Effects of fibrinogen residence time and shear rate on the morphology and procoagulant activity of human platelets adherent to polymeric biomaterials

fibrinogen readily adsorbs to the surface of biomaterials and, because of i ts demonstrated ability to support platelet adhesion and aggregation, plays a role in thrombotic events associated with the implantation of synthetic materials in the human body. Thus, understanding the factors influencing th e interactions of fibrinogen with biomaterials, and how platelet responses are affected, is crucial for the development of synthetic materials exhibit ing improved blood compatibility. In this study, the effects of fibrinogen residence time and shear rate on the procoagulant activity of adherent plat elets, along with their morphologic status, as deduced from scanning electr on microscopy, were investigated. To examine whether adherent platelets pro moted the generation of thrombin, polymeric materials (polytetrafluoroethyl ene, polyethylene, and silicone rubber) preadsorbed with fibrinogen were ex posed to platelet suspensions at different wall shear rates and then incuba ted with clotting factors for 5 minutes under static conditions. The amount of thrombin generated per platelet was calculated from the optical density of the color developed by adding substrate S-2238. Scanning electron micro scopy images of the platelets revealed that the platelets exhibited differe nt morphologies, depending on the shear rate and residence time of the adso rbed fibrinogen, Platelets ranged from their normal discoid shape observed primarily under static conditions, to that of fully spread platelets. Resul ts from this study show that platelets, in the presence of shear forces, un dergo activation on exposure to surfaces on which adsorbed fibrinogen has r esided for short residence times rather than long residence times. Interest ingly, studies examining the procoagulant responses of such adherent platel ets demonstrated that the platelets attached to the fibrinogen coated mater ials did not promote significant thrombin generation. Such low prothrombina se activity of adherent platelets suggests that adsorbed fibrinogen, while capable of supporting platelet adhesion and spreading on biomaterials, does not necessarily enhance the procoagulant activity of adherent platelets.