Tissue factor pathway inhibitor release induced by defibrotide and heparins
| Autor: | Giovanna Motta, Paolo Carraro, Giuseppe M. Andreozzi, Alessandra Sbarai, Jawed Fareed, Giuseppe Cella, Gabriella Mazzaro, Debra Hoppensteadt |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male medicine.drug_mechanism_of_action medicine.drug_class Lipoproteins Thrombomodulin Factor Xa Inhibitor Low molecular weight heparin 030204 cardiovascular system & hematology Pharmacology Defibrotide Thromboplastin 03 medical and health sciences 0302 clinical medicine Tissue factor pathway inhibitor Polydeoxyribonucleotides Fibrinolytic Agents Antithrombotic medicine Humans 030212 general & internal medicine Enoxaparin business.industry Heparin Antithrombin Anticoagulants Nadroparin Hematology General Medicine Middle Aged Anesthesia Female Endothelium Vascular business medicine.drug Factor Xa Inhibitors |
| Zdroj: | Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 7(3) |
| ISSN: | 1076-0296 |
| Popis: | 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 μg/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. |
| Databáze: | OpenAIRE |
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