Antithrombotic effects of heparin oligosaccharides.
Size homogeneous heparin oligosaccharides were prepared from nitrous acid depolymerized heparin by means of repeated gel filtration chromatography. These oligosaccharides were then further separated with respect to affinity for antithrombin by means of affinity chromatography. All the high-affinity oligosaccharides thus obtained had a strong ability to potentiate factor Xa inhibition while their ability to inhibit factor IIa abruptly dropped below a chain length of 20 monosaccharides. In a rabbit stasis model, high-affinity oligosaccharides below a chain length of 20 units also showed a continuous decrease in antithrombotic effect with increasing degree of depolymerization. However, there was no distinct drop paralleling the thrombin inhibiting capacity. Low-affinity oligosaccharides also exhibited a weak antithrombotic effect, although they did not always contribute to an increased anti-factor Xa activity ex vivo. This was the case whether or not they were administered alone or in combination with high-affinity oligosaccharides. Low-affinity oligosaccharides may therefore exert an antithrombotic effect per se with a mechanism of action that is independent of antithrombin III.
Mattsson
C
C
Kabi Cardiovascular, Stockholm, Sweden.
Palm
M
M
Söderberg
K
K
Holmer
E
E
D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D015951:Factor Xa; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D009608:Nitrous Acid; D009844:Oligosaccharides / Q000302:isolation & purification / Q000627:therapeutic use*; D010314:Partial Thromboplastin Time; D011817:Rabbits; D015842:Serine Proteinase Inhibitors; D013927:Thrombosis / Q000188:drug therapy*
D000991:Antithrombins; D009844:Oligosaccharides; D015842:Serine Proteinase Inhibitors; D006493:Heparin; D015951:Factor Xa; D009608:Nitrous Acid