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Influence of Lepirudin, Argatroban, and Melagatran on Prothrombin Time and Additional Effect of Oral Anticoagulation

¹ Fourth Department of Medicine, University Hospital Mannheim, Ruprecht-Karls-University Heidelberg, Theodor-Kutzer-Ufer 1, 68167 Mannheim, Germany

^aauthor for correspondence: fax 49-621-383-3308, e-mail j-harenberg@t-online.de

The first 300 words of the full text of this article appear below.

Oral anticoagulation (OAC) with coumarin derivatives decreases the activities of coagulation factors II, VII, IX, and X by inhibiting their vitamin K-dependent carboxylation (1). The effectiveness and safety of therapy with oral anticoagulants for primary or secondary prophylaxis of thromboembolism are usually monitored by the prothrombin time (PT), expressed as international normalized ratio (INR), prothrombin ratio, or percentage of normal (2)(3). INR was standardized through large international reference studies (4)(5)(6)(7).

The direct thrombin inhibitors (DTIs) lepirudin and argatroban are used to achieve effective anticoagulation in patients with heparin-induced thrombocytopenia with or without thrombosis (type II) (8)(9)(10). Melagatran is currently under investigation in clinical trials (11)(12)(13)(14). DTIs prolong clotting times in PT assays and therefore interfere with oral anticoagulants (15)(16)(17)(18). During treatment of deep venous thrombosis, heparins or DTIs are switched to oral anticoagulants. During treatment for invasive diagnostics or surgery, patients on oral anticoagulant therapy may temporarily be switched to a DTI. Decreased thrombin activity in the plasma of these patients leads to prolongations of the PT (15)(16)(18). These additive effects make it difficult to adjust dosage of either of the drugs during concomitant use. In the case of heparins, additive effects are antagonized by addition of protamine or heparinase to PT reagents (19). For DTIs, such antagonists are missing. Antibodies against hirudin have been unsuitable for neutralizing the drug’s anti-factor IIa effects because of polyclonality, producing neutralizing or enhancing antibodies, depending on the individual (20)(21). Argatroban and melagatran are small molecules and have not been reported to be antigenic. Without the . . . [Full Text of this Article]

The following articles in journals at HighWire Press have cited this article:

				Z. Taimeh and B. Weksler Review: Recent Advances in Argatroban-Warfarin Transition in Patients With Heparin-induced Thrombocytopenia Clinical and Applied Thrombosis/Hemostasis, February 1, 2010; 16(1): 5 - 12. [Abstract] [PDF]

				J. M. Walenga, A. F. Drenth, M. Mayuga, D. A. Hoppensteadt, M. Prechel, S. Harder, H. Watanabe, M. Osakabe, and H.-K. Breddin Transition From Argatroban to Oral Anticoagulation With Phenprocoumon or Acenocoumarol: Effect on Coagulation Factor Testing Clinical and Applied Thrombosis/Hemostasis, July 1, 2008; 14(3): 325 - 331. [Abstract] [PDF]

				M. J. Hursting, B. E. Lewis, and D. E. Macfarlane Transitioning from Argatroban to Warfarin Therapy in Patients with Heparin-induced Thrombocytopenia Clinical and Applied Thrombosis/Hemostasis, July 1, 2005; 11(3): 279 - 287. [Abstract] [PDF]

				C. Verme-Gibboney, J. W. Dubb, S. A. Spinler, and A. Greinacher Direct thrombin inhibitors in heparin-induced thrombocytopenia Am. J. Health Syst. Pharm., February 1, 2005; 62(3): 247 - 250. [Full Text] [PDF]