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Gap between recommended and actual initial continuous heparin doses. Histogram shows number of patients receiving initial continuous heparin doses that fell below or above the recommended dose (18 units/kg/h) by the indicated amounts (units/h). N=84.
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Aggressive weight-based dosing guidelines help achieve prompt therapeutic anticoagulation in patients with venous thromboembolism (VTE). While obese patients with VTE face an increased risk of recurrence, physicians typically resist prescribing doses two to three times the usual dose because of concern about bleeding complications.
To examine the u...
Citations
... Körpergewicht (≥ 120 kg). Retrospektive Untersuchungen zeigen, dass adipöse Patienten den Zielbereich der aPTT langsamer erreichen [25,26]. Pragmatische Dosierungen von beispielsweise "1000 IE/h" führen bei ca. ...
... Pragmatische Dosierungen von beispielsweise "1000 IE/h" führen bei ca. 30 % der Patienten zu keiner therapeutischen Heparinisierung [25]. Bezogen auf das Körpergewicht benötigen diese Patienten eine ca. 10 % geringere Dosis im Vergleich zu nichtadipösen Patienten (Tab. ...
... Bezogen auf das Körpergewicht benötigen diese Patienten eine ca. 10 % geringere Dosis im Vergleich zu nichtadipösen Patienten (Tab. 5; [25,27]). Heparinresistenz. ...
Monitoring of vitamin K antagonist treatment with the international normalized ratio (INR) is obligatory, whereas this only applies to direct oral anticoagulants (DOAC) or low molecular weight heparin in the context of selected clinical scenarios. For DOAC the focus is on the determination of trough and peak plasma levels of the drug but for low molecular weight heparins the focus is on anti-Xa activity. The timing of blood sampling in relation to drug intake is essential for the interpretation of the results. A new-onset thrombocytopenia during hospitalization is common. The cause can frequently be identified based on the classification of the underlying disease, the day of onset and documentation of the dynamics of thrombocytopenia as well as the medication history. The importance of thrombophilia testing following a venous thromboembolism has decreased in the absence of clear therapeutic consequences; however, antiphospholipid antibody syndrome must not be overlooked as both the duration of treatment and the choice of anticoagulant depend on this.
... This work is licensed under the Creative Commons Attribution 4.0 International License (VTE) [2]. VTE is primarily treated by unfractionated heparin (UFH) that requires actual body weight (ABW)-based dosing to achieve therapeutic activated partial thromboplastin time (aPTT) within 24 hours of starting the UFH infusion per The American College of Chest Physicians (ACCP) guidelines; however, there is a paucity of literature regarding the dosing of UFH in obese patients [3][4][5][6][7][8]. Few studies introduced adjusted body weight (AjBW)-based dosing of UFH in obese patients due to the concern of excessive anticoagulation and bleeding risk with ABWdosing [9,10]. ...
Purpose: To evaluate the effectiveness of adjusted body weight (AjBW)-based dosing of unfractionated heparin (UFH) in obese patients vis a vis actual body weight (ABW)-based dosing in non-obese patients with venous thromboembolism (VTE).Methods: A retrospective chart review was conducted for obese and non-obese patients initiated on UFH for treating VTE from September 2013 to December 2014. Patients were excluded from the study if they were under 18 years old, developed heparin-induced thrombocytopenia during treatment, received thrombolytic therapy prior to UFH, or received UFH at a dose that did not follow the institution’s protocol. The primary objective was to assess the efficacy of dosing UFH based on AjBW in achieving a therapeutic activated partial thromboplastin time (aPTT) within the first 24 h in obese patients, in comparison to the standard ABW-dosing for non-obese.Results: Of the 57 patients included in the study, 27 patients (47.4 %) were obese, and 30 patients (52.6 %) were non-obese; 16 (59.25 %) of the obese patients achieved a therapeutic aPTT within the first 24 h of AjBW-based dosed UFH, while 18 (60 %) of the non-obese patients achieved a therapeutic aPTT within the first 24 h of ABW-based dosed UFH (p = 0.45).Conclusion: AjBW-based dosing of UFH in obese patients demonstrates comparable efficacy to ABWbased dosing in non-obese patients. Keywords: Obesity, Unfractionated heparin, Venous thromboembolism, Adjusted body weight, Ideal body weight
... In practice, UFH dosing protocols involve two kinds of injections, basal and bolus [3]. Basal is a long-time continuous injection with a small amount, while bolus is a one-time injection with a large amount. ...
