Appearance of heparin antithrombin-active chains in vivo after injection of commercial heparin and in anaphylaxis

Abstract

Recently it has been demonstrated that only one-third of commercial heparin binds with antithrombin III to enhance antithrombin activity, and that heparin is rapidly taken up by the RES. Commercial heparin was given to rabbits, dogs and men by subcutaneous and intravenous injection. Plasma samples were deproteinized with phenol, urine samples precipitated with benzidine, and the separated heparin measured for both antithrombin and metachromatic (dye-binding) activity compared to a reference heparin. Urinary excretion as heparin and uroheparin accounted for approximately 5% of the injected heparin. The extraction of heparin added to blood in vitro gave identical values in metachromatic and antithrombin assays, as did heparin from blood samples immediately after intravenous injection. However, later blood samples after injection gave much higher values in the test for antithrombic activity than in the metachromatic test. Subcutaneous injection of heparin subjected to acid inactivation in vitro, reducing its antithrombin activity, likewise resulted in heparin appearing in vivo with higher antithrombin activity. Endogenous heparin released to the circulation in canine anaphylaxis also gave much higher values in anti-thrombin assays. It is concluded that the difference in values is due to the conversion of antithrombin-inactive heparin chains to antithrombin-active heparin chains.