Systems biology of bleeding disorders

FVIIa
Predicting bleeding in genetic bleeding disorders using computational and microfluidic models. Here, we show hemophilia response to bypass therapy for an individual with hemophilia A. Fibrin (green) and platelet (blue) accumulation in a microfluidic hemostasis model before and after treatment with a bypass agent. Dynamic fibrin deposition in the experiment is in good agreement with thrombin generation predicted by a spatial-temporal computational model of clot formation.

In recent years, significant advances in understanding the molecular basis of bleeding disorders have been made, but a large portion of the variability in bleeding severity remains unexplained. In this project, the focus is on hemophilia and von Willebrand disease (VWD), where the observed variability in bleeding patterns cannot be assigned to a single measurable parameter. The objective of this project is to identify biochemical and biophysical modifiers of bleeding in hemophilia and VWD using a systems biology approach consisting of computational models, microfluidic devices, and clinical genotyping and phenotyping. Our team includes Aaron Fogelson at the University of Utah, Karin Leiderman at University of California, Merced, and Jorge Di Paola at University of Colorado, Denver.

Related Publications

A.A. Onasoga-Jarvis, K. Leiderman, A.L. Fogelson, M. Wang, M.J. Manco-Johnson, J.A. Di Paola, K.B. Neeves. The effect of factor VIII deficiencies and replacement and bypass therapies on thrombus formation under venous flow conditions in microfluidic and computational models. PLoS One, 8 (2013): e78732. PMID: 24236042