The low-molecular-weight heparins (LMWHs) are anti-coagulants used in the treatment and prevention of thromboembolic diseases [1, 2]. At therapeutic doses, the LMWHs are appealing alternatives to other anti-coagulants such as unfractionated heparin (UFH) due to their linear pharmacokinetics and more predictable dose–response relationship. Linear pharmacokinetics help facilitate simple fixed or weight based dosing, without the need for plasma anti-Xa (aXa) monitoring, which is reflected in the current product labels (PLs) [3–7].
LMWHs are hydrophilic compounds with clearance (CL) described by a composite of renal elimination and metabolism , processes that are proportional to lean body weight (LBW) . Subjects who are dosed using total body weight (TBW) are therefore at risk of supra-therapeutic drug exposure, which can result in excessive inhibition of factor-Xa and adverse events such as bleeding. This is particularly problematic in subjects with renal impairment and/or obesity and has resulted in much uncertainty and debate on how to dose LMWHs in these populations. To add to this dilemma, little effectiveness or adverse outcome data exist for these populations as they were generally excluded from confirmatory clinical trials [10–12]. As specific dosing regimens in these subjects are unknown, clinicians often elect to choose empirical dose strategies in an effort to normalize drug exposure to that of a subject who was typically recruited during the drug development process.
Selecting optimal dosing strategies for subjects with renal impairment and/or obesity is an important issue for clinicians. The number of people worldwide who are overweight or obese has now reached epidemic proportions with approximately 1.6 billion adults now classified as overweight (body mass index ≥ 25 kg m−2) and 400 million obese (body mass index ≥ 30 kg m−2) . In Australia, 62.7% of females and 72.1% of males are now overweight or obese and these figures are matched in the United Kingdom (UK) and the United States (US) . The worldwide prevalence of renal disease is also escalating and mirrors the increase in diabetes, obesity and hypertension .
As there appears to be much debate on the most suitable dosing and monitoring strategies for LMWHs, in particular for populations with obesity and/or renal impairment, we aimed to investigate how these subjects were being dosed in contemporary clinical practice. Firstly we aimed to quantify the proportion of hospitals that dose LMWHs according to the PL. Second, we sought to determine the proportion of hospitals that individualize the dose of LMWHs using one or more of either: renal function, body weight, or the post-dose monitoring of aXa-activity. Finally, we explored the specific methods that hospitals use to dose-individualize therapy thus enabling hospitals to compare and critique their own dose strategies against their global counterparts.