warfarin and Obesity

Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Obesity; Observational Studies as Topic; Pyridones; Stroke; Venous Thromboembolism; Warfarin

The purpose of this review is to examine the safety and effectiveness of direct oral anticoagulants and provide recommendations for the treatment of venous thromboembolism and atrial fibrillation in obese patients, elderly patients, and patients with chronic kidney disease.. Multiple retrospective cohort studies have shown no difference in bleeding, stroke, or venous thromboembolism outcomes between DOACs and warfarin in patients who are obese, elderly, or those with chronic kidney disease or on dialysis. Some studies have shown that DOACs have a lower bleeding risk than warfarin in these populations. DOACs may be a safe and effective alternative to warfarin for the prevention of stroke in atrial fibrillation patients who are obese, elderly, or those with chronic kidney disease or on dialysis. Apixaban may improve clinical outcomes by lowering the risk of bleeding versus warfarin. DOACs may also be an effective and safe alternative to warfarin for the treatment of venous thromboembolism in obese patients; however, additional studies are needed to assess their use in elderly patients and those with CKD.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Humans; Obesity; Pyridones; Retrospective Studies; Stroke; Warfarin

Obesity has become a major threat to health worldwide. The prevalence of obesity is rapidly increasing, so much so that the World Health Organization has declared obesity as a global epidemic. Obesity is associated with multiple health problems, including venous thromboembolism and atrial fibrillation, both of which are treated with anticoagulation. However, obesity and treatments for obesity such as bariatric surgery can influence absorption, excretion, pharmacokinetics, and pharmacodynamics of various anticoagulants. This results in uncertainty regarding the best antithrombotic strategies in this population, particularly in the morbidly obese. In the recent years, several studies have attempted to investigate anticoagulation use in this population and provided more insight. Herein, we present 4 cases of anticoagulant use in the obese to illustrate the common challenges faced by clinicians and discuss our approach. Whenever possible, we provide a review of the literature and base our recommendations on the best available evidence.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Bariatric Surgery; Drug Monitoring; Humans; Obesity; Premedication; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thromboembolism; 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

Numerous factors are well documented to affect the response to vitamin K antagonists (VKA), including dietary vitamin K, other drugs, age, pharmacogenetics, and disease states. Body weight is perhaps not as well known as a variable affecting VKA dose. Our aim was to review the literature regarding body weight and VKA dose requirements.. We reviewed the English-language literature via PubMed and Scopus using the search terms VKA, warfarin, acenocoumarol, phenprocoumon, fluindione, AND body weight.. Among 32 studies conducted since the widespread use of the international normalized ratio, 29 found a correlation with body weight or body surface area and VKA dose requirement. Warfarin was evaluated in 27 studies and acenocoumarol, phenprocoumon, or fluindione were assessed in 5 investigations.. Because of varying study methodologies, further study is warranted. Based on current evidence, clinicians should include body weight, along with other established variables when dosing VKA. Most important, obese and morbidly obese patients may require a 30% to 50% increase with the initial dosing of VKA.

Topics: Acenocoumarol; Anticoagulants; Body Weight; Comorbidity; Drug Dosage Calculations; Humans; Obesity; Obesity, Morbid; Phenindione; Phenprocoumon; Vitamin K; Warfarin

The risk of recurrent thromboembolic disorders in the 10-year period following an episode of unprovoked venous thromboembolism (VTE) ranges between 30 and 50%, the rate being higher in patients with primary deep venous thrombosis (DVT) than in those with primary pulmonary embolism (PE). The clinical presentation with primary PE increases by more than three times the risk of a new PE episode over that with isolated DVT. Baseline parameters that increase this risk are the proximal location of DVT, obesity, old age and male sex, whereas the role of thrombophilia is controversial. An increasing role is played by post-baseline parameters such as the ultrasound assessment of residual vein thrombosis and the determination of D-dimer. While the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, new scenarios are being offered by the identification of risk stratification models and by strategies that have the potential to help identify patients in whom anticoagulation can be safely discontinued, such as those that incorporate the assessment of D-dimer and residual vein thrombosis. New opportunities are being offered by low-dose aspirin, which has recently been reported to decrease by more than 30% the risk of recurrent events without increasing the bleeding risk; and especially by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving at least the same effectiveness, do not require laboratory monitoring, and can be used immediately after the thrombotic episode.

Topics: Age Factors; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Dabigatran; Disease Management; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Fondaparinux; Humans; Male; Morpholines; Obesity; Polysaccharides; Postthrombotic Syndrome; Pulmonary Embolism; Risk Assessment; Risk Factors; Rivaroxaban; Secondary Prevention; Sex Factors; Thiophenes; Thrombophilia; Ultrasonography; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Antiviral Agents; Child; Evidence-Based Medicine; Humans; Influenza, Human; Integrative Medicine; International Normalized Ratio; Obesity; Oseltamivir; Pain Management; Warfarin

The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that the clearance of anticoagulants increases with weight. As obesity is associated with an increased risk of venous thromboembolism and arterial disease, there is an urgent need to establish appropriate anticoagulation regimens for this patient group. Research studies applying the method of pharmacokinetic-pharmacodynamic modelling and simulation could establish an appropriate evidence base and provide direction and reassurance to prescribing clinicians.

Topics: Acute Coronary Syndrome; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Humans; Morpholines; Multicenter Studies as Topic; Obesity; Polysaccharides; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Venous Thrombosis; Warfarin

Recent studies have indicated that osteocalcin, a peptide secreted by osteoblasts, functions as an anti-diabetogenic hormone in mice. Osteocalcin knock out mice exhibit obesity, hyperglycemia, and decreased insulin secretion relative to wild-type mice. Treatment with non-carboxylated osteocalcin upregulates energy expenditure, and ameliorates obesity and diabetes in mouse models of obesity-related diabetes. Of interest, the beneficial effects of osteocalcin were shown to be specific to non-carboxylated osteocalcin. This appears, however, inconsistent with recent clinical studies showing insulin-sensitizing effects of vitamin K, which promotes gamma-carboxylation of osteocalcin. These findings shed new light on the crosstalk between bone and energy expenditure, and lead to new questions. These questions include: (1) Does non-carboxylated osteocalcin exert the beneficial effects in humans?; (2) Does warfarin, a vitamin K antagonist, improve insulin, sensitivity and lower blood glucose levels?; (3) and Do estrogen and bisphosphonate, which reduce circulating osteocalcin, contribute to insulin resistance and obesity? These issues await further investigations.

