Hemofiltration of Recombinant Hirudin by Different Hemodialyzer Membranes

Abstract

Recombinant hirudin (lepirudin) is a potent direct thrombin inhibitor that is used particularly for treatment of immunemediated heparin-induced thrombocytopenia. Because hirudin is almost exclusively eliminated by the kidneys, its half-life is markedly prolonged in patients with severe renal insufficiency. Therefore, these patients are at risk for bleeding, particularly because no antidote is available. To use hirudin safely in patients who are on renal replacement therapy, knowledge of hirudin-sieving characteristics of different hemodialyzers is required. Data on this issue are sparse and in part contradictory. Eight different conventional low-flux and high-flux hemodialyzers were tested in an in vitro circuit with ultrafiltrate reinfusion. In each experiment, lepirudin concentration was repetitively measured during 3 h in the prefilter, the postfilter, and the filtration line using a chromogenic assay. On the basis of these data, sieving coefficients were calculated. All high-flux hemodialyzers tested allowed filtration of hirudin yet with marked differences in steady-state sieving (sieving coefficients in whole blood: polysulfone

Clinical review: Use of renal replacement therapies in special groups of ICU patients

“…High-flux membranes allow filtration of lepirudin, with the highest sieving coefficient for polysulfone (0.97) and lesser sieving coefficients for polymethylmethacrylate and polyarylethersulfone (0.75 and 0.73, respectively). Low-flux membranes do not filter lepirudin [30]. Dependent on the dialysis frequency, the dialysis membrane, and the activated partial thromboplastin time, measured before the start of the dialysis session, a reduced dose should be used from the second dialysis.…”

Antithrombotic Therapy in Atrial Fibrillation - Evaluation and Positioning of New Oral Anticoagulant Agents -

“…Other supportive strategies to control severe bleeding include mechanical compression and transfusion of blood products (packed red cells or fresh frozen plasma, depending on associated anemia or coagulopathy), hemodialysis 19,53 and high-volume hemofiltration. 54 Within 2 h of oral administration, gastric lavage and adsorption to activated charcoal can be considered.…”

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement

“…Isolated products (fresh frozen plasma and cryoprecipitate) or factors (activated factor VII) have been shown to be of inconsistent benefit in DTI-associated bleeding (66)(67)(68)(69). The definitive reversal therapy is renal replacement therapy (70)(71)(72). Adult protocols for reversal and management of DTI-associated hemorrhage are reported elsewhere (73).…”