Effect of direct thrombin inhibitors, bivalirudin, lepirudin, and argatroban, on prothrombin time and INR values

Direct thrombin inhibitors (DTIs) represent a new class of promising anticoagulation agents. The DTIs frequently are used to provide initial anticoagulation, with long-term therapy requiring eventual transition to coumarins. Unfortunately, DTIs not only prolong the activated partial thromboplastin t...

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Bibliographic Details
Published in:American journal of clinical pathology 2004-04, Vol.121 (4), p.593-599
Main Authors: GOSSELIN, Robert C, DAGER, William E, KING, Jeffrey H, JANATPOUR, Kim, MAHACKIAN, Kathleen, LARKIN, Edward C, OWINGS, John T
Format: Article
Language:English
Subjects:
Antithrombins - pharmacology
Biological and medical sciences
Dose-Response Relationship, Drug
General aspects
Hirudins - analogs & derivatives
Hirudins - pharmacology
Humans
In Vitro Techniques
International Normalized Ratio
Medical sciences
Peptide Fragments - pharmacology
Pipecolic Acids - pharmacology
Prothrombin Time
Recombinant Proteins - pharmacology
Tumors
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Summary:Direct thrombin inhibitors (DTIs) represent a new class of promising anticoagulation agents. The DTIs frequently are used to provide initial anticoagulation, with long-term therapy requiring eventual transition to coumarins. Unfortunately, DTIs not only prolong the activated partial thromboplastin time but also can affect international normalized ratio (INR) values. We approximated the DTI effect on INRs by each drug to pooled plasma at concentrations between 0.1 and 1.2 microg/mL. We then concurrently tested these samples using 14 prothrombin time (PT) reagents. By using repeated measures analysis of variance, we found significant differences (P < .05) between the median INRs for lepirudin and argatroban for all PT reagents, between lepirudin and bivalirudin for all reagents except PT-Fibrinogen HS Plus (P = .07), and between bivalirudin and argatroban for all reagents except Thromborel S (P = .05). The DTI effect on INRs was dependent on drug, drug concentration, and reagent. Argatroban had the most effect on INRs, while lepirudin had the least effect. Reagents with a lower international sensitivity index were less affected by DTI; ThromboMax HS was the least sensitive PT reagent to any DTI.
ISSN:0002-9173
1943-7722
DOI:10.1309/d79k4yg78ntnyy38