Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

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Biological activity of partially purified low molecular weight luteinizing hormone binding inhibitor in porcine follicular fluids

Acta Endocrinologica ◽

10.1530/acta.0.1280088 ◽

1993 ◽

Vol 128 (1) ◽

pp. 88-94 ◽

Cited By ~ 2

Author(s):

Nobuyoshi Kokawa ◽

Mareo Yamoto ◽

Kenichi Furukawa ◽

Ryosuke Nakano

Keyword(s):

Molecular Weight ◽

Luteinizing Hormone ◽

Competitive Inhibition ◽

Biological Activities ◽

Partial Purification ◽

Low Molecular Weight ◽

Dependent Manner ◽

Hormone Binding ◽

Dose Dependent ◽

Follicular Fluids

We performed partial purification of low molecular weight luteinizing hormone binding inhibitor from porcine follicular fluids and examined its biological activities. Following ultrafiltration, gel filtration and anion exchange of the pooled porcine follicular fluids, low molecular weight fractions (500–10,000 MW) inhibited [125I]hLH binding to porcine granulosa cells in a dose-dependent manner. The binding inhibition kinetics study revealed that the luteinizing hormone binding inhibitor may indicate a non-competitive inhibition with [125I]hLH binding. In vitro bioassay using adult mouse testicular interstitial cells revealed that the partially purified luteinizing hormone binding inhibitor reduced ovine LH-stimulated testosterone and cAMP production in a dose-dependent manner, whereas the luteinizing hormone binding inhibitor did not affect basal production of testosterone and cAMP. The inhibitory activity was heat stable and did not disappear with activated charcoal adsorption. The results of the present study suggest that the luteinizing hormone binding inhibitor may play an important role as an ovarian non-steroidal regulator modulating the receptor binding of LH and LH-mediated steroidogenesis.

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Effect of long‐term use of unfractionated or low‐molecular‐weight heparin on bone mineral density in maintenance hemodialysis patients

Hemodialysis International ◽

10.1111/hdi.12854 ◽

2020 ◽

Vol 24 (3) ◽

pp. 374-382

Author(s):

Shuo Yang ◽

Qingyu Niu ◽

Liangying Gan ◽

Xiaobo Zhang ◽

Lingxue Tu ◽

...

Keyword(s):

Bone Mineral Density ◽

Molecular Weight ◽

Bone Mineral ◽

Low Molecular Weight Heparin ◽

Hemodialysis Patients ◽

Maintenance Hemodialysis ◽

Low Molecular Weight ◽

Mineral Density ◽

Maintenance Hemodialysis Patients

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Effect of Low-Molecular-Weight Heparin (Tinzaparin) and Unfractionated Heparin on Platelet Aggregation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602969600200311 ◽

1996 ◽

Vol 2 (3) ◽

pp. 209-212 ◽

Cited By ~ 1

Author(s):

Hanne B. Ravn ◽

Claus Bregengaard ◽

Henrik Vissinger ◽

Per Østergaard ◽

Jan Holst ◽

...

Keyword(s):

Molecular Weight ◽

Platelet Aggregation ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Ex Vivo ◽

Subcutaneous Administration ◽

Low Molecular Weight ◽

Pronounced Difference ◽

Dose Dependent

A low-molecular-weight heparin (LMWH), when anti-IIa activity was compared. In the ex vivo part Tinzaparin, was compared with unfractionated heparin of the study, a significant enhancement of ADP-induced (UFH) for their effects on platelet aggregation in vitro and platelet aggregation was observed after i.v. administra ex vivo. Both heparins showed a dose-dependent proag- tion of both Tinzaparin and UFH with no difference in gregatory effect on ADP- and collagen-induced platelet potency. Subcutaneous administration of Tinzaparin in aggregation in vitro, but LMWH was less potent. The two different doses did not have any effect on platelet differences in potency between Tinzaparin and UFH de- activity. In conclusion, Tinzaparin appears, like other pended on how the compounds were compared. The most LMWHs, to have less proaggregatory effect on platelets pronounced difference was found when molar concentra- than UFH both in vitro and ex vivo.

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P-079 Long term use of low-molecular-weight heparin during pregnancy does not affect postpartum bone mineral density

Thrombosis Research ◽

10.1016/s0049-3848(13)70125-7 ◽

2013 ◽

Vol 131 ◽

pp. S97

Author(s):

G. Mitic ◽

A. Novakov-Mikic ◽

J. Novakovic-Paro ◽

D. Popov ◽

S. Novakovic-Anucin ◽

...

Keyword(s):

Bone Mineral Density ◽

Molecular Weight ◽

Bone Mineral ◽

Low Molecular Weight Heparin ◽

Low Molecular Weight ◽

Mineral Density

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P-007: Prolonged low-molecular-weight heparin use during pregnancy and subsequent bone mineral density

Thrombosis Research ◽

10.1016/s0049-3848(17)30105-6 ◽

2017 ◽

Vol 151 ◽

pp. S111-S112

Author(s):

P. Galambosi ◽

V. Hiilesmaa ◽

V.M. Ulander ◽

L. Laitinen ◽

A. Tiitinen ◽

...

Keyword(s):

Bone Mineral Density ◽

Molecular Weight ◽

Bone Mineral ◽

Low Molecular Weight Heparin ◽

Low Molecular Weight ◽

Mineral Density

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Lipoprotein-associated coagulation inhibitor (LACI) is a cofactor for heparin: synergistic anticoagulant action between LACI and sulfated polysaccharides

Blood ◽

10.1182/blood.v79.2.430.bloodjournal792430 ◽

1992 ◽

Vol 79 (2) ◽

pp. 430-438

Author(s):

TC Wun

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Dermatan Sulfate ◽

Factor Viia ◽

Threshold Concentration ◽

Sulfated Polysaccharides ◽

Low Molecular Weight ◽

Dependent Manner ◽

Normal Plasma ◽

Coagulation Inhibitor

Lipoprotein-associated coagulation inhibitor (LACI) is a plasma-derived protein that inhibits tissue factor (TF)/factor VIIa-induced coagulation in a factor Xa-dependent manner. The roles of endogenous plasma LACI and exogenously added LACI and heparin, in the regulation of coagulation, initiated via the intrinsic and extrinsic pathways, were studied using the activated partial thromboplastin time (APTT) and the modified prothrombin time (PT) assays, respectively. Both LACI- depleted plasma and normal plasma have identical APTTs and similar prolongations of the APTT in response to heparin; both are fully anticoagulated (arbitrarily defined as clotting times of greater than 1 hour) at similar concentrations of heparin. These results indicate that heparin is an effective anticoagulant when coagulation is initiated by the intrinsic pathway and that endogenous LACI is not significantly involved in the regulation of this pathway. The PT of normal plasma is only marginally longer than that of LACI-depleted plasma in the absence of heparin, suggesting that endogenous plasma LACI has a very limited capacity to inhibit TF-induced clotting. However, in the presence of heparin, the PTs of LACI-depleted plasma and normal plasma are different. Prolongation of the PT occurred only moderately and linearly with increasing concentrations of heparin in LACI-depleted plasma. In contrast, normal plasma showed a greater extent of PT prolongation in response to heparin and the plasma became fully anticoagulated at a certain threshold concentration of heparin. These results suggest that LACI serves as a cofactor for heparin and thus greatly enhances the inhibition of TF-induced coagulation. LACI-depleted plasma was supplemented with purified recombinant LACI and/or heparin and the effects on TF-induced clotting were studied. A combination of LACI and heparin greatly enhanced anticoagulation compared with LACI or heparin alone. Many sulfated polysaccharides were also found to enhance the LACI-dependent inhibition of TF-induced clotting. By weight, the relative potencies of these compounds are: low molecular weight heparin (mean Mr, 5,100) greater than unfractionated heparin greater than low molecular weight heparin (mean Mr, 3,700) greater than pentosan polysulfate greater than dermatan sulfate greater than dextran sulfate greater than heparan sulfate. Based on the above results, it is concluded that LACI is a cofactor for heparin in the inhibition of TF- induced clotting and that LACI and sulfated polysaccharides act synergistically in whole plasma.

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Human Urinary Soluble Thrombomodulin (MR-33) Improves Disseminated Intravascular Coagulation without Affecting Bleeding Time in Rats: Comparison with Low Molecular Weight Heparin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656051 ◽

1997 ◽

Vol 77 (04) ◽

pp. 789-795 ◽

Cited By ~ 14

Author(s):

Yasuo Takahashi ◽

Yoshitaka Hosaka ◽

Kazunori Imada ◽

Takehiro Adachi ◽

Hiromi Niina ◽

...

Keyword(s):

Molecular Weight ◽

Disseminated Intravascular Coagulation ◽

Low Molecular Weight Heparin ◽

Bleeding Time ◽

Low Molecular Weight ◽

Soluble Thrombomodulin ◽

Intravascular Coagulation ◽

Significant Prolongation ◽

Dose Dependent Fashion ◽

Dose Dependent

SummaryWe compared the antithrombotic and hemorrhagic effects of naturally existing human urinary soluble thrombomodulin (MR-33) with those of low molecular weight heparin (LMW-heparin) in rats. In in vitro experiments, MR-33 prolonged APTT in a dose-dependent fashion; its effect in this respect was as potent as that of LMW-heparin, but it was less potent than unfractionated heparin (UF-heparin). MR-33 was effective on endotoxin- or thromboplastin-induced disseminated intravascular coagulation (DIC) in rats. In both DIC models, infusion of MR-33 improved hematological abnormalities compatible with DIC in a dose-dependent fashion without excessive prolongation effect on APTT. Although LMW-heparin and UF-heparin also improved both DIC models, excessive prolongation of APTT was observed at high doses. It is well-known that the excessive prolongation of APTT with antithrombotic drugs like heparins is an index for hemorrhage, which is a major side effect in the treatment of DIC. We therefore further compared the antithrombotic (Benefit: dose required for 50% inhibition of fibrinogen decrease: ED50) and hemorrhagic (Risk: minimum dose required for significant prolongation of bleeding time) effects of MR-33 and LMW-heparin in the thromboplastin-induced DIC model. As a result, Benefit-Risk ratio was 1:27 for MR-33 and 1:3 for LMW heparin. These results indicate that MR-33 may be a clinically useful antithrombotic agent with reduced risk for hemorrhage compared with LMW-heparin.

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