PMID- 11441984
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20191105
IS  - 1076-0296 (Print)
IS  - 1076-0296 (Linking)
VI  - 7
IP  - 3
DP  - 2001 Jul
TI  - Tissue factor pathway inhibitor release induced by defibrotide and heparins.
PG  - 225-8
AB  - We evaluated the release of tissue factor pathway inhibitor (TFPI) induced by 
      defibrotide (DF), a single-stranded, negatively charged polydeoxyribonucleotide 
      extracted from mammalian organ. Ten normal volunteers were injected with an 
      intravenous bolus of 400 mg DF and 2,000 IU unfractionated heparin (UFH). In 
      addition, three volunteers were also injected with an intravenous bolus of 2,000 
      anti-Xa U of two low-molecular-weight heparins (LMWHs), enoxaparin and 
      nadroparin. UFH caused a 4-fold increase in plasma TFPI at 5 minutes, with a 
      decrease that was parallel to the heparin level measured by the anti-Xa assay. 
      However, at 80 minutes, although the plasma anti-Xa activity of UFH was almost 
      undetectable, the level of TFPI remained 2-fold baseline. DF induced an increase 
      of TFPI that was 2-fold higher than the baseline level, with a steady state 
      achieved between 5 and 20 minutes. At 40 minutes, the TFPI levels returned to 
      basal level. This pattern was not coincident with the clearance of DF and at 40 
      minutes, the concentration of DF was still one third of the levels at 5 minutes 
      (25.4 +/- 4.04 microg/mL). Both of the LMWHs induced a similar TFPI peak level at 
      5 minutes (1.5-fold increase) and at 40 minutes the TFPI levels returned to the 
      initial levels. At 5 minutes, both LMWHs showed a higher plasma anti-Xa activity 
      than UFH, which was detectable even at 80 minutes. The current study demonstrated 
      that one of the mechanisms of the antithrombotic activity of DF is mediated via 
      TFPI. Furthermore, the release of TFPI by heparin is mediated by non-antithrombin 
      III binding fragments. Thus, polyanionic electrolytes are capable of releasing 
      TFPI irrespective of their antithrombin III effect.
FAU - Cella, G
AU  - Cella G
AD  - Department of Medical and Surgical Sciences, University of Padova Medical School, 
      Italy. giuseppe.cella@unipd.it
FAU - Sbarai, A
AU  - Sbarai A
FAU - Mazzaro, G
AU  - Mazzaro G
FAU - Motta, G
AU  - Motta G
FAU - Carraro, P
AU  - Carraro P
FAU - Andreozzi, G M
AU  - Andreozzi GM
FAU - Hoppensteadt, D A
AU  - Hoppensteadt DA
FAU - Fareed, J
AU  - Fareed J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Clin Appl Thromb Hemost
JT  - Clinical and applied thrombosis/hemostasis : official journal of the 
      International Academy of Clinical and Applied Thrombosis/Hemostasis
JID - 9508125
RN  - 0 (Anticoagulants)
RN  - 0 (Enoxaparin)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Lipoproteins)
RN  - 0 (Nadroparin)
RN  - 0 (Polydeoxyribonucleotides)
RN  - 0 (Thrombomodulin)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 438HCF2X0M (defibrotide)
RN  - 9005-49-6 (Heparin)
RN  - 9035-58-9 (Thromboplastin)
SB  - IM
MH  - Adult
MH  - Anticoagulants/*pharmacology
MH  - Endothelium, Vascular/*metabolism
MH  - Enoxaparin/*pharmacology
MH  - Factor Xa Inhibitors
MH  - Female
MH  - Fibrinolytic Agents/*pharmacology
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Lipoproteins/blood/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Nadroparin/*pharmacology
MH  - Polydeoxyribonucleotides/*pharmacology
MH  - Thrombomodulin/blood
MH  - Thromboplastin/analysis
EDAT- 2001/07/10 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/07/10 10:00
PHST- 2001/07/10 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/07/10 10:00 [entrez]
AID - 10.1177/107602960100700308 [doi]
PST - ppublish
SO  - Clin Appl Thromb Hemost. 2001 Jul;7(3):225-8. doi: 10.1177/107602960100700308.