Topics: Animals; Bone Density Conservation Agents; Diabetes Mellitus; Diphosphonates; Estrogens; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Mice; Obesity; Osteoblasts; Osteocalcin; Vitamin K; Warfarin

To investigate the relationship between body mass index (BMI) and outcomes in patients with atrial fibrillation (AF).. In the ENGAGE AF-TIMI 48 trial, patients with AF were randomized to warfarin (international normalized ratio 2.0-3.0) or edoxaban. The cohort (N = 21 028) included patients across BMI categories (kg/m2): underweight (<18.5) in 0.8%, normal (18.5 to <25) in 21.4%, overweight (25 to <30) in 37.6%, moderately obese (30 to <35) in 24.8%, severely obese (35 to <40) in 10.0%, and very severely obese (≥40) in 5.5%. In an adjusted analysis, higher BMI (continuous, per 5 kg/m2 increase) was significantly and independently associated with lower risks of stroke/systemic embolic event (SEE) [hazard ratio (HR) 0.88, P = 0.0001], ischaemic stroke/SEE (HR 0.87, P < 0.0001), and death (HR 0.91, P < 0.0001), but with increased risks of major (HR 1.06, P = 0.025) and major or clinically relevant non-major bleeding (HR 1.05, P = 0.0007). There was a significant interaction between sex and increasing BMI category, with lower risk of ischaemic stroke/SEE in males and increased risk of bleeding in women. Trough edoxaban concentration and anti-Factor Xa activity were similar across BMI groups >18.5 kg/m2, while time in therapeutic range for warfarin improved significantly as BMI increased (P < 0.0001). The effects of edoxaban vs. warfarin on stroke/SEE, major bleeding, and net clinical outcome were similar across BMI groups.. An increased BMI was independently associated with a lower risk of stroke/SEE, better survival, but increased risk of bleeding. The efficacy and safety profiles of edoxaban were similar across BMI categories ranging from 18.5 to >40.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Body Mass Index; Comorbidity; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Obesity; Overweight; Proportional Hazards Models; Pyridines; Stroke; Thiazoles; Treatment Outcome; Warfarin

Obesity has been associated with increased cardiovascular risk in atrial fibrillation, but little is known in elderly patients with atrial fibrillation.. Post hoc analysis of data from the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial.. We studied 1588 elderly patients, who were categorized as normal body mass index (BMI, 18.5-25 kg/m(2); n=515 [32.4%]), overweight (BMI, 25-30 kg/m(2); n=711 [44.8%]), and obese (BMI≥30 kg/m(2); n=362 [22.8%]). There was a significant reduction in the composite outcome of cardiovascular death and stroke/systemic embolism with increasing BMI category, being 5.0%, 3.2%, and 1.5% per 100 patient-years, respectively (P for trend=0.01). Cox proportional hazards analysis found obesity to be associated with a lower risk of the primary composite outcome (hazard ratio, 0.29; 95% confidence interval, 0.11-0.77; P=0.01). In the warfarin arm (n=814), multivariate logistic regression analysis demonstrated that obesity was independently related to higher odds of time in therapeutic range ≥60% (odds ratio, 1.84; 95% confidence interval, 1.21-2.80; P=0.004).. Obesity was associated with a lower stroke and mortality rate in elderly anticoagulated atrial fibrillation patients. Obesity was related to good quality anticoagulation control.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Comorbidity; Embolism; Factor Xa Inhibitors; Female; Humans; Logistic Models; Male; Multivariate Analysis; Obesity; Oligosaccharides; Overweight; Proportional Hazards Models; Risk Factors; Stroke; Warfarin

Despite the lack of an optimum dosing strategy in obese patients, warfarin remains the most commonly used anticoagulant. Body mass index (BMI) >30 has been linked to increased time to obtain a therapeutic international normalized ratio on initiation of warfarin as well as higher maintenance dose. Despite higher dosage requirements, few studies have examined the relationship between warfarin and bleeding events in obese individuals. We examined the performance of BMI in predicting the incidence of bleeding at an anticoagulation clinic (ACC) over a 1 year period. Eight hundred and sixty-three patients followed in the ACC over a 1 year period were evaluated for bleeds in relation to BMI [defined as weight (kg)/height (m(2))]. Seventy-one of the 863 patients had a bleeding event (8.2 %); mean age 69.5 years and 44 % females. BMI categories were normal weight (21 %), overweight (38 %), obese class I (21 %), II (9 %), and III (11.3 %), respectively. Prevalence of major and minor bleeding events were 4.4 and 3.8 %, respectively. In univariate analyses, hazard ratio (HR) for major bleeding risks increases with higher obesity categories (HR 1.3, 1.85, and 1.93 for classes I, II, III, respectively). In multivariable adjusted model obesity classes II and III significantly increased the risk of major bleeds (HR 1.84, p < 0.001). Bleeding risk is higher in obese compared to normal weight individuals who are on warfarin. These results suggests that BMI plays a role in bleeding events in patients on warfarin.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Body Mass Index; Female; Hemorrhage; Humans; Male; Middle Aged; Obesity; Retrospective Studies; Risk Factors; Sex Factors; Warfarin

This study examines whether obesity accelerates atherogenic progression or adverse outcomes after coronary artery bypass graft (CABG) surgery.. Obesity is a major risk factor for developing coronary heart disease. Whether obesity accelerates disease progression after CABG is unclear.. We examined how body mass index (BMI) related to atherosclerotic graft progression and a clinical composite outcome of death, nonfatal myocardial infarction, stroke, CABG surgery, or angioplasty among 1,314 participants in the Post CABG trial. Participants who had undergone CABG surgery were randomly assigned in a 2 x 2 factorial design to warfarin versus placebo and aggressive low-density lipoprotein cholesterol (LDL-C) lowering with lovastatin 40 to 80 mg/day (to achieve LDL-C of 60 to 85 mg/dl) versus moderate LDL-C lowering with lovastatin 2.5 to 5 mg/day (to achieve LDL-C of 130 to 140 mg/dl). Angiographic progression was assessed by coronary angiography at 4 to 5 years.. Higher BMI was associated with a higher likelihood of angiographic progression (p trend = 0.003) after adjustment for demographic factors, treatment assignment, smoking status, and years since CABG surgery, but not with clinical events (p trend = 0.81). In stratified analyses, higher BMI was associated with angiographic progression in the low-dose lovastatin group (p trend <0.001) but not in the high-dose group (p = 0.03 for test for interaction of BMI and statin treatment). In the high-dose lovastatin group, higher BMI appeared to be protective against clinical events (p trend = 0.06, test of interaction: 0.02).. Higher BMI is strongly associated with atherogenic progression after CABG surgery. Aggressive statin therapy may be protective against obesity-related acceleration of coronary heart disease.

