Argatroban heparin-induced thrombocytopenia

Figure 24.4 The decision-analytic model shows the three strategies that were examined by Arnold and researchers [22] to evaluate the financial implications of the direct thrombin inhibitor argatroban for early treatment (<48 hours after thrombocytopenia onset), compared with delayed treatment, of heparin-induced thrombocytopenia (HIT) with or without thrombosis.

Arnold R, Kim R, Zhou Y, Tang B. Budgetary impact of heparin-induced thrombocytopenia with thrombosis and treatment with the direct thrombin inhibitor Argatroban (P401E). ASHP 39th Midyear Clinical Meeting. Orlando, FL, 2004. 

Arnold R, Kim R, Tang B. The cost-effectiveness of argatroban treatment in heparin-induced thrombocytopenia the effect of early versus delayed treatment. Cardiol Rev 2005 14 7-13. 

Initial dosage in HIT or heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) Before administering argatroban, discontinue heparin therapy and obtain a baseline activated partial thromboplastin time (aPTT). The recommended initial dose of argatroban for adults without hepatic impairment is 2 mcg/kg/min administered as a continuous infusion (see table). 

Argatroban is a small molecule thrombin inhibitor that is FDA approved for use in patients with heparin-induced thrombocytopenia (HIT) with or without thrombosis and coronary angioplasty in patients with HIT. It, too, has a short half-life, is given by continuous intravenous infusion, and monitoring is done by aPTT. Its clearance is not affected by renal disease but is dependent on liver function. The drug requires dose reduction in patients with liver disease. Patients on argatroban will demonstrate elevated INRs because of test interference, rendering the transition to warfarin difficult. 

The use of unfractionated heparin has been optimized by the development of the LMWHs. This is primarily due to our current understanding of the chemistry and biology of heparin. Antithrombin drugs such as hirudin, argatroban, and bivalirudin have been in development for many years. These drugs are useful as substitutes for heparin in such conditions as heparin-induced thrombocytopenia however, these drugs do not have an antidote and cannot be used for surgical indications at... 

Matthai WH Jr, Use of argatroban during percutaneous coronary interventions in patients with heparin-induced thrombocytopenia, Semin Thromb Hemost 1999 25(suppl I) 57-60,... 

Lewis BE, Matthai WH Jr, Cohen M, et al. Argatroban anticoagulation during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia. Catheter Cardiovasc Interv 2002 57 177-184. 

Matsuo T Kario K, Chikahira Y et al. Treatment of heparin-induced thrombocytopenia by use of argatroban, a synthetic thrombin inhibitor. BrJ Haematol 1992 82 627-629. 

Walenga JM, Ahmad S, Hoppensteacft D, et al. Argatroban therapy does not generate antibodies that after its anticoagulant activity in patients with heparin-induced thrombocytopenia. Thromb Res 2002 105 401 -405. 

Kondo LM, WrttkowskyAK, Wiggins BS. Argatroban for prevention and treatment of thromboembolism in heparin-induced thrombocytopenia. Ann Pharmacother 2001 35 440-451. 

Reichert MG, MacGregor DA, Kincaid EH, et al, Excessive argatroban anticoagulation for heparin-induced thrombocytopenia, Ann Pharmacother 2003 37 652-654,... 

Suzuki S, Sakamoto S, Koide M, etal. Effective anticoagulation by argatroban during coronary stent implantation in a patient with heparin-induced thrombocytopenia. Thromb Res 1997 88 499-502. 

Argatroban has been approved in the USA and Canada for the prophylaxis and treatment of thrombosis in patients with heparin-induced thrombocytopenia, and in Japan and Korea for various thrombotic disorders. Its effects can be monitored using the activated partial thromboplastin time for low doses and the activated clotting time for high doses. Its pharmacology, clinical pharmacology, and uses have been reviewed (7-14). 

In the case of heparin-induced thrombocytopenia with thrombosis, all forms of heparin must be discontinued, including heparin flushes, and anticoagulation with argatroban or the recombinant hirudin lepirudin initiated.These agents should also be considered for the treatment of patients who have acute heparin-induced thrombocytopenia without thombosis because of the increased risk... 

ARGATROBAN Argatroban, a synthetic compound based on the structure of L-Arg, binds reversibly to the catalytic site of thrombin. Administered intravenously, it has an immediate onset of action and a t j of 40-50 minutes. Argatroban is metabolized by hepatic CYPs and is excreted in the bile therefore dosage reduction is required for patients with hepatic insufficiency. The dosage is adjusted to maintain an aPTT of 1.5-3 times the baseline value. Argatroban can be used as an alternative to lepirudin for prophylaxis or treatment of patients with or at risk of developing heparin-induced thrombocytopenia. 

Lewis BE, Hursting MJ. Argatroban therapy in heparin-induced thrombocytopenia. In Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia. 3rd Ed. New York Marcel Dekker, 2004 437-474. 

Hematologic Numerous papers on heparin-induced thrombocytopenia continue to appear, including a systematic review of the use of argatroban as an alternative anticoagulant [16 ]. Two prospective, multicenter, non-randomized, open studies of the use of argatroban... 

Hematologic The use of argatroban in patients with heparin-induced thrombocytopenia has been reviewed [33 , 34 , 35 ]. 

Babuin L, Pengo V. Argatroban in the management of heparin-induced thrombocytopenia. Vase Health Risk Manag 2010 6 813-9. 

Taimeh Z, Weksler B. Review recent advances in argatroban-warfarin transition in patients with heparin-induced thrombocytopenia. Clin Appl Thromb Hemost 2010 16(1) 5-12. 

Schmitz ML, Massicotte P, Faulkner SC, Bhutta AT, Johnson CE, Seib PM, Frazier EA, Fiser Jr. WP, Imamura M, Jaquiss RD. Management of a pediatric patient on the Berlin Heart Excor ventricular assist device with argatroban after heparin-induced thrombocytopenia. ASAIO J 2008 54(5) 546-7. 

Ciccolo ML, Bernstein J, Collazos JC, Acherman RJ, Restrepo H, Winters JM, Krueger J, Evans WN. Argatroban anticoagulation for cardiac surgery with cardiopulmonary bypass in an infant with double outlet right ventricle and a history of heparin-induced thrombocytopenia. Congenit Heart Dis 2008 3(4) 299-302. 

Raaz U, Maegdefessel L, Buerke M, Janusch M, Werdan K, Schlitt A. INR matters a case on managing argatroban for bridging oral anticoagulation in a patient with heparin induced thrombocytopenia type n after mechanical heart valve replacement. Thromb Res 2009 124(2) 242-3. 

Ekbatani A, Asaro LR, Malinow AM. Anticoagulation with argatroban in a parturient with heparin-induced thrombocytopenia. Int J Obstet Anesth 2010 19(1) 82-7. 

Salto T, Uchida E, Saima S, Chiba A, Aral T, Okuda Y. Anesthetic management for a patient with heparin-induced thrombocytopenia (HIT) undergoing off-pump coronary bypass surgery using argatroban, a direct thrombin inhibitor. Masui 2009 58(9) 1169-71. 

Ansara AJ, Arif S, Warhurst RD. Weight-based argatroban dosing nomogram for treatment of heparin-induced thrombocytopenia. Ann Pharmacother 2009 43 (1) 9 18. 

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