Abstract:
: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, Aswiéres-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.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Hansen JB,Svensson B,Sandset PM,Thijssen Fdoi
10.1016/s0049-3848(00)00343-1subject
Has Abstractpub_date
2000-12-01 00:00:00pages
389-96issue
5eissn
0049-3848issn
1879-2472pii
S0049-3848(00)00343-1journal_volume
100pub_type
杂志文章abstract::Despite clear potential benefits of outpatient care, most patients suffering from pulmonary embolism (PE) are currently hospitalized due to the fear of possible adverse events. Nevertheless, some teams have increased or envisage to increase outpatient treatment or early discharge. We performed a narrative systematic r...
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pub_type: 杂志文章,meta分析
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pub_type: 杂志文章
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journal_title:Thrombosis research
pub_type: 杂志文章
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pub_type: 杂志文章
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