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INR matters: A case on managing argatroban for bridging oral anticoagulation in a patient with heparin induced thrombocytopenia type II after mechanical heart valve replacement
Thrombosis Research 124 (2009) 242–243
Contents lists available at ScienceDirect
Thrombosis Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / t h r o m r e s
Letter to the Editors-in-Chief
INR matters: A case on managing argatroban for bridging oral anticoagulation in a patient with heparin induced thrombocytopenia type II after mechanical heart valve replacement
existing OAC to argatroban-bridging and back with respect to safely guide this procedure by repeated simultaneous measurements of INR and aPTT. Case
Introduction Lifelong oral anticoagulation (OAC) is essential for prevention of thromboembolic events after implantation of mechanical heart valves [1]. OAC treatment may be interrupted, however, in preparation for surgical procedures or non-surgical interventions such as cardiac catheterization. The gold standard for adapting oral to parenteral anticoagulation (“bridging therapy”) in patients at high risk for thromboembolic complications is intravenous administration of unfractionated heparin (UFH) [1]. In cases of heparin-induced thrombocytopenia type 2 (HIT II) alternative anticoagulants need to be employed – such as the direct thrombin inhibitor argatroban. Studies have been published on the topic of transitioning from intravenous argatroban medication to OAC in patients with HIT II [2–4]. In the present case report we discuss the transition from pre-
A 66 years old female patient with mechanical mitral valve replacement (St. Jude-Medical, 29 mm) and need for surgical nasolacrimal duct abscess treatment was admitted to our department in January 2008. Mitral valve replacement (MVR) had been performed due to severe mitral valve stenosis in October 2007. On admission we found normal left ventricular dimensions with slightly impaired global left-ventricular function (ejection fraction 45%) by echocardiography. MVR hemodynamics presented with regular flow profile. Having received surgical ablation of atrial fibrillation during heart valve surgery the patient's ECG showed sinus rhythm. As HIT II was diagnosed perioperatively during mitral valve replacement in October 2007, argatroban was employed as heparinalternative bridging agent for interruption of oral anticoagulation.
Fig. 1. Course of activated partial thromboplastin time (aPTT, plotted as ●) and international normalized ratio (INR, plotted as □) during period of argatroban bridging. Dates are indicated as day and month (DD.M). Time intervals of phenprocoumon (Phen) and argatroban administration are depicted by bars. Phases 1-3 indicate intervals of fading (1), vanished (2) and re-increasing (3) OAC efficacy. Dosage of phenprocoumon administered is plotted in milligrams (mg) above the date of administration. 0049-3848/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2008.08.023
Letter to the Editors-in-Chief
After discontinuation of OAC, intravenous administration of argatroban (dose aPTT-adjusted; average dosage 0.8 µg/kg/min) was initiated when the international normalized ratio (INR) decreased to a level below 2.5. Here we found the INR – as the measure of OAC efficacy – significantly to be elevated by argatroban co-medication. Therefore an accurate estimation of the remaining OAC efficacy was not possible under argatroban application. However, as for the patient's suitability for surgery knowledge about the remaining OAC efficacy was essential, a simultaneous analysis of the course of activated partial thromboplastin time (aPTT) – which is the standard parameter used for monitoring argatroban's anti-coagulatory efficacy – and of INR was performed throughout the entire procedure of argatroban bridging (Fig. 1): Here we found aPTT dynamics to be accompanied by analogous changes of INR thus reflecting argatroban's influence on INR. However, the initial phase (phase 1; 25.01.–30.01.08) was characterized by a disproportionate decline of INR indicating the fading OAC effect. Subsequently we found the INR strictly linked to aPTT kinetics (phase 2; 30.01.-11.02.) which now indicated the breakdown of OAC necessary for performance of surgery. Here argatroban was discontinued 6 hours prior to surgery resulting in a decline of INR suitable for surgical procedure (05.02). After completion of nasolacrimal duct surgery overlapping reestablishment of OAC was performed. This process was reflected by an INR regaining independence from the aPTT course (phase 3; 11.02.–14.02). Finally, under discontinued argatroban medication (14.2.) INR did not fall below 2.5 indicating a sufficient OAC efficacy. During the whole clinical course the patient did not present any bleeding or thrombotic events. The patient was discharged in good clinical condition. Discussion Argatroban may be employed as bridging agent for a pre-existing OAC. During overlapping administration of argatroban the remaining OAC efficacy – due to argatroban's INR-elevating effect – cannot be monitored solely using the parameter of INR. Here we show that additional analysis of the aPTT course reveals information about the status of OAC which is needed for initiation of surgical procedures.