Unfractionated heparin (UFH) is commonly used in the intensive care unit (ICU) to prevent blood clotting. Recently, many researchers focus on the development of data- driven methods to solve UFH related problems, which usually involves time series analysis. The performance of data-driven methods depends on whether the inter-correlation of attributes (or variables) in the dataset is closely examined and addressed. This study performs attribute selection, optimal time delay and inter-attributes relations on ICU time series data, in order to provide insights of time series data for UFH related problems. Medical records of 3211 patients with 22 attributes extracted from MIMIC (Medical Information Mart for Intensive Care) III database are used for the experiment. Experimental result shows that some of commonly selected attributes in the literature are less sensitive to the variations of UFH injection. Furthermore, some attributes are inter-dependent, which can increase the complexity of data-driven models, implying that the number of attributes could be reduced. There are 9 attributes found highly related and fast responding in 22 commonly used attributes. This study shows strong potential to provide clinicians with information about sensitive attributes that can help determine the UFH injection policy in ICU.
... All patients enrolled in our study received loading dose of heparin in a dose of 80 IU/kg that was followed by infusion rate of 18 IU/kg/h (Bergqvist et al. 1983). All doses and rates were calculated based on total body weight (TBW), except for patients weighing more than 125 kg; adjusted body weight (ABW) [ideal body weight (IBW) plus 40% of the difference between TBW and IBW)] was used in that population (Khan et al. 2005). ...
Background
Unfractionated heparin (UFH) infusion therapy needs accurate tight control to prevent overanticoagulation that may result in hemorrhagic complications and also to prevent sub therapeutic level that may result in thrombotic complications. The aim of this study was to compare the most popular monitoring tool activated aPTT versus antifactor Xa to reach accurate monitor to UFH therapy in critically ill pregnant females.
Results
Time to reach therapeutic level as well as total heparin dose required to reach this therapeutic level were much lower in the anti-Xa group when compared to aPTT group.
Conclusion
The use of anti-Xa-based protocol to monitor UFH infusion therapy resulted in better therapeutic control as it resulted in earlier achievement of therapeutic level and lower heparin dose requitments.
... [1][2][3] Even though several case reports and studies have been published exploring outcomes with weight-based dosing of UFH in obese and morbidly obese patients, the methodologies, indications for use, and results are highly mixed, making consensus difficult. [4][5][6][7][8][9][10][11][12][13][14][15][16] The largest study to date, which consisted of 1054 patients who received UFH dosed using ABW without a dose cap, demonstrated no differences in Unfractionated heparin infusion for treatment of venous thromboembolism based on actual body weight without dose capping percent of initial aPTTs within goal range. Because this study was conducted in patients with non-VTE indications, such as acute coronary syndrome and atrial fibrillation, where a lower UFH bolus, rate, and aPTT were utilized, applicability to patients with VTE is unclear. ...
Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m ² ), obese (30–39.9 kg/m ² ), and morbidly obese (⩾ 40 kg/m ² ). In this single-center, retrospective cohort study, patients were included if they ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours. Weight-based UFH doses were calculated using actual body weight. A total of 423 patients met the inclusion criteria, with 230 (54.4%), 146 (34.5%), and 47 (11.1%) patients in the non-obese, obese, and morbidly obese cohorts, respectively. Median times to therapeutic aPTT were 16.4, 16.6, and 17.1 hours in each cohort. Within 24 hours, the cumulative incidence rates for therapeutic aPTT were 70.7% for the non-obese group, 69.9% for the obese group, and 61.7% for the morbidly obese group (obese vs non-obese: HR = 1.02, 95% CI: 0.82–1.26, p = 0.88; morbidly obese vs non-obese: HR = 0.87, 95% CI: 0.62–1.21, p = 0.41). There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98). Based on our study, heparin dosing based on actual body weight without a dose cap is safe and effective.
... Moreover, a weight-based regimen of low-molecular-weight heparin may be a good choice to prevent perioperative venous thromboembolism after esophagectomy in obese individuals. 39,69 Systematic cooperation of surgical and intensive care teams is vital for the smooth discharge of underweight patients. Additionally, underweight patients may benefit from preoperative nutritional assessments and nutritional supplementation due to their higher risk of malnutrition and cachexia. ...
