title: Safety and dose-finding study of activated protein C (drotrecogin alfa activated) as an anticoagulant in end-stage renal disease patients treated with hemodialysis.
abstract: OBJECTIVE
  End-stage renal disease (ESRD) patients treated with hemodialysis (HD) experience a high risk of death. ESRD patients with elevated levels of pro-inflammatory cytokines are at increased risk of death from cardiovascular events and infection. HD is often facilitated by the use of an anticoagulant. We hypothesized that the use of an anticoagulant that also possessed anti-inflammatory qualities without significant immunosuppressive effects may reduce the risk of death. In this pilot study, we sought to determine the optimal dose of activated protein C (APC) to achieve adequate regional anticoagulation for HD and determine if the drug can be safely used in ESRD patients treated with HD.
  
  
  METHODS
  Twelve stable HD patients were enrolled into this safety and dose-finding study. Varying doses of APC were administered in place of usual heparin at varying doses to determine the range of APC that can be used for extracorporeal circuit anticoagulation. Partial thromboplastin time was assessed at fixed intervals during the HD treatment.
  
  
  RESULTS
  The average age of study patients was 49 ± 12 years. 75% of patients were African-American and 66.7% were male. The optimal dose of APC to induce adequate anticoagulation was 24-30 μg/kg/h. No patients experienced any serious adverse events. One patient had their infusion stopped early due to refractory intradialytic hypertension.
  
  
  CONCLUSIONS
  For ESRD patients undergoing HD, an initial starting dose of 24-30 μg/kg/h achieves a target partial thromboplastin time that should be adequate for circuit anticoagulation. This dose appears safe and was well tolerated.
authors: Department of Anesthesiology and Critical Care Medicine, George Washington University Medical Center, Washington, D.C., USA.
authors: Ermira
authors: E
authors: Brasha-Mitchell
authors: Ashte
authors: A
authors: Collins
authors: Lindita
authors: L
authors: Shehu
authors: Michael G
authors: MG
authors: Seneff
authors: Samir S
authors: SS
authors: Patel
authors: Lakhmir S
authors: LS
authors: Chawla
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011486:Protein C / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D006435:Renal Dialysis
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated