Weight-based LMWH dosing without capping is OK for obese patients

Weight-based dosing of enoxaparin with no maximum dose appears to result in similar therapeutic drug levels in obese patients compared to non-obese patients with acute venous thromboembolism (VTE).

A five-year retrospective study compared outcomes in patients >100 kg treated with 1 mg/kg enoxaparin twice daily, patients <100 kg on the same dosing schedule and patients >100 kg prescribed <1 mg/kg.

The Melbourne study found the median anti-Xa level in obese patients on 1mg/kg was 0.93 U/mL, with more than half of patients (56%) in the range 0.5 to 1.0 U/mL.

Similarly, patients <100kg given the same dose of enoxaparin had a median anti-Xa level of 0.87 U/mL, with 44% in the range of 0.5 to 1.0 U/mL.

In patients >100kg receiving doses <1mg/kg the median anti-Xa level was 0.77 U/mL and fewer patients (46%) were in the 0.5 to 1.0 U/mL range.

“We have shown that 1 mg/kg twice daily enoxaparin in patients weighing > 100 kg with an eGFR > 30 mL/min results in variable anti-Xa levels. However, the median anti-Xa levels and the proportion of patients within and above the therapeutic range were not significantly different to a population weighing < 100 kg,” the study authors said.

“Not surprisingly, those patients weighing > 100 kg but prescribed doses below 1 mg/kg had a lower median anti-Xa level and were more frequently subtherapeutic compared with those prescribed 1 mg/kg.”

No major bleeding or recurrence of VTE in the obese patients on 1 mg/kg enoxaparin was recorded within 30 days of follow-up, however there was higher incidence of both in the group of patients <100kg.

Researcher Dr Kylee Maclachlan, from Monash Medical Centre, told the limbic one of the main findings was that bleeding risk was mainly determined by clinical features.

“The majority of the bleeding was observed in the group <100 kg, where patients had a higher average age, more renal impairment and a higher incidence of concurrent malignancy.”

“There was no significant difference in the median anti-Xa levels between those <100 kg and >100 kg, nor any difference in the distribution. Taking specifically those above 150 kg (n=24), 50% were in the proposed therapeutic range of 0.5-1.0 U/mL and 50% were >1.0 U/mL, however this was not associated with an increased risk of bleeding. On the converse, in the group in whom doses had been capped, 20% had an anti-Xa below 0.5U/mL, raising concern for inadequate anti-coagulation.”

“We think our strategy of 1mg/kg without capping is a reasonable approach for those with normal renal function.”

She added dosing remains controversial and evidence was limited for patients weighing more than 200 kg.

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