Study of bioaccumulation of dalteparin at a therapeutic dose in patients with renal insufficiency.
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.


OBJECTIVE
Evaluate pharmacokinetic data of dalteparin at a therapeutic dose in patients with RI.


METHODS
Prospective observational cohort study. Inpatients were included into three groups according to glomerular filtration rate (GFR): A > or = 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 > or = 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) x 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) x 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.


CONCLUSIONS
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.
Schmid
P
P
Division of Hematology and Central Hematology Laboratory, Department of Medicine, Luzerner Kantonsspital, CH-6000 Luzern 16, Switzerland.
Brodmann
D
D
Odermatt
Y
Y
Fischer
A G
AG
Wuillemin
W A
WA
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017985:Dalteparin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D065427:Factor Xa Inhibitors; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007279:Injections, Subcutaneous; D007297:Inpatients; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D017985:Dalteparin