The effect of different anticoagulants on thrombin generation.
Decrease in thrombin generation is the key effect in anticoagulation. The aim of the present study was to investigate the effect of anticoagulants on thrombin generation and the relation to platelet count. Plasma samples from 10 healthy volunteers (mean age 43.0 +/- 9 years) were incubated at preset platelet counts with different doses of the anticoagulants lepirudin, fondaparinux and low molecular weight heparins. Thrombin generation was measured in a tissue factor-mediated assay using a fluorometer and a slow-reacting fluorogenic substrate. The endogenous thrombin potential, the lag phase, the maximum reaction velocity (Vmax) and the concentration of a given anticoagulant required for 50% inhibition of thrombin generation (IC50) are presented. All three anticoagulants decreased endogenous thrombin potential and prolonged the lag phase in a dose-dependent manner. Fondaparinux and low molecular weight heparins, but not hirudin, decreased Vmax in a concentration-dependent manner. With increasing platelet count, the IC50 increased but the extent of this increase was not uniform for the three anticoagulants and the three variables investigated. The influence of anticoagulants on thrombin generation is variable, depending on their basic mechanism of action. In defining and comparing their effects, the endogenous thrombin potential, the lag phase and the maximum reaction velocity should be considered together. Platelets have a considerable influence on the magnitude of thrombin generation.
University of Leipzig, Centre of Internal Medicine, Clinical Haemostaseology and Adult Haemophilia Centre, Leipzig, Germany. pets@medizin.uni-leipzig.de
Sirak
S
Petros
Thomas
T
Siegemund
Annelie
A
Siegemund
Lothar
L
Engelmann
D000328:Adult; D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000737:chemistry* / Q000494:pharmacology; D000077425:Fondaparinux; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry* / Q000494:pharmacology; D006629:Hirudins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology; D013917:Thrombin / Q000032:analysis*; D013918:Thrombin Time / Q000379:methods
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D011134:Polysaccharides; D013917:Thrombin; D000077425:Fondaparinux