Danaparoid dosing during continuous venovenous hemofiltration - a randomized controlled pilot study investigating two danaparoid dosing schemes with a standard heparin dosing scheme

Critically ill patients often suffer from low platelet counts or platelet
dysfunction. However, this does not obviate the need for systemic anticoagulant
treatment in some of these patients. Therefore, anticoagulants with little
effect on platelet function are needed in the intensive care unit.
Although extensive experience with danaparoid has been gained in the clinical
setting, there is little evidence on its use in patients with acute renal
failure, especially in those patients dependent on continuous renal replacement
therapy (CRRT). The elimination of danaparoid is predominantly renal and an
antidote is lacking. Dosing of danaparoid is based on the guideline of the
Dutch Society of Intensive Care Medicine, recommending an intravenous (iv)
loading dose ranging from 750 to 2250 U and a dose for continuous infusion
ranging from 1- 3 U/kg/h (5). In a small retrospective study however, the
authors conclude that a loading dose of 750 U iv, followed by a maintenance
dose of 50-150 U/h iv might be sufficient to maintain an effective and safe
level of anticoagulation.

The aims of the current study are
1. to investigate the efficacy and safety of a continuous infusion of 'low
dose' danaparoid in patients with acute renal failure needing CRRT
2. to investigate whether repeated measurements of anti-Xa levels are necessary
for adequate dosing of a continuous infusion of danaparoid used as an
anticoagulant in patents with acute renal failure needing CRRT
3. to study a continuous infusion of 'low dose' danaparoid, danaparoid titrated
by anti-Xa levels and unfractionated heparin in patients with acute renal
failure needing CRRT

Prospective randomized pilot study

After having obtained informed consent, eighteen critically ill patients with
acute renal failure needing CRRT will be randomized into 3 groups receiving
either danaparoid or unfractionated heparin iv in different dosing schemes:
Group 1: 'Low dose' danaparoid: continuous infusion of 0.6 U/kg/h without a
loading dose
Group 2: 'Titrated dose danaparoid': continuous infusion of danaparoid
titrated on anti-Xa levels after a loading dose of 9 U/kg, aiming at an anti-Xa
level of 0.3-0.7 anti-Xa U/ml
Group 3: 'Heparin control': continuous infusion of 6 U/kg/h unfractionated
heparin after a loading dose of 30 U/kg
Anti-Xa levels and markers of thrombin generation (thrombin-antithrombin
complexes, prothrombin fragment F1+2 and endogenous thrombin potential) will be
measured at the following timepoints: t=0, 5, 15, 30 min, 2, 4, 6, 12, 24, 48
and 72h after the loading dose.

The anticoagulant strategies in group 2 and 3 are presently considered standard
regimens, whereas the strategy in group 1 is not. However, since group 1 uses a
lower danaparoid dose than group 2, less bleeding complications are expected.