Effect of the anti-factor Xa and anti-factor IIa activities of low-molecular-weight heparins upon the phases of thrombin generation.
BACKGROUND
Low-molecular-weight heparins (LMWHs), derived from unfractionated heparin (UFH) by different depolymerization procedures, vary in both their relative abilities to enhance the inhibition of FXa (anti-FXa) and thrombin (anti-FIIa), and in their physicochemical properties.


OBJECTIVE
We aimed to profile the inhibition of thrombin generation induced by bemiparin, enoxaparin, nadroparin, dalteparin and tinzaparin in platelet-rich plasma (PRP), and to compare them with UFH and fondaparinux (a synthetic pentasaccharide that specifically enhances FXa inhibition).


METHODS
Different LMWHs, UFH or fondaparinux were added to normal PRP. Thereafter, tissue factor-triggered thrombin generation was assessed using the Thrombogram-Thrombinoscope assay.


RESULTS
At equivalent anti-FIIa activity concentrations, LMWHs and UFH exhibited similar inhibitory effects upon thrombin generation. However, when used at equivalent anti-FXa activity concentrations, tinzaparin was significantly more active than the other LMWHs at inhibiting thrombin generation, and had similar activity to that of UFH. Enoxaparin, nadroparin and dalteparin all showed similar inhibitory activities. In these experiments, bemiparin exhibited the lowest inhibitory effect on thrombin generation of all the LMWHs. At 0.1 microg mL(-1) (0.093 anti-FXa IU mL(-1)), fondaparinux inhibited the rate of thrombin generation by 50%. A 7-fold higher concentration of fondaparinux was required to inhibit the endogenous thrombin potential by 50%.


CONCLUSIONS
LMWHs have a variable inhibitory effect on thrombin generation in vitro when compared by anti-FXa activity, but are similar when compared by their anti-FIIa activities. The rate of thrombin generation during the propagation phase, rather than the endogenous thrombin potential, is more sensitive to the anticoagulant activity of fondaparinux and the polysaccharide chains of LMWHs possessing only anti-FXa activity.
Gerotziafas
G T
GT
Service d'Hématologie Biologique, Hôpital Tenon, Assistance Publique Hôpitaux de Paris, Paris, France. gerotziafasgrigoris@hotmail.com
Petropoulou
A D
AD
Verdy
E
E
Samama
M M
MM
Elalamy
I
I
D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D011516:Prothrombin / Q000037:antagonists & inhibitors*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013917:Thrombin / Q000096:biosynthesis*
D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D015842:Serine Proteinase Inhibitors; D011516:Prothrombin; C025337:Factor IIa; D013917:Thrombin