Topics: Anticoagulants; Body Mass Index; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Disease Progression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Obesity; Postoperative Period; Prognosis; Prospective Studies; Warfarin

Direct oral anticoagulants (DOACs) are often used in patients with atrial fibrillation or flutter instead of warfarin and although supporting evidence is limited, available studies suggest this may be an acceptable route of care. Our study assessed the question: are DOACs as effective and safe as warfarin in patients with atrial fibrillation and class III obesity specifically in a rural population?. A retrospective analysis was conducted by examining the first 6-12 months of therapy with a DOAC (apixaban or rivaroxaban) or warfarin in patients with weight >120kg or class III obesity. Events of interest, thrombosis and bleeding, were documented for analysis. The risk and odds of events of interest for both groups were calculated and compared.. Characteristics of both arms were similar (DOAC n=42; warfarin n=43). A lack of thrombosis events limited efficacy analysis. A total of 22 bleeds occurred with 8 in patients prescribed a DOAC (7 minor; 1 major) and 14 in those prescribed warfarin (12 minor; 2 major). Weight in kg (p<0.001), BMI (p=0.013) and HAS-BLED score (p=0.035) were predictive of a first bleeding event in patients prescribed warfarin. The odds ratio for any type of bleed on DOAC vs warfarin was 0.55 (0.180-1.681; 95% CI).. In patients with atrial fibrillation and class III obesity, regarding safety, DOACs appear to be non-inferior to warfarin during the first six to 12 months of therapy in our rural population - consistent with other analyses; however, the lack of thrombosis events limited the efficacy analysis.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Obesity; Retrospective Studies; Rural Population; Stroke; Warfarin

Direct oral anticoagulants (DOACs) are a favored treatment to prevent stroke in patients with atrial fibrillation (AF). There are limited data concerning the efficacy and safety of DOACs in obese. Obesity leads to wide structural and physiological changes that may affect the pharmacokinetics and pharmacodynamics of drugs. The optimal dosing strategies for DOACs in this significant and growing sub-group remain unknown. The study aimed to evaluate on a large scale the safety and efficacy of DOAC treatment in extreme obese patients with AF. In this retrospective cohort study, we included patients with AF treated with DOACs. Patients were divided according to body mass index (BMI). Study outcomes included stroke, major bleeding, and death. Between 2012 and 2017, 5183 patients with AF were included in the analysis (2,688, 2137, and 358 patients had a BMI <30, 30 to 40, and >40 accordingly). There was no significant difference in the prevalence of ischemic events (9.9%, 8.2%, and 7.5% of patients with BMI <30, 30 to 40, and >40, respectively, p = 0.088), major bleeding events (13%, 14.1%, and 11.2% of patients with BMI <30, 30 to 40, and >40, respectively, p value = 0.257) or net ischemic and major bleeding events (18.7%, 18.7%, and 15.4% of patients with BMI <30, 30 to 40, and >40 respectively, p = 0.297) between the BMI groups. In conclusion, DOACs treatment for prevention of ischemic events in AF is effective and safe through the BMI spectrum, including extreme obesity.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Obesity; Retrospective Studies; Stroke; Warfarin

The 2021 International Society on Thrombosis and Haemostasis' (ISTH) recommends standard doses of apixaban and rivaroxaban regardless of high body mass index (BMI) and weight, but had not compare DOACs head-to-head in obesity or address underweight patients.. Our aim is to evaluate the safety and efficacy of DOACs in underweight and obese patients compared to warfarin. The primary endpoints include incidence of thromboembolic and bleeding events. Descriptive statistics was used for continuous variables. The Kruskal-Wallis test was used to compare the four-groups for continuous measures and the chi-square test or Fisher's exact test was used to analyze categorical data. The chi-square test or Fisher's exact test, was used for categorical variables, and the Mann-Whitney test (the non-parametric counterpart to the two-sample t-test) for continuous data.. Of 2940 patients receiving anticoagulation for venous thromboembolism (VTE) treatment or atrial fibrillation (AF), 492 met eligibility criteria. Within each group, 248 patients received warfarin, 101 received apixaban, 100 received rivaroxaban and 43 received dabigatran. Patients were characterized in 4 body mass index (BMI) categories, in which 80 were underweight and 412 were obese.. When each DOAC was compared to warfarin in rates of VTE, apixaban showed statistically significant lower rate of VTE (p = 0.0149). However, no statistical significance was identified in the rate of VTE between DOACs combined vs. warfarin (p = 0.1529). When each DOAC was compared to warfarin, apixaban showed the lowest rate of overall bleeding (p = 0.0194). However, no statistical difference in the rate of bleeding was observed between DOACs combined vs. warfarin (p = 0.3284). Patients with extreme body weights requiring anticoagulation for VTE and AF may safety benefit from DOAC therapy. This evaluation showed apixaban with the lowest rate of VTE and bleeding compared to warfarin, rivaroxaban, and dabigatran. These results provide experience for the clinician to use DOACs, particularly apixaban, in underweight and obese populations.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Obesity; Pyridones; Rivaroxaban; Thinness; Venous Thromboembolism; Warfarin

Current evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications.. This retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/m. A total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70-0.84; p < 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81-1.06; p = 0.2842), and results were consistent across the three polypharmacy groups.. In this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Obesity; Polypharmacy; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Obesity; Retrospective Studies; Stroke; Warfarin

There is limited efficacy and safety data for direct oral anticoagulants (DOACs) in patients with obesity, and it has been suggested to avoid DOACs in this patient population.. Describe the prescribing pattern of oral anticoagulants in obese patients in an urban university setting and assess efficacy, safety, and adherence.. Of the 276 patients who met eligibility criteria, 158 (57.2%) were prescribed warfarin and 118 (42.8%) were prescribed a DOAC. There was no difference in the rate of stroke or recurrent VTE between groups (3.2% vs. 3.4%, p = 0.944). There was also no difference in the rate of bleeding between groups (16.1% vs. 17.8%, p = 0.707). The TTR for the warfarin group was 44.8 ± 23%, and appointment adherence was 78.6 ± 20%. The MPR for the DOAC group was 0.93 ± 0.24.. Despite limited data in obese patients, DOACs are prescribed in this population. Results suggest no difference in safety and efficacy compared to warfarin, but barriers to quality anticoagulation may exist in this population.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Hemorrhage; Humans; Obesity; Retrospective Studies; Stroke; Venous Thromboembolism; Warfarin

