Center for Industrial Mathematics and Statistics » REU 2019 – Extending the Systems Model of Platelet Homeostasis to Understand Platelet Dynamics in Immune Thrombocytopenia Purpura

Website Jessica Cerbone

Alexa Shreeve

Overview

Industrial Sponsor: Pfizer Inc

Industrial Liaisons: Sarita Koride and Matthew Cardinal

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

Immune Thrombocytopenia Purpura (ITP) is an autoimmune disease that results in lower than normal platelet counts in a patient’s circulatory system. The disease symptoms are a result of accelerated platelet destruction by autoantibodies against platelets. In a healthy individual a feedback mechanism of the platelet production system controls an inverse relationship between platelet levels and Thrombopoietin (TPO),a glycoprotein and main stimulator of platelet production. This feedback mechanism, however, is inhibited in a patient with ITP. As a result, ITP is characteristic of lower than normal platelet counts, with relatively unchanged levels in TPO concentrations.To explore the mechanisms related to ITP, we extend a Pfizer, Inc ordinary differential equations model of platelet homeostasis in healthy individuals to include macrophage dynamics that result in accelerated platelet destruction. The new model is used to investigate changes in both total platelet levels and TPO concentrations affected by macrophage dynamics at varying degrees of ITP.

We find that as we accelerate platelet destruction, TPO levels rise—a response seen in healthy individuals, but undesirable for modeling ITP. Therefore, to compensate for the rise in TPO levels we must change the parameters involved with TPO consumption to model the inhibited feedback loop that exists in ITP patients.