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Updated: Apr 4, 2026

In Vitro Microfluidic Disease Model to Study Whole Blood-Endothelial Interactions and Blood Clot Dynamics in Real-Time
Published on: May 24, 2020
Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on
S Nayak1, D Lee2, S Patel-Hett3
1Pharmacometrics, Global Innovative Pharma Business (GIPB), Pfizer Inc. Cambridge, Massachusetts, USA.
Abstract:
A number of therapeutics have been developed or are under development aiming to modulate the coagulation network to treat various diseases. We used a systems model to better understand the effect of modulating various components on blood coagulation. A computational model of the coagulation network was built to match in-house in vitro thrombin generation and activated Partial Thromboplastin Time (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or factor Xa added to normal human plasma or factor VIII-deficient plasma. Sensitivity analysis applied to the model revealed that lag time, peak thrombin concentration, area under the curve (AUC) of the thrombin generation profile, and aPTT show different sensitivity to changes in coagulation factors' concentrations and type of plasma used (normal or factor VIII-deficient). We also used the model to explore how variability in concentrations of the proteins in coagulation network can impact the response to FVIIa treatment.
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