PMID: 9422339Jan 9, 1998Paper

The variable anticoagulant response to unfractionated heparin in vivo reflects binding to plasma proteins rather than clearance

The Journal of Laboratory and Clinical Medicine
L MansonE Young

Abstract

The anticoagulant response to fixed doses of unfractionated heparin is variable in patients with acute illness, and some patients with venous thromboembolism require high doses of heparin to achieve a therapeutic anticoagulant response. To investigate the mechanism responsible for the variable anticoagulant response to heparin in acute illness, heparin clearance and nonspecific protein binding were compared in control and endotoxin-treated rabbits. The plasma half-life (t 1/2) of radiolabeled heparin increased in a dose-dependent fashion. At all doses of heparin studied, the t 1/2 of radiolabeled heparin was unaffected by experimental endotoxemia when compared with control animals. In contrast, the amount of heparin recovered was lower in the plasma of endotoxemic animals because of increased binding to plasma proteins. A chemically modified heparin with low affinity for antithrombin III was added ex vivo or in vivo to displace heparin bound nonspecifically to plasma proteins. The proportion of heparin bound to plasma proteins was significantly greater in the plasma of endotoxemic animals than in controls. These findings indicate that acute inflammation alters heparin recovery but does not affect heparin clearance. The variabil...Continue Reading

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Citations

Dec 5, 2009·Critical Care : the Official Journal of the Critical Care Forum·Heleen M Oudemans-van StraatenAnja Leyte
Feb 25, 2011·Critical Care : the Official Journal of the Critical Care Forum·Heleen M Oudemans-van StraatenRinaldo Bellomo
Jul 28, 2015·Biomacromolecules·Thi H NguyenHeather D Maynard
Jun 7, 2011·International Journal of Obstetric Anesthesia·H BoyceG M Stocks
Oct 18, 2011·Seminars in Hematology·Shannon M Bates
Mar 6, 2010·International Journal of Obstetric Anesthesia·A J Butwick, B Carvalho
Oct 16, 2016·Biomacromolecules·Samantha J PaluckHeather D Maynard
Mar 22, 2000·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·C H MielkeW A Dittman
Jun 9, 2017·British Journal of Clinical Pharmacology·Jenneke LeentjensCornelis Kramers
Dec 5, 2018·Expert Opinion on Pharmacotherapy·Marc LaineLaurent Bonello
Aug 20, 2009·Anesthesia and Analgesia·Carl-Erik DempfleMartin Borggrefe
Dec 30, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nagina ParmarAnthony K C Chan
Sep 21, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xiaoli LiuJohn L Brash

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