Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lepirudin is a direct thrombin inhibitor indicated for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. In patients with normal renal function, a bolus dose of 0.4 mg/kg is injected over 15-20 seconds, followed by a continuous infusion of 0.15 mg/kg/hour adjusted to prolong the activated partial thromboplastin time (aPTT) to 1.5-2.5 times the patient's baseline. Because renal function directly influences lepirudin elimination, patients with renal impairment require significant adjustments in the initial infusion rate. Current recommendations suggest that patients with dialysis-dependent renal failure should receive an initial bolus of 0.2 mg/kg, followed by 0.1 mg/kg every other day if the aPTT falls below the lower limit of the therapeutic range; however, this dosing may result in significant and prolonged overanticoagulation. A review of available literature regarding pharmacokinetics of lepirudin in renal failure suggests considerable variability in patient response over a narrow creatinine clearance range. Because there is no antidote for lepirudin if significant bleeding occurs, lower and less frequent dosing, guided by aPTT results, is recommended.
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PMID:Lepirudin dosing in dialysis-dependent renal failure. 1099 7

Treatment of critically ill patients who have heparin-induced thrombocytopenia and thrombosis (HITT) and also renal failure is a challenge. Recombinant hirudin (Refludan, Hoechst Marion Roussel) is a direct thrombin inhibitor indicated for anticoagulation in HITT and approved by the United States Food and Drug Administration. Because this drug is renally cleared, a single dose of hirudin may induce prolonged (up to one week) unpredictable anticoagulation in patients with renal insufficiency. There are a few case reports of patients with renal failure and suspected heparin-induced thrombocytopenia (HIT) in which patients were anticoagulated with Refludan for catheter thrombosis. There is no literature on the therapeutic use of Refludan to treat HITT in patients with diffuse thrombosis and renal failure. The authors report the case of a 44-year-old female dialysis patient with HITT and extensive life-threatening thrombosis. The patient developed common iliac vein occlusion extending to the right atrium with progressive right internal jugular vein thrombus developing while on heparin. Her platelet count dropped to 60,000/microL. She was lethargic and hemodynamically unstable. Refludan was initially given as a bolus of 0.2 mg/kg (total, 12 mg) at a 50% dose reduction based on the patient's ideal body weight. This dose was based on the published pharmacokinetics of Refludan in patients with renal failure. Only 2 additional boluses of 6 mg and 3 mg were needed to extend the duration of therapeutic anticoagulation (measured by PTT) to 140 hours. The patient improved both clinically and radiographically after the treatment with Refludan. There were no additional thromboembolic events or bleeding complications. The platelets returned to normal within a few days. The patient was transitioned to coumadin and discharged from the hospital. She remains stable at 1-year follow-up.
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PMID:Use of recombinant hirudin in heparin-induced thrombocytopenia and thrombosis (HITT) and renal failure--a case report. 1166 36

Lepirudin (recombinant hirudin), a direct thrombin inhibitor, is an effective alternative method of anticoagulation in patients with heparin-induced thrombocytopenia. However, because it is eliminated by the kidneys, the half-life of lepirudin may be substantially prolonged in patients with renal failure. Patients undergoing hemodialysis must be closely monitored, and therapy must be individualized based on each patient's ability to clear the drug. Current literature on the removal of lepirudin by dialysis or plasmapheresis is limited, but available data suggest that lepirudin can be removed with these methods. The ability of filtration systems to remove lepirudin from the blood is highly dependent on the membrane material used in the system. Understanding the effects of hemodialysis, hemofiltration, and plasmapheresis on lepirudin levels is important, especially since no antidote is available to treat elevated serum lepirudin concentrations.
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PMID:Removal of lepirudin, a recombinant hirudin, by hemodialysis, hemofiltration, or plasmapheresis. 1193 84

