title: Characterization of PF4-Heparin Complexes by Photon Correlation Spectroscopy and Zeta Potential.
abstract: Heparin-induced thrombocytopenia (HIT) is associated with antibodies to complexes between heparin and platelet factor 4 (PF4), a basic protein usually found in platelet alpha granules. Heparin-induced thrombocytopenia antibodies preferentially recognize macromolecular complexes formed between positively charged PF4 and polyanionic heparins over a narrow range of molar ratios. The aim of this work was to study the complexes that human PF4 forms with heparins from various species, such as porcine, bovine, and ovine; heparins from various organs, such as mucosa and lung; and different low-molecular-weight heparins (LMWHs) at several stoichiometric ratios to evaluate their sizes and charges by photo correlation spectroscopy and zeta potential measurements. The resulting data of the PF4 complexes with unfractionated heparins (UFHs), LMWHs and their fractions, and oligosaccharide components suggest that the size of aggregates is not only a simple function of average molecular weight but also of the molecular weight distribution of the sample. Moreover, it was found that lower concentrations of the tested ovine-derived mucosal heparin are required to form the large PF4/heparin complexes as compared to mucosal porcine and bovine heparin.
authors.affiliation: 1 G. Ronzoni Institute for Chemical and Biochemical Research, Milan, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bertini
authors.affiliation: 2 Department of Pathology, Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
authors.affiliation: 1 G. Ronzoni Institute for Chemical and Biochemical Research, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Madaschi
authors.affiliation: 1 G. Ronzoni Institute for Chemical and Biochemical Research, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Risi
authors.affiliation: 1 G. Ronzoni Institute for Chemical and Biochemical Research, Milan, Italy.
authors.forename: Giangiacomo
authors.initials: G
authors.lastname: Torri
authors.affiliation: 1 G. Ronzoni Institute for Chemical and Biochemical Research, Milan, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Naggi
mesh_terms: D000818:Animals; D002417:Cattle; D006493:Heparin / Q000737:chemistry / Q000276:immunology*; D006495:Heparin, Low-Molecular-Weight; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry* / Q000276:immunology; D010978:Platelet Factor 4 / Q000737:chemistry / Q000276:immunology*; D012756:Sheep; D013057:Spectrum Analysis; D013552:Swine
chemical_list: D006495:Heparin, Low-Molecular-Weight; D046911:Macromolecular Substances; D010978:Platelet Factor 4; D006493:Heparin
keywords: heparin; heparin-induced thrombocytopenia; photon correlation spectroscopy; platelet factor 4; zeta potential