Background
The association between body mass index (BMI) and short-term outcomes after esophagectomy remains controversial.
Methods
A meticulous search for articles describing the association between BMI and perioperative outcomes after esophagectomy was conducted using PubMed, EMBASE, and the Cochrane Library. The study classified BMI according to the World Health Organization definitions and Asian-specific BMI cutoff values. Normal weight was selected as the comparator, and the odds ratio (OR) was calculated as the primary effect.
Results
This meta-analysis included 13 studies with 5480 patients. Obese patients exhibited higher risks of overall complication (OR 1.37; P = 0.013), anastomotic leakage (OR 1.74; P = 0.001), and thromboembolic complications (OR 2.05; P = 0.039). Subgroup analysis indicated that obese patients from Western countries had a higher risk of wound infection (OR 2.22; P = 0.022), whereas obese Asians were more likely to experience pulmonary complications (OR 1.64; P = 0.002). Overweight patients displayed no significant differences in major complications relative to normal-weight patients, except for the increased risk of overall complications (OR 1.32; P = 0.030). Additionally, underweight patients showed increased incidence of pulmonary complications (OR 1.92; P = 0.020 and anastomotic leakage (OR 1.64; P = 0.034). Morbid obesity also was analyzed separately with limited data, and this group displayed a higher risk of wound infection (OR 1.62; P = 0.027) and thromboembolic complications (OR 2.65; P = 0.003). No significant differences in mortality were observed among patients in different BMI categories.
Conclusions
Obesity and underweight statuses were confirmed risk factors for several complications after esophagectomy, whereas overweight patients tended to experience greater benefit from surgery.
... However, clinicians should be aware of the increased frequency of supratherapeutic APTT in obese patients and consider this in dosing individual patients. Further research and validation is required to evaluate whether a reduced infusion rate or capped infusion rate protocol for obese patients, in particular those with a BMI >40 kg/ m 2 , is efficacious and safe, as reduced dosing can lead to delays in therapeutic anticoagulation [27]. In both obese and underweight patients, clinicians should pay careful attention to achieving a target APTT in a timely manner. ...
Introduction: The landscape of therapeutic anticoagulation has changed dramatically over the past decade, with availability of direct oral anticoagulants (DOACs), which inhibit factor Xa or thrombin. However, the optimal anticoagulant agent and dosing strategy for patients at both extremes of body weight has not been established for any anticoagulant, including DOACs, vitamin K antagonists (VKA) and the various heparin options.
Areas covered: This paper reviews available evidence to assist clinicians in prescribing of anticoagulation therapy at the extremes of body weight.
Expert commentary: There is limited data to guide prescribing of all available anticoagulants at the extremes of weight and further research regarding efficacy and safety outcomes in these groups is required. Laboratory monitoring to guide dosing of traditional anticoagulants provides reassurance of ‘predictable’ efficacy. In contrast agents that are not routinely monitored by laboratory testing provide greater challenges. For example, underweight patients are at risk of receiving higher drug exposures of DOACs, whereas the use of fixed dose DOACs in obese patients may be associated with lower drug exposures.
... Multiple clinical cases also have demonstrated that obese patients have inadequate levels of both fractionated and unfractionated heparin, suggesting a negative association between body weight and serum heparin level (Allman-Farinelli, 2011;Dager, 2010;Freeman et al., 2010). Furthermore, obese patients have low heparin sensitivity and need a high heparin infusion rate to reduce venous thromboembolism (Hurewitz et al., 2011;Myzienski et al., 2010), and BMI is strongly associated with increased rates of heparin-induced thrombocytopenia (Bloom et al., 2016). There is also some indirect evidence regarding another member of the glycosaminoglycan family, heparan sulfate, which shares a very similar structure with heparin. ...
Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin treatment increases food intake and body weight gain. By using electrophysiological, pharmacological, molecular biological, and chemogenetic approaches, we provide evidence that heparin increases food intake by stimulating AgRP neurons and increasing AgRP release. Our results support a model whereby heparin competes with insulin for insulin receptor binding on AgRP neurons, and by doing so it inhibits FoxO1 activity to promote AgRP release and feeding. Heparin may be a potential drug target for food intake regulation and body weight control.
