refludan and Kidney-Failure--Chronic

Native hirudin is the most potent natural direct thrombin inhibitor currently known; it is capable of inhibiting not only fluid phase, but also clot-bound thrombin. Recombinant technology now allows production of recombinant hirudins (r-hirudins), which are available in sufficient purity and quantity with essentially unaltered thrombin-inhibitory potency. As thrombin is known to play a key role in a number of thrombotic disorders, numerous studies focused on the impact of r-hirudins on the clinical course in these diseases. R-hirudins provided significantly more stable anticoagulation than standard heparin, but demonstrated a relatively narrow therapeutic range with relevant bleeding risk even at clinically effective doses. In doses that are not associated with an increased bleeding risk, r-hirudins often failed to demonstrate significant superiority to heparin. To date, r-hirudins have a definite role in the treatment of heparin-induced thrombocytopenia, where they markedly reduce the high risk of thrombosis. For prophylaxis of deep vein thrombosis, r-hirudins have been shown to be superior to both unfractionated and low molecular weight heparin, but are not extensively used in this indication. In acute coronary syndromes, a definite role of r-hirudins has not yet been firmly established. When applied in an appropriate dose as adjunct to thrombolysis in patients with acute myocardial infarction, randomized, controlled trials did not show a consistent benefit of r-hirudins, especially in the long-term. In patients undergoing coronary balloon angioplasty for acute coronary syndromes, promising effects in the early postprocedural phase did not translate to an improved outcome after 6 months. In patients with unstable angina pectoris, efficacy and safety of r-hirudins as primary antithrombotic therapy are still under debate. In the future, r-hirudins are to be compared with alternative or additional potent antithrombotic agents or treatment strategies. This comparison will ultimately lead to their final placement in the management of thrombotic disorders.

Topics: Clinical Trials as Topic; Coronary Disease; Fibrinolytic Agents; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Partial Thromboplastin Time; Recombinant Proteins; Thrombin; Thrombocytopenia; Tissue Distribution; Venous Thrombosis

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.

Topics: Aged; Aged, 80 and over; Anticoagulants; Drug Evaluation; Female; Half-Life; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Systemic Inflammatory Response Syndrome

Topics: Aged; Anticoagulants; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Time Factors

A patient with triple heart valve disease, heparin-induced thrombocytopenia, and terminal renal insufficiency was treated successfully using lepirudin for anticoagulation of cardiopulmonary bypass (CPB) and during the postoperative course. Anticoagulatory monitoring was performed with ecarin clotting time during CPB and aPTT postoperatively.

Topics: Aged; Anticoagulants; Cardiopulmonary Bypass; Female; Follow-Up Studies; Heart Failure; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Myocardial Ischemia; Recombinant Proteins; Thrombocytopenia

We identified the incidence of heparin-induced thrombocytopenia and the antiheparin-platelet factor 4 (PF4) antibody in pediatric patients undergoing cardiac surgery and documented the differences in the anticoagulation management for the extracorporeal circulation.. Between January 2001 and September 2003, 559 cardiac procedures with extracorporeal circulation in 415 patients with congenital heart defects were performed in our institution. Because the development of heparin-induced thrombocytopenia requires previous exposition to heparin, only the 144 patients undergoing a scheduled second procedure on extracorporeal circulation were screened preoperatively. Of these 144 patients, 41 underwent also a third procedure and were screened before each procedure for presence of antiheparin-PF4 antibodies and for clinical signs of heparin-induced thrombocytopenia.. The incidence of antiheparin-PF4 antibodies during the study period was 1.4% (2 of 144 patients). Patients with clinically significant heparin-induced thrombocytopenia could not be identified. Outside the study protocol, 2 more patients with antiheparin-PF4 antibodies were found. In these 4 patients, surgery was performed using lepirudin (Schering, Berlin, Germany) instead of the usual heparin management for extracorporeal circulation. Three of these 4 patients had an uneventful procedure and postoperative course. In 1 patient after total cavopulmonary connection, a reoperation was necessary on the seventh postoperative day owing to partial thrombosis of the lateral tunnel.. The incidence of heparin-induced thrombocytopenia and of antiheparin-PF4 antibodies in patients undergoing repeated cardiac surgery is low. In antiheparin-PF4 antibody positive patients, the complete avoidance of heparin can be achieved and may account for an uneventful perioperative course.

Topics: Anticoagulants; Cardiac Surgical Procedures; Contraindications; Extracorporeal Circulation; Heart Defects, Congenital; Heparin; Hirudins; Humans; Incidence; Infant; Kidney Failure, Chronic; Platelet Factor 4; Postoperative Complications; Preoperative Care; Recombinant Proteins; Reoperation; Retrospective Studies; Thrombocytopenia

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.

Topics: Adult; Anticoagulants; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Thrombocytopenia; Thrombosis; Warfarin

Topics: Anticoagulants; Drug Overdose; Heart Failure; Hemodiafiltration; Hemorrhage; Hirudins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Partial Thromboplastin Time; Recombinant Proteins; Renal Dialysis