Elimination of high affinity heparin fractions and their anticoagulant and
lipase activity
CA de Swart, B Nijmeyer, LO Andersson, E Holmer, L Verschoor, BN Bouma and JJ Sixma
High and low affinity heparin (HA and LA heparin) were prepared from
commercial heparin by affinity chromatography to insolubilized antithrombin
III. HA heparin was radiolabeled with 35S and subdivided by gel
chromatography into high molecular weight (HMW, average 17,000- 26,000
daltons), intermediate molecular weight (MMW, average 12,000- 13,000
daltons), low molecular weight (LMW, average 5,000-7,000 daltons), and very
low molecular weight (VLMW, average 4,600 daltons) fractions. The kinetics
of lipolytic and anticoagulant activity and protein-bound radioactivity
were studied after intravenous injection of these fractions. LA heparin
failed to induce anticoagulant activity but released the hepatic
triglyceride lipase (H-TGL) and lipoprotein lipase (LPL) activities
normally. VLMW and LMW heparin failed to release both lipolytic enzymes and
did not induce anticoagulant activity measurable by the activated partial
thromboplastin time (APTT). A powerful anticoagulant effect was found in
the anti-Xa assay, which disappeared according to a continuously concave
curve in semilogarithmic plots, with elimination rates similar to those of
the protein-bound radiolabel. The other heparin preparations induced all
activities measured. Heparin anticoagulant activity estimated by the two
assays disappeared following a convex curve, preceded by a rapid initial
elimination phase in semilogarithmic plots. The disappearance rates of
plasma protein-bound heparin radioactivity and heparin anticoagulant
activity estimated by factor Xa inactivation were similar. Peak values of
the two lipolytic activities were attained rapidly. H- TGL activity, as
well as LPL activity, disappeared following convex curves in
semilogarithmic plots, with elimination rates similar to those of plasma
protein-bound heparin radioactivity. On the basis of these kinetics, we
suggest that, after intravenous administration of heparin, the two
lipolytic enzymes present in plasma are complexed with heparin, analogous
to the heparin-antithrombin III complex. Finally, the kinetic data indicate
that elimination of these activities is determined by the heparin part of
the complexes, probably by removal of free heparin.
Volume 63,
Issue 4,
pp. 836-842,
04/01/1984
Copyright © 1984 by The American Society of Hematology
