Authors: SCHMID, P.¹; BRODMANN, D.²; ODERMATT, Y.¹; FISCHER, A. G.²; WUILLEMIN, W. A.

Source: Journal of Thrombosis and Haemostasis, Volume 7, Number 10, October 2009 , pp. 1629-1632(4)

Publisher: Wiley-Blackwell

Abstract:

Summary. 

Background: Low-molecular-weight heparins (LMWH) are effective, safe and convenient for anticoagulation. Their use is limited in patients with renal insufficiency (RI) because of bioaccumulation. Objectives: Evaluate pharmacokinetic data of dalteparin at a therapeutic dose in patients with RI. Patients and methods: Prospective observational cohort study. Inpatients were included into three groups according to glomerular filtration rate (GFR): A ≥ 60, B 30-59, C < 30 mL min⁻¹ 1.73 m⁻². Dalteparin was injected subcutaneously (s.c.) twice daily. Peak plasma anti-factor Xa activity (anti-Xa) was measured and adjusted to applied dose and body weight after the first dose, on day 2, and every 2nd day afterwards. Bioaccumulation factor R was calculated as quotient of the last and the first adjusted anti-Xa. Data are shown as median (interquartile range, IQR). Results: Thirty-two patients (23 men) receiving dalteparin for ≥ 2 days were analyzed. Follow-up was 6 days (IQR 4-10, range 2-22). Median dose was 90 (73-106) units kg⁻¹ per 12 h (P = 0.68). After the first dose, adjusted anti-Xa levels were 3.5 (2.6-5.0), 4.8 (3.3-5.5), 4.5 (3.7-7.5) × 10⁻³ for the groups A, B, C; P = 0.26. On the last day, they were 6.1 (3.7-7.3), 7.1 (5.6-8.3), 10.2 (7.8-13.2) × 10⁻³; A compared with C, P = 0.002. R was 1.46 (1.15-1.82), 1.36 (1.20-2.16) and 2.28 (1.53-2.93); A compared with C, P = 0.18. Conclusion: Therapeutically dosed dalteparin accumulates in patients with severe RI (group C). Dose adjustments according to anti-Xa are recommended for dalteparin if used in this patient population. However, no simple dosing scheme can be suggested yet because of wide inter-individual variation.

Keywords: dalteparin; low-molecular-weight heparin; pharmacokinetics; renal insufficiency; therapy

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1538-7836.2009.03556.x

Affiliations: 1: Division of Hematology and Central Hematology Laboratory, Department of Medicine, Luzerner Kantonsspital, Luzern 2: Division of Nephrology, Department of Medicine, Luzerner Kantonsspital, Luzern

Publication date: 2009-10-01

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