title: Contact activation of blood-plasma coagulation.
abstract: This opinion identifies inconsistencies in the generally-accepted surface biophysics involved in contact activation of blood-plasma coagulation, reviews recent experimental work aimed at resolving inconsistencies, and concludes that this standard paradigm requires substantial revision to accommodate new experimental observations. Foremost among these new findings is that surface-catalyzed conversion of the blood zymogen factor XII (FXII, Hageman factor) to the enzyme FXIIa (FXII [surface] --> FXIIa, a.k.a. autoactivation) is not specific for anionic surfaces, as proposed by the standard paradigm. Furthermore, it is found that surface activation is moderated by the protein composition of the fluid phase in which FXII autoactivation occurs by what appears to be a protein-adsorption-competition effect. Both of these findings argue against the standard view that contact activation of plasma coagulation is potentiated by the assembly of activation-complex proteins (FXII, FXI, prekallikrein, and high-molecular weight kininogen) directly onto activating surfaces (procoagulants) through specific protein/surface interactions. These new findings supplement the observation that adsorption behavior of FXII and FXIIa is not remarkably different from a wide variety of other blood proteins surveyed. Similarity in adsorption properties further undermines the idea that FXII and/or FXIIa are distinguished from other blood proteins by unusual adsorption properties resulting in chemically-specific interactions with activating anionic surfaces. IMPACT STATEMENT: This review shows that the consensus biochemical mechanism of contact activation of blood-plasma coagulation that has long served as a rationale for poor hemocompatibility is an inadequate basis for surface engineering of advanced cardiovascular biomaterials.
authors.affiliation: Department of Bioengineering, The Pennsylvania State University, University Park, PA 16802, USA. eav3@psu.edu
authors.forename: Erwin A
authors.initials: EA
authors.lastname: Vogler
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Siedlecki
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D005174:Factor XII / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010949:Plasma / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D005174:Factor XII