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Semin Vasc Med 2005; 5(3): 259-265
DOI: 10.1055/s-2005-916165
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

A Step Change in Oral Anticoagulation: Lack of Coagulation Monitoring with Ximelagatran

Stefan C. Carlsson1 , Sam Schulman2 , 3
  • 1AstraZeneca R&D Mölndal, Mölndal, Sweden
  • 2Hamilton Health Sciences-General Hospital, Hamilton, Ontario, Canada
  • 3Coagulation Unit, Karolinska University Hospital, Stockholm, Sweden
Further Information

Publication History

Publication Date:
25 August 2005 (online)

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ABSTRACT

The clinical development of ximelagatran for the treatment and prevention of various arterial and venous thromboembolic disorders has used fixed-dose regimens without coagulation monitoring in all indications. Although monitoring is not required, effects on the various coagulation assays that are available are seen with its active form melagatran, and there are situations where an assessment of anticoagulant effect may help to inform clinical decisions. However, the sensitivity of different coagulation assays varies considerably. The thrombin clotting time (TT) and ecarin clotting time (ECT) are highly sensitive to plasma melagatran concentrations (IC50 ∼0.01 μmol/L and ∼0.15 μmol/L, respectively), with an approximate linear relationship between plasma melagatran concentration and prolongation of clotting time. In comparison, the activated partial thromboplastin time (APTT) (IC50 ∼0.3 to 0.8 μmol/L) and prothrombin time (PT) (IC50 ∼0.9 to 2.9 μmol/L) are relatively insensitive, and the concentration-response relationship shows a flattening with increasing plasma melagatran concentration. Commercially available APTT and PT reagents varied considerably in their sensitivity to melagatran. Comparing the various coagulation assays, the APTT, ECT, and TT are suitable choices when an indicator of the anticoagulant effect of ximelagatran is required, although the absence of international standards requires calibration of each test in individual laboratories and the ECT is not widely available.

KEYWORDS

Ximelagatran - coagulation monitoring - prothrombin time - activated partial thromboplastin time

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Stefan C CarlssonM.D. Ph.D. 

Integrative Pharmacology, DISCOVERY, AstraZeneca R&D Mölndal

S-431 83 Mölndal, Sweden