Low-molecular-weight heparin use in the obese, elderly, and in renal insufficiency

摘要

Superior bioavailability and simple weight-based dosing have made low-molecular-weight heparins (LMWH) the preferred agents for treatment and prevention of venous thromboembolism (VTE) for most indications. Despite improved pharmacokinetics, there remain populations where appropriate LMWH dose intensity and frequency are open to question. Obese patients have a lower proportion of lean body mass as a percentage of total body weight. As a result, LMWH dosing based on total body weight could cause supra-therapeutic anticoagulation. Elderly patients also have less lean body mass in addition to a higher incidence of age-related renal disease and increased risk of bleeding. Renal insufficiency presents a risk of LMWH accumulation as well as increased risk of bleeding. Among LMWH products, only dalteparin labeling recommends a maximum dose. Prospective data call into question the validity of this dose limitation. Additionally, because obese patients are already at higher risk of VTE recurrence, they may be particularly sensitive to subtherapeutic anticoagulation. Prospective data evaluating LMWH use in elderly patients have been limited to in-patient treatment. Few recommendations can be made in this population other than close monitoring. Renal insufficiency is a risk for bleeding during LMWH use. Available evidence supports the potential for enoxaparin accumulation, but not tinzaparin. Enoxaparin dose adjustment, either empiric or based on anti-Xa monitoring, has insufficient data to support widespread implementation. Unfractionated heparin is not reliant on renal elimination and is a sensible option for VTE treatment in patients with a creatinine clearance < 30 ml/min.