Treatment dosing of low-molecular-weight heparins and the dose cap dilemma: considerations for patients in Canada.

BACKGROUND: In Canada, there is a dose cap for weight-based treatment with low-molecular-weight (LMW) heparins.
OBJECTIVE: To review whether capping of LMW heparin doses is warranted for patients with obesity.
METHODS: English-language publications concerning the use of LMW heparin in Canada were reviewed, and the literature regarding use of these drugs at treatment doses in patients with obesity was assessed.
RESULTS: Five pharmacokinetic or pharmacodynamic studies meeting the inclusion criteria were identified. The evidence in those studies pointed toward no excess accumulation of LMW heparin in patients with obesity. In addition, 5 trials involving patients with acute coronary syndromes and 6 trials involving patients with venous thromboembolism and other indications were identified, but only 7 of these 11 trials included sufficient information for review. Subgroup analysis of patients with acute coronary syndrome whose LMW heparin dose was not capped showed no increased risk of bleeding for obese patients treated with enoxaparin. For patients with venous thromboembolism and other indications, the best evidence was for dalteparin, with anti-Xa levels used as a surrogate end point. In this setting, excess accumulation did not occur when there was no dose cap. DISCUSSION: There is little literature dedicated to the dosing of LMW heparin for obese patients. In particular, there are few data for those with body weight above 150 kg. Despite the limitations of these studies, there appears to be little justification for capping the doses of these drugs. On the basis of the available literature, it is suggested that treatment doses of LMW heparin be based on body weight up to 150 kg.