patients with renal failure and suspected heparin-induced thrombocytopenia (HIT) in which patients were anticoagulated with Refludan for catheter thrombosis. There is no literature on the therapeutic use of Refludan to treat HITT in patients with diffuse thrombosis and renal failure. The authors report the case of a 44-year-old female dialysis patient with HITT and extensive life-threatening thrombosis. The patient developed common iliac vein occlusion extending to the right atrium with progressive right internal jugular vein thrombus developing while on heparin. Her platelet count dropped to 60,000/microL. She was lethargic and hemodynamically unstable. Refludan was initially given as a bolus of 0.2 mg/kg (total, 12 mg) at a 50% dose reduction based on the patient's ideal body weight. This dose was based on the published pharmacokinetics of Refludan in patients with renal failure. Only 2 additional boluses of 6 mg and 3 mg were needed to extend the duration of therapeutic anticoagulation (measured by PTT) to 140 hours. The patient improved both clinically and radiographically after the treatment with Refludan. There were no additional thromboembolic events or bleeding complications. The platelets returned to normal within a few days. The patient was transitioned to coumadin and discharged from the hospital. She remains stable at 1-year follow-up.

Topics: Adult; Anticoagulants; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Thrombocytopenia; Thrombosis; Warfarin

Vascular access-related complications are an important cause of morbidity, and they account for 14% to 17% of dialysis patients' hospitalizations with an annual cost in the United States of approximately $1 billion. Previous studies have related the major predisposing factor of thrombotic complications to stenosis of the graft anastomosis. Several recent reports suggest that antiphospholipid antibodies may cause frequent thrombotic complications. The broad spectrum of diseases that cause hypercoagulable states has not been correlated with frequent PTFE graft thrombosis.. A retrospective case series study was performed to determine the frequency of hypercoagulable states in dialysis patients who had repeated thrombotic complications of their PTFE grafts. Between May 1996 and June 1998, 91 operations were performed on 34 patients with end-stage renal disease. All arteriovenous fistulas were created with PTFE grafts and placed by a single surgeon. All patients were evaluated at operation for anastomotic stenosis, and the majority of patients were studied for hypercoagulable states. Patients with a documented hypercoagulable state were considered for warfarin therapy.. Twenty-two individuals (64.7%) developed 67 thrombotic complications. Twelve of the 14 patients tested (85.7%) were shown to have hypercoagulable states of various causes and degrees. Thirteen patients developed multiple thrombotic complications, 11 (81.8%) were tested and proved to be hypercoagulable. Thirty-eight of the thrombotic complications had nonanatomic causes and 28 (41.8%) had hypercoagulability as the only determinable cause. Ten of the 12 hypercoagulable patients (83.3%) were relegated to intermediate to high-intensity warfarin therapy to reduce the incidence of thrombotic events. Hypercoagulable patients not receiving warfarin had a thrombosis rate of 4.0 events per year; patients on warfarin had a rate of 1.2 events per year. Twenty-three thrombotic events occurred in the anticoagulated group all with an International Normalized Ratio (INR) less than 2.7. This incidence of vascular access thrombosis may be prevented when patients are maintained at an optimal INR of 2.7-3.0.. Hypercoagulability has been a major etiologic factor in PTFE graft thrombosis. Hypercoagulable states are often found in patients with multiple graft thromboses and in patients with nonanatomic causes for thrombosis. Antiphospholipid antibodies are prevalent in the patients with PTFE graft thrombosis, as well as abnormalities in the Protein-C, Protein-S, and Antithrombin III systems. PTFE graft thrombosis has been a frequent cause of morbidity in patients on hemodialysis, and diagnostic evaluation should include a hypercoagulability profile. Based on our data, warfarin therapy should be instituted when hypercoagulable states are found, unless otherwise contraindicated, and INR maintained at 2.7-3.0 to decrease morbidity and frequency of graft thrombosis.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis; Female; Graft Occlusion, Vascular; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Polytetrafluoroethylene; Renal Dialysis; Retrospective Studies; Thrombophilia; Thrombosis; Warfarin

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

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

Topics: Adult; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Warfarin

Serum level of vitamin K1 (= phylloquinone, hereinafter K1) and K dependent blood coagulation factors were determined by HPLC in normal subject, liver cirrhosis, hepatocellular carcinoma, acute hepatitis, chronic hepatitis, chronic renal failure with hemodialysis and patients under warfarin therapy. Normal range of serum K1 concentration was decided on 0.20-2.30 (0.87 +/- 0.53, n = 96) ng/ml. Serum K1 level showed no significant differences among normal subject, various diseases and warfarin therapy. Correlation between serum K1 level and F-VII (r = 0.879, p less than 0.001) or protein C activity (r = 0.839, p less than 0.01) was found in patients whose thrombotest was 20% and less. However serum K1 level didn't correlate with any K dependent coagulation factors in patients if thrombotest was over 20%.

