A b s t r a c t 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 µg/mL.

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... e 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. Direct thrombin inhibitors (DTIs) represent a new class of promising anticoagulation agents. The most common uses of parenteral DTIs are in the initial management of heparininduced thrombocytopenia (HIT) and for anticoagulation in acute coronary syndromes. 1,2 The DTIs frequently are used to provide initial anticoagulation, with long-term therapy requiring eventual transition to coumarins. The presently available DTIs used in this setting are argatroban, bivalirudin, and lepirudin. Because the DTIs have a fairly narrow therapeutic window, it is desirable to have a reliable means for measuring the intensity of anticoagulation. The activated partial thromboplastin time (aPTT) has served as the traditional means of monitoring the degree of anticoagulation for DTI regimens. 1,2 Within the target range, a rise in aPTT has a linear correlation to DTI plasma concentrations. With the exception of percutaneous coronary intervention (PCI), the target ranges for thromboprophylaxis or treatment of thromboembolism are aPTT ratios from 1.5 to 2.5 or 3.0, depending on the individual agent. Data for these target aPTT ratios were provided mostly from trials using DTIs in the management of HIT. Unfortunately, DTIs not only prolong the aPTT, but also can have some crossover effect on international normalized ratio (INR) values, 3-5 which can create a challenge when making the transition to warfarin therapy during concurrent DTI administration. The presently available data on the INR elevation are limited to a few reagents used to measure the prothrombin time (PT) and the concurrently reported INR. In the present study, we added DTIs to pooled plasma at various concentrations to estimate the relative anticoagulation effect of these agents on 14 PT reagents available in the United States.