A retrospective study on dalteparin dosage and anti-Xa levels in renal impairment
Summary
Abstract
Background and aims: Different recommendations are given in international guidelines regarding the correct LMWH dose using anti-Xa levels for renally impaired patients. This multi-centre retrospective cohort study researched which therapeutic dosage of the LMWH dalteparin for patients with renal impairment is most resembling to the standard therapeutic dosage of dalteparin for patients without renal impairment. Moreover, it was researched how many anti-Xa levels were measured correctly; how many anti-Xa levels reached the target range based on the present guidelines, and how many bleeding incidents happened in the various treatment groups.
Method: All anti-Xa levels that were recorded in the ETZ and FGV between April 2018 and March 2021 were extracted to compile the patients. Patients were split into three groups: a reference group (those with an estimated glomerular filtration rate [eGFR] > 50 ml/min) and two groups (those with an eGFR 30 ml/min) that received dalteparin at either a 100% dose or a 50% dose reduction, respectively. The primary outcome was the median anti-Xa for each group. The Mann-Whitney U test was used to compare the reference group's median anti-Xa levels to those of the two different treatment groups. Potential confounders were considered baseline variables that varied significantly between groups. To determine whether these potential confounders had an impact on the primary outcome, linear regression was performed. The secondary outcomes were the proportion (%) of anti-Xa levels measured in the correct way, the proportion (%) of anti-Xa levels reaching the target range based on the present guidelines, and the proportion (%) of patients where bleeding incidents happened in the various treatment groups.
Results: From the multi-center retrospective cohort study of this thesis, 133 patients were included from which 149 anti-Xa levels were analyzed. Three treatment groups were determined: a reference group (patients with normal renal function (eGFR > 50ml/min) and a standard dalteparin dose (200 IU/kg/day ±20%)), group A (patients with renal impairment (eGFR < 30ml/min) and a standard dalteparin dose (200 IU/kg/day ±20%)), and group B (patients with renal impairment (eGFR < 30ml/min) and a 50% dalteparin dose reduction (100 IU/kg/day ±20%)). The median anti-Xa levels for a once-daily dosing regimen of dalteparin were 0.80 (IQR 0.60-1.16) for the reference group, 0.83 (IQR 0.65-1.02) for group A and 0.42 (IQR 0.42-0.605) for group B. The median anti-Xa levels for dalteparin were 0.5 (IQR 0.345-0.915) for the reference group, 0.5 (IQR 0.315-0.735) for group A, and 0.3 (IQR 0.275-0.403) for group B for a twice-daily dosage regimen. The once-daily dosing regimen (p=.001) and twice-daily dosing regimen (p=.003) were significantly different for group B compared to the reference group. The anti-Xa levels between the treatment groups A and B were also significantly different for both the once-daily dosing regimen (p=.001) and twice-daily dosing regimen (p=.008). A proportion of 52.7% of the anti-Xa levels were measured correctly. Regarding meeting the target range, group A (23.1%) was most resembling to the reference group (28.9%) compared to group B (10.3%). Group A had a bigger chance of getting major bleeding events (12.3%) compared to group B (10.3%). Within the dose regimens, the once-daily group had a higher proportion (13.6%) with major bleeding events compared to the twice-daily dosing group (7.8%).
Conclusion: It was found that for both the once-daily and twice-daily dosage regimen a 100% dalteparin dosage for patients with renal impairment is most resembling to the standard therapeutic dosage of dalteparin for patients with no renal impairment. After 3 administrations, blood sampling can be done to obtain the anti-Xa level and apply dosage reduction if necessary. Due to power limitations of t