PMID- 11668420
OWN - NLM
STAT- MEDLINE
DCOM- 20020305
LR  - 20061115
IS  - 0094-6176 (Print)
IS  - 0094-6176 (Linking)
VI  - 27
IP  - 5
DP  - 2001 Oct
TI  - Molecular weight-dependent influence of heparin on the form of tissue factor 
      pathway inhibitor circulating in plasma.
PG  - 503-11
AB  - The increase of circulating tissue factor pathway inhibitor (TFPI) in plasma by 
      heparins is thought to contribute to their overall antithrombotic activity. In a 
      clinical study in healthy volunteers, we recently found that the specific potency 
      of a heparin to mobilize TFPI from the vessel wall increases with its molecular 
      weight (MW). The released TFPI originally is not associated with lipoproteins, 
      but it is not known whether it remains free circulating in plasma. A further 
      question is whether the MW of heparin influences not only the release of TFPI but 
      also its potential association with lipoproteins. In the present study, the 
      release of free TFPI was compared with the release of total TFPI after 
      application of four heparins with different MWs. Only the TFPI released by 
      unfractionated heparin (UFH) circulated completely as free TFPI. With decreasing 
      heparin MW, the percentage of released free TFPI on released total TFPI decreased 
      to 57%. As a consequence, the longer the heparin chains are, the better they are 
      at preventing the binding of the released, originally free, TFPI to plasma 
      lipoproteins. Because only free TFPI is known to exhibit anticoagulant activity, 
      the activity of released TFPI is better the higher the MW of the applied heparin 
      is. In conclusion, in addition to the potency of heparin to mobilize TFPI, there 
      is its influence on the circulating form, and thus the anticoagulant activity of 
      the released TFPI depends on its MW.
FAU - Alban, S
AU  - Alban S
AD  - Institute of Pharmacy, University of Regensburg, Regensburg, Germany. 
      Susanne.Alban@chemie.uni-regensburg.de
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Semin Thromb Hemost
JT  - Seminars in thrombosis and hemostasis
JID - 0431155
RN  - 0 (Anticoagulants)
RN  - 0 (Lipoproteins)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anticoagulants/administration & dosage/chemistry/*pharmacology
MH  - Blood Circulation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Heparin/administration & dosage/chemistry/*pharmacology
MH  - Humans
MH  - Kinetics
MH  - Lipoproteins/*blood/*drug effects/pharmacokinetics
MH  - Male
MH  - Molecular Weight
MH  - Solubility
MH  - Structure-Activity Relationship
EDAT- 2001/10/23 10:00
MHDA- 2002/03/07 10:01
CRDT- 2001/10/23 10:00
PHST- 2001/10/23 10:00 [pubmed]
PHST- 2002/03/07 10:01 [medline]
PHST- 2001/10/23 10:00 [entrez]
AID - 10.1055/s-2001-17952 [doi]
PST - ppublish
SO  - Semin Thromb Hemost. 2001 Oct;27(5):503-11. doi: 10.1055/s-2001-17952.