Enoxaparin is the most commonly used LMWH. Pharmacodynamic studies in obese and morbidly obese show that peak anti-FXa levels are often below recommended target anti-FXa levels for VTE prevention when standard doses of LMWH are used for VTE prophylaxis [11–13]. Higher doses of LMWH may be required in the morbidly obese patients. Several studies have looked at different dosing regimens and measured anti-FXa levels, in the bariatric surgical patient, to ensure appropriate prophylactic doses. Enoxaparin has been administered with doses ranging from 30 to 60 mg either as daily or twice daily frequency. In one retrospective review of Enoxaparin 30 mg 12 hourly versus 40 mg 12 hourly, a higher incidence of DVT (5.4 % vs 0.6 %) was seen in the 30 mg group with no differences in haemorrhage [14]. In another non-randomised study on comparison of Enoxaparin 30 mg 12 hourly with 40 mg 12 hourly studying levels of anti-Xa levels it was seen that after the first dose, 30.8 % of the patients receiving 40 mg were within an appropriate therapeutic range compared to 0 % in the group receiving 30 mg. After the third dose, only 41 % of patients in the 40 mg group and 9 % of patients in the 30 mg group were within therapeutic range. No patient had any bleeding complications. The authors concluded that 30 mg every 12 h may not be enough to achieve the desired anti-Xa levels and that 40 mg every 12 h shows only a slight improvement over the 30 mg regimen [15]. In one more non-randomised study on comparison of Enoxaparin 40 mg 12 hourly with 60 mg 12 hourly studying levels of anti-Xa levels it was seen that mean anti-Xa levels were higher in the 60 mg group but both groups achieved a therapeutic anti-Xa level [16].

In the multicenter retrospective study of the prophylaxis against VTE outcomes in bariatric surgery patients receiving enoxaparin (PROBE study), enoxaparin prophylaxis dosing in bariatric surgery patients were compared at 5 medical centers. One centre administered only 30 mg subcutaneous once preoperatively, one centre administered 30 mg subcutaneous every 24 h post discharge for 10 days, two centres administered 40 mg subcutaneous every 24 h postoperatively and one centre administered 40 mg subcutaneous every 12 h postoperatively. There were 6 PEs and 1 DVT recorded. 6 of the 7 episodes occurred after discontinuation of enoxaparin. One patient who developed a PE while on enoxaparin and 3 of the 7 episodes were found in the center that provided a dose of 30 mg subcutaneous every 24 h post discharge but not peri-operatively [17]. Thus it can be concluded that 0.4 mg 12 hourly may be the ideal prophylactic dose to be used in morbidly obese patients.

Borkgren-Okonek et al used enoxaparin dosing according to body mass index (BMI). Patients with a BMI less than or equal to 50 kg/m² were given 40 mg of enoxaparin subcutaneous every 12 h, while patients with BMI greater than 50 kg/m² were given 60 mg subcutaneous every 12 h. In the 40 mg group, none of the patients were supratherapeutic, whereas the 60 mg group showed similar numbers of patients with subtherapeutic and supratherapeutic levels. The authors concluded that using higher than standard dosing and stratifying patients by BMI was effective at preventing VTEs [18].

A recent study investigating the correlation between anti-Xa levels and the percentage of patients that reach the desired prophylactic range for anti-Xa levels with 0.4 mg fixed-dose enoxaparin twice daily after bariatric surgery demonstrated a strong negative correlation between body weight and peak anti-Xa levels. Thirty-eight percent of patients with excessive body weight (>150 kg) had subprophylactic anti-Xa levels with fixed-dose twice daily 0.4 mg enoxaparin while 35 % of patients with lower body weight (<110 kg) were above the advised prophylactic range. Thus a weight based dosing may be more appropriate [19]. A pragmatic approach as suggested by the HAT Committee of the UK Clinical Pharmacy Association in the NHS practice guidelines for doses of thromboprophylaxis at extremes of body weight may be followed. Non-obese patients receiving the efficacious enoxaparin 40 mg once daily using data from the MEDENOX trial, translates to a weight based dose of 0.4–0.8 mg/kg. If patients >100 kg receive 40 mg twice daily and patients >150 kg receive 60 mg twice daily they would be receiving a similar weight based dose to non-obese patients. Patients <100 kg can be treated with 0.4 mg once daily. This may be a simple practical option to address patients at extremes of weight.

Thus in summary, strongest data seem to support the use of 40 mg of enoxaparin SC every 12 h. The use of this dose was shown to decrease the risk of VTE in patients undergoing bariatric surgery compared to 0.3 mg 12 hourly and to bring more patients to a desired anti-Xa level with low frequency of sub-prophylactic doses when compared to 0.6 mg 12 hourly which had unlikely sub-prophylactic doses but higher frequency of supraprophylactic doses. However if sub-grouped according to weight, supra-prophylactic and sub-prophylactic are common at extremes of weight (<100 and >150 kg). Thus at weights less than 100 kg standard 0.4 mg once daily dose may be used and above 150 kg 0.6 mg 12 hourly may be used. BMI based dosing of 40 mg enoxaparin SC every 12 h in those <50 BMI and 60 mg of enoxaparin SC every 12 h in those >50 BMI may be considered based on a single well conducted study.

Although it appears that consideration could be made to use higher doses of LMWH to achieve proper therapeutic levels, the true clinical significance of this has yet to be proven. It is not well defined if this practice may lead to a decreased risk of VTE complications and/or if an increased rate of major bleeding complications will occur.

Very few studies have been conducted based on other low molecular weight heparins. In a randomized controlled trial a dose of 5,700 IU Nadroparin was as effective as 9,500 IU dose and with fewer bleeding complications [20]. In a multicenter, open-label, pilot study in bariatric surgical patients a parnaparin dose of 4,250 IU/day was equivalent to 6,400 IU/day for VTE prevention [21]. In a retrospective study it was concluded that 7,500 IU dalteparin dosage was appropriate for the majority of morbidly obese patients undergoing bariatric surgery [22].