Center for Industrial Mathematics and Statistics » REU 2019 – Extension of the Human Blood Coagulation Model to Understand the Role of C1-Inhibitor in Hereditary Angioedema

Noah Chicoine

Alyssa Oswald

Overview

Industrial Sponsor: Pfizer Inc

Industrial Liaisons: Dr. Satyaprakash Nayak, Matthew Cardinal

Faculty Advisors: Dr. Simone Cassani, Prof. Suzanne Weekes, WPI

Hereditary Angioedema (HAE) is a rare genetic disease characterized by a deficiency of the C1 esterase inhibitor protein (C1-INH) that causes sporadic swelling episodes, which can last for days if left untreated. Typically, synthetic C1-INH is administered to HAE patients to prevent or stop swelling attacks. Administering too much synthetic C1-INH, however, presents a risk of bleeding to the HAE patient, as C1-INH inhibits procoagulant factors in the blood stream. In order to better understand the how C1-INH interacts with the coagulation system, we extend the ordinary differential equations coagulation model developed by Pfizer Inc. to include the dynamics of the C1-INH protein. The new model is used to predict the effects of synthetic C1-INH therapies on the coagulation system by simulating the clotting time of hypothetical HAE patients. Results suggest that HAE patients may be able to withstand synthetic C1-INH treatments that use 3x the normal concentration of C1-INH in the human body before clotting time is affected. In addition, the effects of C1-INH on Hemophilia C patients (procoagulant factor XI deficiency) suggests that the C1-INH inhibition of FXI has a substantial impact on coagulation time.