PMID- 11287128
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1526
IP  - 1
DP  - 2001 Apr 3
TI  - Antithrombin binding of low molecular weight heparins and inhibition of factor 
      Xa.
PG  - 105-13
AB  - Fluorescence and stopped flow methods were used to compare clinically used 
      heparins with regard to their ability to bind to antithrombin and to accelerate 
      the inactivation of factor Xa. Titration of antithrombin with both low molecular 
      weight heparin (LMWH) (enoxaparin, fragmin and ardeparin) and unfractionated 
      heparin (UFH) produced an equivalent fluorescence increase and indicates similar 
      affinity of all heparin preparations to antithrombin. However, relative to UFH 
      enoxaparin, the LMWH with the smallest average molecular mass, contained only 12% 
      material with high affinity for antithrombin. The rate of factor Xa inhibition by 
      antithrombin increased with the concentration of the examined heparins to the 
      same limiting value, but the concentration required for maximal acceleration 
      depended on the preparation. According to these data the high affinity fraction 
      of the heparin preparations increased the intrinsic fluorescence and inhibitory 
      activity equally without additional effects by variations in chain length and 
      chemical composition. In contrast, in the presence of Ca UFH accelerated the 
      inhibition of factor Xa by antithrombin 10-fold more efficiently than comparable 
      concentrations of the high affinity fractions of enoxaparin and fragmin. The 
      bell-shaped dependence of this accelerating effect suggests simultaneous binding 
      of both proteins to heparin. In conclusion, under physiologic conditions the 
      anti-factor Xa activity of heparin results from a composite effect of chain 
      length and the content of material with high affinity to antithrombin. Thus, the 
      reduced antithrombotic activity of LMWH relative to UFH results from a smaller 
      content of high affinity material and the absence of a stimulating effect of 
      calcium.
FAU - Lin, P
AU  - Lin P
AD  - Cor Therapeutics, Inc., 256 E. Grand Avenue, South San Francisco, CA 94080, USA.
FAU - Sinha, U
AU  - Sinha U
FAU - Betz, A
AU  - Betz A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Antithrombins)
RN  - 0 (Enoxaparin)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.6 (Factor Xa)
RN  - S79O08V79F (Dalteparin)
RN  - SY7Q814VUP (Calcium)
RN  - VL0L558GCB (ardeparin)
SB  - IM
MH  - Animals
MH  - Antithrombins/*metabolism
MH  - Calcium/metabolism
MH  - Dalteparin/chemistry/metabolism
MH  - Enoxaparin/chemistry/metabolism
MH  - Factor Xa/analysis
MH  - *Factor Xa Inhibitors
MH  - Fluorescence
MH  - Fluorometry
MH  - Heparin/*metabolism/pharmacology
MH  - Heparin, Low-Molecular-Weight/chemistry/*metabolism/pharmacology
MH  - Mathematics
MH  - Protein Binding
MH  - Structure-Activity Relationship
EDAT- 2001/04/05 10:00
MHDA- 2001/05/22 10:01
CRDT- 2001/04/05 10:00
PHST- 2001/04/05 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/04/05 10:00 [entrez]
AID - S0304416501001179 [pii]
AID - 10.1016/s0304-4165(01)00117-9 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2001 Apr 3;1526(1):105-13. doi: 
      10.1016/s0304-4165(01)00117-9.