Effect of lepirudin on the international normalized ratio.
BACKGROUND
Many patients receiving direct thrombin inhibitor (DTI) therapy require transition to warfarin. This transition may be complicated by DTI-induced elevations in the international normalized ratio (INR). While the effect of argatroban on the INR has been characterized, data assessing the effect of lepirudin on the INR are limited.


OBJECTIVE
To evaluate the effect of lepirudin on the INR.


METHODS
Patients receiving lepirudin therapy between January 2000 and May 2001 were identified using the pharmacy database, and a retrospective chart review was conducted. Patients were included for analysis if they had paired activated partial thromboplastin time (aPTT) and INR data while receiving lepirudin monotherapy.


RESULTS
Fifty-three paired aPTT and INR data points from 8 patients receiving lepirudin monotherapy were collected. The Organon MDA 180 instrument was used for aPTT and prothrombin time (PT) determination. Organon MDA Platelin L reagent was used for the aPTT and Organon Simplastin L reagent was used for the PT. The international sensitivity index (ISI) of the Simplastin L thromboplastin was 2.0. The mean +/- SD lepirudin dose was 0.05 +/- 0.04 mg/kg/h. Linear regression was used to identify the INRs that correspond to a therapeutic aPTT value of 45-75 seconds (1.5-2.5 times mean laboratory normal of 30 sec). The correlation between aPTT and INR was 0.77. An aPTT of 45-75 seconds with lepirudin correlated to an INR of 1.6-3.2.


CONCLUSIONS
Based on laboratory results, when using a thromboplastin with an ISI of 2, lepirudin appears to elevate the INR in the absence of warfarin.
Stephens
Jennifer L
JL
Department of Pharmaceutical Services, William Beaumont Hospital, Royal Oak, MI, USA.
Koerber
John M
JM
Mattson
Joan C
JC
Smythe
Maureen A
MA
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology*; D005260:Female; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000494:pharmacology*; D012189:Retrospective Studies
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; C083544:lepirudin