The interaction of protein-bound heparin and antithrombin III.
When commercially prepared porcine mucosal heparin is added to human plasma, some of the heparin fractions form a complex with antithrombin III activating it to an immediate inhibitor of thrombin as well as of other serine proteases. Certain fractions of heparin may complex with other proteins such as alpha 2-macroglobulin, another progressive inhibitor of thrombin. Without complexing with antithrombin III, this protein-bound heparin fraction(s) still retains the capacity to activate it to an immediate inhibitor of thrombin. Protamine sulfate inactivates those heparin fractions that bind to antithrombin III but not those bound to alpha 2-macroglobulin. Activated antithrombin III may undergo a molecular change in the presence of protamine which not only changes it back to a progressive inhibitor but makes it resistant to activation by the protein-bound heparin fraction(s). However, it can still be reactivated by other heparin fractions in fresh whole heparin. The observations presented may help explain heparin "rebound" in patients believed adequately neutralized with protamine.
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism*; D002850:Chromatography, Gel; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D013552:Swine; D000511:alpha-Macroglobulins / Q000378:metabolism
D012709:Serum Albumin; D000511:alpha-Macroglobulins; D000990:Antithrombin III; D006493:Heparin