title: Comparative antithrombotic potencies of direct thrombin inhibitors and low-molecular-weight heparins in an ex vivo human experimental thrombosis model.
abstract: Direct thrombin inhibitors (DTIs) such as hirudins and melagatran are currently developed for antithrombotic therapy. They should possess some advantages over the currently used low-molecular-weight heparins (LMWHs). They may also act through an inhibition of thrombin-induced platelet activation. The antithrombotic effects of DTIs and of LMWHs were investigated in an ex vivo thrombosis model with human blood in order to analyze the inhibition of thrombin-antithrombin as well as the platelet factor 4 formation. The data show that DTIs inhibit both fibrin formation and platelet activation, which is of clinical relevance especially for melagatran.
authors.affiliation: 4th Department of Clinical Medicine, University Hospital Mannheim, University of Heidelberg, Germany. J-Harenberg@t-online.de
authors.forename: Job
authors.initials: J
authors.lastname: Harenberg
authors.forename: Kawei
authors.initials: K
authors.lastname: Zokai
authors.forename: Lukas
authors.initials: L
authors.lastname: Piazolo
authors.forename: Tavidar
authors.initials: T
authors.lastname: Fenyvesi
authors.forename: Ingrid
authors.initials: I
authors.lastname: Jörg
mesh_terms: D000990:Antithrombin III / Q000037:antagonists & inhibitors; D001384:Azetidines; D001596:Benzylamines; D005337:Fibrin / Q000037:antagonists & inhibitors; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008955:Models, Cardiovascular; D010447:Peptide Hydrolases; D015539:Platelet Activation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000096:biosynthesis; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000188:drug therapy*
chemical_list: D001384:Azetidines; D001596:Benzylamines; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; C046193:antithrombin III-protease complex; C104614:polyethyleneglycol-hirudin; C109573:melagatran; D010978:Platelet Factor 4; D000990:Antithrombin III; D005337:Fibrin; D010447:Peptide Hydrolases; D013917:Thrombin; D005998:Glycine