Dosing of Unfractionated Heparin in Obese Patients with Venous Thromboembolism

Hurewitz, Adam N.; Khan, Samar; Groth, Maritza L.; Patrick, Patricia A.; Brand, Donald A.

doi:10.1007/s11606-010-1551-2

Cited by 25 publications

(20 citation statements)

References 17 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Heparin Increases Food Intake through AgRP Neurons

Zhu

et al. 2017

Cell Reports

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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.

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Section: Introductionmentioning

confidence: 99%

Heparin Increases Food Intake through AgRP Neurons

Zhu

et al. 2017

Cell Reports

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“…In addition, patients with low body weight are often associated with an inherently higher risk of bleeding . While traditional anticoagulant therapy often requires pharmacodynamic (PD) monitoring (e.g., international normalized ratio for warfarin dosing) and/or body weight based dosing, or is contraindicated in patients with extremes of body weight , the new generation of oral anticoagulants including rivaroxaban and dabigatran does not require dose adjustment for body weight .…”

Section: Introductionmentioning

confidence: 99%

Effect of extremes of body weight on the pharmacokinetics, pharmacodynamics, safety and tolerability of apixaban in healthy subjects

Upreti

Wang

Barrett

et al. 2013

Brit J Clinical Pharma

247

200

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AIMApixaban is an oral, direct, factor-Xa inhibitor approved for thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. This open label, parallel group study investigated effects of extremes of body weight on apixaban pharmacokinetics, pharmacodynamics, safety and tolerability. METHODFifty-four healthy subjects were enrolled [18 each into low (Յ50 kg), reference (65-85 kg) and high (Ն120 kg) body weight groups]. Following administration of a single oral dose of 10 mg apixaban, plasma and urine samples were collected for determination of apixaban pharmacokinetics and anti-factor Xa activity. Adverse events, vital signs and laboratory assessments were monitored. RESULTSCompared with the reference body weight group, low body weight had approximately 27% [90% confidence interval (CI): 8-51%] and 20% (90% CI: 11-42%) higher apixaban maximum observed plasma concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUC(0,•)), respectively, and high body weight had approximately 31% (90% CI: 18-41%) and 23% (90% CI: 9-35%) lower apixaban Cmax and AUC(0,•), respectively. Apixaban renal clearance was similar across the weight groups. Plasma anti-factor Xa activity showed a direct, linear relationship with apixaban plasma concentration, regardless of body weight group. Apixaban was well tolerated in this study. CONCLUSIONThe modest change in apixaban exposure is unlikely to require dose adjustment for apixaban based on body weight alone. However, caution is warranted in the presence of additional factors (such as severe renal impairment) that could increase apixaban exposure.

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“…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.…”

Section: Introductionmentioning

confidence: 99%