title: Comparative inhibition of LPS-activated human monocyte-induced thrombin generation by unfractionated heparin and low molecular weight heparins.
abstract: Monocyte tissue factor may play a role in the physiological or pathological triggering of blood coagulation. It is well known that unfractionated heparin and low molecular weight heparins inhibit extrinsic thrombin generation. However, this notion has never been confirmed in a physiological model using tissue factor obtained from stimulated human monocytes. This is the purpose of this study. It was important to obtain a pure preparation of monocytes with no platelet contamination. This was possible by leukapheresis and elutriation. Under sterile and endotoxin-free conditions, the process does not activate tissue factor expression by monocytes. We adapted the technique of thrombin generation on an automatic analyzer and used human monocyte tissue factor to trigger thrombin generation. Our results show that unfractionated and low molecular weight heparins potently inhibit monocytic tissue factor induced thrombin generation. The comparison of low molecular weight heparins suggests that molecules with higher anti-IIa/anti-Xa ratios exert a stronger inhibitory effect. These data may be relevant to explain the therapeutic effects of unfractionated and low molecular weight heparins in cardiovascular disorders such as unstable angina.
authors.affiliation: UPRES EA2070, Laboratoire d'Immunologie et d'Hématologie, IFR 53 (Biomolécules), Université Champagne-Ardenne et Laboratoire Central d'Hématologie, CHU Robert-Debré, Reims, France. pnguyen@chu-reims.fr
authors.forename: P
authors.initials: P
authors.lastname: Nguyên
authors.forename: M G
authors.initials: MG
authors.lastname: Rémy
authors.forename: G
authors.initials: G
authors.lastname: Potron
mesh_terms: D018929:Cell Culture Techniques; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism*; D009000:Monocytes / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000187:drug effects; D013925:Thromboplastin / Q000494:pharmacology
chemical_list: D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D008070:Lipopolysaccharides; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D013925:Thromboplastin; D013917:Thrombin