Bivalirudin dosing adjustments for reduced renal function with or without hemodialysis in the management of heparin-induced thrombocytopenia

Ann Pharmacother. 2011 Oct;45(10):1185-92. doi: 10.1345/aph.1Q177. Epub 2011 Aug 31.

Abstract

Background: While not approved by the Food and Drug Administration for treatment of heparin-induced thrombocytopenia (HIT), except in patients undergoing percutaneous interventions, the direct thrombin inhibitor bivalirudin is a treatment option that is gaining use. An initial dose of bivalirudin 0.15-0.2 mg/kg/h, adjusted to an activated partial thromboplastin time (aPTT) of 1.5-2.5 times the baseline value, has been suggested. Initial dosing in patients with renal dysfunction, including those on hemodialysis, is unclear.

Objective: To evaluate initial bivalirudin dosing requirements in patients with and without renal dysfunction, including patients on different forms of dialysis.

Methods: A retrospective analysis of 135 patients treated with bivalirudin for HIT between June 2004 and October 2009 was conducted at a tertiary care medical center. The patients were divided into groups, based on renal function. Patients receiving dialysis were divided into 3 subgroups based on the mode of hemodialysis: intermittent hemodialysis (IHD, n = 24), sustained low-efficiency daily diafiltration (SLEDD, n = 12), or continuous renal replacement therapy (CRRT, n = 5). Patients not receiving dialysis were separated into 3 subgroups based on calculated creatinine clearance (CrCl): CrCl >60 mL/min (n = 52), CrCl 30-60 mL/min (n = 26), and CrCl <30 mL/min (n = 16).

Results: Compared with patients with normal renal function (CrCl >60 mL/min), patients with differing degrees of renal dysfunction (CrCl 30-60 and <30 mL/min) required lower doses of bivalirudin to achieve aPTT goal (0.13 vs 0.08 vs 0.05 mg/kg/h, respectively; p < 0.001). Patients on dialysis (IHD, SLEDD, CRRT) also required dose reductions (0.07, 0.09, and 0.07 mg/kg/h) compared with patients with normal renal function, but higher dosing requirements than patients not receiving dialysis with CrCl <30 mL/min.

Conclusions: Patients with renal dysfunction require a reduced dose of bivalirudin to reach a therapeutic aPTT goal. Slightly higher doses may be observed in patients receiving hemodialysis.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects*
  • Antithrombins / administration & dosage*
  • Antithrombins / adverse effects
  • Antithrombins / therapeutic use
  • Creatinine / blood
  • Creatinine / metabolism
  • Drug Monitoring
  • Female
  • Heparin / adverse effects*
  • Hirudins / administration & dosage*
  • Hirudins / adverse effects
  • Humans
  • Male
  • Medical Records
  • Middle Aged
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / adverse effects
  • Peptide Fragments / therapeutic use
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Renal Dialysis* / methods
  • Renal Insufficiency / complications
  • Renal Insufficiency / physiopathology
  • Renal Insufficiency / therapy*
  • Retrospective Studies
  • Severity of Illness Index
  • Thrombocytopenia / blood
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / complications
  • Thrombocytopenia / drug therapy*
  • Young Adult

Substances

  • Anticoagulants
  • Antithrombins
  • Hirudins
  • Peptide Fragments
  • Recombinant Proteins
  • Heparin
  • Creatinine
  • bivalirudin