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    ABSTRACT: Argatroban was used as the anticoagulant during cardiopulmonary bypass (CPB) in a patient with heparin-induced thrombocytopenia (HIT) type II undergoing mitral valve replacement. Dosage was reduced because of preoperative congestive liver disorder. Perioperative coagulability was poor, and, ultimately, failure of hemostasis led to a fatal outcome. Although argatroban use as an anticoagulant for HIT is reported, the optimal dose has not been established. During long-term CPB, increasing the total dosage may extend anticoagulant ability, leading to dose dependence. Because no antagonist for argatroban exists, failure of hemostasis might occur.
    Journal of anesthesia. 05/2013;
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    ABSTRACT: To compare the effectiveness of bivalirudin and argatroban in achieving anticoagulation goals and to compare clinical outcomes assessing the safety and efficacy in patients with known or suspected heparin-induced thrombocytopenia (HIT). Single-center, retrospective analysis. Large tertiary care academic medical center. A total of 138 adults who received either bivalirudin (92 patients) or argatroban (46 patients) for at least 24 hours for known or suspected HIT between January 2007 and July 2008. MEASUREMENTS AND MAIN RESULTS. Data regarding demographics, direct thrombin inhibitor (DTI) dosing and monitoring, and related clinical outcomes were collected; statistical analysis was performed to compare results for patients receiving bivalirudin versus those receiving argatroban. Duration of DTI use ranged from 24-658 hours. At the time of DTI initiation, 108 patients (78%) were in an intensive care unit, with the highest proportion (61/138 [44%]) in the cardiothoracic surgery intensive care unit. The median (interquartile range [IQR]) DTI doses at the time of first reaching therapeutic goal were bivalirudin 0.06 mg/kg/hour (0.04-0.08 mg/kg/hr) and argatroban 1.0 μg/kg/minute (0.5-2.0 μg/kg/min). The median percentage of activated partial thromboplastin time (aPTT) values within therapeutic range while patients were receiving DTI therapy were similar for bivalirudin and argatroban (75% and 70%, respectively, p=0.238). A greater percentage of aPTT values were supratherapeutic with argatroban versus bivalirudin treatment (18% vs 8%, p=0.046). Median time to therapeutic goal was similar for bivalirudin (5.50 hrs [IQR 4-14.5 hrs]) and argatroban (5.75 hrs [IQR 3-17.7 hrs], p=0.499). New thromboembolic events occurred in seven patients (8%) receiving bivalirudin and two (4%) receiving argatroban (p=0.718). Bleeding events occurred at similar rates in both groups (9% for bivalirudin vs 11% for argatroban, p>0.999). Bivalirudin and argatroban were similar in achieving and maintaining therapeutic anticoagulation goals, clinical outcomes, and safety. This study suggests that bivalirudin represents an alternative in the management of HIT, but prospective studies are needed.
    Pharmacotherapy. 12/2010; 30(12):1229-38.
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    ABSTRACT: OBJECTIVE:To report our experience of reduced-dose argatroban in a patient with suspected heparin-induced thrombocytopenia (HIT) and Child-Pugh class C liver disease and review the relevant literature to summarize current recommendations on argatroban use in patients with severe liver disease.CASE SUMMARY:A 58-year-old male with Child-Pugh class C liver disease (Model for End-Stage Liver Disease [MELD] score = 31, total bilirubin 4.5 mg/dL) and hemodialysis-dependent renal failure was hospitalized with acute deep vein thrombosis (DVT). Three days after heparin initiation for DVT, he developed thrombocytopenia. Given his heparin exposure (both for treatment of DVT and ongoing hemodialysis), HIT was suspected and all heparinoids were immediately discontinued. Argatroban was initiated for the treatment of HIT while laboratory testing for HIT antibodies and the serotonin release assay were completed. Because of the patient's advanced liver disease, the starting dose of argatroban was reduced to 0.2 µg/kg/min, with frequent monitoring of the activated partial thromboplastin time (aPTT) (goal 60-85 seconds). Despite this dose reduction, the aPTT was supratherapeutic. Following further dose reductions, a final argatroban maintenance dose of 0.05 µg/kg/min was necessary for the attainment of goal aPTTs.DISCUSSION:Reducing the starting dose of argatroban to 0.5 µg/kg/min is recommended in patients with liver disease. Nevertheless, this recommended dose is largely based on data from patients with more moderate liver disease (eg, Child- Pugh class A or B), and dosing in more advanced liver disease remains largely unexplored. Patients with more advanced liver disease may require additional dose reductions to avoid supratherapeutic concentrations of anticoagulation agents and to minimize bleeding risk.CONCLUSIONS:This report illustrates the importance of careful selection of argatroban dosing and appropriate aPTT monitoring in patients with severe liver disease. Excessive anticoagulation may precipitate major bleeding complications, placing patients with this complicated disease at undue risk.
    The Annals of pharmacotherapy. 10/2012;

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