People with sickle cell disease (SCD) have chronically high levels of thrombin production, which causes a condition known as systemic hypercoagulability. The endogenous serine protease inhibitor antithrombin-III (ATIII) blocks a number of coagulation cascade enzymes, including thrombin. For a study, researchers sought to investigate the effectiveness of ATIII in preventing the adherence of red blood cells (RBCs) from SCD patients and EC retraction by modeling the shape, and adhesive capabilities of endothelial cells (ECs) stimulated by thrombin.
ECs were seeded into microfluidic devices, then incubated under physiological shear stress. The next step was to activate the cells using either an ATIII pretreatment or thrombin. RBC adherence to ECs was investigated using blood samples from individuals with homozygous SCD (HbSS) and those with normal hemoglobin (HbAA). Additionally assessed were endothelial cell surface adhesion molecules’ expression and confluency in response to thrombin and ATIII treatments.
They discovered that pretreatment with ATIII of ECs decreased the adherence of HbSS RBC to thrombin-activated endothelium. Additionally, ATIII inhibited thrombin-mediated vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor surface expression, as well as cellular contraction.
The research suggested that ATIII may lessen the thromboinflammatory symptoms of SCD by reducing thrombin-mediated EC damage and RBC adherence to endothelium.