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Conclusion This case demonstrates that argatroban bridging can safely be performed only using standard monitoring parameters as INR and aPTT. Conflict of Interest The authors were supported by a unrestricted grant from MITSUBISHI TANABE PHARMA CORPORATION. References [1] Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J 2007;28: 230–68. [2] Bartholomew JR, Hursting MJ. Transitioning from argatroban to warfarin in heparininduced thrombocytopenia: an analysis of outcomes in patients with elevated international normalized ratio (INR). J Thromb Thrombolysis 2005;19: 183–8. [3] Hursting MJ, Lewis BE, Macfarlane DE. Transitioning from argatroban to warfarin therapy in patients with heparin-induced thrombocytopenia. Clin Appl Thromb Hemost 2005;11:279–87. [4] Arpino PA, Demirjian Z, Van Cott EM. Use of the chromogenic factor X assay to predict the international normalized ratio in patients transitioning from argatroban to warfarin. Pharmacotherapy 2005;25:157–64.
Uwe Raaz ⁎ Lars Maegdefessel Michael Buerke Matthias Janusch Karl Werdan Axel Schlitt Department of Medicine III, Martin Luther-University Halle-Wittenberg, Germany ⁎Corresponding author. Department of Medicine III, Martin Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany. Tel.: +49 345 557 2601; fax: +49 345 557 4951 E-mail address: [email protected] (U. Raaz). 27 June 2008
Contents lists available at ScienceDirect
Thrombosis Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / t h r o m r e s
Letter to the Editors-in-Chief
INR matters: A case on managing argatroban for bridging oral anticoagulation in a patient with heparin induced thrombocytopenia type II after mechanical heart valve replacement
existing OAC to argatroban-bridging and back with respect to safely guide this procedure by repeated simultaneous measurements of INR and aPTT. Case
Introduction Lifelong oral anticoagulation (OAC) is essential for prevention of thromboembolic events after implantation of mechanical heart valves [1]. OAC treatment may be interrupted, however, in preparation for surgical procedures or non-surgical interventions such as cardiac catheterization. The gold standard for adapting oral to parenteral anticoagulation (“bridging therapy”) in patients at high risk for thromboembolic complications is intravenous administration of unfractionated heparin (UFH) [1]. In cases of heparin-induced thrombocytopenia type 2 (HIT II) alternative anticoagulants need to be employed – such as the direct thrombin inhibitor argatroban. Studies have been published on the topic of transitioning from intravenous argatroban medication to OAC in patients with HIT II [2–4]. In the present case report we discuss the transition from pre-
A 66 years old female patient with mechanical mitral valve replacement (St. Jude-Medical, 29 mm) and need for surgical nasolacrimal duct abscess treatment was admitted to our department in January 2008. Mitral valve replacement (MVR) had been performed due to severe mitral valve stenosis in October 2007. On admission we found normal left ventricular dimensions with slightly impaired global left-ventricular function (ejection fraction 45%) by echocardiography. MVR hemodynamics presented with regular flow profile. Having received surgical ablation of atrial fibrillation during heart valve surgery the patient's ECG showed sinus rhythm. As HIT II was diagnosed perioperatively during mitral valve replacement in October 2007, argatroban was employed as heparinalternative bridging agent for interruption of oral anticoagulation.
