In vivo Effects of Low Molecular Weight Heparins on Experimental Thrombosis and Bleeding

1986 ◽  
Vol 16 (2) ◽  
pp. 82-86
Author(s):  
Jack Hirsh
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Experimental Thrombosis ◽  
In Vivo Effects

In Vivo Effects of a Low Molecular Weight Heparin Fragment on Platelet Aggregation and Platelet Dependent Hemostasis in Dogs

1988 ◽  
Vol 60 (02) ◽  
pp. 232-235 ◽  
Author(s):  
B Ljungberg ◽  
H Johnsson
Keyword(s):  
Molecular Weight ◽  
Platelet Aggregation ◽  
Low Molecular Weight Heparin ◽  
Platelet Rich Plasma ◽  
Skin Flap ◽  
Low Molecular Weight ◽  
Dog Plasma ◽  
In Vivo Effects ◽  
Induced Aggregation

SummaryPlasma defibrinogenated dogs were used to study the influence of conventional heparin and a low molecular weight heparin fragment (Fragmin®, mean MW 5,000 d) on platelet dependent hemostasis. The heparins were given intravenously in gravimetri- cafly equal doses. The bleeding from standardized skin flap wounds and platelet aggregation (ADP and thrombin) was studied. In comparison, higher doses of the fragment than of heparin were required to increase the bleeding. ADP-induced aggregation in defibrinogenated platelet rich plasma (after addition of normal dog plasma) was potentiated by both heparins. After injection of heparin or the fragment, ADP induced platelet aggregation without prior addition of normal plasma to the testtube.In conclusion the heparin fragment affected bleeding to a less extent than conventional heparin. One explanation might be a weaker inhibition of thrombin-induced platelet aggregation.

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.

scholarly journals Anticoagulant Profile of Low Molecular Weight Heparinoids (KB-101) and its in Vivo Effects on Experimental DIC

1992 ◽  
Vol 3 (3) ◽  
pp. 169-177 ◽  
Author(s):  
Hiroaki TAKABUCHI ◽  
Hajime TSUJI ◽  
Mitsuru YONEDA ◽  
Osamu TAKADA ◽  
Masahiko WATANABE ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
In Vivo Effects

The In Vitro and In Vivo Effects of a Low-Molecular-Weight Fucoidan on the Osteogenic Capacity of Human Adipose-Derived Stromal Cells

2014 ◽  
Vol 20 (1-2) ◽  
pp. 275-284 ◽  
Author(s):  
Jessica Pereira ◽  
Sophie Portron ◽  
Blandine Dizier ◽  
Claire Vinatier ◽  
Martial Masson ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Stromal Cells ◽  
Low Molecular Weight ◽  
Adipose Derived Stromal Cells ◽  
In Vivo Effects

scholarly journals Rational design of low-molecular weight heparins with improved in vivo activity

2003 ◽  
Vol 100 (2) ◽  
pp. 651-656 ◽  
Author(s):  
M. Sundaram ◽  
Y. Qi ◽  
Z. Shriver ◽  
D. Liu ◽  
G. Zhao ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Rational Design ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins
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