title: Development and evaluation of a prototype of a novel clotting time test to monitor enoxaparin.
abstract: OBJECTIVE
  Dosing of the anticoagulant enoxaparin may result in bleeding following excessive doses or thrombosis if dose is too low. Rarely, anti-Xa activity is used to assess the dose for enoxaparin, but its utility to predict clotting or bleeding remains uncertain. We aimed to develop a clotting time test to monitor enoxaparin therapy.
  
  
  METHODS
  A previously developed mathematical model of the coagulation network was used to identify suitable targets for monitoring enoxaparin therapy. In vitro experiments were then carried out to demonstrate proof of mechanism of the clotting time test activated by the new target activator.
  
  
  RESULTS
  Using the mathematical model, we identified Xa as a plausible activating agent for a clotting time test for enoxaparin. In vitro experiments showed a prolongation of the Xa clotting time of 4.6-fold in the presence of enoxaparin (0.5 IU/ml) where 10 nM Xa was used to activate clotting.
  
  
  CONCLUSIONS
  Using both simulations and in vitro experiments, we provide a proof of mechanism for the Xa clotting time (XaCT) test, which can be considered for further development to provide a biomarker of the effect of enoxaparin on the clotting system.
authors.affiliation: School of Pharmacy, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand. abhishek.gulati@otago.ac.nz
authors.forename: Abhishek
authors.initials: A
authors.lastname: Gulati
authors.forename: James M
authors.initials: JM
authors.lastname: Faed
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors; D006801:Humans; D008954:Models, Biological; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D017984:Enoxaparin; D065427:Factor Xa Inhibitors