refludan and Acute-Kidney-Injury

Recombinant hirudin (lepirudin) is a potent direct thrombin inhibitor, which has been approved for the treatment of heparin-induced thrombocytopenia type II (HIT). Because the drug is mainly eliminated by the kidneys, a single loading dose of hirudin may induce therapeutic anticoagulation for up to one week in patients with renal insufficiency. Thus, the use of hirudin in critically ill patients with renal failure could markedly increase their bleeding risk. In this study, hirudin was used in critically ill patients with suspected HIT while on continuous venovenous hemodialysis (CVVHD).. Hirudin anticoagulation was performed in seven critically ill patients with suspected HIT. Four patients were initially anuric. Three patients had residual renal function. In all 64 CVVHD treatments (mean duration 12 hr), a polysulfone high-flux hemodialyzer (0.75 m2) with a dialysate flow rate of 1.5 liter/hr and an ultrafiltration rate of up to 200 ml/hr was used. Hirudin was given either as continuous intravenous infusion or as repetitive intravenous boli. Monitoring of anticoagulation was performed by measurements of the systemic activated partial thromboplastin time (aPTT).. Hirudin dosage had to be individualized according to the risk of bleeding or clotting. During CVVHD, a continuous intravenous infusion (0.006 to 0.025 mg/kg body wt/hr, N = 2) or repetitive intravenous boli (0.007 to 0.04 mg/kg, N = 5) were given. Two patients required blood transfusions prior to and during hirudin treatment. In five patients without a high bleeding risk, the hirudin dose was adjusted to achieve the target aPTT (1.5 to 2.0 x baseline) in order to prevent thrombotic complications or frequent clotting in the extracorporal circuit. Hirudin dose requirements depended on residual renal function and extracorporal clearance.. We conclude from these first clinical data that anticoagulation with hirudin in critically ill patients on continuous hemodialysis can be performed without excessive bleeding risk by combining close clinical and laboratory monitoring. The hirudin dose has to be reduced because of renal failure, and may require adjustment for residual or recovering renal function and extracorporal elimination.

Topics: Acute Kidney Injury; Adult; Aged; Anticoagulants; Critical Care; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Platelet Count; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Treatment Outcome

The decision for an anticoagulant for renal replacement therapy (RRT) in patients with acute renal failure and heparin-induced thrombocytopenia (HIT) has to be made carefully. Based on results from the literature argatroban is favoured in patients without hepatic dysfunction, referring to its short halftime and easy feasable monitoring. In the case of coexsisting hepatic disorder, danaparoid provides a safe alternative therapy. However, long halftime and the difficult elimination of the substance are unfavourable. Lepirudin represents another possible anticoagulant therapy. Bleeding complications and monitoring of the ecarin clotting time imposes limitations. Experiences with bivalirudin, fondaparinux and prostaglandines are limited and future trials will have to determine the significance of their application in RRT in HIT patients. Furthermore it has to be proven whether the combination of alternative anticoagulants with citrate prolongates circuit halftime of CVVH.

Topics: Acute Kidney Injury; Anticoagulants; Arginine; Blood Coagulation Tests; Chondroitin Sulfates; Citrates; Critical Care; Dermatan Sulfate; Diagnostic Errors; Dose-Response Relationship, Drug; Epoprostenol; Fondaparinux; Hemofiltration; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudins; Humans; Iloprost; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sodium Citrate; Sulfonamides; Thrombocytopenia; Thrombosis

A 56-year-old man with heparin-induced thrombocytopenia with thrombosis syndrome (HITTS) received anticoagulation with recombinant hirudin (lepirudin) for emergency coronary artery bypass graft (CABG) surgery and aortic valve replacement. The patient experienced life-threatening refractory bleeding that was successfully treated with recombinant factor VIIa. He had a history of infective endocarditis that resulted in severe aortic insufficiency, three-vessel coronary artery disease, and acute renal failure requiring hemodialysis. The patient was transferred from another hospital for the emergency surgery, but before his transfer, he developed HITTS secondary to therapeutic heparin for a deep vein thrombosis of the lower extremity. The presence of HITTS, the urgent nature of the case, and the availability of the direct thrombin inhibitor led the surgical team to select lepirudin for anticoagulation to facilitate cardiopulmonary bypass. After separation from cardiopulmonary bypass, the patient was in a coagulopathic state due to the inability to reverse the lepirudin and the slowed elimination of the drug secondary to inadequate renal function. As a result, the patient experienced excessive generalized oozing that was unresponsive to traditional therapies and blood product transfusions. Recombinant factor VIIa 35 microg/kg was given as rescue therapy. The bleeding slowed, which allowed placement of chest tubes and closing of the sternum. The patient was transferred to the intensive care unit in stable condition with no evidence of thrombosis in the freshly placed bypass grafts or on the bioprosthetic valve. Recombinant factor VIIa appears to be a suitable option as salvage therapy in patients with refractory bleeding secondary to anticoagulation with a direct thrombin inhibitor during cardiac surgery.

Topics: Acute Kidney Injury; Anticoagulants; Coronary Artery Bypass; Factor VII; Factor VIIa; Heparin; Hirudins; Humans; Male; Middle Aged; Postoperative Hemorrhage; Recombinant Proteins; Thrombin; Thrombocytopenia; Thrombosis

Topics: Acute Kidney Injury; Aged; Anticoagulants; Creatinine; Drug Monitoring; Heparin; Hirudins; Humans; Infusions, Intravenous; International Normalized Ratio; Male; Platelet Count; Recombinant Proteins; Renal Dialysis; Thrombocytopenia