scholarly journals Determination of the Levels of Unfractionated and Low-Molecular-Weight Heparins in Plasma: Their Effect on Thrombin-Mediated Feedback Reactions in vivo

1991 ◽  
Vol 21 (4) ◽  
pp. 258-272 ◽  
Author(s):  
H.C. Hemker ◽  
S. Béguin ◽  
A.V. Bendetowicz ◽  
S. Wielders
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins

PHARMACOLOGIC INEQUIVALENCE OF LOW MOLECULAR WEIGHT HEPARINS

1987 ◽  
Author(s):  
J Fareed ◽  
J M Walenga ◽  
D Hoppensteadt ◽  
R N Emanuele ◽  
A Racanell
Keyword(s):  
Molecular Weight ◽  
Animal Models ◽  
Comparative Study ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
In Vivo Test ◽  
In Vitro Effects

Compared to unfractionated heparin, low molecular weight heparins (LMWHs) have been found to exhibit marked variations in in vitro effects due to variations in molecular weight and structure. Moreover, when the in vitro potency of these agents is equally adjusted bypharmacopeial assay (current and proposed) wide variations in the in vivo responses have been noted. These variations were strongly dependent on the route of administration. Utilizing defined animal models, a systematic comparative study of the in vivo responses of seven commercial LMWHs was undertaken. Choay Fraxiparine (CY 216} Choay CY 222, NovoLHN, Kabi Fragmin, Opocrin 2123 (OP), Hepar RD 11885 (RD), Pharmuka Enoxaparin (PK) and Choay porcine mucosal heparin (PMH) were tested in identical settings at equigravimetric dosages. The graded results are given in the following.Wide variations in the in vivo pharmacologic and toxicity responseswere noted suggesting that different LMWHs are not bioequivalent at equigravimetric levels. When these responses were expressed in anti-factor Xa or pharmacopeial potency, these differences were further magnified. The clinically reported dosimetric and safety problems may be minimized by profiling LMWHs in defined in vivo test systems to optimize their safety/efficacy ratio.

Cyclodextrins in Nasal Delivery of Low-Molecular-Weight Heparins: In Vivo and in Vitro Studies

2004 ◽  
Vol 21 (7) ◽  
pp. 1127-1136 ◽  
Author(s):  
Tianzhi Yang ◽  
Alamdar Hussain ◽  
Jennifer Paulson ◽  
Thomas J. Abbruscato ◽  
Fakhrul Ahsan
Keyword(s):  
Molecular Weight ◽  
In Vitro Studies ◽  
Nasal Delivery ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins

scholarly journals Rat and human HARE/stabilin-2 are clearance receptors for high- and low-molecular-weight heparins

2009 ◽  
Vol 296 (6) ◽  
pp. G1191-G1199 ◽  
Author(s):  
Edward N. Harris ◽  
Bruce A. Baggenstoss ◽  
Paul H. Weigel
Keyword(s):  
Molecular Weight ◽  
Rat Liver ◽  
Binding Sites ◽  
Keratan Sulfate ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Chondroitin Sulfates ◽  
293 Cells ◽  
Clearance Receptor

The human hyaluronic acid (HA) receptor for endocytosis (HARE/stabilin-2) is the primary clearance receptor for systemic HA, chondroitin sulfates, and heparin, but not for heparan sulfate or keratan sulfate (Harris EN, Weigel JA, Weigel PH. J Biol Chem 283: 17341–17350, 2008). HARE is expressed in the sinusoidal endothelial cells (SECs) of liver and lymph nodes where it acts as a scavenger for uptake and degradation of glycosaminoglycans, both as free chains and proteoglycan fragments. Unfractionated heparin (UFH; ∼14 kDa) and low-molecular-weight heparin (LMWH; ∼4 kDa) are commonly used in treatments for thrombosis and cancer and in surgical and dialysis procedures. The reported half-lives of UFH and LMWH in the blood are ∼1 h and 2–6 h, respectively. In this study, we demonstrate that anti-HARE antibodies specifically block the uptake of LMWH and UFH by isolated rat liver SECs and by human 293 cells expressing recombinant human HARE (hHARE). hHARE has a significant affinity ( Kd= 10 μM) for LMWH, and higher affinity ( Kd= 0.06 μM) for the larger UFH. Rat liver SECs or cells expressing the recombinant 190-kDa HARE isoform internalized both UFH and LMWH, and both heparins cross-compete with each other, suggesting that they share the same binding sites. These cellular results were confirmed in ELISA-like assays using purified soluble 190-hHARE ectodomain. We conclude that both UFH and LMWH are cleared by HARE/Stab2 and that the differences in the affinities of HARE binding to LMWH and UFH likely explain the longer in vivo circulating half-life of LMWH compared with UFH.

Determination of Low-Molecular-Weight Heparins and Their Binding to Protamine and a Protamine Analog Using Polyion-Sensitive Membrane Electrodes

1999 ◽  
Vol 266 (1) ◽  
pp. 116-124 ◽  
Author(s):  
Narayanan Ramamurthy ◽  
Narayan Baliga ◽  
Thomas W. Wakefield ◽  
Philip C. Andrews ◽  
Victor C. Yang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Membrane Electrodes ◽  
Low Molecular Weight Heparins ◽  
Sensitive Membrane
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