Flow-based coagulation and fibrinolysis assays

Abstract

Blood flow regulates coagulation and fibrinolysis by determining the rate of delivery of plasma proteins, the rate of dilution of reaction products, and the rate of accumulation of blood cells and extracellular vesicles. Most clinical assays of coagulation and fibrinolysis do not incorporate these features. Flow assays are an ex vivo method to measure thrombus formation and dissolution under physiologic and pathologic hemodynamics and in anatomically inspired geometries. This chapter reviews the state of the art in flow assays with a particular emphasis on discoveries reported in microfluidic devices. This chapter is organized into five sections that include devices for studying (i) the extrinsic and intrinsic coagulation pathways, (ii) fibrinolysis, (iii) pathologic hemodynamics, (iv) bleeding, and (v) trauma. Each section discusses new discoveries, and where applicable, preclinical results using samples from individuals with coagulopathies. A sixth section discusses the opportunities and challenges in translating flow assays into the clinic.