Lepirudin (Refludan) is a recombinant derivative of hirudin that is a direct thrombin inhibitor which is used as an anticoagulant in patients with heparin-induced thrombocytopenia. Hirudin was isolated initially from the salivary glands of medicinal leeches. It has a short half-life (about 1.3 hours in normal volunteers) and shows no cross-reactivity with anti-heparin antibodies. It is expensive, with a week's therapy costing thousands of dollars.


NOTE: This dosing is for a patient with a creatinine clearance > 60 mL/min. The dose for a patient with renal insufficiency is determined in the next section.


Monitoring of lepirudin uses a ratio of the activated prothrombin time test (aPTT) and the mean of the normal reference range.


aPTT ratio =

= (patient's aPTT result in second) / (mean of normal reference aPTT in seconds)


Therapy with lepirudin should not be started if the aPTT ratio is >= 2.5 prior to therapy initiation.


Initial dosing of lepirudin for the patient with normal renal function:

(1) A bolus dose is given at a rate of 0.4 mg/kg, up to a maximum dose of 44 mg (achieved at a body weight of 110 kg). This is given over 15 to 20 seconds.

(2) An infusion of 0.15 mg/kg/h is started, up to a maximum of 16.5 mg/h (achieved at a body weight of 110 kg).


The aPTT ratio is determined at 4 hours after initiating therapy. The target ratio is 2. If the ratio is < 1.5 or > 2.5, then the testing is repeated before any adjustments are made to the infusion rate.


If the ratio is > 2.5:

(1) Stop the infusion for 2 hours.

(2) Decrease the infusion rate by 50%.

(3) Repeat the aPTT ratio in 4 hours.


If the ratio is < 1.5:

(1) Increase the infusion rate by 20%, not to exceed 0.21 mg/kg/h. (If this is limited to an upper weight of 110 kilograms, as the other doses are, then this would be 23.1 mg/h).

(2) Repeat the aPTT ratio in 4 hours.

(3) If the patient reaches the upper infusion level of 0.21 mg/kg/h without improvement of the aPTT ratio, then the patient should be investigated for coagulation abnormalities leading to a hypercoagulable state.


Many patients will develop anti-lepirudin antibodies, which may limit repeat usage.


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