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Transition From Argatroban to Oral Anticoagulation With Phenprocoumon or Acenocoumarol: Effect on Coagulation Factor Testing

Cardiovascular Institute, Loyola University Medical Center at Chicago, Maywood, Illinois, jwaleng{at}lumc.edu

Amanda F. Drenth, BS

Cardiovascular Institute, Loyola University Medical Center at Chicago, Maywood, Illinois

Myttle Mayuga, BS

Cardiovascular Institute, Loyola University Medical Center at Chicago, Maywood, Illinois

Debra A. Hoppensteadt, PhD

Cardiovascular Institute, Loyola University Medical Center at Chicago, Maywood, Illinois

Margaret Prechel, PhD

Cardiovascular Institute, Loyola University Medical Center at Chicago, Maywood, Illinois

Sebastian Harder, PhD

Department of Clinical Pharmacology, J.W. Goethe University, Frankfurt, Germany

Hikari Watanabe, PhD

Mitsubishi Pharma Corporation, Tokyo, Japan

Masanori Osakabe, PhD

Mitsubishi Pharma Corporation, Tokyo, Japan

Hans-Klaus Breddin, MD

International Institute for Thrombosis and Vascular Diseases, Frankfurt, Germany

Treatment with the thrombin inhibitor argatroban is often followed by vitamin K-antagonist treatment. In this study, the behavior of coagulation factors measured under these treatment regimens is shown. Healthy subjects received infusions of 1.0, 2.0, or 3.0 µg/kg/hr argatroban before and during phenprocoumon or acenocoumarol dosing. Quantitation of factors II, VII, IX, and X by clot-based assays resulted in dose dependent, approximately 20%, lower than expected values in the presence of argatroban. On the contrary, values for the inhibitors, protein C and protein S, were higher. Cotherapy exaggerated the effect by vitamin K-antagonist alone. However, testing by immunologic and chromogenic assays did not show any effect by argatroban. Coupled with a lack of bleeding in the subjects, these data suggests that argatroban does not affect coagulation proteins and that the observations are only an assay artifact. Assay interferences must be considered when measuring coagulation proteins in patients receiving thrombin inhibitors.

Key Words: argatroban • coagulation factors • assays • phenprocoumon • acenocoumarol

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