Background: The choice of whether to monitor antifactor Xa (anti-Xa) activity in patients who are obese and who are receiving low-molecularweight heparin (LMWH) therapy is controversial. To the authors' knowledge, no systematic review of monitoring of anti-Xa activity in such patients has been published to date. Objective: To systematically ascertain the utility of monitoring anti-Xa concentrations for LMWH therapy in obese patients. Data Sources: MEDLINE (1946 to September 2014), the Cochrane Database of Systematic Reviews, Embase (1974 to September 2014), PubMed (1947 to September 2014), International Pharmaceutical Abstracts (1970 to September 2014), and Scopus were searched using the terms obesity, morbid obesity, thrombosis, venous thrombosis, embolism, venous thromboembolism, pulmonary embolism, low-molecular weight heparin, enoxaparin, dalteparin, tinzaparin, anti-factor Xa, anti-factor Xa monitoring, anti-factor Xa activity, and anti-factor Xa assay. The reference lists of retrieved articles were also reviewed. Study Selection and Data Extraction: English-language studies describing obese patients treated with LMWH or reporting anti-Xa activity were reviewed using a 9-step decision-making algorithm to determine whether monitoring of LMWH therapy by means of anti-Xa activity in obesity is warranted. Studies published in abstract form were excluded. Data Synthesis:The analysis showed that anti-Xa concentrations are not strongly associated with thrombosis or hemorrhage. In clinical studies of LMWH for thromboprophylaxis in bariatric surgery, orthopedic surgery, general surgery, and medical patients, and for treatment of venous thrombo embolism and acute coronary syndrome, anti-Xa activity can be predicted from dose of LMWH and total body weight; no difference in clinical outcome was found between obese and non-obese participants. Conclusions: Routinely determining anti-Xa concentrations in obese patients to monitor the clinical effectiveness of LMWH is not warranted on the basis of the current evidence. Circumstances where measurement of anti-Xa concentration may help in clinical decision-making in either obese or non-obese patients would be cases where elimination of LMWH is impaired or there is an unexpected clinical response, as well as to confirm compliance with therapy or to identify deviation from predicted pharmacokinetics.
Objective: To evaluate the appropriate dose of enoxaparin for venous thromboembolism (VTE) prophylaxis in patients with extreme obesity.
Methods: A literature search was performed using MEDLINE (1950-April 2013) to analyze all English-language articles that evaluated incidence of VTE and/or anti-Xa levels with enoxaparin for thromboprophylaxis in patients with extreme obesity.
Results: Eight studies were included in the analysis. Six of the studies were done in patients undergoing bariatric surgery. Mean body mass index ranged from 44.9 to 63.4 kg/m2within studies. Studies done with bariatric surgery patients utilized doses of enoxaparin that ranged from the standard dose of 30 mg subcutaneous (SQ) every 12 hours to 60 mg SQ every 12 hours. Other studies evaluated doses ranging from 40 mg SQ every 24 hours to 0.5 mg/kg/day. Only 3 studies evaluated the incidence of VTE as the primary endpoint; the other studies evaluated anti-Xa levels. The studies showed that appropriate anti-Xa levels were achieved more often with higher than standard doses of enoxaparin. One study showed that enoxaparin 40 mg SQ every 12 hours decreased the incidence of VTE in patients undergoing bariatric surgery compared to standard doses. Overall risk of bleeding was similar between study groups.
Conclusions: Higher than standard doses of enoxaparin may be needed for patients with extreme obesity. Patients undergoing bariatric surgery may benefit from enoxaparin 40 mg SQ every 12 hours. Additional large randomized, controlled trials are needed to determine the efficacy and safety of higher than standard doses of enoxaparin for VTE prophylaxis in patients with extreme obesity.
BACKGROUND: Venous thromboembolism (VTE) is a prevalent and avoidable complication of hospitalization. Patients hospitalized with trauma, traumatic brain injury, burns, or liver disease; patients on antiplatelet therapy; obese or underweight patients; those having obesity surgery; or with acute or chronic renal failure have unequal risks for bleeding and thrombosis and may benefit differently from prophylactic therapy medication.
OBJECTIVES: To systematically review the comparative effectiveness and safety of pharmacological and mechanical methods of prophylaxis of VTE in these special populations.
DATA SOURCES: We searched MEDLINE(®), Embase(®), SCOPUS, CINAHL(®), www.clinicaltrials.gov, International Pharmaceutical Abstracts (IPA), and the Cochrane Library in July 2012. This was complemented by hand searches from the reference lists and unpublished studies provided by sponsors.
REVIEW METHODS: We included randomized controlled trials on these special populations. Since these populations may be excluded from trials, we also included controlled observational studies of pharmacologic agents, and uncontrolled observational studies and case series of inferior vena cava (IVC) filter use. Two reviewers evaluated studies for eligibility, serially abstracted data using standardized forms, and independently evaluated the risk of bias in the studies and strength of evidence for major outcomes and comparisons. We qualitatively synthesized the evidence and also pooled the relative risks from the controlled studies.
RESULTS: After a review of 30,902 unique citations, we included 101 studies of which just 6 were trials. The majority of observational studies had a high risk of bias. The strength of evidence is low that IVC filter placement is associated with a lower incidence of pulmonary embolism and fatal pulmonary embolism in hospitalized patients with trauma compared with no IVC filter placement. The strength of evidence is low that enoxaparin reduces deep vein thrombosis and that unfractionated heparin reduces mortality in patients with traumatic brain injury when compared with patients without anticoagulation. Low-grade evidence supports the idea that IVC filters with usual care are associated with increased mortality and do not decrease the risk of pulmonary embolism in patients undergoing bariatric surgery compared with usual care alone. All other comparisons, for all of the Key Questions, had insufficient evidence to permit conclusions.
