Effects of low-molecular-weight heparin on platelets as compared with commercial heparin

Cella, Giuseppe; Scattolo, Novella; Luzzatto, Guido; Girolami, Antonio

doi:10.1007/bf01852381

Cited by 14 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

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: 69%

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: 69%

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

“…These observations suggest that K-2I65 at this dose is less efticient at mobilising PF 4 from the pool and that some remains to be mobilised by the subsequent challenge by heparin. This suggestion is in contrast to the findings of Cella et al (8). They compared the HMP.PF 4 after UF heparin and after a low molecular weight heparin ( likely, the pool becomes refractory.…”

Section: Discussioncontrasting

confidence: 57%

The Heparin-Mobilisable Pool of Platelet Factor 4: A Comparison of Intravenous and Subcutaneous Heparin and Kabi Heparin Fragment 2165

O'Brien

Etherington

1985

Thromb Haemost

View full text Add to dashboard Cite

SummarySome clinical advantages are claimed for low molecular weight heparin so the mobilisation of platelet factor 4 (PF 4) from the endothelial pool by the heparins may be relevant. Unfractionated (UF) heparin has been compared with Kabi heparin fragment 2165. A single intravenous (i. v.) injection of 60 iu/kg heparin was compared with 5000 anti-Xa units of Kabi-2165. Less PF 4 was mobilised by Kabi-2165 and some apparently remained in the pool and was released when the pool was subsequently challenged by giving i.v. heparin. Subcutaneous (s. c.) injections of 5000 iu heparin twice daily were compared with 5000 anti-Xa units of Kabi-2165 once daily, each given for a week. The plasma PF 4 was never raised yet when finally challenged with i.v. heparin the pool was “empty” or refractory after the s.c. heparin but some PF 4 remained after the s.c. Kabi-2165. The two glycosaminogly-cans (GAGs) had widely differing half-lives but the t/2 of the PF 4 mobilised by the two GAGs was similar even though the PF 4 is apparently bound to the GAG.

show abstract

“…As shown in Figure 1A, although addition of heparin by itself induced neither aggregation nor granule secretion, it potentiated both reactions in the presence of low-dose ADP, confirming previous observations. 4,22 LMWH and the synthetic pentasaccharide fondaparinux (Arixtra) had similar potentiating effects (supplemental Figures 1A, 2A, available on the Blood Web site; see the Supplemental Materials link at the top of the online article). Human platelets also bound to and spread on immobilized heparin ( Figure 1B) and fondaparinux (supplemental Figure 2C), suggesting that adhesion to heparin and heparin-like substances, much like exposure to them in solution, results in the transmission of outside-in signals that potentiate cytoskeletal rearrangements associated with platelet activation.…”

Section: Heparin Potentiates Platelet Responsiveness By Initiating Plmentioning

confidence: 88%

Heparin promotes platelet responsiveness by potentiating αIIbβ3-mediated outside-in signaling

Gao

Boylan

Fang

et al. 2011

Blood

111

View full text Add to dashboard Cite

Unfractionated heparin (UFH) is a widely used anticoagulant that has long been known to potentiate platelet responses to subthreshold doses of platelet agonists. UFH has been reported to bind and induce modest conformational changes in the major platelet integrin, ␣IIb␤3, and induce minor changes in platelet morphology. The mechanism by which UFH elicits these platelet-activating effects, however, is not well understood. We found that both human and murine platelets exposed to UFH, either in solution or immobilized onto artificial surfaces, underwent biochemical and morphologic changes indicative of a potentiated state, including phosphorylation of key cytosolic signaling molecules and cytoskeletal changes leading to cell spreading. Low molecular weight heparin and the synthetic pentasaccharide, fondaparinux, had similar plateletpotentiating effects. Human or mouse platelets lacking functional integrin ␣IIb␤3 complexes and human platelets pretreated with the fibrinogen receptor antagonists eptifibatide or abciximab failed to become potentiated by heparin, demonstrating that heparin promotes platelet responsiveness via its ability to initiate ␣IIb␤3-mediated outside-in signaling. Taken together, these data provide novel insights into the mechanism by which platelets become activated after exposure to heparin and heparin-coated surfaces, and suggest that currently used glycoprotein IIb-IIIa inhibitors may be effective inhibitors of nonimmune forms of heparin-induced platelet activation.

show abstract

Effects of low-molecular-weight heparin on platelets as compared with commercial heparin

Cited by 14 publications

References 8 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

The Heparin-Mobilisable Pool of Platelet Factor 4: A Comparison of Intravenous and Subcutaneous Heparin and Kabi Heparin Fragment 2165

Heparin promotes platelet responsiveness by potentiating αIIbβ3-mediated outside-in signaling

Contact Info

Product

Resources

About