Heparin-induced thrombocytopenia (HIT), a serious side effect of heparin treatment, requires alternative anticoagulation in most affected patients. The recombinant hirudin (r-hirudin) lepirudin has been approved for this purpose after two prospective trials in laboratory-confirmed HIT patients. Other drugs available for this purpose are danaparoid sodium (a heparinoid) and argatroban, a synthetic direct thrombin inhibitor. In this article, recommendations for optimal use of r-hirudin in HIT are given, covering therapy in uncomplicated patients as well as in special situations such as heparin reexposure of HIT patients. Because lepirudin's half-life depends on renal function, it may vary between 1 and 200 hours, which requires individual dose adjustments. Lepirudin compares favorably with danaparoid, based on retrospective data. No direct comparisons of lepirudin with argatroban are available, but argatroban might offer advantages in patients with renal failure, because it is mainly eliminated hepatically. Major hemorrhage, the main risk of lepirudin treatment, occurring in about 15% of patients, makes close monitoring important. New monitoring tools, such as the ecarin clotting time (ECT), might further reduce bleeding risks. Antihirudin antibodies, which can alter the pharmacokinetics as well as the pharmacodynamics of hirudin, can also be countered by close monitoring and appropriate dose adjustments. Whereas hirudins have not yet managed to gain importance in non-HIT indications such as unstable coronary syndromes, they have a major role to play in the treatment of HIT. The choice between the available drugs for HIT, namely lepirudin, danaparoid, and argatroban, has to be made according to the clinical presentation of the patient.
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PMID:Hirudin in heparin-induced thrombocytopenia. 1242 Feb 38

Refludan (lepirudin-rDNA for injection) is the first direct thrombin inhibitor approved by the United States FDA for anticoagulation to patients with heparin-induced thrombocytopenia (HIT). It was monitored by ecarin clotting time (ECT) assay in patients with HIT. Case histories and clotting parameters for three patients undergoing off-pump coronary artery revascularization procedure are discussed. The first patient received r-hirudin at a dose of 0.2 mg/kg intravenous (IV) bolus followed by 0.15 mg/kg/hour infusion. The second patient received 0.4 mg/kg IV bolus followed by infusion of 0.15 mg/kg/hour infusion. The third patient with renal failure received 0.2 mg/kg IV bolus followed by an infusion of 0.02 mg/kg/hour. Blood samples were drawn at baseline, 5 minutes post bolus and every 15 minutes during the coronary artery revascularization procedure. ECT was performed immediately on the citrated whole blood samples using the ECT cards in conjunction with the point-of-care, the thrombolytic assessment system (TAS) Analyzer (Pharmanetics, Raleigh, NC). The plasma samples were then analyzed for APTT and liquid ECT assay performed on a kinetic centrifugal analyzer (ACL 300 Plus). The ECT by cards was ideally maintained above 600 seconds during the surgical procedure. Additional boluses of Refludan were given as and when necessary (ECT < 600 sec) in order to maintain adequate anticoagulation. The calculated circulating concentrations of Refludan, following a bolus administration, based on the ECT cards, liquid ECT and APTT were 3.20 +/- 1.3, 3.51 +/- 1.35 and 2.02 +/- 1.19 microg/mL, respectively.
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PMID:Successful use of recombinant hirudin and its monitoring by ecarin clotting time in patients with heparin-induced thrombocytopenia undergoing off-pump coronary artery revascularization. 1567 9

Lepirudin is a potent, direct thrombin inhibitor used for anticoagulation in patients with heparin-induced thrombocytopenia type II (HIT). The half-life of lepirudin is prolonged in patients with renal insufficiency. Preliminary studies suggest that it is safe to use lepirudin in patients being treated with intermittent hemodialysis but information regarding its use with continuous renal replacement therapy (CRRT) is scarce. CRRT is used in acute care settings to remove fluid and uremic toxins in patients with renal failure with hemodynamic instability. Patients with HIT, renal failure, and hemodynamic instability pose a complex situation for clinical management. These patients require anticoagulation with nonheparin agents with simultaneous CRRT. There are no guidelines in the literature regarding the management of this patient group. We report our experience with lepirudin at managing four such patients with HIT, being treated with CRRT.
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PMID:Lepirudin for anticoagulation in patients with heparin-induced thrombocytopenia treated with continuous renal replacement therapy. 1710 86