Premium
Non‐antithrombin affinity Semuloparin and it's component oligosaccharides release endogenous TFPI in a molecular weight dependent fashion
Author(s) -
Fareed Jawed,
Khan Hussein,
Litinas Evangelos,
Cunanan Josephine,
Hoppensteadt Debra,
Viskov Christian
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.832.5
Subject(s) - tissue factor pathway inhibitor , oligosaccharide , chemistry , antithrombin , thrombin , heparin , saline , antigen , endogeny , pharmacodynamics , biochemistry , pharmacology , tissue factor , microbiology and biotechnology , coagulation , pharmacokinetics , endocrinology , medicine , immunology , biology , platelet
Semuloparin (S) is an ultra low molecular weight heparin (uLMWH) with a unique composition. The purpose of this study was to determine the effect of non‐AT affinity semuloparin (NATAS) and it's oligosaccharide components on TFPI release. Non‐human primates (n=4–6; Macaca mulatta) were administered with 1.0 mg/kg IV, S, it's non‐AT affinity fraction and isolated hexasaccharide (H), dodecasaccharide (D) and octasaccharide (O) components. Citrated plasma samples were drawn at baseline and 15 minutes post‐administration. TFPI antigen levels by ELISA and tissue factor mediated thrombin generation using a fluorogenic assay were measured. S produced a sizable release of TFPI (156 ± 15 ng/ml). NATAS produced a slightly lower but statistically significant release of TFPI (142 ± 12 ng/ml). The oligosaccharide components produced a molecular weight dependent release of TFPI, with H producing minimal TFPI release (86 ± 8 ng/ml) vs. saline (78 ± 9 ng/ml). D produced a statistically significant increase in the release of TFPI (116+15 ng/ml). While S exhibited a measurable anti‐Xa response and produced a strong inhibition of thrombin generation (84% inhibition) whereas NATAS and it's fractions produced < 20% inhibition of thrombin generation. These results suggest that the NATAS and it's oligosaccharide components enhance TFPI antigen release which may mediate some of it's pharmacodynamic actions.