PMID- 12871355
OWN - NLM
STAT- MEDLINE
DCOM- 20040116
LR  - 20230829
IS  - 1538-7933 (Print)
IS  - 1538-7836 (Linking)
VI  - 1
IP  - 5
DP  - 2003 May
TI  - The inhibition of blood coagulation by heparins of different molecular weight is 
      caused by a common functional motif--the C-domain.
PG  - 907-14
AB  - BACKGROUND: Heparins in clinical use differ considerably as to mode of 
      preparation, molecular weight distribution and pharmacodynamic properties. 
      OBJECTIVES: Find a common basis for their anticoagulant action. METHODS: In 50 
      fractions of virtually single molecular weight (Mr), prepared from unfractionated 
      heparin (UFH) and four low-molecular-weight heparins (LMWH), we determined: (i) 
      the molar concentration of material (HAM) containing the antithrombin binding 
      pentasaccharide (A-domain); (ii) the specific catalytic activity in thrombin and 
      factor Xa inactivation; (iii) the capacity to inhibit thrombin generation (TG) 
      and prolong the activated partial thromboplastin time (APTT). We also calculated 
      the molar concentration of A-domain with 12 sugar units at its non-reducing end, 
      i.e. the structure that carries antithrombin activity (C-domain). RESULTS: The 
      antithrombin activity and the effects on TG and APTT are primarily determined by 
      the concentration of C-domain and independent of the source material (UFH or 
      LMWH) or Mr. High Mr fractions (>15 000) are less active, probably through 
      interaction with non-antithrombin plasma proteins. Anti-factor Xa activity is 
      proportional to the concentration of A-domain, it is Ca2+- and Mr-dependent and 
      does not determine the effect on TG and APTT. CONCLUSION: For any type of 
      heparin, the capacity to inhibit the coagulation process in plasma is primarily 
      determined by the concentration of C-domain, i.e. the AT-binding pentasaccharide 
      with 12 or more sugar units at its non-reducing end.
FAU - Al Dieri, R
AU  - Al Dieri R
AD  - Synapse BV, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the 
      Netherlands.
FAU - Wagenvoord, R
AU  - Wagenvoord R
FAU - van Dedem, G W K
AU  - van Dedem GW
FAU - Beguin, S
AU  - Beguin S
FAU - Hemker, H C
AU  - Hemker HC
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
CIN - J Thromb Haemost. 2003 May;1(5):884-5. PMID: 12871351
MH  - Amino Acid Motifs
MH  - Anticoagulants/chemistry/*pharmacology
MH  - Blood Coagulation/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Heparin/chemistry/*pharmacology
MH  - Humans
MH  - Molecular Weight
MH  - Partial Thromboplastin Time
MH  - Protein Structure, Tertiary
MH  - Structure-Activity Relationship
MH  - Thrombin/biosynthesis
EDAT- 2003/07/23 05:00
MHDA- 2004/01/17 05:00
CRDT- 2003/07/23 05:00
PHST- 2003/07/23 05:00 [pubmed]
PHST- 2004/01/17 05:00 [medline]
PHST- 2003/07/23 05:00 [entrez]
AID - S1538-7836(22)15011-7 [pii]
AID - 10.1046/j.1538-7836.2003.00211.x [doi]
PST - ppublish
SO  - J Thromb Haemost. 2003 May;1(5):907-14. doi: 10.1046/j.1538-7836.2003.00211.x.