Retrospective study of plasma anti-Xa levels in renally impaired patients receiving reduced or non-reduced therapeutic doses of dalteparin.

Background: In renally impaired patients, guidelines recommend a 25-50% dalteparin dose reduction with anti-Xa monitoring to reduce bleeding risk. However, pharmacokinetic considerations and results from previous studies dispute the need for dose reduction. Therefore, in our hospitals an alternative dose reduction to 75% or a 100% is used. This study aimed to assess anti-Xa levels to confirm or refute the need for dose reduction and to investigate the association between dose, anti-Xa levels and bleeding events.

Methods: This multicentre retrospective observational study included patients aged ≥18 years during a 3-year period with an estimated glomerular filtration rate of <60 mL/min/1.73 m² or on renal replacement therapy, receiving ≥7500 IU dalteparin daily. Only correctly sampled plasma anti-Xa levels were included and stratified into intensive care unit (ICU) and non-ICU patients. Stratum-adjusted odds ratios were determined to compare the likelihood of achieving adequate anti-Xa levels between a 75% and 100% dose. Bleeding events were classified into minor and major events.

Results: A total of 167 anti-Xa levels were included, with 148 anti-Xa levels belonging to patients receiving a 75% or 100% dose. Anti-Xa levels were highly scattered: 55% below and 6% above the anti-Xa ranges. In all patients the probability that anti-Xa levels fell within the range was higher for patients receiving a 100% dose than for those receiving a 75% dose (OR 2.66, 95% CI 1.24 to 5.70, p=0.012). Eight bleeding events occurred, including one minor event in a patient with an anti-Xa level above range and five events in patients on renal replacement therapy with anti-Xa levels within or below range.

Conclusions: In renally impaired patients a 100% dalteparin dose increases the likelihood of achieving adequate anti-Xa levels compared with a 75% dose, without leading to over-exposure. The occurrence of bleeding events did not differ between the 75% and 100% dose groups and appeared unrelated to anti-Xa levels. Pre-emptive dose reduction of dalteparin in renally impaired patients is likely to be unnecessary.