Anticoagulant activities and effects on platelets of a heparin fragment with high affinity for antithrombin

Holmer, E.; Lindahl, Ulf; Bäckström, G.; Thunberg, Lennart; Sandberg, Helena; Söderström, Gunilla; Andersson, Lars‐Olov

doi:10.1016/0049-3848(80)90208-x

Cited by 127 publications

(54 citation statements)

References 20 publications

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“…In contrast, it has been suggested that heparin potentiation of antithrombin III inhibition of Xa may not require a polysaccharideproteinase interaction (Holmer, Lindahl, Backstrom, Thunberg, Sandberg, Soderstrom & Andersson, 1980). This view is supported by our demonstration that the polysaccharides examined do not alter a1-antitrypsin inhibition of Xa.…”

Section: Colorimetnic Experimentssupporting

confidence: 72%

EFFECT OF SULPHATED POLYSACCHARIDES ON THE α₁‐ANTITRYPSIN INHIBITION OF AMIDOLYSIS CATALYSED BY COAGULATION CASCADE PROTEINASES

Long¹,

Williamson²

1981

British J Pharmacology

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The ability of several sulphated polysaccharide anticoagulants to prevent α1‐antitrypsin inhibition of thrombin paralleled their ability to potentiate antithrombin III inhibition of thrombin. None of the compounds examined altered the ability of α1‐antitrypsin to inhibit activated coagulation factor X (Xa). These results are consistent with the possibility that a direct polysaccharide‐proteinase interaction may be involved in the sulphated polysaccharide‐modulated inhibition of thrombin by antithrombin III.

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Section: Colorimetnic Experimentssupporting

confidence: 72%

EFFECT OF SULPHATED POLYSACCHARIDES ON THE α₁‐ANTITRYPSIN INHIBITION OF AMIDOLYSIS CATALYSED BY COAGULATION CASCADE PROTEINASES

Long¹,

Williamson²

1981

British J Pharmacology

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“…Furthermore, it has been shown that a low molecular weight fragment of heparin appears to possess less ability to enhance platelet aggregation (Holmer et al, 1980). Both heparin and heparinoid did not alter the rate of decay of PGI2 in PPP or fatty acid free human albumin solutions in vitro.…”

Section: Discussionmentioning

confidence: 97%

“…Since these properties of heparin are potentially hazardous, a search for 'safer' heparins and heparin-like substances is essential. It is therefore of interest that a low molecular weight heparin derivative has been shown to possess less platelet aggregation enchancing capacity than conventional heparin (Holmer et al, 1980).…”

Section: Introduction Methodsmentioning

confidence: 99%

Comparison of the effect of a conventional heparin and a low molecular weight heparinoid on platelet function.

Mikhailidis¹,

Barradas²,

Mikhailidis³

et al. 1984

Brit J Clinical Pharma

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In a study comparing the in vitro effects of heparin and a low molecular weight heparinoid (Organon 10172) on aggregation of platelets from normal subjects, we have demonstrated that whereas heparin markedly enhances platelet aggregation induced by other aggregators and inhibits the anti‐aggregatory effect of epoprostenol (prostacyclin, PGI2), heparinoid does not produce such effects. The use of heparinoid may thus have a significant advantage over that of heparin in situations where enhanced platelet aggregation is the main factor leading to thrombosis or where heparin treatment is followed by thrombocytopaenia.

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“…Carter et al (1981) demonstrated that a low molecular weight heparin fraction with a high affinity for anti-thrombin III has a smaller influence on platelet function than high molecular weight heparin or low molecular weight heparin with low affinity for anti-thrombin III. These investigators suggested that high molecular weight heparin possesses both platelet and anti-thrombin III binding sites whilst low molecular weight heparin has lost the platelet binding site (Holmer et al, 1980). Since part of the haemorrhagic effect of heparin is related to its effect on platelet function, loss of the platelet binding site might reduce its haemorrhagic tendency.…”

Section: Introductionmentioning

confidence: 99%

ORG 10172: a low molecular weight heparinoid anticoagulant with a long half‐life in man.

Bradbrook

Magnani

Moelker

et al. 1987

Brit J Clinical Pharma

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ORG 10172 is a heparinoid with mean molecular weight 6500 daltons. Intravenous bolus injections of ORG 10172 were compared with placebo and heparin injections in 91 separate studies in 83 healthy male subjects. 6400 units ORG 10172 produced a mean maximum change of 14.7 s in kaolin cephalin time (c.f. greater than 120 s for 5000 units heparin). Changes in prothrombin time were minimal (1.6 s for 6400 units ORG 10172 and 4.5 s after 5000 units heparin). A dose‐related increase in bleeding time occurred after ORG 10172 and at high doses (greater than 3200 units) some secondary bleeding, which was never serious, occurred at between 1 and 4 h after incision. A dose‐dependent reduction in ex vivo platelet adhesiveness was found at 10 min after ORG 10172 injection. ORG 10172 promoted a much smaller release of lipoprotein lipase as compared with heparin. The effect of ORG 10172 on plasma factor Xa activity (one measure of its action) was described by a biexponential decay with a mean distribution half‐life of 2.34 (s.e. mean 0.16) h and mean disposition half‐life of 17.6 (s.e. mean 1.1) h. It thus has a much longer duration of effect than heparin. There was a linear relationship of plasma anti‐Xa response to increasing dose although there was some variability only partly explained by differences in body weight or surface area. ORG 10172 administration by bolus intravenous injection was well tolerated and there was no evidence of adverse effects on clinical chemistry or haematology tests.

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Anticoagulant activities and effects on platelets of a heparin fragment with high affinity for antithrombin

Cited by 127 publications

References 20 publications

EFFECT OF SULPHATED POLYSACCHARIDES ON THE α₁‐ANTITRYPSIN INHIBITION OF AMIDOLYSIS CATALYSED BY COAGULATION CASCADE PROTEINASES

EFFECT OF SULPHATED POLYSACCHARIDES ON THE α₁‐ANTITRYPSIN INHIBITION OF AMIDOLYSIS CATALYSED BY COAGULATION CASCADE PROTEINASES

Comparison of the effect of a conventional heparin and a low molecular weight heparinoid on platelet function.

ORG 10172: a low molecular weight heparinoid anticoagulant with a long half‐life in man.

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Anticoagulant activities and effects on platelets of a heparin fragment with high affinity for antithrombin

Cited by 127 publications

References 20 publications

EFFECT OF SULPHATED POLYSACCHARIDES ON THE α1‐ANTITRYPSIN INHIBITION OF AMIDOLYSIS CATALYSED BY COAGULATION CASCADE PROTEINASES

EFFECT OF SULPHATED POLYSACCHARIDES ON THE α1‐ANTITRYPSIN INHIBITION OF AMIDOLYSIS CATALYSED BY COAGULATION CASCADE PROTEINASES

Comparison of the effect of a conventional heparin and a low molecular weight heparinoid on platelet function.

ORG 10172: a low molecular weight heparinoid anticoagulant with a long half‐life in man.

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Product

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EFFECT OF SULPHATED POLYSACCHARIDES ON THE α₁‐ANTITRYPSIN INHIBITION OF AMIDOLYSIS CATALYSED BY COAGULATION CASCADE PROTEINASES

EFFECT OF SULPHATED POLYSACCHARIDES ON THE α₁‐ANTITRYPSIN INHIBITION OF AMIDOLYSIS CATALYSED BY COAGULATION CASCADE PROTEINASES