PMID- 11150580
OWN - NLM
STAT- MEDLINE
DCOM- 20010208
LR  - 20190727
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 100
IP  - 5
DP  - 2000 Dec 1
TI  - Reduction of factor FVIIa activity during heparin therapy. Evidence for assay 
      interactions with tissue factor pathway inhibitor and antithrombin.
PG  - 389-96
AB  - Heparin is known to exert its antithrombotic effects by accelerating the effect 
      of antithrombin (AT) and by mobilizing tissue factor pathway inhibitor (TFPI) 
      into the circulation from vascular endothelium. Heparin treatment has been 
      reported to decrease FVIIa activity by 40%; this was suggested as a new 
      antithrombotic action of heparins. The present study was conducted to investigate 
      whether the apparent reduction in FVIIa activity induced by unfractionated 
      heparin (UFH) infusion in vivo is due to interactions between AT and TFPI with 
      the FVIIa assay or due to an actual decrease in FVIIa. Blocking plasma TFPI in 
      affinity purified anti-TFPI IgG caused a 25% increase in plasma FVIIa activity 
      (Staclot VII - rTF, Diagnostica Stago, Aswieres-sur-Seine, France). In vitro 
      heparinization of plasma caused a dose-dependent decrease in FVIIa (up to 56 +/- 
      8%) at high heparin concentrations (1.0-5.0 IU/mL UFH), a reduction abolished by 
      Hexadimethine Bromide (HDB) to neutralize heparin-induced activation of AT. Thus, 
      heparin-induced activation of AT is apparently responsible for decreased FVIIa 
      under in vitro conditions. Bolus injection followed by continuous infusion of 
      heparin to healthy volunteers was accompanied by a prompt 50% reduction in FVIIa 
      activity, which was sustained throughout heparin infusion and normalized within 
      24 hours after discontinuation of treatment. Addition of anti-TFPI IgG to 
      postheparin plasma reversed the heparin-induced reduction in FVIIa by 
      approximately 50%, and combined pretreatment of postheparin plasma with anti-TFPI 
      IgG and HDB brought FVIIa to preheparin levels. The present study shows that the 
      FVIIa assay is sensitive to TFPI and AT, especially during heparin treatment, and 
      thereby indicates that the heparin-induced decrease in FVIIa is affected by 
      interactions between TFPI and AT with the FVIIa assay.
FAU - Hansen, J B
AU  - Hansen JB
AD  - Department of Medicine, Institute of Clinical Medicine, University of Tromsoo, 
      Tromsoo, Norway. johnbh@fagmed.uit.no
FAU - Svensson, B
AU  - Svensson B
FAU - Sandset, P M
AU  - Sandset PM
FAU - Thijssen, F
AU  - Thijssen F
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Antithrombins)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Lipoproteins)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.21 (Factor VIIa)
SB  - IM
MH  - Adult
MH  - Antithrombins/*metabolism
MH  - Factor VIIa/*metabolism
MH  - Fibrinolytic Agents/*pharmacology/therapeutic use
MH  - Heparin/*pharmacology/therapeutic use
MH  - Humans
MH  - Lipoproteins/*blood
MH  - Male
EDAT- 2001/01/11 11:00
MHDA- 2001/03/03 10:01
CRDT- 2001/01/11 11:00
PHST- 2001/01/11 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/01/11 11:00 [entrez]
AID - S0049-3848(00)00343-1 [pii]
AID - 10.1016/s0049-3848(00)00343-1 [doi]
PST - ppublish
SO  - Thromb Res. 2000 Dec 1;100(5):389-96. doi: 10.1016/s0049-3848(00)00343-1.