Fig. 1. Course of activated partial thromboplastin time (aPTT, plotted as ●) and international normalized ratio (INR, plotted as □) during period of argatroban bridging. Dates are indicated as day and month (DD.M). Time intervals of phenprocoumon (Phen) and argatroban administration are depicted by bars. Phases 1-3 indicate intervals of fading (1), vanished (2) and re-increasing (3) OAC efficacy. Dosage of phenprocoumon administered is plotted in milligrams (mg) above the date of administration. 0049-3848/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2008.08.023
Letter to the Editors-in-Chief
After discontinuation of OAC, intravenous administration of argatroban (dose aPTT-adjusted; average dosage 0.8 µg/kg/min) was initiated when the international normalized ratio (INR) decreased to a level below 2.5. Here we found the INR – as the measure of OAC efficacy – significantly to be elevated by argatroban co-medication. Therefore an accurate estimation of the remaining OAC efficacy was not possible under argatroban application. However, as for the patient's suitability for surgery knowledge about the remaining OAC efficacy was essential, a simultaneous analysis of the course of activated partial thromboplastin time (aPTT) – which is the standard parameter used for monitoring argatroban's anti-coagulatory efficacy – and of INR was performed throughout the entire procedure of argatroban bridging (Fig. 1): Here we found aPTT dynamics to be accompanied by analogous changes of INR thus reflecting argatroban's influence on INR. However, the initial phase (phase 1; 25.01.–30.01.08) was characterized by a disproportionate decline of INR indicating the fading OAC effect. Subsequently we found the INR strictly linked to aPTT kinetics (phase 2; 30.01.-11.02.) which now indicated the breakdown of OAC necessary for performance of surgery. Here argatroban was discontinued 6 hours prior to surgery resulting in a decline of INR suitable for surgical procedure (05.02). After completion of nasolacrimal duct surgery overlapping reestablishment of OAC was performed. This process was reflected by an INR regaining independence from the aPTT course (phase 3; 11.02.–14.02). Finally, under discontinued argatroban medication (14.2.) INR did not fall below 2.5 indicating a sufficient OAC efficacy. During the whole clinical course the patient did not present any bleeding or thrombotic events. The patient was discharged in good clinical condition. Discussion Argatroban may be employed as bridging agent for a pre-existing OAC. During overlapping administration of argatroban the remaining OAC efficacy – due to argatroban's INR-elevating effect – cannot be monitored solely using the parameter of INR. Here we show that additional analysis of the aPTT course reveals information about the status of OAC which is needed for initiation of surgical procedures.
243
Conclusion This case demonstrates that argatroban bridging can safely be performed only using standard monitoring parameters as INR and aPTT. Conflict of Interest The authors were supported by a unrestricted grant from MITSUBISHI TANABE PHARMA CORPORATION. References [1] Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J 2007;28: 230–68. [2] Bartholomew JR, Hursting MJ. Transitioning from argatroban to warfarin in heparininduced thrombocytopenia: an analysis of outcomes in patients with elevated international normalized ratio (INR). J Thromb Thrombolysis 2005;19: 183–8. [3] Hursting MJ, Lewis BE, Macfarlane DE. Transitioning from argatroban to warfarin therapy in patients with heparin-induced thrombocytopenia. Clin Appl Thromb Hemost 2005;11:279–87. [4] Arpino PA, Demirjian Z, Van Cott EM. Use of the chromogenic factor X assay to predict the international normalized ratio in patients transitioning from argatroban to warfarin. Pharmacotherapy 2005;25:157–64.
Uwe Raaz ⁎ Lars Maegdefessel Michael Buerke Matthias Janusch Karl Werdan Axel Schlitt Department of Medicine III, Martin Luther-University Halle-Wittenberg, Germany ⁎Corresponding author. Department of Medicine III, Martin Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany. Tel.: +49 345 557 2601; fax: +49 345 557 4951 E-mail address: [email protected] (U. Raaz). 27 June 2008