Obesity and gastric bypass surgery can complicate anticoagulation therapy. In general, patients post-bariatric surgery are considered to be at a moderate risk for deep venous thromboembolism or pulmonary embolism. American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists guidelines recommend chemical prophylaxis with unfractionated heparin or low molecular weight heparin after surgery until the patient is fully mobile, and for those who require chronic anticoagulation, the International Society of Thrombosis and Haemostasis recommend warfarin if body mass index (BMI) is above 40 kg/m

Topics: Anticoagulants; Bariatric Surgery; Enoxaparin; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Obesity; Rivaroxaban; Venous Thromboembolism; Warfarin

To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes.. Patients aged ≥18 years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and ≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models.. A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74-0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78-1.09).. In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Embolism; Hemorrhage; Humans; Obesity; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Data are limited addressing anticoagulant reversal in obese patients using activated prothrombin complex concentrate (aPCC).. Assess the impact of obesity on INR reversal with fixed aPCC dosing.. Institutional review board-approved, retrospective cohort conducted in a large academic medical center. Patients 18 years or older who received fixed-dose aPCC for warfarin-associated hemorrhage were included. Patients who received aPCC for any other indications or who had no follow-up INR after aPCC administration were excluded. Patients with an INR of 5 or greater received 1000 units aPCC, whereas those with INR less than 5 received 500 units aPCC, per institutional protocol. Patients were stratified into obese and nonobese based on body mass index. Primary end point was INR reversal, defined as repeat INR of 1.4 or less within 4 hours following aPCC treatment, without a repeated dose. Secondary end points included percentage change in INR, proportion of patients requiring an additional dose of aPCC, bleeding complications, thrombotic complications, hospital length of stay, and in-hospital mortality.. 259 patients were included, of whom 83 were obese (32%). A significantly higher proportion of nonobese patients achieved an INR of 1.4 or less within 4 hours of treatment (169 [96.02%] vs 69 [83.13%];. When fixed-dose aPCC is used for warfarin reversal, obesity is associated with a significantly lower rate of INR reversal, without increased bleeding. This study adds to the limited amount of literature on aPCC dosing in obesity.

Topics: Anticoagulants; Blood Coagulation Factors; Humans; International Normalized Ratio; Obesity; Retrospective Studies; Warfarin

IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.

Topics: Adult; Anaphylaxis; Anticoagulants; Autoantibodies; Autoantigens; Blood Platelets; Drug Therapy, Combination; False Negative Reactions; Female; Heart Arrest; Heparin; Humans; Immunoenzyme Techniques; Immunoglobulin G; Immunoglobulin M; Medical Errors; Obesity; Platelet Activation; Platelet Factor 4; Pulmonary Embolism; Recurrence; Sensitivity and Specificity; Serotonin; Thrombocytopenia; Venous Thrombosis; Warfarin

There are currently more than 7 million patients taking a direct oral anticoagulant (DOAC), with more new prescriptions per year than warfarin. Despite impressive efficacy and safety data for the treatment of venous thromboembolism, patients with obesity or advanced renal impairment represented a small portion of the patients enrolled in the phase 3 clinical trials. Therefore, to evaluate the potential use of DOACs in these special populations, clinicians need to have an understanding of the pharmacokinetics and pharmacodynamics of these agents in these settings. Since data from randomized controlled trials are limited, data from observational trials are helpful in gaining comfort with the use of DOACs in these special populations. Selecting the appropriate dose for each agent is imperative in achieving optimal patient outcomes. We provide an extensive review of the pharmacokinetics, pharmacodynamics, phase 3 clinical trials, and observational studies on the use of DOACs in patients with advanced renal impairment, obesity, or other weight-related special populations to provide clinicians with a comprehensive understanding of the data for optimal drug and dose selection.

Topics: Administration, Oral; Anticoagulants; Humans; Obesity; Venous Thromboembolism; Warfarin

Current evidence indicates that the pharmacokinetic profile of rivaroxaban is not significantly impacted by body weight. However, real-world data are needed to better assess the potential clinical benefits and risks associated with rivaroxaban in non-valvular atrial fibrillation (NVAF) patients with obesity. Thus, our objectives were to assess the real-world effectiveness and safety of rivaroxaban versus warfarin among NVAF patients with obesity in the US nationally representative commercially-insured population.. Health insurance claims data from the IQVIA PharMetrics Plus database (January 2010-September 2019) were used to identify NVAF patients with obesity (based on diagnosis codes) initiated on rivaroxaban or warfarin. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances between groups. Study outcomes of interest were evaluated up to 36 months post-treatment initiation and included the composite of stroke or systemic embolism (stroke/SE) and major bleeding. Outcomes were compared using Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (CIs).. These results suggest that rivaroxaban is an effective and safe treatment option among NVAF patients with obesity in a commercially-insured US population.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Obesity; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Guidelines caution against the use of non-vitamin K antagonist oral anticoagulants in patients with extremely high (>120 kg) or low (≤60 kg) body weight because of a lack of data in these populations.. In a post hoc analysis of ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201), a randomized trial comparing apixaban with warfarin for the prevention of stroke in patients with atrial fibrillation, we estimated the randomized treatment effect (apixaban versus warfarin) stratified by body weight (≤60, >60-120, >120 kg) using a Cox regression model and tested the interaction between body weight and randomized treatment. The primary efficacy and safety outcomes were stroke or systemic embolism and major bleeding.. Of the 18 139 patients with available weight and outcomes data, 1985 (10.9%) were in the low-weight group (≤60 kg), 15 172 (83.6%) were in the midrange weight group (>60-120 kg), and 982 (5.4%) were in the high-weight group (>120 kg). The treatment effect of apixaban versus warfarin for the efficacy outcomes of stroke/systemic embolism, all-cause death, or myocardial infarction was consistent across the weight spectrum (interaction P value>0.05). For major bleeding, apixaban had a better safety profile than warfarin in all weight categories and even showed a greater relative risk reduction in patients in the low (≤60 kg; HR, 0.55; 95% CI, 0.36-0.82) and midrange (>60-120 kg) weight groups (HR, 0.71; 95% CI, 0.61-0.83; interaction P value=0.016).. Our findings provide evidence that apixaban is efficacious and safe across the spectrum of weight, including in low- (≤60 kg) and high-weight patients (>120 kg). The superiority on efficacy and safety outcomes of apixaban compared with warfarin persists across weight groups, with even greater reductions in major bleeding in patients with atrial fibrillation with low to normal weight as compared with high weight. The superiority of apixaban over warfarin in regard to efficacy and safety for stroke prevention seems to be similar in patients with atrial fibrillation across the spectrum of weight, including in low- and very high-weight patients. Thus, apixaban appears to be appropriate for patients with atrial fibrillation irrespective of body weight.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Body Weight; Ethnicity; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Obesity; Proportional Hazards Models; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk; Stroke; Thinness; Thromboembolism; Treatment Outcome; Warfarin

