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      Challenges encountered with argatroban anticoagulation during cardiopulmonary bypass

      case-report

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          Abstract

          Use of argatroban as an alternative to heparin during cardiopulmonary bypass (CPB) in patients with heparin-induced thrombocytopenia has gained some attention in the past two decades. Dosing of argatroban during CPB is complex due to lack of complete understanding of its pharmacokinetic profile and the various elements during CPB that may alter its plasma levels. We report a case where the challenges in dosing argatroban led to failure to provide adequate anticoagulation during CPB, as evidenced by clot formation in the oxygenator, and extensive bleeding in the postoperative period.

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          A prospective comparison of three argatroban treatment regimens during hemodialysis in end-stage renal disease.

          Patrick T. Murray, Bharathi V Reddy, Eric Grossman … (2004)
          We prospectively evaluated 3 treatment regimens of argatroban, a direct thrombin inhibitor, for providing adequate, safe anticoagulation in patients with end-stage renal disease (ESRD) during hemodialysis. In this randomized, 3-way crossover study, ESRD patients underwent hemodialysis sessions of 3- or 4-hour duration using high-flux membranes and each of 3 argatroban treatment regimens (A: 250-microg/kg bolus, with an additional 250-microg/kg bolus allowed; B: 250-microg/kg bolus followed by 2-microg/kg/min infusion; C: steady-state, 2-microg/kg/min infusion initiated 4 hours before dialysis). Pharmacodynamic effects including activated clotting times (ACTs); hemodialysis efficacy including single-pool Kt/V, urea reduction ratio (URR), and circuit flow; and safety through a 3-day follow-up were monitored. Argatroban pharmacokinetic parameters including dialytic clearance were evaluated during regimen C. Thirteen patients completed 38 hemodialysis sessions (1 patient withdrew consent after 2 sessions). Mean +/- SD ACTs increased from 131 +/- 14 seconds at baseline to 153 +/- 24, 200 +/- 30, and 197 +/- 33 seconds, respectively, after 60 minutes of hemodialysis using regimens A, B, and C. Across regimens, mean Kt/Vs (1.5-1.6) and URRs (70%-73%) were comparable. No dialyzer was changed; 1 session was shortened 15 minutes because of circuit clot formation. Systemic argatroban clearance increased approximately 20% during hemodialysis, without clinically significantly affecting ACTs. Upon argatroban discontinuation, ACTs and plasma argatroban decreased concurrently (elimination half-life, 35 +/- 6 min). No thrombosis, bleeding, serious adverse events, or clinically significant changes in vital signs or routine laboratory measures occurred. Argatroban, administered by each treatment regimen, provides safe, adequate anticoagulation to enable successful hemodialysis in ESRD patients. Argatroban dialytic clearance by high-flux membranes is clinically insignificant.
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            Argatroban and renal replacement therapy in patients with heparin-induced thrombocytopenia.

            Emily Murray, I. Tang, Kruti Patel … (2005)
            Argatroban, a direct thrombin inhibitor, is an effective anticoagulant for patients who have heparin-induced thrombocytopenia (HIT). Anticoagulation is usually required for renal replacement therapy (RRT). To prospectively evaluate the pharmacokinetics, pharmacodynamics, and safety of argatroban during RRT in hospitalized patients with or at risk for HIT. Five patients with known or suspected HIT underwent hemodialysis (n = 4) or continuous venovenous hemofiltration (CVVH, n = 1), while receiving a continuous infusion of argatroban 0.5-2 microg/kg/min. Activated partial thromboplastin times (aPTTs), activated clotting times (ACTs), argatroban concentrations (plasma, dialysate, CVVH effluent), and safety were assessed before, during, and after a 4-hour session of RRT. Systemic and dialytic argatroban clearances were calculated. Among the 4 hemodialysis patients, aPTT, ACT, and plasma argatroban concentrations remained stable during RRT, with respective mean +/- SD values of 74.3 +/- 34.2 seconds, 198 +/- 23 seconds, and 499 +/- 353 ng/mL before RRT, and 70.6 +/- 21.4 seconds, 181 +/- 12 seconds, and 453 +/- 295 ng/mL 2 hours after starting RRT (p values NS). Systemic clearance was 17.7 +/- 12.8 L/h before hemodialysis and 17.0 +/- 9.5 L/h during hemodialysis (n = 2). The dialyzer clearance (dialysate recovery method) was 1.5 +/- 0.4 L/h (n = 4). Generally similar responses occurred in the CVVH patient: systemic argatroban clearance was 4.8 L/h before CVVH and 4 L/h during CVVH. The hemofilter argatroban clearance was 0.9 L/h. No bleeding or thrombosis occurred. Argatroban provides effective alternative anticoagulation in patients with or at risk for HIT during RRT. Argatroban clearance by high-flux membranes during hemodialysis and CVVH is clinically insignificant, necessitating no dose adjustment.
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              Alternative anticoagulation management strategies for the patient with heparin-induced thrombocytopenia undergoing cardiac surgery.

              Mary Marymont, K. G. Murphy (2007)
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Anaesthesiol Clin Pharmacol
                Journal ID (publisher-id): JOACP
                Title: Journal of Anaesthesiology, Clinical Pharmacology
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 0970-9185
                ISSN (Electronic): 2231-2730
                Publication date (Print): Jan-Mar 2012
                Volume: 28
                Issue: 1
                Pages: 106-110
                Affiliations
                [1]Department of Anesthesiology, Wayne State University/Detroit Medical Center, Detroit, MI, USA
                Author notes
                Address for correspondence: Dr. Shvetank Agarwal, Department of Anesthesiology, Wayne State University/Detroit Medical Center, 3990 John R., Box 162, Detroit, MI 48201, USA. E-mail: shvetank_agarwal@ 123456yahoo.com
                Article
                Publisher ID: JOACP-28-106
                DOI: 10.4103/0970-9185.92458
                PMC ID: 3275940
                PubMed ID: 22345956
                SO-VID: 843e9d4e-2c66-4301-8d66-725e9f22dbce
                Copyright © Copyright: © Journal of Anaesthesiology Clinical Pharmacology
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: argatroban,heparin alternative,cardio-pulmonary bypass,heparin induced thrombocytopenia,anti-coagulation
                Data availability:
                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: argatroban, heparin alternative, cardio-pulmonary bypass, heparin induced thrombocytopenia, anti-coagulation

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