Anticoagulant properties of heparin preparations from different animal sources with equivalent high affinity for antithrombin III.
Three kinds of heparins from different animal sources--hog-intestinal heparin (167 USP units/mg), bovine-lung heparin (149 USP units/mg) and whale-intestinal heparin (Balaenoptera borealis L., 174 USP units/mg)--were fractionated through an antithrombin III-Sepharose column and high-affinity (HA) subfractions (1.2-1.8 M NaCl eluted fractions) were separated. These HA heparin specimens, which were confirmed to be equivalent in strength of binding to antithrombin III, were compared with respect to the anticoagulant properties by means of [1] whole blood clotting assay and [2] thrombin or [3] factor Xa inhibition assay. The activities of whale HA heparin were [1] 82%, [2] 38%, and [3] 45%, respectively, of those of the hog and bovine HA heparins (which showed approximately identical activities). Since it was confirmed that the affinity for antithrombin III of whale heparin is of the same nature as those of hog and bovine heparins by (a) fluorometric titration and (b) affinity chromatography on an antithrombin III-Sepharose column saturated with hog HA heparin, the above difference in anticoagulant properties between the whale HA heparin and hog and bovine HA heparins may be considered to be due to a difference in undescribed saccharide-sequence structures at sites other than the well-characterized antithrombin III-binding sites, suggesting strongly that some heparin saccharide structures other than antithrombin III-binding oligosaccharide participate in the anticoagulant activity dependent on antithrombin III-heparin binding--at least in the manifestation of anti-thrombin activity and the enhancement of anti-Xa activity.
D000818:Animals; D000925:Anticoagulants; D000990:Antithrombin III / Q000378:metabolism*; D002417:Cattle; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D006493:Heparin / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D011485:Protein Binding; D013045:Species Specificity; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors; D014907:Whales
D000925:Anticoagulants; D000990:Antithrombin III; D005170:Factor X; D006493:Heparin; D013917:Thrombin; D015951:Factor Xa