PMID- 15570242
OWN - NLM
STAT- MEDLINE
DCOM- 20041223
LR  - 20131121
IS  - 0022-2143 (Print)
IS  - 0022-2143 (Linking)
VI  - 144
IP  - 5
DP  - 2004 Nov
TI  - Intravascular release and urinary excretion of tissue factor pathway inhibitor 
      during heparin treatment.
PG  - 246-53; discussion 226-7
AB  - Tissue-factor-pathway inhibitor is the principal regulator of tissue 
      factor-induced coagulation. Heparin treatment mobilizes TFPI into the circulation 
      and contributes to the anticoagulant effects of heparins. Previous studies have 
      demonstrated a selective depletion of intravascular TFPI by unfractionated 
      heparin (UFH) but not by low-molecular-weight heparin (LMWH). In this study we 
      sought to investigate the time- and dose-dependent relationships between release 
      of TFPI and lipoprotein lipase (LPL) in respons to UFH and LMWH and to 
      investigate whether the selective depletion of TFPI by UFH but not by LMWH is 
      related to differential urinary excretion of TFPI. Eight healthy males 
      participated in an open crossover study in which participants were assigned to 
      receive (1) continuous infusion of unfractionated heparin (UFH, 450 IU/kg/24 hr); 
      (2) subcutaneous dalteparin, 100 IU/kg given twice at a 12-hr interval; (3) 
      subcutaneous dalteparin, 200 IU/kg given once; or (4) saline-solution infusion. 
      Similar dose-dependent mobilization of TFPI and lipoprotein lipase (LPL), another 
      glucosaminoglycan (GAG)-anchored protein of the endothelial membrane, was 
      observed after both subcutaneous and intravenous administration of heparins. 
      However, UFH induced a more efficient release of both TFPI and LPL into plasma 
      than did LMWH at equivalent anti-Xa levels, indicating molecular-weight 
      dependence of the release reactions. However, LPL reached peak levels faster and 
      was more rapidly cleared from the circulation than was TFPI, regardless of the 
      treatment modality. Only trace amounts of TFPI were detected in the urine in a 
      native form (38 kD). UFH and LMWH treatment reduced renal clearance of TFPI 
      compared with the control regimen. Our findings suggest that displacement of TFPI 
      from the endothelial-surface GAG is the main mechanism for TFPI release during 
      heparin treatment in vivo and that differential urinary excretion of TFPI is not 
      the explanation for selective depletion of TFPI during UFH treatment.
FAU - Brodin, Ellen
AU  - Brodin E
AD  - Center for AtherothromboticResearch, Institute of Clinical Medicine, University 
      of Tromso, Tromso, Norway. ellenb@fagmed.uit.no
FAU - Svensson, Birgit
AU  - Svensson B
FAU - Paulssen, Ruth H
AU  - Paulssen RH
FAU - Nordoy, Arne
AU  - Nordoy A
FAU - Hansen, John-Bjarne
AU  - Hansen JB
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Lab Clin Med
JT  - The Journal of laboratory and clinical medicine
JID - 0375375
RN  - 0 (Antibodies)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Lipoproteins)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.1.1.34 (Lipoprotein Lipase)
RN  - EC 3.4.21.6 (Factor Xa)
RN  - S79O08V79F (Dalteparin)
SB  - IM
MH  - Adult
MH  - Antibodies/blood
MH  - Cross-Over Studies
MH  - Dalteparin/administration & dosage
MH  - Factor Xa/immunology
MH  - Female
MH  - Heparin/*administration & dosage
MH  - Heparin, Low-Molecular-Weight/administration & dosage
MH  - Humans
MH  - Kidney/metabolism
MH  - Kinetics
MH  - Lipoprotein Lipase/blood
MH  - Lipoproteins/*blood/*urine
MH  - Male
MH  - Middle Aged
EDAT- 2004/12/01 09:00
MHDA- 2004/12/24 09:00
CRDT- 2004/12/01 09:00
PHST- 2004/12/01 09:00 [pubmed]
PHST- 2004/12/24 09:00 [medline]
PHST- 2004/12/01 09:00 [entrez]
AID - S002221430400215X [pii]
AID - 10.1016/j.lab.2004.08.001 [doi]
PST - ppublish
SO  - J Lab Clin Med. 2004 Nov;144(5):246-53; discussion 226-7. doi: 
      10.1016/j.lab.2004.08.001.