Pharmaceutical Research

, Volume 29, Issue 1, pp 225–235 | Cite as

Development and Evaluation of a Prototype of a Novel Clotting Time Test to Monitor Enoxaparin

  • Abhishek Gulati
  • James M. Faed
  • Geoffrey K. Isbister
  • Stephen B. Duffull
Research Paper

ABSTRACT

Purpose

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.

KEY WORDS

coagulation network enoxaparin low molecular weight heparins mathematical model monitoring 

ABBREVIATIONS

ACT

activated clotting time

aPTT

activated partial thromboplastin time

AT

antithrombin

INR

international normalised ratio

LMWH

low-molecular-weight heparin

PT

prothrombin time

TF

tissue factor

UFH

unfractionated heparin

XaCT

Xa clotting time

Notes

ACKNOWLEDGMENTS & DISCLOSURES

The authors acknowledge the support of University of Otago Postgraduate Scholarship.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Abhishek Gulati
    • 1
  • James M. Faed
    • 2
  • Geoffrey K. Isbister
    • 3
    • 4
  • Stephen B. Duffull
    • 1
  1. 1.School of PharmacyUniversity of OtagoDunedinNew Zealand
  2. 2.Department of Pathology, School of MedicineUniversity of OtagoDunedinNew Zealand
  3. 3.Department of Clinical Toxicology and PharmacologyCalvary Mater NewcastleWaratahAustralia
  4. 4.School of Medicine and Public HealthUniversity of NewcastleNewcastleAustralia

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