In Vivo Studies on the Binding of Heparin and Its Fractions with Platelet Factor 4

Walz, Daniel A.; Hung, Guo-Long

doi:10.1055/s-2007-1004358

Cited by 31 publications

(10 citation statements)

References 43 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The rapid initial decay of LMW hep arin anti-Xa activity together with the raised levels of PF4 observed after the LMW hepa rin injections suggest, as in other studies [12,13], that the LMW heparin tested can bind to endothelial cells. The following part of the disappearance curves of LMW heparin antiXa activity appeared to be obviously differ ent as compared to the elimination curves of standard heparin.…”

Section: Discussionsupporting

confidence: 66%

Pharmacokinetic Studies of Standard Heparin and Low Molecular Weight Heparin in Patients with Chronic Renal Failure

Folléa

Laville

Pozet

et al. 1986

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

The disappearance of the anticoagulant activities of a standard commercial heparin and of a low molecular weight (LMW) heparin (PK 10169), administered as single intravenous injections, was studied in patients with chronic renal failure. Heparin and LMW heparin anticoagulant activities were determined by activated partial thromboplastin time (APTT) and chromogenic assays of anti-Xa and anti-IIa activities. Following heparin injection, a fast initial decay of anticoagulant activities preceded a slow convex disappearance curve, in semilogarithmic plots. These experimental data are in agreement with a model based on a predominant saturable mechanism of elimination of heparin in patients with renal failure. The disappearance of LMW heparin anti-Xa activity was obviously different, with linear or concave elimination curves, and longer apparent half-life. Taken together, our kinetic data and those previously reported in normal subjects strongly suggest that the mechanism of elimination of the LMW heparin studied is not saturable (at least for the tested dosages), and that the kidneys play a minimal role in the elimination.

show abstract

Section: Discussionsupporting

confidence: 66%

Pharmacokinetic Studies of Standard Heparin and Low Molecular Weight Heparin in Patients with Chronic Renal Failure

Folléa

Laville

Pozet

et al. 1986

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

show abstract

“…1A) slightly reduced the platelet deposition to 85% of placebo. At higher doses of 80 and 320 anti-Xa U/kg Orgaran@ only marginally inhibited platelet deposition up to 20 and 15 min, respectively. Thereafter, plateaus were reached for 80 U at 37o/" and for 320 U at 26% of placebo, after which the numbers of deposited platelets gradually declined.…”

Section: Thrombus Growth and Platelet Consumptionmentioning

confidence: 89%

Pentasaccharide and Orgaran® Arrest, whereas Heparin Delays Thrombus Formation in a Rat Arteriovenous Shunt

Vogel¹,

Amsterdam²,

Kop³

et al. 1993

Thromb Haemost

View full text Add to dashboard Cite

SummaryThe mode of action of glycosaminoglycans (GAGs) towards thrombus formation in a rat arteriovenous shunt was studied by simultaneous examination of thrombus weight, platelet consumption and thrombin generation during 45 min of blood circulation. A comparison was made between the effects of heparin, the heparinoid Org 10172 (Orgaran®), and the chemically synthesized methoxy derivative of the antithrombin III binding pentasaccharide fragment of heparin (Org 31540).All three compounds inhibited thrombus growth by 30% at a dose of 80 anti-Xa U/kg i. v. when assessed after 15 min of circulation through the shunt. In addition, a systemic decrease of 27% of platelet numbers in the placebo group was inhibited by heparin and Orgaran® with 63% and by pentasaccharide with 48%. At a later stage, after 45 min of circulation, at comparable plasma anti-Xa levels, thrombi which had formed in the presence of Orgaran® or pentasaccharide, but not in the presence of heparin, became less or non thrombogenic. This non-thrombogenicity was reflected by i) an inhibition of the local deposition of [51Cr]platelets of 75% with Orgaran® and of 57% with pentasaccharide, and ii) an inhibition of ex-vivo thrombus-induced thrombin generation in pooled rat plasma of 67% with Orgaran® and of 52% with pentasaccharide (inhibition compared to placebo).Although the mechanism of inducing non-thrombogenicity of a (developing) thrombus by Orgaran® and pentasaccharide requires further investigation, the suppression of the local thrombin generation potency, measured by thrombus-induced thrombin generation in pooled plasma, is much more correlated with thrombus growth than systemic anticoagulant activity. This suppression is likely to be due to the anti-Xa activity, as reflected by the efficacy of the pure Xa inhibiting pentasaccharide. Limitation of thrombus growth adds to the prophylactic perspective of Orgaran® and pentasaccharide in preventing thrombosis.

show abstract

“…Both β-TG and PF4 are stored in similar quantities in the α-granules of platelets and are released extracellularly upon platelet activation (Kaplan and Owen 1981). As PF4 has a very short half life in vivo (<3 min), probably because of rapid binding of released PF4 to vascular endothelial cells (Walz et al 1985), it is frequently used as an indicator for undesired in vitro platelet activation due to sample handling. In vivo platelet activation is characterised by the concurrent presence of increased concentrations of β-TG and normal to slightly increased PF4 concentrations, whereas in vitro release can be recognised by increased concentrations of both β-TG and PF4 in combination with a β-TG/ PF4 ratio <2.…”

Section: Discussionmentioning

confidence: 99%

Determination of the source of increased serotonin (5‐HT) concentrations in blood and peritoneal fluid of colic horses with compromised bowel

Delesalle

Walle

Nolten

et al. 2008

Equine Veterinary Journal

View full text Add to dashboard Cite

In horses with compromised bowel, significant amounts of 5-HT can be released into the systemic circulation, through massive release of platelet-stored 5-HT. 5-HT is a very potent proinflammatory, vasoconstrictive and immunomodulatory agent. In view of the rapid and prolonged tachyphylaxia, shown for the jejunal 5-HT1A-like receptors, this increased systemic 5-HT release could play a role in the pathophysiology of ileus in horses.

show abstract

In Vivo Studies on the Binding of Heparin and Its Fractions with Platelet Factor 4

Cited by 31 publications

References 43 publications

Pharmacokinetic Studies of Standard Heparin and Low Molecular Weight Heparin in Patients with Chronic Renal Failure

Pharmacokinetic Studies of Standard Heparin and Low Molecular Weight Heparin in Patients with Chronic Renal Failure

Pentasaccharide and Orgaran® Arrest, whereas Heparin Delays Thrombus Formation in a Rat Arteriovenous Shunt

Determination of the source of increased serotonin (5‐HT) concentrations in blood and peritoneal fluid of colic horses with compromised bowel

Contact Info

Product

Resources

About