Topics: Atrial Fibrillation; Body Mass Index; Heart Failure; Humans; Obesity; Pyridines; Thiazoles; Warfarin

We aimed to investigate the association between obesity and deep venous thrombosis (DVT) in a country with a high prevalence of obesity. This is a retrospective cohort study of patients who presented with DVT between 2008 and 2012. Data were analyzed and compared based on body mass index (BMI), and patients were classified into normal (<25), overweight (≥25 to <30), obese I (30 to <35), obese II (35 to <40), and obese III (≥40). Among 662 patients with DVT, 28% were overweight and 49% were obese. The mean age was 50.3 (16.5) years, and 51% were females. Diabetes mellitus and prior venous thromboembolism were significantly higher among obese patients. History of malignancy was more common in nonobese patients. Protein S and antithrombin III deficiency and hyperhomocysteinemia were more prevalent among morbid obese patients. Also, obese patients had higher incidence of thrombosis in the distal veins ( P = .03). Warfarin use and long-term therapy were more frequent in obese than nonobese. Postthrombotic syndrome was comparable in obese and nonobese groups. Recurrent DVT was higher in obese I ( P < .01), whereas mortality rates were greater in nonobese groups ( P = .001). Malignancy, diabetes mellitus, and common femoral vein involvement were predictors of mortality, whereas BMI ≥30 was the predictor of survival. Cox regression models showed that after adjusting for age, sex, pulmonary embolism, and duration of warfarin treatment, BMI ≥40 had better survival (hazard ratio: 0.177, 95% confidence interval: 0.045-0.691, P = .013). There is a significant association between obesity and DVT. Obese patients have characteristic risk factors and better survival. This obesity paradox needs further studies to assess its clinical and pharmacotherapeutic implications.

Topics: Adult; Aged; Antithrombin III; Diabetes Complications; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Obesity; Postthrombotic Syndrome; Prospective Studies; Protein S; Survival Rate; Venous Thrombosis; Warfarin

The absorption of drugs and fat-soluble vitamins is impaired after bariatric surgery on which intestinal length and function are altered. In this context, the anticoagulant effect of warfarin is difficult to predict in the postoperative period.. This study aimed at describing the average weekly warfarin dose required to maintain a therapeutic international normalized ratio (INR) before and up to 1 year after sleeve gastrectomy with biliopancreatic diversion and duodenal switch (BPD/DS). Secondary end points included the number of patients requiring a minimal 20% reduction in their weekly dose of warfarin following the BPD/DS.. This descriptive and retrospective longitudinal population study included 20 patients using warfarin who underwent BPD/DS. An INR was considered nontherapeutic if it was below or above 15% of the targeted therapeutic range for any given patient.. One month after the surgery, the median weekly dose of warfarin was 55% lower than the preoperative dose ( P < 0.0001). In the 9 patients with full follow-up data, the warfarin dose at 1 year was still 39% lower than the preoperative dose ( P < 0.05). At that time, all patients presented a minimal dose reduction of 20%.. BPD/DS robustly reduced the requirement of warfarin, which resulted in lower doses after surgery. This persisted over the first year after the surgery, likely because of enhanced sensitivity. The mechanisms for this effect remain multifactorial, and the exact extent of change in dose cannot be predicted.

Topics: Adult; Anticoagulants; Bariatric Surgery; Biliopancreatic Diversion; Female; Gastrectomy; Humans; International Normalized Ratio; Longitudinal Studies; Male; Middle Aged; Obesity; Retrospective Studies; Warfarin

Several studies have demonstrated an association between body mass index (BMI) and warfarin therapeutic dose, but none evaluated the association of BMI with the clinically important outcome of major bleeding in a community setting. To address this evidence gap, we conducted a case-control study to evaluate the association between BMI and major bleeding risk among patients receiving warfarin.. We used a case-control study design to evaluate the association between obesity (BMI >30.0 kg/m. Overall, the sample was 55% male, 94% Caucasian, and mean age was 70 years. Cases and controls had an average of 3.4 and 3.7 years of warfarin use, respectively. Obese patients had significantly lower major bleeding risk relative to non-obese patients (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.92). The OR was 0.56 (95% CI 0.35-0.90) in patients with ≥1 year of warfarin use, and 0.78 (95% CI 0.40-1.54) in patients with <1 year of warfarin use. An exploratory analysis indicated a statistically significant interaction between CYP4F2*3 genetic status and obesity (P = .049), suggesting a protective effect of obesity on the risk of major bleeding among those wild type for CYP4F2*3, but not among variants.. Our findings suggest that BMI is an important clinical factor in assessing and managing warfarin therapy. Future studies should confirm the major bleeding associations, including the interaction between obesity and CYP4F2*3 status identified in this study, and evaluate potential mechanisms.

