Role of Fibrinogen in Activation of Platelets by Artificial Surfaces

Activation of platelets by contact with artificial surfaces is a key event in the thromboembolic complications of prosthetic devices in contact with the blood,’*2 but the mechanism of these events is not fully understood. It is known that a film of plasma protein adsorbs on artificial materials exposed to blood and that this event precedes interaction of the surface with blood cell^.^*^ A corollary of this thesis is that the blood cells do not react directly with the underlying surface but rather with the adsorbed protein coat. The composition of the protein film and the configuration of its molecular constituents must relay to the blood elements information describing the nature of the underlying surface. Fibrinogen appears to be an important component of the adsorbed protein film and may be an essential player in the early events of platelet a c t i v a t i ~ n , ~ ~ ~ adsorbing preferentially on many surfaces in a concentration relatively higher than in the bulk plasma and participating in the platelet response to the prosthetic Fibrinogen is now recognized as an indispensible element in platelet aggregat i ~ n . ’ ~ . ’ ~ An early feature of activation of platelets by soluble agonists such as ADP or thrombin is exposure of specific membrane glycoproteins (GP IIb-IIIa), to which fibrinogen molecules bind with high According to current dogma, the divalent fibrinogen molecule is necessary for the formation of connecting bridges between contiguous platelets, perhaps in conjunction with other “adhesive prot e i n ~ , ” ’ ~ ’ ~ such as von Willebrand’s factor, thrombospondin, or fibronectin. It should be noted that fibrinogen dissolved in plasma does not induce platelet aggregation but rather acts as a cofactor in the process. Fibrinogen normally circulates in peaceful coexistence with platelets without any obvious interaction. It is claimed that platelets have membrane receptors of low affinity for fibrinogen,’”’’ which would permit reversible interactions at physiologic fibrinogen concentrations, but the prevailing view is that it is only in the “activated” platelet (i.e., the platelet stimulated by agonists such as thrombin or ADP) that fibrinogen forms a detectable complex with its glycoprotein membrane receptors, which are “masked” or otherwise unavailable in intact nonactivated circulating I f adsorbed fibrinogen were involved in some way in platelet adhesion to surfaces, perhaps by bridging the gap between platelet and surface in a manner analogous to its action in platelet aggregation, an important question would be whether prior activation of the platelet would be required or whether interaction with adsorbed fibrinogen molecules might occur without preliminary alteration of the basal platelet. It has been suggested that fibrinogen molecules adsorbed on artificial surfaces undergo conformational changes that lead platelets to regard them as “foreign” and that might even