Effect of Lepirudin on the International Normalized Ratio

• Published in: The Annals of pharmacotherapy Vol. 39; no. 1; pp. 28 - 31
• Main Authors: Stephens, Jennifer L, Koerber, John M, Mattson, Joan C, Smythe, Maureen A
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA Harvey Whitney Books 01-01-2005; SAGE Publications; Whitney
• Subjects: Aged; Aged, 80 and over; Anticoagulants - pharmacology; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Female; Hirudins - analogs & derivatives; Hirudins - pharmacology; Humans; International Normalized Ratio; Male; Medical sciences; Partial Thromboplastin Time; Pharmacology. Drug treatments; Prothrombin Time; Recombinant Proteins - pharmacology; Retrospective Studies; direct thrombin inhibitor; thromboplastin; international normalized ratio; lepirudin; Human; Pharmacologic test; Peptides; Serine endopeptidases; Hemostatic; Enzyme; Toxicity; Enzyme inhibitor; Thrombin; Antithrombin; Thromboplastin; Peptidases; Polypeptide; Thromboplastin time; Antithrombotic agent; Hydrolases; Recombinant protein; Lepirudin
• ISSN: 1060-0280; 1542-6270
• DOI: 10.1345/aph.1E126

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.