... 6,7 Because of limited distribution into adipose tissue, dosing lower than institutional protocol has been observed in obese patients to avoid potential overdosing and subsequent adverse bleeding events. 8 Subjects included in early trials establishing weight-based heparin dosing for acute VTE had a mean weight of 80 kg, and these studies did not address dosing in the obese patient population. 9,10 More than 2 decades since those studies, the average weight of patients has increased, leaving the question of what weight is the most appropriate to use when dosing heparin for VTE treatment. ...
... They separately interviewed 8 physicians who stated that they were aware of weight-based dosing, but the large doses required for obese patients was concerning for bleeding events, leading them to decrease the dose. 8 Additionally, 28.6% and 14.3% of the study patients failed to achieve therapeutic aPTTs within 24 and 48 hours, respectively. 8 These results highlight the need to reassess and clearly define dosing strategies in the increasingly prevalent obese population. ...
... 8 Additionally, 28.6% and 14.3% of the study patients failed to achieve therapeutic aPTTs within 24 and 48 hours, respectively. 8 These results highlight the need to reassess and clearly define dosing strategies in the increasingly prevalent obese population. ...
Background:
Despite large interpatient variability in dose response, heparin is utilized for treatment of venous thromboembolism (VTE). Current data on the optimal heparin dosing in obese patients are conflicting.
Objective:
The objective was to evaluate the time and dose required to achieve a therapeutic activated partial thromboplastin time (aPTT) in nonobese, obese, and severely obese patients using a pharmacist-directed heparin dosing protocol.
Methods:
This was a retrospective cohort study in a single-center community hospital inpatient setting. Adult patients receiving heparin for VTE treatment from July 1, 2013, to July 31, 2015, were evaluated. Patients were categorized into 3 groups: nonobese (BMI < 30 kg/m(2)), obese (BMI = 30-39.9 kg/m(2)), and severely obese (BMI ≥ 40 kg/m(2)). Data on height, weight, initial bolus dose, initial infusion rate, time to therapeutic aPTT, and therapeutic infusion rate were collected. Dosing body weight (DBW) was utilized for patients 20% over their ideal body weight (IBW). The primary outcome was time to therapeutic aPTT.
Results:
Analysis included 298 patients. Median times to therapeutic aPTT (hours:minutes) in the nonobese, obese, and severely obese were 15:00 (interquartile range [IQR] = 8:05-23:21), 15:40 (IQR = 9:22-25:10), and 15:22 (IQR = 7.54-23:40), respectively ( P = 0.506). There was no difference in bleeding among the nonobese (14%), obese (13.9%), or severely obese groups (7.9%; P = 0.453). No adverse thrombotic events occurred during hospitalization.
Conclusion:
Using a DBW for heparin dosing in patients 20% over their IBW resulted in similar times to therapeutic aPTT and adverse events in the nonobese, obese, and severely obese.
... Multiple clinical cases also have demonstrated that obese patients have inadequate levels of both fractionated and unfractionated heparin, suggesting a negative association between body weight and serum heparin level (Allman-Farinelli, 2011;Dager, 2010;Freeman et al., 2010). Furthermore, obese patients have low heparin sensitivity and need a high heparin infusion rate to reduce venous thromboembolism (Hurewitz et al., 2011;Myzienski et al., 2010), and BMI is strongly associated with increased rates of heparin-induced thrombocytopenia (Bloom et al., 2016). There is also some indirect evidence regarding another member of the glycosaminoglycan family, heparan sulfate, which shares a very similar structure with heparin. ...
Graphical Abstract Highlights d Heparin increases food intake and body weight in both male and female mice d Heparin promotes feeding by stimulating AgRP neurons and increasing AgRP release d Heparin competes with insulin for insulin receptor binding on AgRP neurons d Orexigenic effects of heparin are driven by FoxO1-mediated AgRP release In Brief Zhu et al. demonstrate that heparin competes with insulin for insulin receptor binding on AgRP neurons, and by doing so it inhibits FoxO1 activity to promote AgRP release and feeding. Heparin is identified as a potential drug target for food intake regulation and body weight control. SUMMARY Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin treatment increases food intake and body weight gain. By using electrophysiological, pharmacological, molecular biological, and chemogenetic approaches, we provide evidence that heparin increases food intake by stimulating AgRP neurons and increasing AgRP release. Our results support a model whereby heparin competes with insulin for insulin receptor binding on AgRP neurons, and by doing so it inhibits FoxO1 activity to promote AgRP release and feeding. Heparin may be a potential drug target for food intake regulation and body weight control.
