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

作者：Gulati Abhishek^*; Faed James M; I**ister Geoffrey K; Duffull Stephen B

来源：Pharmaceutical Research, 2012, 29(1): 225-235.

DOI：10.1007/s11095-011-0537-z

• coagulation network
• enoxaparin
• low molecular weight heparins
• mathematical model
• monitoring

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2012-1