CONCLUSIONS: Our systematic review demonstrates that there is a paucity of high-quality evidence to inform treatment of these special populations. Future research using robust observational studies that control for confounding by indication and disease severity are needed as randomized controlled trials typically exclude or do not report on these populations.
OBJECTIF: Pour élaborer des recommandations pratiques pour l'utilisation de faible poids moléculaire héparines (HBPM) en tant que prophylaxie et le traitement de la thromboembolie veineuse et les syndromes coronariens aigus chez les patients atteints d'insuffisance rénale ou d'obésité. SOURCES DES DONNÉES: Plusieurs recherches ont été effectuées dans MEDLINE (Novembre 2008) pour identifier les études pour l'inclusion, à l'aide d'une liste exhaustive de termes de recherche, y compris, mais sans s'y limiter, les HBPM, l'énoxaparine, daltéparine, tinzaparine, obésité, poids, rénale, les reins, les personnes âgées, le suivi et l'anti-Xa. SÉLECTION DES ÉTUDES ET EXTRACTION DES DONNÉES: Seuls les articles publiés en anglais qui étaient pertinents pour cette étude ont été inclus. SYNTHÈSE DES DONNÉES: Dans la majorité des patients, des doses standardisées prophylaxie ou le traitement de HBPM peuvent être utilisées sans la nécessité de contrôler et d'ajuster les régimes. Pour les patients atteints d'insuffisance rénale sévère (clairance de la créatinine [CrCl] <30 mL / min), les doses de certains HBPM doivent être ajustés ou héparine non fractionnée doit être utilisé à la place. Clairance de la créatinine doit être estimée en utilisant la méthode de Cockcroft-Gault. Les différences sont notées dans le degré d'accumulation des HBPM chez les patients atteints de diverses modérée à une insuffisance rénale sévère, et donc, le degré de ajustement de la dose peut varier entre les différentes HBPM. L'augmentation des doses prophylactiques d'HBPM peut être appropriée chez les patients souffrant d'obésité morbide (indice de masse corporelle> ou = 40 kg / m (2)). L'utilisation du poids corporel total est approprié pour des doses thérapeutiques d'HBPM chez les patients obèses. Surveillance en laboratoire de l'effet anticoagulant des HBPM n'est généralement pas nécessaire, mais doit être envisagée chez les patients présentant une obésité morbide (poids> 190 kg), ceux présentant une insuffisance rénale sévère, et ceux présentant une insuffisance rénale modérée avec prolongée (> 10 jours) d'une HFPM . Lorsque activité anti-Xa est surveillé, il doit être déterminé en utilisant une méthode chromogénique et une courbe d'étalonnage sur la base de l'HBPM utilisée. CONCLUSIONS: Les données supplémentaires sont nécessaires pour guider dose spécifique chez les patients obèses et insuffisant rénal, qui sont souvent exclus des essais cliniques plus larges. Recommandations pratiques sont fondées sur les preuves disponibles et les opinions des auteurs cliniques.
Background: The choice of whether to monitor antifactor Xa (anti-Xa) activity in patients who are obese and who are receiving low-molecularweight heparin (LMWH) therapy is controversial. To the authors' knowledge, no systematic review of monitoring of anti-Xa activity in such patients has been published to date. Objective: To systematically ascertain the utility of monitoring anti-Xa concentrations for LMWH therapy in obese patients. Data Sources: MEDLINE (1946 to September 2014), the Cochrane Database of Systematic Reviews, Embase (1974 to September 2014), PubMed (1947 to September 2014), International Pharmaceutical Abstracts (1970 to September 2014), and Scopus were searched using the terms obesity, morbid obesity, thrombosis, venous thrombosis, embolism, venous thromboembolism, pulmonary embolism, low-molecular weight heparin, enoxaparin, dalteparin, tinzaparin, anti-factor Xa, anti-factor Xa monitoring, anti-factor Xa activity, and anti-factor Xa assay. The reference lists of retrieved articles were also reviewed. Study Selection and Data Extraction: English-language studies describing obese patients treated with LMWH or reporting anti-Xa activity were reviewed using a 9-step decision-making algorithm to determine whether monitoring of LMWH therapy by means of anti-Xa activity in obesity is warranted. Studies published in abstract form were excluded. Data Synthesis:The analysis showed that anti-Xa concentrations are not strongly associated with thrombosis or hemorrhage. In clinical studies of LMWH for thromboprophylaxis in bariatric surgery, orthopedic surgery, general surgery, and medical patients, and for treatment of venous thrombo embolism and acute coronary syndrome, anti-Xa activity can be predicted from dose of LMWH and total body weight; no difference in clinical outcome was found between obese and non-obese participants. Conclusions: Routinely determining anti-Xa concentrations in obese patients to monitor the clinical effectiveness of LMWH is not warranted on the basis of the current evidence. Circumstances where measurement of anti-Xa concentration may help in clinical decision-making in either obese or non-obese patients would be cases where elimination of LMWH is impaired or there is an unexpected clinical response, as well as to confirm compliance with therapy or to identify deviation from predicted pharmacokinetics.
