title: Bivalirudin dosing adjustments for reduced renal function with or without hemodialysis in the management of heparin-induced thrombocytopenia.
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.
authors: Davis Medical Center, University of California, Sacramento, CA, USA.
authors: Laura V
authors: LV
authors: Tsu
authors: William E
authors: WE
authors: Dager
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D016903:Drug Monitoring; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006629:Hirudins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006435:Renal Dialysis / Q000379:methods; D051437:Renal Insufficiency / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; D003404:Creatinine; C074619:bivalirudin