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Technical Briefs |
1
Texas Biotechnology Corporation, 7000 Fannin Street, Suite 1920, Houston, TX 77030, and
2
Department of Pathology, Stanford University Medical Center, Stanford, CA 94305;
a address correspondence to this author at: 3912 Marlowe St., Houston, TX 77005
Oral anticoagulants such as warfarin induce depletion of vitamin K-dependent coagulation factors, causing prolongation of the prothrombin time (PT) and the PT-International Normalized Ratio (INR). The available thromboplastins used for measuring the PT vary in their sensitivity to coagulation factor depletion, and each is assigned an International Sensitivity Index (ISI) that is used when calculating the INR. Traditional monitoring of oral anticoagulant therapy using the INR is confounded during concurrent therapy with direct thrombin inhibitors, such as argatroban, that also prolong the INR (1)(2)(3). Although alternative monitoring methods have been suggested for use in this setting (2)(3), guidelines allowing for refined interpretation of the INR would also be useful. To facilitate the development of such guidelines, we have characterized in vitro the differential effects of warfarin and argatroban, as well as the choice of thromboplastin used, on the INR during anticoagulation with both agents.
For this study, plasma specimens were obtained from 10 healthy donors (laboratory personnel) and 35 patients on warfarin therapy, in accordance with policies of the institution's responsible committee. Blood was collected into evacuated tubes (38 g/L sodium citrate), and plasma was prepared by the centrifugation of the blood within 30 min of collection. The only selection criterion for the patient group was that each was on warfarin therapy, and both inpatients and outpatients were included. In addition, four plasma pools (each prepared from at least 10 individuals) were obtained from Harris Laboratories. One plasma pool was from healthy donors, and three pools were from patients on warfarin therapy exhibiting generally similar levels of oral anticoagulation. Plasma specimens were stored at -30 °C for up to 2 weeks and thawed rapidly immediately before testing.
The PT of each individual or pooled plasma specimen was determined in
the
Footnotes
References
The following articles in journals at HighWire Press have cited this article:
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  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]
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S. A Spinler and W. Dager Comment: extensive prolongation of aPTT with argatroban in an elderly patient with improving renal function, normal hepatic enzymes, and metastatic lung cancer Ann. Pharmacother., November 1, 2005; 39(11): 1955 - 1956. [Full Text] [PDF]
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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]
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 I.-K. Jang and M. J. Hursting When Heparins Promote Thrombosis: Review of Heparin-Induced Thrombocytopenia Circulation, May 24, 2005; 111(20): 2671 - 2683. [Full Text] [PDF]
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J. L Stephens, J. M Koerber, J. C Mattson, and M. A Smythe Effect of Lepirudin on the International Normalized Ratio Ann. Pharmacother., January 1, 2005; 39(1): 28 - 31. [Abstract] [Full Text] [PDF]
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 M. A. Smythe, W. E. Dager, and N. M. Patel Managing Complications of Anticoagulant Therapy Journal of Pharmacy Practice, October 1, 2004; 17(5): 327 - 346. [Abstract] [PDF]
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W. E Dager and R. H White Low-Molecular-Weight Heparin-Induced Thrombocytopenia in a Child Ann. Pharmacother., February 1, 2004; 38(2): 247 - 250. [Abstract] [Full Text] [PDF]
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A. S Trask, R. C Gosselin, J. A Diaz, and W. E Dager Warfarin Initiation and Monitoring with Clotting Factors II, VII, and X Ann. Pharmacother., February 1, 2004; 38(2): 251 - 256. [Abstract] [Full Text] [PDF]
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W. E Dager and R. H White Argatroban for Heparin-Induced Thrombocytopenia in Hepato-Renal Failure and CVVHD Ann. Pharmacother., September 1, 2003; 37(9): 1232 - 1236. [Abstract] [Full Text] [PDF]
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 B. M. Alving How I treat heparin-induced thrombocytopenia and thrombosis Blood, January 1, 2003; 101(1): 31 - 37. [Full Text] [PDF]
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 T. Fenyvesi, I. Joerg, and J. Harenberg Influence of Lepirudin, Argatroban, and Melagatran on Prothrombin Time and Additional Effect of Oral Anticoagulation Clin. Chem., October 1, 2002; 48(10): 1791 - 1794. [Full Text] [PDF]
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