Heparin, Its Fractions, Fragments and Derivatives Some Newer Perspectives

Fareed, Jawed

doi:10.1055/s-2007-1004350

Cited by 38 publications

(27 citation statements)

References 54 publications

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“…Therefore, the NBSB reference is not suitable for the po tency predictions of these LMWHs in the in vivo settings. The major differences in the bioavailability of different LMWHs have been addressed in our laboratory [6][7][8][9][10]. Considering the chemical inequivalence among these agents, it is readily predictable that each will behave in a distinct way.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports from our laboratories have described the differences in physical, chemical and pharmacologic properties of these agents [6,7], Since each agent is made through a specific process, these products each exhibit a distinct bio chemical and pharmacologic profile. Ini tially the LMWHs were standardized in terms of their anti-Xa and anti-IIa actions against unfractionated heparin and their po tency was expressed in terms of numerous arbitrary units.…”

Section: Introductionmentioning

confidence: 99%

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Validity of the Newly Established Low-Molecular-Weight Heparin Standard in Cross-Referencing Low-Molecular-Weight Heparins

Fareed

Walenga²,

Racanelli³

et al. 1988

Pathophysiol Haemos Thromb

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Four low-molecular-weight-heparin (LMWH) preparations have recently become available for clinical usage. Some ten preparations are currently under preclinical development. The safety/efficacy profile of each of these LMWHs is now known to be quite distinct from one and other. In order to minimize the variations in the pharmacologic responses and to cross-reference different products on a common scale, the WHO has recently introduced a LMWH standard. This standard is a nitrous-acid-depolymerized product provided by KabiVitrum (Stockholm, Sweden) with a specific physiochemical and biological profile. Although the in vitro characteristics of this standard are comparable to other LMWH, the in vivo behavior of this reference and the parent product, Fragmin®, are quite different in comparison to other products. In a well-defined uniform biochemical and pharmacologic screening, seven LMWH were compared at WHO reference-adjusted potency using pharmacologically valid dose-response curves. Cross-referencing of various LMWHs against the WHO standard in terms of anti-Xa activity resulted in a marked elevation of the anti-IIa component of some of the LMWHs. Establishment of this WHO standard stipulated that the clinical performance of cross-referenced LMWHs would be equivalent to one another and variation in potency could be minimized. Our data suggest that utilizing the WHO, standard individual potency (anti-Xa)-adjusted LMWHs exhibit distinct safety/efficacy profiles which were not related in their observed in vitro potency. Each LMWH has distinct multiparametric molecular and biochemical characteristics which determine the pharmacologic activities of individual agents. Thus cross-referencing of LMWHs by one in vitro assay is of questionable value as it may result in serious dosimetric errors, resulting in serious thrombotic and bleeding complications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Validity of the Newly Established Low-Molecular-Weight Heparin Standard in Cross-Referencing Low-Molecular-Weight Heparins

Fareed

Walenga²,

Racanelli³

et al. 1988

Pathophysiol Haemos Thromb

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“…Parallel to the development of low molecular weight heparins, the introduction of heparin oligosaccharides has resulted from an improved understanding of the molecular basis of the coagulation cascade and non-anticoagulant effects associated with heparin [5,9]. Based upon the discovery of the specific binding sequence in heparin to antithrombin, the Choay group succeeded in synthesizing the first chemically defined heparin oligosaccharidespentasaccharide as a potent antithrombotic agent in 1980s [5,10].…”

Section: Introductionmentioning

confidence: 99%

Heparin Oligosaccharides as Potential Therapeutic Agents in Senile Dementia

Ma¹,

Cornelli²,

Hanin³

et al. 2007

CPD

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Heparin is a glycosaminoglycan mixture currently used in prophylaxis and treatment of thrombosis. Heparin possesses non-anticoagulant properties, including modulation of various proteases, interactions with fibroblast growth factors, and anti-inflammatory actions. Senile dementia of Alzheimer's type is accompanied by inflammatory responses contributing to irreversible changes in neuronal viability and brain function. Vascular factors are also involved in the pathogenesis of senile dementia. Inflammation, endogenous proteoglycans, and assembly of senile plagues and neurofibrillary tangles contribute directly and indirectly to further neuronal damage. Neuron salvage can be achieved by anti-inflammation and the competitive inhibition of proteoglycans accumulation. The complexity of the pathology of senile dementia provides numerous potential targets for therapeutic interventions designed to modulate inflammation and proteoglycan assembly. Heparin and related oligosaccharides are known to exhibit antiinflammatory effects as well as inhibitory effects on proteoglycan assembly and may prove useful as neuroprotective agents.

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“…Heparin is well known to have a potent antithrombotic activity [25] besides its anti coagulant properties. Unfractionated and low molecular weight heparins inhibit platelet ad hesion [unpubl.…”

Section: Discussionmentioning

confidence: 99%

Individual and Combined Effects of a Thromboxane Receptor Antagonist and Different Antithrombotic Agents in a Rat Microcirculatory Thrombosis Model

Giedrojć

Fellier²,

Breddin

1992

Pathophysiol Haemos Thromb

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The antithrombotic effect of a thromboxane A₂ receptor antagonist (HN-11501:5-[2-(4-chlorophenylsulfonylamino)-ethyl]-2-thienyloxy-acetic acid) alone and in combination with other antithrombotic agents has been studied in an experimental thrombosis model in which laser lesions are used to induce a defined thrombosis in rat mesenteric venules. The thromboxane receptor antagonist showed a significant and dose-dependent antithrombotic effect if given orally. The strongest additive thrombosis-inhibiting effect was observed after oral administration of HN-11501 at a dose of 2.5 mg/kg together with an intravenous infusion of 1 µg/kg/h of a prostacyclin analogue (cicaprost). An additive antithrombotic effect was also observed after oral application of 2.5 mg/kg of HN-11501 and intravenous injection of 0.2 mg/kg of a low molecular weight heparin (Fraxiparine®). The combination of 2.5 mg/kg of HN-11501 orally with an intravenous injection of 0.1 mg/kg molsidomine also had a significant additive effect. No significant additive effect was observed when 2.5 mg/kg of HN-11501 and 10 mg/kg of acetylsalicylic acid were orally administered simultaneously.

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Heparin, Its Fractions, Fragments and Derivatives Some Newer Perspectives

Cited by 38 publications

References 54 publications

Validity of the Newly Established Low-Molecular-Weight Heparin Standard in Cross-Referencing Low-Molecular-Weight Heparins

Validity of the Newly Established Low-Molecular-Weight Heparin Standard in Cross-Referencing Low-Molecular-Weight Heparins

Heparin Oligosaccharides as Potential Therapeutic Agents in Senile Dementia

Individual and Combined Effects of a Thromboxane Receptor Antagonist and Different Antithrombotic Agents in a Rat Microcirculatory Thrombosis Model

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