Interaction of immobilised unfractionated and LMW heparins with proteins in whole human plasma.
The profile of proteins bound to immobilised heparins in hirudin-anticoagulated human plasma was analysed. In molar terms, antithrombin III was the most abundant protein bound to therapeutic doses of unfractionated heparin (M(r) = 12,000), whereas heparin cofactor II constituted < 1% of the protein bound. Histidine-rich glycoprotein was the only plasma protein likely to influence anticoagulant activity by direct competition with antithrombin III, though significant quantities of complement Factor H, fibrinogen, fibronectin, vitronectin and apolipoprotein B were also detected. Only traces of von Willebrand factor, complement factor I, inter-alpha-trypsin inhibitor, alpha 2-macroglobulin, serum amyloid P and transferrin were identified, and neither thrombospondin nor platelet factor 4 were measurable. Binding of both antithrombin III and histidine-rich glycoprotein varied with the ratio of heparin to plasma. Clexane (M(r) = 4,500) also bound antithrombin III, but both histidine-rich glycoprotein and vitronectin were quantitatively significant neutralising proteins. Neutralising proteins dominated the binding profile for Oligo H (M(r) = 2,200).
Zammit
A
A
Heart Research Institute, Sydney, Australia.
Pepper
D S
DS
Dawes
J
J
D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D017984:Enoxaparin / Q000097:blood; D006493:Heparin / Q000097:blood*; D006495:Heparin, Low-Molecular-Weight / Q000097:blood*; D006801:Humans; D008970:Molecular Weight; D011485:Protein Binding
D001798:Blood Proteins; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; D002118:Calcium