A low molecular weight heparin compared with unfractionated heparin

Thomas, Duncan P.; Merton, R E

doi:10.1016/0049-3848(82)90116-5

Cited by 66 publications

(34 citation statements)

References 17 publications

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“…Anticoagulant Action of the Ascidian Dermatan Sulfate Measured by Activated Partial Thromboplastin Time (APTT)-APTT clotting assays were carried out as described (30,31). Normal citrate-anticoagulated human plasma (90 l) was incubated with 10 l of a solution of glycosaminoglycan (0 -100 g) and 100 l of kaolin ϩ bovine brain phospho-…”

Section: Figmentioning

confidence: 99%

Highly Sulfated Dermatan Sulfates from Ascidians

Pavão¹,

Aiello²,

Werneck³

et al. 1998

Journal of Biological Chemistry

170

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Dermatan sulfate from A. nigra has no discernible anticoagulant activity, which indicates that 4-O-sulfation of the N-acetyl-␤-D-galactosamine is essential for the anticoagulant activity of this glycosaminoglycan. In contrast dermatan sulfates from S. plicata and H. pyriformis are potent anticoagulants due to potentiation of thrombin inhibition by heparin cofactor II. These ascidian dermatan sulfates have ϳ10-fold and ϳ6-fold higher activity with heparin cofactor II than native and an oversulfated mammalian dermatan sulfate, respectively. They have no effect on thrombin or factor Xa inhibition by antithrombin. These naturally oversulfated ascidian dermatan sulfates are sulfated at selected sites required for interaction with heparin cofactor II and thus have specific and potent anticoagulant activity.Sulfated polysaccharides constitute a complex group of macromolecules known to possess a wide range of important biological properties. These anionic polymers are widespread in nature, occurring in a great variety of organisms. Marine invertebrates are a rich source of sulfated polysaccharides with novel structures (1-15).The ascidians (Chordata-Tunicata) are marine invertebrates covered by an external supportive tissue called the tunic, surrounding a body. The tunic contains large amounts of a unique high molecular mass sulfated ␣-L-galactan (1, 2, 5-7). Recently, we reported the occurrence of dermatan sulfate-like glycosaminoglycan in the body of this invertebrate (11, 13).Mammalian dermatan sulfate is an anticoagulant due to selective inhibition of thrombin by potentiating heparin cofactor II activity (16,17). Although of lower in vitro anticoagulant potency than heparin, it has efficacy in vivo with less hemorrhagic risk (18). Thus several authors have suggested using mammalian dermatan sulfate as an alternative antithrombotic polysaccharide (18 -21).In view of the increasing interest in the anticoagulant and antithrombotic actions of dermatan sulfate, we have characterized the fine chemical structure of dermatan sulfates extracted from the ascidian body and tested this compound in coagulation assays, including activation of heparin cofactor II. In addition, there is now more interest in therapeutics prepared from nonmammalian sources, thus reducing the risk of contamination with pathogenic agents.In the present work, we report that dermatan sulfates isolated from different ascidian species have distinguishable patterns and proportions of sulfate substitution. These ascidian dermatan sulfates (together with native and oversulfated mammalian dermatan sulfate), where the extent and position of sulfate substitution have been fully characterized, are a valuable tool to trace the relationship between structure versus anticoagulant activity of this glycosaminoglycan. Dermatan sulfates with potent anticoagulant potency and high heparin cofactor II activity have been found. EXPERIMENTAL PROCEDURESMaterials-Heparan sulfate from human aorta was extracted and purified as described previously (22). Chondroitin 4-sulfate fro...

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Section: Figmentioning

confidence: 99%

Highly Sulfated Dermatan Sulfates from Ascidians

Pavão¹,

Aiello²,

Werneck³

et al. 1998

Journal of Biological Chemistry

170

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“…In animal experiments, LH has proved as effective as UH in preventing thrombosis [6][7][8], Animal experiments have also suggested that the bleeding risk using LH is reduced compared to UH [7,8], Further more, LH seems less prone to induce platelet aggregation [9] and lipase activity [10]. Sub cutaneous administration of LH is effective in the prevention of DVT [11], but bleeding is still a potential hazard [12], Increased halflife and improved bioavailability [13,14] of LH as compared to UH suggest that LH is particularly suitable for subcutaneous ad ministration.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous Heparin Treatment of Deep Venous Thrombosis: A Comparison of Unfractionated and Low Molecular Weight Heparin

Holm¹,

Handeland³

et al. 1986

Pathophysiol Haemos Thromb

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In a double-blind study, patients with phlebographically proven deep venous thrombosis (DVT) were treated with subcutanous injections twice a day of either unfractionated heparin (UH; n = 27) or low molecular weight heparin (LH; n = 29) for 7 days, and the dose was adjusted until therapeutic range was reached, according to a chromogenic substrate anti-Xa assay. Forty-eight percent of the LH group did not need dose adjustment as compared to 24% of the UH group. During the course of heparin administration, deviation from initial heparin activity was frequent in both groups, but mean activity did not indicate a cumulative effect in either group. There was 1 incidence of pulmonary embolism (LH) and only 1 minor bleeding episode (UH). Half of the patients in both groups were phlebographically improved. We conclude that subcutaneous heparin treatment with UH or LH appears safe and convenient.

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“…Anticoagulant Action of the Ascidian Dermatan Sulfate Measured by Activated Partial Thromboplastin Time (APTT)-APTT clotting assays were carried out as described previously (31,32). Normal human plasma (90 l) was incubated with 10 l of a solution of glycosaminoglycan (0 -100 g) and 100 l of kaolin ϩ bovine brain phospholipid reagent (National Institute for Biological Standard reference reagent).…”

mentioning

confidence: 99%

A Unique Dermatan Sulfate-like Glycosaminoglycan from Ascidian:

Pavão

Mourāo

Mulloy

et al. 1995

Journal of Biological Chemistry

119

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A dermatan sulfate, similar to the mammalian glycosaminoglycans but not identical with any of them, has been isolated from the body of the ascidian Ascidia nigra. Degradation with chondroitin ABC lyase, analysis of the disaccharide products by digestion with chondro-4-and -6-sulfatases, and We have compared the ascidian dermatan sulfate with mammalian dermatan sulfate and with chemically oversulfated mammalian dermatan sulfate for anticoagulant activity as measured by the activated partial thromboplastin time assay and for its ability to potentiate heparin cofactor II. In spite of its high content of 2-O-sulfated ␣-L-iduronic acid residues, the ascidian compound had no discernible anticoagulant activity and had low ability to potentiate heparin cofactor II. These results suggest that 4-O-sulfation of the N-acetyl-␤-D-galactosamine residues is essential for the anticoagulant activity of dermatan sulfate.

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A low molecular weight heparin compared with unfractionated heparin

Cited by 66 publications

References 17 publications

Highly Sulfated Dermatan Sulfates from Ascidians

Highly Sulfated Dermatan Sulfates from Ascidians

Subcutaneous Heparin Treatment of Deep Venous Thrombosis: A Comparison of Unfractionated and Low Molecular Weight Heparin

A Unique Dermatan Sulfate-like Glycosaminoglycan from Ascidian:

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