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Thromb Haemost 2007; 98(01): 234-242
DOI: 10.1160/TH06-10-0607
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Monitoring direct thrombin inhibitors with a plasma diluted thrombin time

Jason E. Love
1   Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA
,
Chris Ferrell
1   Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA
,
Wayne L. Chandler
1   Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA
› Author Affiliations
Further Information

Publication History

Received 26 October 2006

Accepted after resubmission 08 April 2007

Publication Date:
29 November 2017 (online)

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Summary

Activated partial thromboplastin time (aPTT) monitoring of direct thrombin inhibitors (DTIs) is vulnerable to interference from many sources. If the baseline aPTT is prolonged, as occurs with lupus inhibitors, alternative methods are required to monitor DTI levels. We compared the plasma diluted thrombin time (1:4 dilution of patient plasma with normal plasma) and the aPTT in patient samples spiked with argatroban, bivalirudin, or lepirudin at three concentration levels. Each drug was spiked into five samples with lupus inhibitors, five samples with deficient vitamin K-dependent factors, three samples with elevated D-dimers, and eight samples with normal baseline aPTT values. The aPTT overestimated the spiked DTI concentration in all samples with lupus inhibitors, low levels of vitamin K-dependent factors, and elevated D-dimers. In samples with normal baseline aPTTs, the aPTT failed to correctly estimate the spiked drug concentration in four of 24 samples spiked with argatroban, seven of 24 spiked with lepirudin, and three of 24 spiked with bivalirudin. The plasma diluted thrombin time was not affected by lupus inhibitors, low vitamin K-dependent factor levels or elevated D-dimer levels and correctly estimated the spiked drug level in 63 of 63 samples spiked with argatroban, 63 of 63 samples spiked with bivalirudin, and 62 of 63 samples spiked with lepirudin. In conclusion, the plasma diluted thrombin time appears to be a viable alternative to the aPTT for monitoring DTI levels, especially in patients with lupus inhibitors or low levels of vitamin K-dependent factors.

Keywords

Directthrombin inhibitors - therapeutic drug monitoring - lupus inhibitors
 

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