A supersulfated low‐molecular‐weight heparin (IK‐SSH) increases plasma levels of free and total tissue factor pathway inhibitor after intravenous and subcutaneous administration in humans
作者:
B. Kaiser,
E. Glusa,
D. Hoppensteadt,
H. Breddin,
J. Amiral,
J. Fareed,
期刊:
Blood Coagulation and Fibrinolysis
(OVID Available online 1998)
卷期:
Volume 9,
issue 6
页码: 517-524
ISSN:0957-5235
年代: 1998
出版商: OVID
关键词: low-molecular-weight heparin;TFPI;ELISA measurement;anticoagulant actions
数据来源: OVID
摘要:
Unfractionated as well as low-molecular-weight heparins (LMWH) are known to cause an increase in blood levels of tissue factor pathway inhibitor (TFPI). To study the effect of a newly developed supersulfated LMWH (IK-SSH, Iketon Farmaceutici) on TFPI concentrations in human plasma, the compound was injected into volunteers at doses of 0.14, 0.33 and 0.66 mg/kg intravenously or 0.33, 0.66 and 1.0 mg/kg subcutaneously. At certain known times blood was drawn and plasma levels of both total and free TFPI were measured using enzyme-linked immunosorbent assay methodology. Baseline plasma concentrations of TFPI were 72.2 ± 3.1 ng/ml for total and 10.8 ± 0.8 ng/ml for free TFPI. Intravenous or subcutaneous injection of IK-SSH led to a strong and long-lasting rise in TFPI levels which were increased more than 5-fold for total TFPI and more than 30-fold for free TFPI. Maximum TFPI levels were reached 5–10 min after intraveous and 60 min after subcutaneous administration. IK-SSH caused prolongation of ex-vivo clotting times in the APTT and Heptest® assay, whereas thrombin time was not affected. Anticoagulant actions of IK-SSH showed a significant correlation to plasma concentrations of TFPI and they are thought to be based at least partially on the release of TFPI from vascular sites.
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