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

Abstract

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.

Application of Adaptive DP-optimality to Design a Pilot Study for a Clotting Time Test for Enoxaparin

“…Among the functions evaluated (linear, logarithmic, quadratic, exponential, power, E max ), the function described below was found to result in clotting times that aligned closely with a previously published blood coagulation systems pharmacology model (1,6) and to the results obtained in the preliminary in vitro experiments (data not shown).…”

“…The prior values for these fixed effect parameters are provided in Table I. These values were taken as starting points for the calibration so that the response surface provided similar clotting times to the coagulation systems model published previously (1,6) as well as to the preliminary in vitro experiments. However, it should be noted that this empirical function may not be appropriate for use outside of this particular study.…”

“…They are sensitive to deficiencies in the clotting network as well as the influence of anticoagulants and hence provide information on the overall clot forming potential of the patient. The need for a multi-step CT test for low molecular weight heparins (LMWHs) has been discussed previously and a factor Xa based CT (Ten-a clotting time, TenaCT) test has been shown to have the potential to be used for assessing the effect of enoxaparin, a LMWH anticoagulant, on the clotting system (1). The TenaCT test is generic to all LMWHs but enoxaparin was used as the example here.…”

The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen)

“…ref. [92][93][94][95][96] Although most modern models of coagulation incorporate the role of cells, 1,87,102,103 we shall concentrate here on the strippeddown terminal elements of the extrinsic (and common) pathway, where thrombin plays a crucial role in initiating the polymerisation of fibrinogen. These terminal processes, that are our focus here, are shown in Fig.…”

Scale Reduction of a Systems Coagulation Model With an Application to Modeling Pharmacokinetic–Pharmacodynamic Data

“…ODEs for the model are also provided in the (original_model.m). The values of the parameters in the model can be obtained from our previous publications 5 , 6 , 13 . This model consists of multiple inputs, outputs, and modifiers of these input–output relationships.…”