Topics: Aged; Anticoagulants; Body Mass Index; Case-Control Studies; Cytochrome P-450 CYP2C9; Cytochrome P450 Family 4; Female; Hemorrhage; Humans; Logistic Models; Male; Obesity; Risk Factors; Vitamin K Epoxide Reductases; Warfarin

Not all patients with warfarin-related acute intracranial hemorrhage (ICH) achieve full reversal of international normalized ratio (INR) after the first dose of weight-based prothrombin complex concentrate (PCC). We sought to identify factors associated with anticoagulation reversal failure after the first dose of PCC.. Consecutive patients who were hospitalized with warfarin-related acute ICH at a tertiary center between 1 January 2010 and 31 December 2012 were studied. Anticoagulation reversal failure was defined as INR ≥ 1.5 after the first dose of PCC. Logistic regression was performed to determine the predictors of anticoagulation reversal failure.. Fifty-one patients with acute ICH received PCC for warfarin reversal using a weight-based protocol. Overall, 23 (45%) patients did not achieve full reversal of INR after the first dose. Those with anticoagulation reversal failure were obese (body mass index > 30 kg/m(2)) (41% vs. 14%, p = 0.03), had a higher initial INR (3.0 ± 1.4 vs. 2.0 ± 0.7, p = 0.001), and had a higher prevalence of initial INR >2.0 (22% vs. 67%, p = 0.001), compared with those who were successfully reversed. Multivariable logistic regression identified obesity (odds ratio 7.88, 95% CI 1.12 to 55.68) and initial INR >2.0 (odds ratio 12.49, 95% CI 2.27 to 68.87) as independent predictors of anticoagulation reversal failure.. Obesity and elevated initial INR are independently associated with anticoagulation reversal failure using the weight-based PCC protocol in patients with warfarin-related acute ICH. Further studies are needed to determine more effective dosing protocols and individualized strategies for anticoagulation reversal after acute ICH, especially among obese patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Body Mass Index; Comorbidity; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Models, Biological; Obesity; Retrospective Studies; Risk; Treatment Failure; Warfarin

The volume of intracerebral hemorrhage (ICH) measured at hospital admission is the strongest predictor of clinical outcomes in patients with ICH. Despite the high incidence rate of ICH in Asians, there is lack of data regarding predictors of ICH volume in this ethnic group. The purpose of this study was to determine predictors of deep ICH volume and examine their effect on short-term mortality in Asians.. Hematoma volume was measured using the ABC/2 method. ICH volume was transformed to the natural log scale to normalize distributions for all analyses. We estimated the coefficients of ICH volume based on relevant predictors using multivariable linear regression. We also determined the association between body mass index (BMI) and ICH volume using a regression line and a line determined by a locally weighted scatter plot smoothing.. A total of 1,039 patients from 2 twin hospitals in Korea who were admitted with primary spontaneous supratentorial deep ICH over a 12-year period were enrolled in this study. The median ICH volume was 19.7 ml. The average patient age was 59.2, and 62.4% of patients were men. The mean ICH volume showed a gradual, approximately 2% decrease per 1 BMI increase in the current study, after adjusting for all relevant variables (β = -0.024; SE 0.004; p < 0.001). In addition, patients with frequent alcohol consumption showed a 10% increase in mean ICH volume (β = 0.098; SE 0.041; p = 0.016), and patients undergoing warfarin treatment showed a 30% increase in mean ICH volume after full adjustment of all relevant variables (β = 0.296; SE 0.050; p < 0.001). Relative to overweight patients, there was a 47, 11, and 18% increase in admission mean ICH volume in underweight, normal weight and obese patients, respectively. Patients in the first quartile and underweight BMI groups had 1.45-fold (hazard ratio (HR) 1.45; 95% CI 1.03-2.03; p = 0.035) and 1.77-fold (HR 1.77; 95% CI 1.10-2.84; p = 0.019) higher increased risk of death during the first 3 months after ICH, retrospectively. In addition, patients in groups with frequent alcohol consumption and warfarin use both showed a significant association with mortality 90 days after ICH.. We demonstrated the association between various predictors and admission ICH volume with short-term mortality in Asians. Further studies are needed to account for these observations and determine their underlying mechanisms.

Topics: Aged; Alcohol Drinking; Angiography, Digital Subtraction; Anticoagulants; Asian People; Body Mass Index; Cerebral Angiography; Cerebral Hemorrhage; Computed Tomography Angiography; Female; Humans; Kaplan-Meier Estimate; Linear Models; Magnetic Resonance Angiography; Male; Middle Aged; Multivariate Analysis; Obesity; Patient Admission; Republic of Korea; Retrospective Studies; Risk Factors; Thinness; Time Factors; Warfarin

The aim of this case report is to discuss the issue of nutritional therapy in patients taking warfarin. Patients are often prescribed vitamin K free diets without nutritional counseling, leading to possible health consequences.. A 52-year-old woman with obesity and hypertension was prescribed a low calorie diet by her family doctor in an effort to promote weight loss. After a pulmonary embolism, she was placed on anticoagulant therapy and on hospital discharge she was prescribed a vitamin K free diet to avoid interactions. Given poor control of her anticoagulant therapy, she was referred to our Nutritional Unit outpatients' service.. This case illustrates the importance of a thorough medical nutrition assessment in the management of patients with obesity and the need for a change in the dietary approach of nutritional therapy in the management of vitamin K anticoagulant therapy. In patients taking warfarin, evidence suggest that the aim of nutritional therapy should be to keep dietary intake of vitamin K constant.

Topics: Anticoagulants; Caloric Restriction; Female; Humans; Hypertension; Middle Aged; Nutrition Assessment; Obesity; Pulmonary Embolism; Vitamin K; Warfarin; Weight Loss

Sustained growth in the arrhythmia population at Stanford Health Care led to an independent nurse practitioner-run outpatient direct current cardioversion (DCCV) program in 2012. DCCVs performed by a medical doctor, a nurse practitioner under supervision, or nurse practitioners from 2009 to 2014 were compared for safety and efficacy. A retrospective review of the electronic medical records system (Epic) was performed on biodemographic data, cardiovascular risk factors, medication history, procedural data, and DCCV outcomes. A total of 869 DCCVs were performed on 557 outpatients. Subjects were largely men with an average age of 65 years; 1/3 were obese; most had atrial fibrillation; and majority of subjects were on warfarin. The success rate of the DCCVs was 93.4% (812 of 869) with no differences among the groups. There were no short-term complications: stroke, myocardial infarction, or death. The length of stay was shortest in the NP group compared to the other groups (p <0.001). In conclusion, the success rate of DCCV in all groups was extremely high, and there were no complications in any of the DCCV groups.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; Atrial Fibrillation; Cardiomyopathies; Comorbidity; Diabetes Mellitus, Type 2; Electric Countershock; Female; Humans; Hypertension; Length of Stay; Male; Middle Aged; Nurse Practitioners; Obesity; Patient Safety; Physicians; Practice Patterns, Nurses'; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

Isolated brachiocephalic artery dissection is an extremely rare condition. Its presentation as an acute stroke can pose a significant diagnostic challenge in patients because of its rarity. We present a case of isolated spontaneous brachiocephalic artery dissection presenting as acute cerebrovascular accident. This case also illustrates the treatment dilemma brachiocephalic artery dissection can present, whether to choose antithrombotic/anticoagulation therapy and/or surgery, and also the dilemma in blood pressure management.

