Release and cellular origin of extracellular vesicles during circulation of whole blood over adsorbent polymers for lipid apheresis

Whole blood lipid apheresis is clinically applied in patients with familial hypercholesterolemia to reduce low density lipoprotein and other apolipoprotein B 100 containing lipoproteins. Here, the hemocompatibility of two polyacrylate-coated polyacrylamide-based polymers for lipid apheresis by evaluating the adhesion of blood cells to the adsorbent polymers, their respective activation, as well as the release of microvesicles during circulation of whole blood over the polymers was studied. Characterization of the adsorbents by scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy revealed differences with respect to their surface morphology and their surface chemical composition. Despite these differences, equivalent amounts of leukocytes and platelets adhered to both polymers during circulation of whole blood over the adsorbent columns. The release of phosphatidylserine-exposing microvesicles, in contrast, increased significantly with increasing surface roughness and with the amount of polyacrylate groups at the adsorbent surface. The majority of microvesicles generated during blood-material contact were platelet-derived, and their release was associated with enhanced thrombin generation. Microvesicles were present in free and in cell-bound form, and 75% of all monocytes, but only 0.2% and 2.3% of red blood cells and platelets, respectively, were associated with microvesicles, pointing to a role of monocytes in the clearance of released microvesicles. Taken together, microvesicles are sensitive indicators for biomaterial-induced activation of blood cells in apheresis. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 636-646, 2017.