Comparative antithrombotic potencies of direct thrombin inhibitors and low-molecular-weight heparins in an ex vivo human experimental thrombosis model.
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.
Harenberg
Job
J
4th Department of Clinical Medicine, University Hospital Mannheim, University of Heidelberg, Germany. J-Harenberg@t-online.de
Zokai
Kawei
K
Piazolo
Lukas
L
Fenyvesi
Tavidar
T
Jörg
Ingrid
I
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*
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