Topics: Adult; Anticoagulants; Antihypertensive Agents; Aortic Dissection; Aspirin; Ataxia; Brachiocephalic Trunk; Heparin; Humans; Male; Medical History Taking; Obesity; Platelet Aggregation Inhibitors; Stroke; Warfarin

Topics: Aged; Anticoagulants; Drug Eruptions; Female; Humans; Leg Dermatoses; Necrosis; Obesity; Skin; Warfarin

Current warfarin dosing guidelines for pediatric patients do not account for obesity. Published data from adults suggest that obesity may affect warfarin dosing requirements. Obesity is prevalent in the pediatric population, and current warfarin dosing methods should be evaluated in obese pediatric patients.. Patients aged 2 to 18 years who were obese and initiated on warfarin therapy at our institution as inpatients from 2004 to 2010 were identified and matched in a 1:2 ratio by age and sex with nonobese patients who were initiated on warfarin therapy. Patients were categorized obese per Centers for Disease Control guidelines. Demographic and disease state information, warfarin dosing information, INR values, and interacting medications were collected. Warfarin was dosed according to the institutional guidelines adapted from the published literature. Time to therapeutic INR value was the primary endpoint and percent of patients with supratherapeutic INR values was the secondary endpoint.. A total of 30 patients met the study criteria (10 obese, 20 nonobese), and baseline demographic variables were similar. No significant differences were noted in the number of INR values drawn, number of warfarin doses administered, or length of stay. Initial and maximum doses of warfarin per kg were significantly lower in obese patients compared with nonobese patients (P<0.05). Median time to therapeutic INR value was twice as long in obese patients as in nonobese patients (median=6 [range, 4 to 28 d] versus median=3 [range, 1 to 10 d]; P<0.01).. Obese pediatric patients have an increased time to therapeutic INR value when traditional warfarin dosing guidelines are used.

Topics: Adolescent; Anticoagulants; Body Mass Index; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Institutional Practice; Male; Obesity; Practice Guidelines as Topic; Retrospective Studies; Thrombosis; Warfarin

Hormone replacement therapy increases risk of deep venous thrombosis (DVT) mainly in the extremities and lungs. There are reports of mesenteric ischemia secondary to oral contraceptive pills but no reports on hormone replacement therapy and mesenteric thrombosis. The authors present a case of a 44-year-old obese (BMI 32) woman, on long-term hormone replacement therapy, presented with thrombosis of portal, splenic and superior mesenteric veins. She underwent surgical resection of ischemic bowel and planned re-look laparotomies with further resections and jejuno-ileal anastomosis at final laparotomy. Thorough haematological investigations were normal. The authors conclude that hormone replacement therapy in obese patients with no other risk factors can cause a catastrophic mesenteric thrombosis. Aggressive surgical resection with re-look laparotomies and further resections can be lifesaving.

Topics: Abdominal Pain; Adult; Anticoagulants; Body Mass Index; Female; Hormone Replacement Therapy; Humans; Laparotomy; Mesenteric Veins; Obesity; Portal Vein; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Black or African American; Case Management; Female; Fibrin Fibrinogen Degradation Products; Genetic Predisposition to Disease; Humans; Obesity; Pulmonary Embolism; Risk; Sickle Cell Trait; Thrombophilia; Thrombophlebitis; Ultrasonography; Venous Thrombosis; Warfarin

Practice-based research plays a pivotal role for improving patient care as its primary intent is to solve a clinical dilemma or problem encountered in clinical practice. Its results are immediately applicable to day-to-day clinical practice and essential to the growth of an evidence-based clinical practice. This review emphasizes the importance of this type of research. In addition, it serves to identify common sources for project conception and gives examples based on personal experiences of the author as a clinical practitioner, educator, and researcher. Common barriers to practice-based research are discussed as well as potential solutions offered for consideration.

Topics: Brain Injuries; Calcium; Enteral Nutrition; Evidence-Based Medicine; Food-Drug Interactions; Humans; Hypocalcemia; Insulin; Obesity; Pancreatitis; Phosphorus; Renal Insufficiency, Chronic; Research; Treatment Outcome; Warfarin

Topics: Acanthosis Nigricans; Anti-Bacterial Agents; Anticoagulants; Child; Drug Therapy, Combination; Echocardiography, Doppler; Heart Atria; Heart Diseases; Heparin, Low-Molecular-Weight; Humans; Male; Metabolic Syndrome; Obesity; Penicillanic Acid; Piperacillin; Positive-Pressure Respiration; Tazobactam; Thrombosis; Treatment Outcome; Warfarin

Calciphylaxis is a rare, life-threatening cause of skin necrosis. The condition is primarily reported in patients with end-stage renal disease, and is associated with significant morbidity and mortality. Treatment has mainly been empirical. We report a case of calciphylaxis in a patient with normal renal function and hypoparathyroidism, who responded to treatment with sodium thiosulfate. To our knowledge, this is the first reported case of the use of sodium thiosulfate to treat calciphylaxis in a patient with normal renal function.

Topics: Abdominal Wall; Adult; Anticoagulants; Calciphylaxis; Calcium; Chelating Agents; Female; Humans; Hypoparathyroidism; Kidney; Obesity; Thiosulfates; Treatment Outcome; Warfarin; Xeroradiography

A case of malabsorption- associated warfarin resistance is reported.. A 42-year-old, 111-kg, Caucasian man arrived at the emergency department with atypical pleuritic chest pain. The chest pain was associated with shortness of breath, diaphoresis, nausea, vomiting, and tachycardia. The patient's medical history was significant for multiple episodes of deep venous thrombosis (DVT) in the left upper extremity and both lower extremities, a right above-the-knee amputation due to complications of a previous DVT, insertion of a vena cava filter, pulmonary embolism (PE), asthma, hypertension, and multiple myocardial infarctions. During admission, he was diagnosed presumptively with PE. All potential causes of interference with warfarin absorption were investigated and ruled out. I.V. warfarin therapy at a conventional initial dosage of 5 mg once daily was started on hospital day 2. The International Normalized Ratio (INR) reached the therapeutic range after increasing the i.v. warfarin dosage to 7.5 mg once daily on hospital day 6. The ability to obtain a therapeutic INR on a relatively low dosage of i.v. warfarin but not high dosages of oral warfarin strongly suggests an inherent warfarin malabsorption defect in this patient.. A 42-year-old man with a history of recurrent thromboembolisms demonstrated resistance to oral warfarin therapy due to warfarin malabsorption.

