title: Thrombogenicity of total parenteral nutrition solutions: II. Effect on induction of endothelial cell procoagulant activity.
abstract: Thrombosis is a common sequela of total parenteral nutrition. We have recently demonstrated in vitro that hypertonic total parenteral nutrition solutions are potent inducers of a tissue factor monocyte procoagulant activity, the initiating cofactor of the extrinsic clotting cascade. We have further studied, in vitro, the effects of the component solutions of total parenteral nutrition on the induction and modulation of endothelial cell procoagulant activity. Cultured porcine aortic endothelial cells were incubated with (a) 200 microliters of dextrose solution (5%, 10%, 20%, 25%, and 50%), (b) 200 microliters of amino acid solution [full strength (N), one-fourth strength, and one-half strength], and (c) 200 microliters of 10% lipid emulsion. Cocultures of lipid emulsion and 20% dextrose, lipid emulsion and full-strength 10% amino acid solution (N-amino acid), and lipid emulsion and bacterial lipopolysaccharide also were studied. Cells were incubated for intervals of 3-108 h, washed and frozen, harvested, and assayed for endothelial cell procoagulant activity. Units of endothelial cell procoagulant activity were derived from a standard thromboplastin curve. Our results show that amino acid and hypertonic dextrose total parenteral nutrition solutions are able to strongly induce endothelial cell procoagulant activity expression in vitro. In contrast, lipid emulsion significantly inhibited the induction of endothelial cell procoagulant activity by 20% dextrose, N-amino acid, and lipopolysaccharide. These results provide further evidence for the role of the cellular pathways of coagulation in total parenteral nutrition-induced thrombosis. Furthermore, the inhibitory properties of lipid emulsion may be of practical advantage in reducing total parenteral nut induced thrombosis.
authors.affiliation: University of Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Wakefield
authors.forename: Z
authors.initials: Z
authors.lastname: Cohen
authors.forename: A
authors.initials: A
authors.lastname: Rosenthal
authors.forename: M
authors.initials: M
authors.lastname: Craig
authors.forename: K N
authors.initials: KN
authors.lastname: Jeejeebhoy
authors.forename: A
authors.initials: A
authors.lastname: Gotlieb
authors.forename: G A
authors.initials: GA
authors.lastname: Levy
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005526:Food, Formulated / Q000009:adverse effects*; D066298:In Vitro Techniques; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D013552:Swine; D013925:Thromboplastin; D013927:Thrombosis / Q000209:etiology*
chemical_list: D001779:Blood Coagulation Factors; D005217:Fat Emulsions, Intravenous; C053675:endothelial cell procoagulant activity; D013925:Thromboplastin