Topics: Adolescent; Adult; Blood Coagulation Factors; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Liver Diseases; Male; Protein C; Vitamin K 1; Warfarin

The protein binding of ethinyloestradiol (EE2) was investigated in the plasma from 14 healthy volunteers, 10 patients with hyperbilirubinemia, 10 patients with liver cirrhosis and 10 patients with renal failure. Binding assay was performed by equilibrium dialysis at 37 degrees C. The unbound fraction (mean +/- SD) of EE2 was 1.17 +/- 0.12 (volunteers), 2.74 +/- 0.77 (hyperbilirubinemics; p less than 0.001) 1.51 +/- 0.31 (cirrhotics; p less than 0.01) and 1.44 +/- 0.11 (renal failure; p less than 0.001). Studies with isolated albumin and alpha-1-acid glycoprotein showed that albumin is the major plasma protein to bind EE2. Warfarin (75 microM) and diazepam (75 microM) increased by 5.0% and 3.0%, respectively, the unbound fraction of EE2 when albumin concentration was 15 microM. Under similar conditions, digitoxin did not modify the binding of EE2. At therapeutic concentrations, warfarin and diazepam did not affect the binding of EE2 in plasma.

Topics: Adult; Aged; Blood Proteins; Diazepam; Digitoxin; Drug Interactions; Ethinyl Estradiol; Female; Humans; Hyperbilirubinemia; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Protein Binding; Warfarin

To prevent thrombosis in arteriovenous fistulas it is necessary to obtain the knowledgeable cooperation not only of the whole health care team, but also of the patient. The first step is preservation of forearm veins by avoiding unnecessary venipunctures in patients with chronic renal failure. Fistulas should be constructed well in advance of need and use natural rather than prosthetic veins whenever possible. Major surgery elsewhere is a potential cause of fistula thrombosis. Fistula construction is often best delayed till major surgery is over and until the veins have recovered from the effects of systemic steroid therapy. Avoidance of premature fistula cannulation and correct needling techniques help to prevent vein wall damage. Alertness to the presence of high venous pressures on dialysis and observation of inefficient dialysis due to recirculation should lead to detection of narrowed segments which can be surgically corrected before thrombosis occurs. Antiplatelet drugs are of proven value in the prevention of recurrent thrombotic episodes.

Topics: Arteriovenous Shunt, Surgical; Fibrinolytic Agents; Forearm; Humans; Kidney Failure, Chronic; Patient Compliance; Renal Dialysis; Thrombosis; Venous Pressure; Warfarin

Two patients with progressive systemic sclerosis (scleroderma) developed renal failure which required thrice weekly hemodialysis. While receiving hemodialysis treatments and warfarin, their renal function improved and it was possible to discontinue hemodialysis after 9 mo in Case 1 and after 3 mo in Case 2. The recovery of renal function in these patients suggests therapy with warfarin may play a role in the treatment of scleroderma renal failure.

Topics: Adult; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Renal Dialysis; Scleroderma, Systemic; Warfarin

Topics: Cyanates; Humans; Kidney Failure, Chronic; Kinetics; Protein Binding; Reference Values; Serum Albumin; Warfarin

The risks of intermittent anticoagulation with heparin for hemodialysis and longterm anticoagulation with warfarin to prevent clotting of arteriovenous shunts were assessed in a group of 125 home dialysis patients. Over a 7-year period, there were nine bleeding complications attributable to heparin anticoagulation for an incidence of one complication for every 40 patient year on dialysis. In contrast, 20 of 48 patients anticoagulated with warfarin for an average of 2 years each, had a total of 50 hemorrhagic complications requiring 542 days in the hospital and 15 operative procedures. Concersion to an alternative form of vascular access, the internal arteriovenous fistula, obviated the need for warfarin therapy and its unacceptably high complication rate in this population of patients.

Topics: Blood Coagulation; Hemorrhage; Heparin; Humans; Kidney Failure, Chronic; Renal Dialysis; Warfarin

A secific, sensitive, and reproducible radioimmunoassay for human Hageman factor (HF, factory XII) has been developed with purified human HF and monospecific rabbit antibody. Precise measurements of HF antigen were possible for concentrations as low as 0.1% of that in normal pooled plasma. A good correlation (correlation co-efficient = 0.82) existed between the titers of HF measured by clot-promoting assays and radioimmunoassays among 42 normal adults. Confirming earlier studies, HF antigen was absent in Hageman trait plasma, but other congenital deficient plasmas, including those of individuals with Fletcher trait and Fitzgerald trait, contained normal amounts of HF antigen. HF antigen was reduced in the plasmas of patients with disseminated intravascular coagulation or advanced liver cirrhosis, but it was normal in those of patients with chronic renal failure or patients under treatment with warfarin. HF antigen was detected by this assay in plasmas of primates, but not detectable in plasmas of 11 nonprimate mammalian and one avian species.

Topics: Adult; Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Factor XII; Female; Fetal Blood; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Radioimmunoassay; Warfarin

Topics: Anemia, Aplastic; Blood Coagulation; Blood Transfusion; Erythropoiesis; Erythropoietin; Female; Fluoxymesterone; Humans; Iron; Iron Isotopes; Kidney; Kidney Failure, Chronic; Liver; Liver Function Tests; Long-Term Care; Male; Prothrombin Time; Warfarin

Cephaloridine serum half-life was determined in 11 patients undergoing maintenance haemodialysis. Three of them were anephric. The mean cephaloridine half-life was 10.4 hours. There was an inverse correlation between cephaloridine half-life and the duration of maintenance haemodialysis treatment. Reasons for this are discussed.The effect of haemodialysis with the Kiil dialyser on cephaloridine half-life was studied in three patients.Dosage recommendations for patients on maintenance haemodialysis are suggested.

Topics: Adolescent; Adult; Cephaloridine; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Nephrectomy; Renal Dialysis; Time Factors; Warfarin