Topics: Adult; Anticoagulants; Chest Pain; Drug Resistance; Humans; Injections, Intravenous; International Normalized Ratio; Malabsorption Syndromes; Male; Obesity; Pulmonary Embolism; Venous Thrombosis; Warfarin

Venous thromboembolism and adverse pregnancy outcomes are potential complications of pregnancy. Numerous studies have evaluated both the risk factors for and the prevention and management of these outcomes in pregnant patients. This consensus group was convened to provide concise recommendations, based on the currently available literature, regarding the use of antithrombotic therapy in pregnant patients at risk for venous thromboembolic events and adverse pregnancy outcomes.

Topics: Adult; Anesthesia, Conduction; Anticoagulants; Antithrombin III; Antithrombins; Cesarean Section; Delivery, Obstetric; Female; Fetus; Heparin; Heparin, Low-Molecular-Weight; Humans; Obesity; Odds Ratio; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Risk Assessment; Risk Factors; Thrombocytopenia; Thrombolytic Therapy; Thrombophilia; Venous Thromboembolism; Warfarin

Data evaluating the safety of using weight-based low-molecular-weight heparin in the treatment of obese patients with acute venous thromboembolism are limited. The product monograph of dalteparin suggests the maximum dose should be limited to 18,000 U subcutaneously once daily. There are no specific data regarding the risk of recurrence or bleeding in patients given dalteparin in a weight-based dose of 200 IU kg(-1). We report a retrospective chart review of 193 obese patients who weighed more than 90 kg and who received dalteparin at or near to 200 IU kg(-1) actual body weight for 5-7 days for acute venous thromboembolism with 90 day follow-up information. Of the patients, 77% had idiopathic venous thromboembolism, 16% had an underlying malignancy, and 7% had a transient risk factor. Warfarin was initiated within 2 days with a target International Normalized Ratio range of 2.0-3.0. All patients were followed for 12 weeks post diagnosis. Only two patients had a major hemorrhage, 4 and 8 weeks from diagnosis. This study supports the safety of dosing dalteparin based on actual body weight in obese patients.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Body Weight; Dalteparin; Female; Humans; International Normalized Ratio; Male; Medical Records; Middle Aged; Obesity; Recurrence; Retrospective Studies; Risk Factors; Thromboembolism; Time Factors; Venous Thrombosis; 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

Patients with pulmonary embolism may have no definitive predisposing factors for thrombi. The clinical entity of chronic pulmonary embolism is also uncertain. This study clarified the clinical characteristics of pulmonary embolism without definitive predisposing factors. During the last 10 years, 36 consecutive patients were diagnosed as having pulmonary embolism (mean age 61 years, female 75%). Twenty-four patients (67%) had definitive predisposing factors ("definitive" group). Patients without definitive predisposing factors had the following characteristics. The onset of symptoms was out-hospital and insidious. The main symptom was exertional dyspnea without acute episode compatible with an embolism. In four patients (33%) there was a delay of over 2 years form the onset of symptoms to the diagnosis. Three patients had been treated for depression. Thrombolytic therapy caused an inadequate fall in mean pulmonary artery pressure from 41 +/- 11 to 24 +/- 8 mmHg and in three patients it remained over 30 mmHg. Deep vein thrombosis were found in four of nine patients in whom venography were performed 10 days after thrombolytic therapy, but only one patient showed thrombus in the "definitive" group. During the convalescent stage, all patients were treated with prophylactic warfarin. Home oxygen therapy was indicated in three patients and an inferior vena caval filter was implanted in two patients. One third of patients with pulmonary embolism in our institute had no definitive predisposing factors. In these patients, even with thrombolytic therapy, recovery of pulmonary hypertension was often insufficient and deep vein thrombosis persisted. Clinicians should be aware of this disease to avoid undue delay in its diagnosis.

Topics: Aged; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Neoplasms; Obesity; Prognosis; Pulmonary Embolism; Thrombolytic Therapy; Thrombophlebitis; Warfarin

The idiosyncratic dermatologic reaction to coumarin-like agents, most notably, Coumadin (warfarin sodium) has been well described in the world's literature. Although the incidence is reported to be less than 0.1% of patients treated with Coumadin, pedal cases tend to be striking and their treatment seemingly tenuous.

Topics: Aged; Female; Foot; Heparin; Humans; Middle Aged; Necrosis; Obesity; Skin; Warfarin

Morbid obesity has been associated with increased risks for thrombotic diseases. Patients with morbid obesity are shown to have decreased activity and decreased concentration of antithrombin (AT) III. This deficit can be corrected by giving the patients low doses of the oral anticoagulant warfarin. The same beneficial effect was not observed in normal lean control volunteers in whom the levels of AT III were normal at all times. Thus, it may be possible to offer prophylactic protection against the effects of having depressed levels of AT III in patients at increased risk for thrombotic diseases without using full anticoagulant doses of warfarin, including morbidly obese patients.

Topics: Antithrombin III; Humans; Obesity; Thrombosis; Warfarin

In a warfarin-resistant population of wild mice reared in the laboratory, a dominant gene for adiposity, Ad, was found to segregate. The onset of obesity is at 4--6 months, and adipose mice suffer from hyperinsulinaemia; the sexes differ in penetrance, males having greater penetrance then females. Linkage backcrosses show the gene to be situated on chromosome 7 with about 25% recombination with the closely linked warfarin-resistance genes War, and frizzy, fr. The finding of adipose in two other wild populations also carrying War is discussed as an ecological and physiological problem.

Topics: Animal Population Groups; Animals; Animals, Wild; Drug Resistance; Female; Genes, Dominant; Genetic Linkage; Male; Mice; Mice, Obese; Obesity; Warfarin

Topics: Anticholesteremic Agents; Anticoagulants; Arteriosclerosis; Cholesterol; Choline; Diabetes Complications; Dicumarol; Humans; Hyperlipidemias; Hypertension; Nicotinic Acids; Obesity; Phospholipids; Smoking; Stress, Physiological; Thyroxine; Vasodilator Agents; Warfarin