Medicine and Health Sciences Commons^™

Antithrombin-Iii Mitigates Thrombin-Mediated Endothelial Cell Contraction And Sickle Red Blood Cell Adhesion In Microscale Flow, William J. Wulftange, Erdem Kucukal, Yuncheng Man, Ran An, Karamoja Monchamp, Charlotte D. Sevrain, Himanshu R. Dashora, Allison Bode, Jane A. Little, Umut A. Gurkan

Faculty Scholarship

Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction. Microfluidic devices were fabricated, seeded with ECs, and incubated under physiological shear stress. Cells were then activated with thrombin with or without an ATIII …