PMID- 17461929
OWN - NLM
STAT- MEDLINE
DCOM- 20070620
LR  - 20230829
IS  - 1538-7933 (Print)
IS  - 1538-7836 (Linking)
VI  - 5
IP  - 5
DP  - 2007 May
TI  - Effect of the anti-factor Xa and anti-factor IIa activities of 
      low-molecular-weight heparins upon the phases of thrombin generation.
PG  - 955-62
AB  - 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.
FAU - Gerotziafas, G T
AU  - Gerotziafas GT
AD  - Service d'Hematologie Biologique, Hopital Tenon, Assistance Publique Hopitaux de 
      Paris, Paris, France. gerotziafasgrigoris@hotmail.com
FAU - Petropoulou, A D
AU  - Petropoulou AD
FAU - Verdy, E
AU  - Verdy E
FAU - Samama, M M
AU  - Samama MM
FAU - Elalamy, I
AU  - Elalamy I
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Serine Proteinase Inhibitors)
RN  - 9001-26-7 (Prothrombin)
RN  - 9002-04-4 (Factor IIa)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
EIN - J Thromb Haemost. 2007 Jun;5(6):1343
MH  - *Factor Xa Inhibitors
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Humans
MH  - Prothrombin/*antagonists & inhibitors
MH  - Serine Proteinase Inhibitors/*pharmacology
MH  - Thrombin/*biosynthesis
EDAT- 2007/04/28 09:00
MHDA- 2007/06/21 09:00
CRDT- 2007/04/28 09:00
PHST- 2007/04/28 09:00 [pubmed]
PHST- 2007/06/21 09:00 [medline]
PHST- 2007/04/28 09:00 [entrez]
AID - S1538-7836(22)10422-8 [pii]
AID - 10.1111/j.1538-7836.2007.02477.x [doi]
PST - ppublish
SO  - J Thromb Haemost. 2007 May;5(5):955-62. doi: 10.1111/j.1538-7836.2007.02477.x.