title: Thrombin generation time is a novel parameter for monitoring enoxaparin therapy in patients with end-stage renal disease.
abstract: BACKGROUND
  Patients with end-stage renal disease (ESRD) who receive enoxaparin are at increased risk for adverse bleeding episodes. This phenomenon appears to occur despite judicious monitoring of antifactor Xa (aFXa) activity. Better monitoring parameters are needed to quantify the anticoagulant effects of enoxaparin in the ESRD population.
  
  
  OBJECTIVE
  The objective of this study was to determine the utility of using thrombin generation time (TGT), platelet contractile force (PCF) and clot elastic modulus (CEM) to monitor the degree of anticoagulation in ESRD subjects, and to compare these results to aFXa activity, the current gold-standard monitoring parameter.
  
  
  METHODS
  Eight healthy volunteers without renal dysfunction and eight ESRD subjects were enrolled into this study. Subjects received a single dose of enoxaparin 1 mg kg(-1) subcutaneously, and blood samples were obtained for the determination of aFXa activity, TGT, PCF and CEM at baseline, 4, 8, and 12 h postdose.
  
  
  RESULTS
  Baseline, 4, 8, and 12-h aFXa activity concentrations were not different between groups. However, the corresponding TGT at 8 and 12 h was significantly prolonged in the ESRD group (P = 0.04, and P = 0.008, respectively). The 4-h peak TGT trended toward significance (P = 0.06). There were no differences in PCF or CEM across time.
  
  
  CONCLUSIONS
  These data suggest that the parameter aFXa activity is a poor predictor of the anticoagulant effect of enoxaparin in patients with ESRD. Thrombin generation time appears to be more sensitive to the antithrombotic effects of enoxaparin in this population. Further large-scale trials are needed to corroborate these data.
authors.affiliation: Department of Pharmacy Practice, Virginia Commonwealth University/Medical College of Virginia, Richmond, VA 23298, USA. dbrophy@vcu.edu
authors.forename: D F
authors.initials: DF
authors.lastname: Brophy
authors.forename: E J
authors.initials: EJ
authors.lastname: Martin
authors.forename: T W B
authors.initials: TW
authors.lastname: Gehr
authors.forename: A M
authors.initials: AM
authors.lastname: Best
authors.forename: K
authors.initials: K
authors.lastname: Paul
authors.forename: M E
authors.initials: ME
authors.lastname: Carr
mesh_terms: D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D017984:Enoxaparin / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013918:Thrombin Time
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D000990:Antithrombin III